Early Course Schizophrenia Spectrum Disorder
Conditions
Brief summary
This study will test whether CVL-562 (PF-06412562), a dopamine 1 partial agonist novel compound, affects working memory neural circuits in patients with early episode schizophrenia. The overall aim is to establish neuroimaging biomarkers of the Dopamine Receptor 1/Dopamine Receptor 5 Family (D1R/D5R) target engagement to accelerate development of D1R/D5R agonists in humans to treat cognitive impairments that underlie functional disability in schizophrenia, a key unaddressed clinical and public health concern.
Detailed description
This study proposes to examine the effects of CVL-562 (PF-06412562), a dopamine-1 receptor partial agonist, on the neural signal of brain regions involved in cognition in patients with schizophrenia and related psychotic disorders. The primary objective of this study is to understand the neural circuit targets of this compound as it relates to improving cognition in schizophrenia, using a spatial working memory task (sWM). The secondary objective will quantify dose-related drug effects on sWM precision based on behavioral data collected during scanning and examine effects on functional connectivity. All patients will be psychiatrically stable with early course (psychotic symptom onset within the past 10 years) schizophrenia spectrum disorder (e.g. schizophrenia, schizoaffective disorder, or schizophreniform disorder) and will have working memory deficits (defined as below average performance on the letter n-back task of the PennCNB battery). As part of the study, they will receive oral administration of specified doses of CVL-562 (PF-06412562), in a random order with repeated functional magnetic resonance imaging and cognitive testing during those visits. The most common side effects of this compound are nausea and headache. This is a multi-site study that requires the efforts of 4 study sites in total (Columbia, State University of New York Stony Brook, UPenn, and Yale). At time of results entry, secondary outcome results unavailable due to ongoing restrictions per the NIH
Interventions
DRUGCVL-562 (PF-06412562) 1 mg
Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).
DRUGCVL-562 (PF-06412562) 4 mg
Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).
DRUGCVL-562 (PF-06412562) 15 mg
Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).
DRUGCVL-562 (PF-06412562) 25 mg
Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).
OTHERPlacebo
Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. Each test visit will be separated by at least 48 hours (six half-lives of CVL-562 (PF-06412562)).
Sponsors
Columbia University
University of Pennsylvania
State University of New York Stony Brook
Cerevel Therapeutics, LLC
National Institute of Mental Health (NIMH)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Between the ages of 18 (including 18 years of age) and 45 (up to 45 years and 11 months) at the time of baseline study visit. * Able to provide informed consent (as established by consent interview), and voluntary, signed informed consent prior to the performance of any study-specific procedures * Willing and able to perform study-relevant clinical assessments and Magnetic Resonance Imaging (MRI) as assessed by research staff. * Meet Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder on the basis of the Structured Clinical Interview for DSM-5 (SCID-5). * Be within 10 years of the onset of psychosis based on clinical assessment at the time of Visit 1. * Treatment seeking and willing to accept the constraints on treatment entailed by the study. * Able to demonstrate a basic ability to follow spatial working memory task instructions and perform necessary related motor functions. * Demonstrate a premorbid IQ of ≥80 based on the Penn Reading Assessment (PRA). The PRA correlates with other measures of IQ including the Wide Range Achievement Test (WRAT), but is computerized, based in the laboratory of co-investigators Ruben C. Gur and Raquel E. Gur, and brief to administer, allowing us to lessen the assessment burden on an already lengthy first visit. * Be fluent in English as assessed by research staff. * Clinically stable treatment for at least two months prior to Visit 1 (no hospitalizations, or current suicidal/homicidal active ideation, intent, or plan). * On a stable psychotropic medication regimen (can include no psychotropic medications) for at least 3 weeks prior to Visit 1, and willing to maintain an unchanged regimen during the study. If on depot antipsychotics, participants must have stable dosing for at least two consecutive injections (including the most recent one) as the most recent injections. If on Invega Trinza, there must be no plans to change dosing during the course of the study. * For women of child bearing potential, no intention to become pregnant during the study period, and agreement to use a reliable method of birth control (e.g. Intra-Uterine Device (IUD), hormonal contraception, abstinence, condoms) during the study period. Women will be asked to continue their method of contraception for 1 month after receiving their final dose of medication. Any individual who becomes pregnant during the study will be immediately removed, and discussion of the risks and benefits of ongoing pharmacotherapy will proceed on purely clinical grounds.
