Bipolar Disorder I, Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
time perception, executive function, psychosis, mood symptoms
Brief summary
The goal of this study is to use transcranial magnetic stimulation (TMS) to investigate the impact of modulating cerebellar activity on time perception, executive function, and mood and psychotic symptoms in psychosis patients (i.e., schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features). The investigators hypothesize that abnormally reduced activity in the cerebellum contributes to the abnormalities in patients, that cerebellum-mediated disruptions in time perception may partially underlie executive dysfunction and symptoms, and that cerebellar stimulation will normalize disease-relevant outcome measures.
Detailed description
The cerebellum plays a major role in integrative processing of higher order cognitive and affective functions, but it has not been considered a major treatment target for psychotic disorders. The goal of this study is to administer three different conditions of transcranial magnetic stimulation (TMS)-- excitatory, inhibitory, and sham TMS-- in a cross-over design in psychosis patients (i.e., schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features) to investigate with causal explanatory power the role of the cerebellum as a treatment target for psychotic disorders. More specifically, the investigators will measure the effects of cerebellar excitation and inhibition on time perception, executive function, and symptomatology. TMS will be administered using a theta-burst stimulation (TBS) protocol applied to the posterior cerebellar vermis. Participants will undergo three study sessions, one for each of the three TMS conditions. During each session, the investigators will administer validated cognitive paradigms and clinical measures immediately before and after TMS. The specific aims are to: 1: Investigate the role of the cerebellum in abnormalities of time perception, executive function, and mood and psychotic symptoms by evaluating these functions before and immediately after excitatory, inhibitory, or sham TMS applied to the cerebellar vermis in patients with psychosis. (1a) Time perception hypothesis: Patients with psychotic disorders will have impaired timing perception, i.e., higher number of errors and/or greater inter-trial variability in an interval discrimination task both at baseline and after sham TMS. The investigators predict that the abnormalities in patients will improve after excitatory but not inhibitory TMS. (1b) Executive function hypothesis: Patients will show a higher number of errors and longer reaction times on the N-back working memory task, both at baseline and after sham TMS. The investigators predict that these deficits in patients will improve after excitatory but not inhibitory TMS. (1c) Symptom hypothesis: Symptom ratings using visual analog scales will improve in the period immediately after excitatory but not inhibitory TMS, and show no significant change after sham TMS. 2: Investigate the relationship between time perception and symptomatology in patients with psychotic disorders. Hypothesis: The investigators predict that performance on the time perception task will correlate with performance on a working memory task as well as with mood and psychotic symptoms. This study may improve understanding about the role of the cerebellum in the pathophysiology of psychotic disorders. Such knowledge can potentially guide the development of cerebellar TMS as a therapeutic intervention for psychosis.
Interventions
DEVICEExcitatory TMS
Single session of intermittent theta-burst stimulation (600 pulses in blocks of 2s, separated by 8s of pause) to cerebellar vermis.
DEVICEInhibitory TMS
Single session of continuous theta-burst stimulation of 600 pulses to cerebellar vermis.
DEVICESham TMS
Single session, using the exact same procedures as the active arms but with a sham coil, which is designed to induce the same nonspecific sensory effects of TMS (auditory and somatosensory activation) without inducing the neuromodulatory magnetic fields.