Exclusion criteria
* Any unstable medical, psychiatric, or neurological condition (including active or otherwise remarkable suicidal or homicidal ideation) that may necessitate urgent treatment. Active medical conditions that are minor or well controlled are not exclusionary if they do not affect risk to the patient, metabolism of study drug, or the study results (e.g. well-controlled type II diabetes or hypertension) as per the judgment of the investigator. * Be currently treated with any of the following: olanzapine, clozapine, ziprasidone or asenapine, in order to avoid prominent D1 receptor effects. * Any major neurological disease, brain injury, epilepsy, or history of severe head trauma, including concussion with loss of consciousness greater than or equal to \> 15 minutes, or of psychosurgery. * History of significant cardiac disease (ex: ischemia, arrhythmia). * Any clinically significant abnormality on baseline medical screening tests (electrocardiogram (EKG), complete blood count with differential (CBC), complete metabolic profile (CMP). * Hepatitis B or C (by report or testing) in the presence of abnormal liver function tests * Human Immunodeficiency Virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS) (by report or by testing) due cognitive effects of HIV and AIDS. * Baseline EKG showing prolonged QTc interval (\>450 for males, \>470 for females, Framingham correction(3)), with repeat measurement showing the same abnormality. * Current mood episode meeting criteria for a major depressive episode or a manic or hypomanic episode. * History of electroconvulsive therapy (ECT) or treatment with neurostimulation in the past 6 months, or with plans to begin either such treatment during the study. * History of ADHD pre-morbid to the onset of psychosis or other psychiatric illnesses that may be accompanied by cognitive impairments. * Meeting SCID-5 moderate or severe substance use disorder for any substance other than nicotine within the 3 months prior to the initial assessment. * Positive urine toxicology testing for any substance other than marijuana or those prescribed for medical reasons at Visits 1-6. * Pregnancy or intention to become pregnant during the study. * Lactating/breast-feeding or intending to do so during the study * Any non-MRI compatible metal in the body or other contraindication to MR imaging. A copper IUD is allowable if permitted by local MRI practices. * Severe claustrophobia, back pain, morbid obesity, or other condition that may make an extended MR session difficult or lead to excessive movement during the imaging session. * Color blindness, strabismus or other uncorrectable visual problems. Those wearing glasses would be asked to use MRI-safe glasses. * Daily use of the following medication within 10 days prior to the initial visit or during the study: Long-acting nighttime or daytime gamma aminobutyric acid-A (GABA-A) receptor facilitators; anticonvulsant medications used at high doses or for seizure control, or psychostimulants or medical cannabis. Participants can be re-assessed for eligibility once they have been free of daily use of these medications for \>10 days. Participants may take non-GABAergic sleep medications, short-acting GABA receptor facilitators (benzodiazepine, non-benzodiazepine) prior to and during the study. * Any change in type or dose of psychotropic medications within 3 weeks prior to initial visit or during study to avoid transient effects of medication regimen change. Medication type and dose will be carefully recorded and used as a covariate in analyses. Participants can be re-assessed for eligibility once they have been on a stable dose of medication for \>3 weeks. * CVL-562 is metabolized by P450 CYP3A4. In order to avoid pharmacokinetic interactions, medications or substances that induce (barbiturate, carbamazepine, etc.) or are moderate-strong inhibitors (ketoconazole, etc.; grapefruit juice) are excluded if used within 10 days prior to or during study. Participants can be re-assessed for eligibility once they have been free of these medications/substances for \>10 days. * Active attempts to discontinue smoking, vaping or other nicotine products within the 3 weeks prior to study or during the study. Participants can be re-assessed once quit attempt is stable. * Diastolic blood pressure \>95 or \<50 mmHg or systolic blood pressure \> 170 or \<80 mmHg with repeat measurement showing the same abnormality. * History of allergy or other contraindication to the proposed pharmacotherapy. * Other medication treatment with which proposed pharmacotherapy is contraindicated, in the opinion of study psychiatrists or of a subject's prescribing psychiatrist.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Up to two hours for each fMRI session | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds \[total 16s\]. Each subject will undergo 5 fMRI sessions, one at each dose. |
| Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Up to two hours for each fMRI session | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds \[total 16s\]. Each subject will undergo 5 fMRI sessions, one at each dose. |
| Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Up to two hours for each fMRI session | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds \[total 16s\]. Each subject will undergo 5 fMRI sessions, one at each dose. |
| Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Up to two hours for each fMRI session | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds \[total 16s\]. Each subject will undergo 5 fMRI sessions, one at each dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Change in Blood Oxygen Level Dependent (BOLD) Signal During Spatial Working Memory (sWM) Task. | Up to two hours for each fMRI session. | The dose-response in BOLD signal will be examined for each individual participant to see how many participants exhibit a change in BOLD signal overall. For each individual, binary outcome will be calculated based on a Dose by Condition by Time within subject analysis of BOLD signal. We will report the proportion of participants that exhibits a dose response. |
| Performance During Spatial Working Memory (sWM) Task | Up to two hours for each fMRI session. | During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. Performance will be assessed with the average accuracy measured during this task for each task condition and each CVL-562 (PF-06412562) dose. Accuracy refers to the angular distance between a cued location and a participant's memory of the location. The range of accuracy is between 0-180 degrees. 0 degrees would indicate the best possible performance, and 180 degrees the worst performance. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562). |
| Spatial Similarity of Resting State Global Brain Functional Connectivity With Transcriptomic Maps. | Up to two hours for each fMRI session. | Transcriptomics maps will be derived from the Allen Human Brain Atlas (AHBA), which provides gene expression data mapped to the cortical surface. The spatial similarity of resting state global brain functional connectivity (GBC) and gene expression patterns for the D1/D5 receptors will be assessed for each CVL-562 (PF-06412562) dose. The spatial similarity refers to correlation between GBC maps and the cortical gene expression maps. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562). |
| Association Between Neural Activity and Task Performance | Up to two hours for each fMRI session. | Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during fMRI, where subjects will participate in a spatial working memory (sWM) task. The sWM includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. The performance of sWM at each trial of each condition will be used as the predictor variable, and the BOLD signal at the corresponding trial and condition will be used as the outcome variable. A trial refers to a single probing and measurement of sWM, and is repeatedly presented to get a number of sWM measurements. The performance of sWM from each trial will be regressed with the BOLD signal from that trial, and we will report the resulting beta weights at each condition and dose. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562). |
| Functional Connectivity Across Brain Regions With the Fronto-parietal Network During sWM Task | Up to two hours for each fMRI session. | Functional connectivity will be assessed during each fMRI session. Functional connectivity refers to the correlation between the time series of different brain regions collected during fMRI. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, the functional connectivity of the fronto-parietal network will be measured with the rest of the brain. The range of functional connectivity is between -4.95 and 4.95. -4.95 would indicate highly negative functional connectivity and 4.95 would indicate highly positive functional connectivity. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562). |
| Resting State Global Brain Functional Connectivity | Up to two hours for each fMRI session. | BOLD signal will be collected during the resting state aspect of the fMRI session, using a data-driven global brain connectivity (GBC) metric. GBC examines connectivity from a given voxel (or area) to all other voxels (or areas) simultaneously by computing average connectivity strength. The range of GBC is between -4.95 and 4.95. -4.95 would indicate highly negative broad functional connectivity in synchrony with the rest of the brain and 4.95 would indicate highly positive broad functional connectivity in synchrony with the rest of the brain. GBC will be obtained at each PF-06412562 dose. |
Countries
United States
Participant flow
Pre-assignment details
Data for participants who started test visits at Columbia was required to be removed due to research restrictions per the NIH (see GCE). Secondary outcome results unavailable due to ongoing restrictions per the NIH.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Each subject will complete 5 test visits each involving the administration of CVL-562 (PF-06412562) (at different doses) or placebo. All participants will receive all doses (a different dose at each of the 5 visits.) | 84 |
| Total | 84 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 27.06 years STANDARD_DEVIATION 5.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 62 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 28 Participants |
| Race (NIH/OMB) More than one race | 18 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 29 Participants |
| Region of Enrollment United States | 84 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 84 | 0 / 84 | 0 / 84 | 0 / 84 | 0 / 84 |
| other Total, other adverse events | 20 / 84 | 21 / 84 | 29 / 84 | 35 / 84 | 24 / 84 | 0 / 84 |
| serious Total, serious adverse events | 0 / 84 | 0 / 84 | 1 / 84 | 0 / 84 | 0 / 84 | 1 / 84 |
Outcome results
Primary
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds \[total 16s\]. Each subject will undergo 5 fMRI sessions, one at each dose.
Time frame: Up to two hours for each fMRI session
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 9.6 | -0.056 percentage signal change | Standard Deviation 0.258 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 13.6 | 0.014 percentage signal change | Standard Deviation 0.246 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 12.8 | -0.026 percentage signal change | Standard Deviation 0.241 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 3.2 | 0.025 percentage signal change | Standard Deviation 0.228 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 8.0 | -0.013 percentage signal change | Standard Deviation 0.254 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 1.6 | -0.086 percentage signal change | Standard Deviation 0.2 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 0.8 | -0.070 percentage signal change | Standard Deviation 0.155 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 12.0 | -0.041 percentage signal change | Standard Deviation 0.235 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 4.0 | 0.071 percentage signal change | Standard Deviation 0.243 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 7.2 | 0.011 percentage signal change | Standard Deviation 0.25 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 15.2 | 0.146 percentage signal change | Standard Deviation 0.279 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 14.4 | 0.079 percentage signal change | Standard Deviation 0.251 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 11.2 | -0.053 percentage signal change | Standard Deviation 0.233 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 4.8 | 0.089 percentage signal change | Standard Deviation 0.243 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 6.4 | 0.054 percentage signal change | Standard Deviation 0.255 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 2.4 | -0.042 percentage signal change | Standard Deviation 0.2 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 8.8 | -0.038 percentage signal change | Standard Deviation 0.256 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 10.4 | -0.068 percentage signal change | Standard Deviation 0.246 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 5.6 | 0.087 percentage signal change | Standard Deviation 0.251 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 16.0 | 0.200 percentage signal change | Standard Deviation 0.286 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 5.6 | 0.145 percentage signal change | Standard Deviation 0.219 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 9.6 | 0.027 percentage signal change | Standard Deviation 0.223 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 6.4 | 0.126 percentage signal change | Standard Deviation 0.212 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 14.4 | 0.142 percentage signal change | Standard Deviation 0.234 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 8.8 | 0.043 percentage signal change | Standard Deviation 0.216 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 7.2 | 0.088 percentage signal change | Standard Deviation 0.213 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 8.0 | 0.056 percentage signal change | Standard Deviation 0.207 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 1.6 | -0.036 percentage signal change | Standard Deviation 0.197 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 12.8 | 0.037 percentage signal change | Standard Deviation 0.227 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 13.6 | 0.077 percentage signal change | Standard Deviation 0.231 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 2.4 | 0.013 percentage signal change | Standard Deviation 0.214 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 15.2 | 0.203 percentage signal change | Standard Deviation 0.246 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 3.2 | 0.074 percentage signal change | Standard Deviation 0.225 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 0.8 | -0.040 percentage signal change | Standard Deviation 0.148 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 12.0 | 0.032 percentage signal change | Standard Deviation 0.211 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 4.0 | 0.131 percentage signal change | Standard Deviation 0.223 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 11.2 | 0.028 percentage signal change | Standard Deviation 0.21 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 4.8 | 0.151 percentage signal change | Standard Deviation 0.223 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 16.0 | 0.247 percentage signal change | Standard Deviation 0.265 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 10.4 | 0.024 percentage signal change | Standard Deviation 0.214 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 9.6 | -0.038 percentage signal change | Standard Deviation 0.265 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 7.2 | 0.032 percentage signal change | Standard Deviation 0.279 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 8.0 | -0.009 percentage signal change | Standard Deviation 0.273 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 14.4 | 0.101 percentage signal change | Standard Deviation 0.281 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 16.0 | 0.209 percentage signal change | Standard Deviation 0.307 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 0.8 | -0.060 percentage signal change | Standard Deviation 0.164 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 1.6 | -0.076 percentage signal change | Standard Deviation 0.218 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 2.4 | -0.039 percentage signal change | Standard Deviation 0.216 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 3.2 | 0.025 percentage signal change | Standard Deviation 0.22 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 4.0 | 0.081 percentage signal change | Standard Deviation 0.245 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 4.8 | 0.109 percentage signal change | Standard Deviation 0.266 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 5.6 | 0.096 percentage signal change | Standard Deviation 0.287 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 6.4 | 0.067 percentage signal change | Standard Deviation 0.28 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 8.8 | -0.033 percentage signal change | Standard Deviation 0.269 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 10.4 | -0.032 percentage signal change | Standard Deviation 0.267 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 11.2 | -0.024 percentage signal change | Standard Deviation 0.267 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 12.0 | 0.000 percentage signal change | Standard Deviation 0.269 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 12.8 | 0.005 percentage signal change | Standard Deviation 0.272 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 13.6 | 0.046 percentage signal change | Standard Deviation 0.273 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 15.2 | 0.165 percentage signal change | Standard Deviation 0.29 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 4.0 | 0.060 percentage signal change | Standard Deviation 0.207 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 4.8 | 0.091 percentage signal change | Standard Deviation 0.224 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 12.8 | -0.029 percentage signal change | Standard Deviation 0.217 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 11.2 | -0.038 percentage signal change | Standard Deviation 0.206 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 2.4 | -0.045 percentage signal change | Standard Deviation 0.197 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 15.2 | 0.134 percentage signal change | Standard Deviation 0.246 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 16.0 | 0.172 percentage signal change | Standard Deviation 0.258 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 