Sponsors
Massachusetts General Hospital
Mclean Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients * Men and women * Ages 18-50 years * Patients diagnosed with schizophrenia (SZ), schizoaffective disorder (SZA), or psychotic bipolar disorder (BP). * On a stable psychiatric medication regimen for at least a month prior to and during study participation * Healthy Controls: * Men and women * Ages 18-50 years * Without major psychiatric illness
Exclusion criteria
* Patients * Any change in psychiatric medications within a month prior to and during study participation * Legal or mental incompetency * Intellectual disability * Substance use disorder (abuse or dependence) with active use within the last 3 months * Significant medical or neurological illness * Prior neurosurgical procedure * History of seizures * History of electroconvulsive therapy (ECT) or clinical TMS within the past three months * History of participation in a cerebellar TMS study * Implanted cardiac pacemakers * Patients who have conductive, ferromagnetic or other magnetic-sensitive metals implanted in their head or neck, or are non-removable and within 30 cm of the treatment coil. These include: * Aneurysm clips or coils * Carotid or cerebral stents * Metallic devices implanted in the head (e.g. Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, or ventriculo-peritoneal shunt) * Magnetically active dental implants * Cochlear/otologic implants * CSF shunts * Ferromagnetic ocular implants * Pellets, bullets, fragments less than 30 cm from the coil * Facial tattoos with metallic ink, permanent makeup less than 30 cm from the coil * Pregnant women * Healthy Controls: * History of major psychiatric illness, including psychosis * Has a first-degree relative with psychosis * Active use of psychotropic medications * Legal or mental incompetency * Intellectual disability * Substance use disorder (abuse or dependence) with active use within the last 3 months * Significant medical or neurological illness * Prior neurosurgical procedure * History of seizures * History of ECT treatment or clinical TMS within the past three months * History of participation in a cerebellar TMS study * Implanted cardiac pacemakers * Individuals who have conductive, ferromagnetic or other magnetic-sensitive metals implanted in their head or neck, or are non-removable and within 30 cm of the treatment coil. These include: * Aneurysm clips or coils * Carotid or cerebral stents * Metallic devices implanted in the head (e.g. Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, transcutaneous electrical nerve stimulation (TENS) unit, or ventriculo-peritoneal shunt) * Magnetically active dental implants * Cochlear/otologic implants * Cerebrospinal fluid (CSF) shunts * Ferromagnetic ocular implants * Pellets, bullets, fragments less than 30 cm from the coil * Facial tattoos with metallic ink, permanent makeup less than 30 cm from the coil * Pregnant women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS | In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances. | In each trial, participants are presented with two tones separated by 1200 ms (the standard interval), a 1s delay, then a comparison pair of tones. The time interval of the second tone pair will be either equal to (E-condition), longer than (L-condition), or shorter than (S-condition) that of the first pair. Participants are asked to indicate using a keyboard whether the second time interval is equal, longer, or shorter than the first. The tones for all conditions were 700Hz in frequency, 50ms in duration, and presented binaurally via headphones. Participants completed 15 trials during each pre- or post-TMS session for a total of up to 90 total trials across the three study visits. Prior to each IDT session, participants performed a practice run consisting of six trials. The primary outcome for this task was overall accuracy (proportion of correct responses). |
| Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS | In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances. | Participants are presented with a series of words or numbers and prompted to indicate as quickly as possible whether the currently presented stimulus is the same as the one presented n-stimuli previously. For example, in a 2-back task a subject would be asked to indicate whether the current stimulus was identical to that presented 2 stimuli before. To increase the likelihood of detecting change in task performance with each TMS condition (and minimize potential ceiling or floor effects), the difficulty level was individualized so that each participant performed at approximately 80% accuracy; during the pre session of the first study visit, a trial session established the difficulty level, i.e., how many presentations back (n-stimuli) at which the task would start. After the trial session, a session with 50 presentations was carried out and recorded whether the response was correct (accuracy) and the time from presentation to response (reaction time). |
| Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS | In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances. | Participants are presented with a series of words or numbers and prompted to indicate as quickly as possible whether the currently presented stimulus is the same as the one presented n-stimuli previously. For example, in a 2-back task a subject would be asked to indicate whether the current stimulus was identical to that presented 2 stimuli before. To increase the likelihood of detecting change in task performance with each TMS condition (and minimize potential ceiling or floor effects), the difficulty level was individualized so that each participant performed at approximately 80% accuracy; during the pre session of the first study visit, a trial session established the difficulty level, i.e., how many presentations back (n-stimuli) at which the task would start. After the trial session, a session with 50 presentations was carried out and recorded whether the response was correct (accuracy) and the time from presentation to response (reaction time). |
| Change (Δ) in Symptoms (Depressed Mood) | In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances. | Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks. |
| Change (Δ) in Symptoms (Anxiety) | In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances. | Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks. |
| Change (Δ) in Symptoms (Elated Mood) | In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances. | Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent/no elation, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. Higher VAS scores for elation indicate more elation (suggestive of mania). The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks. |
| Change (Δ) in Symptoms (Auditory Hallucinations) | In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances. | Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks. |
| Change (Δ) in Symptoms (Visual Hallucinations) | In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances. | Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks. |
| Change (Δ) in Symptoms (Paranoid Ideation) | In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances. | Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks. |
| Change (Δ) in Symptoms (Ideas/Delusions of Reference) | In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances. | Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks. |
| Change (Δ) in Symptoms (Delusions of Control) | In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances. | Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks. |
Countries
United States
Participant flow
Recruitment details
N=28 participants were enrolled (provided informed consent to participate in the study). (Note: when I enter the number in the Protocol Enrollment field, the number does not save.)