13.6 | 0.002 percentage signal change | Standard Deviation 0.222 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 1.6 | -0.079 percentage signal change | Standard Deviation 0.184 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 0.8 | -0.065 percentage signal change | Standard Deviation 0.151 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 14.4 | 0.056 percentage signal change | Standard Deviation 0.235 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 10.4 | -0.031 percentage signal change | Standard Deviation 0.216 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 3.2 | 0.010 percentage signal change | Standard Deviation 0.193 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 5.6 | 0.089 percentage signal change | Standard Deviation 0.228 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 8.0 | 0.019 percentage signal change | Standard Deviation 0.243 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 7.2 | 0.040 percentage signal change | Standard Deviation 0.238 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 12.0 | -0.040 percentage signal change | Standard Deviation 0.229 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 9.6 | -0.022 percentage signal change | Standard Deviation 0.223 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 8.8 | -0.010 percentage signal change | Standard Deviation 0.228 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 6.4 | 0.067 percentage signal change | Standard Deviation 0.236 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 8.8 | -0.018 percentage signal change | Standard Deviation 0.242 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 5.6 | 0.090 percentage signal change | Standard Deviation 0.228 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 9.6 | -0.042 percentage signal change | Standard Deviation 0.246 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 4.8 | 0.098 percentage signal change | Standard Deviation 0.224 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 10.4 | -0.042 percentage signal change | Standard Deviation 0.237 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 4.0 | 0.068 percentage signal change | Standard Deviation 0.216 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 15.2 | 0.150 percentage signal change | Standard Deviation 0.269 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 11.2 | -0.044 percentage signal change | Standard Deviation 0.233 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 3.2 | 0.012 percentage signal change | Standard Deviation 0.204 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 8.0 | 0.000 percentage signal change | Standard Deviation 0.24 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 12.0 | -0.038 percentage signal change | Standard Deviation 0.235 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 2.4 | -0.053 percentage signal change | Standard Deviation 0.198 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 0.8 | -0.081 percentage signal change | Standard Deviation 0.152 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 12.8 | -0.029 percentage signal change | Standard Deviation 0.236 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 1.6 | -0.093 percentage signal change | Standard Deviation 0.187 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 14.4 | 0.086 percentage signal change | Standard Deviation 0.249 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 13.6 | 0.019 percentage signal change | Standard Deviation 0.242 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 7.2 | 0.032 percentage signal change | Standard Deviation 0.245 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 6.4 | 0.059 percentage signal change | Standard Deviation 0.237 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 1 | Second 16.0 | 0.204 percentage signal change | Standard Deviation 0.287 |
Primary
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds \[total 16s\]. Each subject will undergo 5 fMRI sessions, one at each dose.
Time frame: Up to two hours for each fMRI session
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 8.8 | -0.036 percentage signal change | Standard Deviation 0.292 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 8.0 | -0.009 percentage signal change | Standard Deviation 0.294 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 15.2 | 0.138 percentage signal change | Standard Deviation 0.281 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 0.8 | -0.076 percentage signal change | Standard Deviation 0.165 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 4.8 | 0.119 percentage signal change | Standard Deviation 0.261 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 3.2 | 0.024 percentage signal change | Standard Deviation 0.238 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 16.0 | 0.187 percentage signal change | Standard Deviation 0.29 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 14.4 | 0.073 percentage signal change | Standard Deviation 0.278 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 11.2 | -0.049 percentage signal change | Standard Deviation 0.292 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 1.6 | -0.090 percentage signal change | Standard Deviation 0.217 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 13.6 | 0.015 percentage signal change | Standard Deviation 0.275 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 10.4 | -0.054 percentage signal change | Standard Deviation 0.289 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 9.6 | -0.045 percentage signal change | Standard Deviation 0.288 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 6.4 | 0.078 percentage signal change | Standard Deviation 0.28 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 5.6 | 0.105 percentage signal change | Standard Deviation 0.271 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 12.8 | -0.017 percentage signal change | Standard Deviation 0.275 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 7.2 | 0.038 percentage signal change | Standard Deviation 0.287 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 4.0 | 0.092 percentage signal change | Standard Deviation 0.24 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 2.4 | -0.045 percentage signal change | Standard Deviation 0.235 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 12.0 | -0.025 percentage signal change | Standard Deviation 0.289 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 12.0 | 0.051 percentage signal change | Standard Deviation 0.25 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 8.0 | 0.064 percentage signal change | Standard Deviation 0.26 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 2.4 | -0.042 percentage signal change | Standard Deviation 0.231 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 11.2 | 0.036 percentage signal change | Standard Deviation 0.237 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 8.8 | 0.045 percentage signal change | Standard Deviation 0.248 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 10.4 | 0.027 percentage signal change | Standard Deviation 0.235 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 9.6 | 0.032 percentage signal change | Standard Deviation 0.242 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 0.8 | -0.090 percentage signal change | Standard Deviation 0.177 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 3.2 | 0.028 percentage signal change | Standard Deviation 0.239 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 16.0 | 0.229 percentage signal change | Standard Deviation 0.251 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 15.2 | 0.177 percentage signal change | Standard Deviation 0.248 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 4.0 | 0.094 percentage signal change | Standard Deviation 0.256 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 1.6 | -0.097 percentage signal change | Standard Deviation 0.225 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 14.4 | 0.124 percentage signal change | Standard Deviation 0.242 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 4.8 | 0.137 percentage signal change | Standard Deviation 0.259 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 13.6 | 0.072 percentage signal change | Standard Deviation 0.238 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 5.6 | 0.144 percentage signal change | Standard Deviation 0.263 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 6.4 | 0.118 percentage signal change | Standard Deviation 0.256 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 12.8 | 0.049 percentage signal change | Standard Deviation 0.243 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 7.2 | 0.097 percentage signal change | Standard Deviation 0.257 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 16.0 | 0.225 percentage signal change | Standard Deviation 0.31 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 0.8 | -0.072 percentage signal change | Standard Deviation 0.18 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 1.6 | -0.083 percentage signal change | Standard Deviation 0.223 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 2.4 | -0.039 percentage signal change | Standard Deviation 0.235 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 3.2 | 0.031 percentage signal change | Standard Deviation 0.245 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 4.0 | 0.104 percentage signal change | Standard Deviation 0.246 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 4.8 | 0.143 percentage signal change | Standard Deviation 0.257 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 5.6 | 0.153 percentage signal change | Standard Deviation 0.265 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 6.4 | 0.127 percentage signal change | Standard Deviation 0.26 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 7.2 | 0.086 percentage signal change | Standard Deviation 0.251 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 8.0 | 0.055 percentage signal change | Standard Deviation 0.238 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 8.8 | 0.020 percentage signal change | Standard Deviation 0.227 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 10.4 | -0.015 percentage signal change | Standard Deviation 0.237 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 11.2 | -0.012 percentage signal change | Standard Deviation 0.232 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 12.0 | -0.005 percentage signal change | Standard Deviation 0.24 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 12.8 | 0.003 percentage signal change | Standard Deviation 0.247 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 13.6 | 0.033 percentage signal change | Standard Deviation 0.257 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 14.4 | 0.083 percentage signal change | Standard Deviation 0.269 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 9.6 | -0.007 percentage signal change | Standard Deviation 0.23 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 15.2 | 0.153 percentage signal change | Standard Deviation 0.288 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 8.0 | -0.059 percentage signal change | Standard Deviation 0.228 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 11.2 | -0.092 percentage signal change | Standard Deviation 0.212 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 7.2 | -0.028 percentage signal change | Standard Deviation 0.239 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 12.0 | -0.073 percentage signal change | Standard Deviation 0.216 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 6.4 | 0.006 percentage signal change | Standard Deviation 0.243 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 15.2 | 0.091 percentage signal change | Standard Deviation 0.238 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 12.8 | -0.052 percentage signal change | Standard Deviation 0.216 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 10.4 | -0.093 percentage signal change | Standard Deviation 0.209 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 13.6 | -0.025 percentage signal change | Standard Deviation 0.214 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 4.8 | 0.027 percentage signal change | Standard Deviation 0.251 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 0.8 | -0.136 percentage signal change | Standard Deviation 0.169 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 14.4 | 0.028 percentage signal change | Standard Deviation 0.223 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 4.0 | -0.012 percentage signal change | Standard Deviation 0.235 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 3.2 | -0.066 percentage signal change | Standard Deviation 0.228 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 16.0 | 0.130 percentage signal change | Standard Deviation 0.277 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 2.4 | -0.135 percentage signal change | Standard Deviation 0.213 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 9.6 | -0.091 percentage signal change | Standard Deviation 0.207 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 8.8 | -0.087 percentage signal change | Standard Deviation 0.22 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 5.6 | 0.033 percentage signal change | Standard Deviation 0.246 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 1.6 | -0.167 percentage signal change | Standard Deviation 0.207 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 10.4 | -0.030 percentage signal change | Standard Deviation 0.253 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 1.6 | -0.067 percentage signal change | Standard Deviation 0.212 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 11.2 | -0.038 percentage signal change | Standard Deviation 0.248 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 7.2 | 0.061 percentage signal change | Standard Deviation 0.254 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 14.4 | 0.056 percentage signal change | Standard Deviation 0.281 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 0.8 | -0.064 percentage signal change | Standard Deviation 0.161 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 8.0 | 0.025 percentage signal change | Standard Deviation 0.259 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 12.0 | -0.034 percentage signal change | Standard Deviation 0.258 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 3.2 | 0.020 percentage signal change | Standard Deviation 0.223 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 5.6 | 0.113 percentage signal change | Standard Deviation 0.246 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 15.2 | 0.127 percentage signal change | Standard Deviation 0.287 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 9.6 | -0.020 percentage signal change | Standard Deviation 0.247 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 12.8 | -0.033 percentage signal change | Standard Deviation 0.262 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 6.4 | 0.100 percentage signal change | Standard Deviation 0.257 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 4.8 | 0.110 percentage signal change | Standard Deviation 0.248 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 2.4 | -0.043 percentage signal change | Standard Deviation 0.232 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 8.8 | 0.001 percentage signal change | Standard Deviation 0.262 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 13.6 | -0.004 percentage signal change | Standard Deviation 0.271 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 16.0 | 0.175 percentage signal change | Standard Deviation 0.297 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 2 | Second 4.0 | 0.072 percentage signal change | Standard Deviation 0.237 |
Primary
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds \[total 16s\]. Each subject will undergo 5 fMRI sessions, one at each dose.
Time frame: Up to two hours for each fMRI session
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 13.6 | 0.091 percentage signal change | Standard Deviation 0.137 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 2.4 | -0.063 percentage signal change | Standard Deviation 0.153 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 4.0 | 0.074 percentage signal change | Standard Deviation 0.151 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 8.0 | 0.052 percentage signal change | Standard Deviation 0.159 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 15.2 | 0.148 percentage signal change | Standard Deviation 0.145 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 7.2 | 0.062 percentage signal change | Standard Deviation 0.171 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 1.6 | -0.108 percentage signal change | Standard Deviation 0.15 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 8.8 | 0.084 percentage signal change | Standard Deviation 0.145 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 14.4 | 0.116 percentage signal change | Standard Deviation 0.135 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 9.6 | 0.127 percentage signal change | Standard Deviation 0.146 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 12.8 | 0.107 percentage signal change | Standard Deviation 0.147 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 0.8 | -0.108 percentage signal change | Standard Deviation 0.134 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 4.8 | 0.108 percentage signal change | Standard Deviation 0.145 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 12.0 | 0.136 percentage signal change | Standard Deviation 0.141 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 11.2 | 0.161 percentage signal change | Standard Deviation 0.141 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 10.4 | 0.158 percentage signal change | Standard Deviation 0.14 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 5.6 | 0.100 percentage signal change | Standard Deviation 0.162 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 3.2 | 0.017 percentage signal change | Standard Deviation 0.147 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 16.0 | 0.180 percentage signal change | Standard Deviation 0.182 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 6.4 | 0.086 percentage signal change | Standard Deviation 0.167 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 13.6 | 0.049 percentage signal change | Standard Deviation 0.137 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 2.4 | -0.072 percentage signal change | Standard Deviation 0.122 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 3.2 | -0.004 percentage signal change | Standard Deviation 0.122 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 4.0 | 0.044 percentage signal change | Standard Deviation 0.134 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 10.4 | 0.130 percentage signal change | Standard Deviation 0.136 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 9.6 | 0.119 percentage signal change | Standard Deviation 0.147 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 5.6 | 0.072 percentage signal change | Standard Deviation 0.12 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 6.4 | 0.051 percentage signal change | Standard Deviation 0.122 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 0.8 | -0.100 percentage signal change | Standard Deviation 0.112 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 7.2 | 0.035 percentage signal change | Standard Deviation 0.132 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 12.8 | 0.057 percentage signal change | Standard Deviation 0.149 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 14.4 | 0.065 percentage signal change | Standard Deviation 0.14 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 15.2 | 0.095 percentage signal change | Standard Deviation 0.162 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 12.0 | 0.094 percentage signal change | Standard Deviation 0.153 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 16.0 | 0.131 percentage signal change | Standard Deviation 0.171 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 8.0 | 0.042 percentage signal change | Standard Deviation 0.128 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 8.8 | 0.083 percentage signal change | Standard Deviation 0.143 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 11.2 | 0.125 percentage signal change | Standard Deviation 0.144 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 1.6 | -0.116 percentage signal change | Standard Deviation 0.118 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 4.8 | 0.067 percentage signal change | Standard Deviation 0.134 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 8.8 | 0.095 percentage signal change | Standard Deviation 0.113 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 5.6 | 0.095 percentage signal change | Standard Deviation 0.128 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 0.8 | -0.122 percentage signal change | Standard Deviation 0.13 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 16.0 | 0.165 percentage signal change | Standard Deviation 0.164 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 13.6 | 0.042 percentage signal change | Standard Deviation 0.114 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 9.6 | 0.128 percentage signal change | Standard Deviation 0.109 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 3.2 | -0.003 percentage signal change | Standard Deviation 0.131 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 1.6 | -0.129 percentage signal change | Standard Deviation 0.137 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 8.0 | 0.059 percentage signal change | Standard Deviation 0.111 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 10.4 | 0.126 percentage signal change | Standard Deviation 0.109 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 11.2 | 0.116 percentage signal change | Standard Deviation 0.128 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 4.8 | 0.087 percentage signal change | Standard Deviation 0.129 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 7.2 | 0.059 percentage signal change | Standard Deviation 0.111 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 14.4 | 0.068 percentage signal change | Standard Deviation 0.118 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 12.8 | 0.063 percentage signal change | Standard Deviation 0.113 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 2.4 | -0.073 percentage signal change | Standard Deviation 0.137 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 15.2 | 0.108 percentage signal change | Standard Deviation 0.141 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 4.0 | 0.053 percentage signal change | Standard Deviation 0.127 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 12.0 | 0.094 percentage signal change | Standard Deviation 0.123 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 6.4 | 0.079 percentage signal change | Standard Deviation 0.126 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 13.6 | 0.077 percentage signal change | Standard Deviation 0.125 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 0.8 | -0.072 percentage signal change | Standard Deviation 0.119 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 8.8 | 0.089 percentage signal change | Standard Deviation 0.104 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 4.0 | 0.069 percentage signal change | Standard Deviation 0.114 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 4.8 | 0.102 percentage signal change | Standard Deviation 0.105 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 5.6 | 0.095 percentage signal change | Standard Deviation 0.11 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 6.4 | 0.058 percentage signal change | Standard Deviation 0.109 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 14.4 | 0.094 percentage signal change | Standard Deviation 0.134 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 15.2 | 0.129 percentage signal change | Standard Deviation 0.142 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 7.2 | 0.040 percentage signal change | Standard Deviation 0.104 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 16.0 | 0.169 percentage signal change | Standard Deviation 0.156 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 8.0 | 0.048 percentage signal change | Standard Deviation 0.098 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 1.6 | -0.077 percentage signal change | Standard Deviation 0.127 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 2.4 | -0.043 percentage signal change | Standard Deviation 0.127 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 3.2 | 0.025 percentage signal change | Standard Deviation 0.121 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 9.6 | 0.125 percentage signal change | Standard Deviation 0.113 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 10.4 | 0.147 percentage signal change | Standard Deviation 0.127 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 11.2 | 0.139 percentage signal change | Standard Deviation 0.137 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 12.0 | 0.117 percentage signal change | Standard Deviation 0.142 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 12.8 | 0.085 percentage signal change | Standard Deviation 0.13 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 10.4 | 0.141 percentage signal change | Standard Deviation 0.119 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 1.6 | -0.128 percentage signal change | Standard Deviation 0.105 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 0.8 | -0.122 percentage signal change | Standard Deviation 0.095 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 8.0 | 0.037 percentage signal change | Standard Deviation 0.103 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 4.8 | 0.074 percentage signal change | Standard Deviation 0.116 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 11.2 | 0.144 percentage signal change | Standard Deviation 0.119 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 16.0 | 0.181 percentage signal change | Standard Deviation 0.16 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 7.2 | 0.033 percentage signal change | Standard Deviation 0.11 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 15.2 | 0.138 percentage signal change | Standard Deviation 0.15 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 4.0 | 0.054 percentage signal change | Standard Deviation 0.116 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 12.0 | 0.117 percentage signal change | Standard Deviation 0.125 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 14.4 | 0.098 percentage signal change | Standard Deviation 0.14 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 13.6 | 0.077 percentage signal change | Standard Deviation 0.134 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 6.4 | 0.046 percentage signal change | Standard Deviation 0.11 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 3.2 | 0.004 percentage signal change | Standard Deviation 0.111 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 12.8 | 0.086 percentage signal change | Standard Deviation 0.129 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 9.6 | 0.115 percentage signal change | Standard Deviation 0.109 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 8.8 | 0.074 percentage signal change | Standard Deviation 0.098 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 2.4 | -0.078 percentage signal change | Standard Deviation 0.099 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 3 | Second 5.6 | 0.070 percentage signal change | Standard Deviation 0.115 |
Primary
Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during functional magnetic resonance (fMRI) sessions. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, BOLD signal will be assessed over 20 timepoints, each measuring for 0.8 seconds \[total 16s\]. Each subject will undergo 5 fMRI sessions, one at each dose.
Time frame: Up to two hours for each fMRI session
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 7.2 | 0.048 percentage signal change | Standard Deviation 0.141 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 6.4 | 0.068 percentage signal change | Standard Deviation 0.141 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 4.0 | 0.043 percentage signal change | Standard Deviation 0.142 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 14.4 | 0.042 percentage signal change | Standard Deviation 0.158 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 5.6 | 0.085 percentage signal change | Standard Deviation 0.144 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 4.8 | 0.078 percentage signal change | Standard Deviation 0.143 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 13.6 | 0.010 percentage signal change | Standard Deviation 0.15 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 1.6 | -0.120 percentage signal change | Standard Deviation 0.133 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 15.2 | 0.074 percentage signal change | Standard Deviation 0.169 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 12.8 | 0.026 percentage signal change | Standard Deviation 0.163 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 12.0 | 0.060 percentage signal change | Standard Deviation 0.145 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 11.2 | 0.084 percentage signal change | Standard Deviation 0.148 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 2.4 | -0.079 percentage signal change | Standard Deviation 0.139 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 0.8 | -0.124 percentage signal change | Standard Deviation 0.119 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 10.4 | 0.096 percentage signal change | Standard Deviation 0.143 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 9.6 | 0.090 percentage signal change | Standard Deviation 0.137 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 8.8 | 0.066 percentage signal change | Standard Deviation 0.127 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 3.2 | -0.021 percentage signal change | Standard Deviation 0.139 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 16.0 | 0.118 percentage signal change | Standard Deviation 0.161 |
| CVL-562 (PF-06412562) 1 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 8.0 | 0.046 percentage signal change | Standard Deviation 0.129 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 7.2 | 0.017 percentage signal change | Standard Deviation 0.147 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 0.8 | -0.120 percentage signal change | Standard Deviation 0.134 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 1.6 | -0.123 percentage signal change | Standard Deviation 0.144 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 2.4 | -0.090 percentage signal change | Standard Deviation 0.134 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 3.2 | -0.023 percentage signal change | Standard Deviation 0.137 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 4.0 | 0.034 percentage signal change | Standard Deviation 0.138 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 4.8 | 0.060 percentage signal change | Standard Deviation 0.136 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 5.6 | 0.050 percentage signal change | Standard Deviation 0.135 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 6.4 | 0.028 percentage signal change | Standard Deviation 0.14 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 8.0 | 0.033 percentage signal change | Standard Deviation 0.146 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 8.8 | 0.085 percentage signal change | Standard Deviation 0.15 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 9.6 | 0.109 percentage signal change | Standard Deviation 0.143 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 10.4 | 0.125 percentage signal change | Standard Deviation 0.137 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 11.2 | 0.118 percentage signal change | Standard Deviation 0.131 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 12.0 | 0.084 percentage signal change | Standard Deviation 0.126 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 12.8 | 0.053 percentage signal change | Standard Deviation 0.129 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 13.6 | 0.037 percentage signal change | Standard Deviation 0.121 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 14.4 | 0.058 percentage signal change | Standard Deviation 0.118 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 15.2 | 0.095 percentage signal change | Standard Deviation 0.138 |
| CVL-562 (PF-06412562) 4 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 16.0 | 0.122 percentage signal change | Standard Deviation 0.148 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 2.4 | -0.090 percentage signal change | Standard Deviation 0.137 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 15.2 | 0.129 percentage signal change | Standard Deviation 0.172 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 10.4 | 0.115 percentage signal change | Standard Deviation 0.12 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 7.2 | 0.051 percentage signal change | Standard Deviation 0.133 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 13.6 | 0.046 percentage signal change | Standard Deviation 0.135 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 12.8 | 0.047 percentage signal change | Standard Deviation 0.128 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 14.4 | 0.089 percentage signal change | Standard Deviation 0.151 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 11.2 | 0.097 percentage signal change | Standard Deviation 0.116 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 4.0 | 0.044 percentage signal change | Standard Deviation 0.124 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 1.6 | -0.138 percentage signal change | Standard Deviation 0.132 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 0.8 | -0.133 percentage signal change | Standard Deviation 0.118 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 12.0 | 0.073 percentage signal change | Standard Deviation 0.12 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 8.8 | 0.073 percentage signal change | Standard Deviation 0.123 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 6.4 | 0.078 percentage signal change | Standard Deviation 0.131 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 4.8 | 0.079 percentage signal change | Standard Deviation 0.118 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 3.2 | -0.022 percentage signal change | Standard Deviation 0.124 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 5.6 | 0.093 percentage signal change | Standard Deviation 0.118 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 9.6 | 0.101 percentage signal change | Standard Deviation 0.115 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 8.0 | 0.048 percentage signal change | Standard Deviation 0.131 |
| CVL-562 (PF-06412562) 15 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 16.0 | 0.172 percentage signal change | Standard Deviation 0.154 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 1.6 | -0.146 percentage signal change | Standard Deviation 0.113 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 3.2 | -0.040 percentage signal change | Standard Deviation 0.111 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 7.2 | 0.010 percentage signal change | Standard Deviation 0.142 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 8.0 | 0.026 percentage signal change | Standard Deviation 0.131 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 8.8 | 0.043 percentage signal change | Standard Deviation 0.136 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 2.4 | -0.109 percentage signal change | Standard Deviation 0.113 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 16.0 | 0.091 percentage signal change | Standard Deviation 0.19 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 9.6 | 0.077 percentage signal change | Standard Deviation 0.144 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 10.4 | 0.085 percentage signal change | Standard Deviation 0.135 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 15.2 | 0.059 percentage signal change | Standard Deviation 0.148 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 11.2 | 0.067 percentage signal change | Standard Deviation 0.131 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 6.4 | 0.039 percentage signal change | Standard Deviation 0.139 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 12.0 | 0.052 percentage signal change | Standard Deviation 0.133 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 12.8 | 0.025 percentage signal change | Standard Deviation 0.123 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 13.6 | 0.003 percentage signal change | Standard Deviation 0.118 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 0.8 | -0.137 percentage signal change | Standard Deviation 0.109 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 4.0 | 0.011 percentage signal change | Standard Deviation 0.119 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 4.8 | 0.039 percentage signal change | Standard Deviation 0.138 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 5.6 | 0.049 percentage signal change | Standard Deviation 0.146 |
| CVL-562 (PF-06412562) 25 mg | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 14.4 | 0.033 percentage signal change | Standard Deviation 0.125 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 0.8 | -0.110 percentage signal change | Standard Deviation 0.124 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 16.0 | 0.120 percentage signal change | Standard Deviation 0.144 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 10.4 | 0.079 percentage signal change | Standard Deviation 0.111 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 14.4 | 0.049 percentage signal change | Standard Deviation 0.134 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 13.6 | 0.021 percentage signal change | Standard Deviation 0.128 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 6.4 | 0.044 percentage signal change | Standard Deviation 0.109 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 4.0 | 0.046 percentage signal change | Standard Deviation 0.131 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 5.6 | 0.062 percentage signal change | Standard Deviation 0.118 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 9.6 | 0.071 percentage signal change | Standard Deviation 0.097 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 8.8 | 0.041 percentage signal change | Standard Deviation 0.093 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 3.2 | -0.013 percentage signal change | Standard Deviation 0.133 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 4.8 | 0.079 percentage signal change | Standard Deviation 0.134 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 15.2 | 0.086 percentage signal change | Standard Deviation 0.142 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 2.4 | -0.066 percentage signal change | Standard Deviation 0.14 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 12.0 | 0.062 percentage signal change | Standard Deviation 0.12 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 11.2 | 0.070 percentage signal change | Standard Deviation 0.11 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 7.2 | 0.021 percentage signal change | Standard Deviation 0.106 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 1.6 | -0.109 percentage signal change | Standard Deviation 0.137 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 8.0 | 0.026 percentage signal change | Standard Deviation 0.094 |
| Placebo | Neural Activity Across Brain Regions During a Spatial Working Memory (sWM) Task- Condition 4 | Second 12.8 | 0.033 percentage signal change | Standard Deviation 0.123 |
Secondary
Association Between Neural Activity and Task Performance
Neural activity will be measured by blood oxygen level dependent (BOLD) signal that will be assessed during fMRI, where subjects will participate in a spatial working memory (sWM) task. The sWM includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. The performance of sWM at each trial of each condition will be used as the predictor variable, and the BOLD signal at the corresponding trial and condition will be used as the outcome variable. A trial refers to a single probing and measurement of sWM, and is repeatedly presented to get a number of sWM measurements. The performance of sWM from each trial will be regressed with the BOLD signal from that trial, and we will report the resulting beta weights at each condition and dose. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562).
Time frame: Up to two hours for each fMRI session.
Secondary
Functional Connectivity Across Brain Regions With the Fronto-parietal Network During sWM Task
Functional connectivity will be assessed during each fMRI session. Functional connectivity refers to the correlation between the time series of different brain regions collected during fMRI. During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. For each condition, the functional connectivity of the fronto-parietal network will be measured with the rest of the brain. The range of functional connectivity is between -4.95 and 4.95. -4.95 would indicate highly negative functional connectivity and 4.95 would indicate highly positive functional connectivity. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562).
Time frame: Up to two hours for each fMRI session.
Secondary
Performance During Spatial Working Memory (sWM) Task
During each fMRI session, subjects will participate in a sWM task that involves the ability to keep a spatial location in mind over a short period of time. The sWM task includes four conditions: 1) only sWM; 2) a motor response without sWM; 3) sWM with a distracter presented near the original memory location; and 4) sWM with a distractor presented far away from the original memory location. Performance will be assessed with the average accuracy measured during this task for each task condition and each CVL-562 (PF-06412562) dose. Accuracy refers to the angular distance between a cued location and a participant's memory of the location. The range of accuracy is between 0-180 degrees. 0 degrees would indicate the best possible performance, and 180 degrees the worst performance. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562).
Time frame: Up to two hours for each fMRI session.
Secondary
Proportion of Participants With Change in Blood Oxygen Level Dependent (BOLD) Signal During Spatial Working Memory (sWM) Task.
The dose-response in BOLD signal will be examined for each individual participant to see how many participants exhibit a change in BOLD signal overall. For each individual, binary outcome will be calculated based on a Dose by Condition by Time within subject analysis of BOLD signal. We will report the proportion of participants that exhibits a dose response.
Time frame: Up to two hours for each fMRI session.
Secondary
Resting State Global Brain Functional Connectivity
BOLD signal will be collected during the resting state aspect of the fMRI session, using a data-driven global brain connectivity (GBC) metric. GBC examines connectivity from a given voxel (or area) to all other voxels (or areas) simultaneously by computing average connectivity strength. The range of GBC is between -4.95 and 4.95. -4.95 would indicate highly negative broad functional connectivity in synchrony with the rest of the brain and 4.95 would indicate highly positive broad functional connectivity in synchrony with the rest of the brain. GBC will be obtained at each PF-06412562 dose.
Time frame: Up to two hours for each fMRI session.
Secondary
Spatial Similarity of Resting State Global Brain Functional Connectivity With Transcriptomic Maps.
Transcriptomics maps will be derived from the Allen Human Brain Atlas (AHBA), which provides gene expression data mapped to the cortical surface. The spatial similarity of resting state global brain functional connectivity (GBC) and gene expression patterns for the D1/D5 receptors will be assessed for each CVL-562 (PF-06412562) dose. The spatial similarity refers to correlation between GBC maps and the cortical gene expression maps. Each subject will undergo 5 fMRI sessions, each at a different dose of CVL-562 (PF-06412562).
Time frame: Up to two hours for each fMRI session.