Pre-assignment details
Two participants did not undergo TBS after enrollment. N=1 participant enrolled and completed the pre-intervention clinical evaluation but withdrew prior to randomization (no specific reason given by the participant). N=1 participant had a positive urine drug screen after enrollment; as active substance use within the prior 3 months is an exclusion criterion, the participant was excluded prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All enrolled participants (study was designed for all participants to receive all 3 interventions- iTBS, cTBS, and sham TBS). | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Study Visit 2 (1 Day) | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 |
| Washout 1 (≥ 36 Hours) | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 |
| Washout 1 (≥ 36 Hours) | Protocol violation: Excluded due to change in psychiatric medications | 0 | 0 | 0 | 0 | 1 | 0 |
| Washout 1 (≥ 36 Hours) | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
| Washout 2 (≥ 36 Hours) | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 |
| Washout 2 (≥ 36 Hours) | Excluded due to hospitalization for substance misuse | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 31.8 years STANDARD_DEVIATION 7.6 |
| Chlorpromazine equivalent dose (CPZ) | 242.4 mg/day STANDARD_DEVIATION 311.6 |
| Diagnosis Bipolar disorder with psychotic features | 10 Participants |
| Diagnosis Schizoaffective disorder | 12 Participants |
| Diagnosis Schizophrenia | 6 Participants |
| Education College/bachelor's degree | 8 Participants |
| Education Graduate/professional school | 4 Participants |
| Education High School/GED | 6 Participants |
| Education Part-college or 2-year college | 10 Participants |
| Estimated Intelligence Quotient (IQ) [(North American Adult Reading Test (NAART)] Full scale IQ | 118.7 units on a scale STANDARD_DEVIATION 9.1 |
| Estimated Intelligence Quotient (IQ) [(North American Adult Reading Test (NAART)] Performance IQ | 114.5 units on a scale STANDARD_DEVIATION 4.9 |
| Estimated Intelligence Quotient (IQ) [(North American Adult Reading Test (NAART)] Verbal IQ | 118.3 units on a scale STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Montgomery-Asberg Depression Rating Scale (MADRS) | 10.9 units on a scale STANDARD_DEVIATION 11.2 |
| Not taking any psychotropic medication | 4 Participants |
| Positive and Negative Syndrome Scale (PANSS) PANSS, general psychopathology | 20.9 units on a scale STANDARD_DEVIATION 13.5 |
| Positive and Negative Syndrome Scale (PANSS) PANSS, negative | 10.4 units on a scale STANDARD_DEVIATION 7.3 |
| Positive and Negative Syndrome Scale (PANSS) PANSS, positive | 9.8 units on a scale STANDARD_DEVIATION 7.3 |
| Positive and Negative Syndrome Scale (PANSS) PANSS, total | 41.0 units on a scale STANDARD_DEVIATION 27.3 |
| Psychotic Symptom Rating Scale (PSYRATS-AH) | 4.1 units on a scale STANDARD_DEVIATION 9.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 15 Participants |
| Taking antipsychotic medication | 17 Participants |
| Taking either antipsychotic or mood stabilizer | 23 Participants |
| Taking mood stabilizer | 14 Participants |
| Young Mania Rating Scale (YMRS) | 7.3 units on a scale STANDARD_DEVIATION 9.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 21 | 0 / 25 |
| other Total, other adverse events | 2 / 22 | 0 / 21 | 1 / 25 |
| serious Total, serious adverse events | 0 / 22 | 0 / 21 | 0 / 25 |
Outcome results
Primary
Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS
Participants are presented with a series of words or numbers and prompted to indicate as quickly as possible whether the currently presented stimulus is the same as the one presented n-stimuli previously. For example, in a 2-back task a subject would be asked to indicate whether the current stimulus was identical to that presented 2 stimuli before. To increase the likelihood of detecting change in task performance with each TMS condition (and minimize potential ceiling or floor effects), the difficulty level was individualized so that each participant performed at approximately 80% accuracy; during the pre session of the first study visit, a trial session established the difficulty level, i.e., how many presentations back (n-stimuli) at which the task would start. After the trial session, a session with 50 presentations was carried out and recorded whether the response was correct (accuracy) and the time from presentation to response (reaction time).
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Population: Cross-over design in which patients were assigned to 3 sessions of cerebellar TBS: one session each of iTBS, cTBS, and sham TBS. Analyses were conducted for all participants (patients who completed at least one study visit; n=26) as well as for completers only (patients who completed all 3 study visits; n=20; results not reported here). The fields for overall number of participants analyzed (above) indicate all participants who completed each of the sessions (iTBS, cTBS, sham TBS).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Intermittent TBS (iTBS) | Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS | Post-TBS | 0.795 accuracy (proportion correct) | Standard Error 0.0138 |
| Intermittent TBS (iTBS) | Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS | Pre-TBS | 0.780 accuracy (proportion correct) | Standard Error 0.0144 |
| Intermittent TBS (iTBS) | Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS | Ratio (post/pre) | 1.10 accuracy (proportion correct) | Standard Error 0.074 |
| Continuous TBS (cTBS) | Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS | Post-TBS | 0.778 accuracy (proportion correct) | Standard Error 0.0147 |
| Continuous TBS (cTBS) | Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS | Pre-TBS | 0.753 accuracy (proportion correct) | Standard Error 0.0156 |
| Continuous TBS (cTBS) | Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS | Ratio (post/pre) | 1.15 accuracy (proportion correct) | Standard Error 0.077 |
| Sham TBS | Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS | Pre-TBS | 0.775 accuracy (proportion correct) | Standard Error 0.0143 |
| Sham TBS | Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS | Ratio (post/pre) | 1.05 accuracy (proportion correct) | Standard Error 0.065 |
| Sham TBS | Change (Δ) in Accuracy of N-back Working Memory Task Pre- and Post-TMS | Post-TBS | 0.784 accuracy (proportion correct) | Standard Error 0.0139 |
Comparison: Conducted a generalized linear mixed model fit by maximum likelihood (Laplace Approximation) \['glmerMod' in R\] with binomial (logit) distribution.~N-back accuracy was the dependent variable. Time (pre vs. post), condition (iTBS vs. sham, cTBS vs. sham), and the interaction of time x condition (time x iTBS, time x cTBS) were the independent variables. P-value here is for the iTBS (vs. sham) x time interaction.p-value: 0.626Mixed Models Analysis
Comparison: Conducted a generalized linear mixed model fit by maximum likelihood (Laplace Approximation) \['glmerMod' in R\] with binomial (logit) distribution.~N-back accuracy was the dependent variable. Time (pre vs. post), condition (iTBS vs. sham, cTBS vs. sham), and the interaction of time x condition (time x iTBS, time x cTBS) were the independent variables. P-value here is for the cTBS (vs. sham) x time interaction.p-value: 0.322Mixed Models Analysis
Primary
Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS
In each trial, participants are presented with two tones separated by 1200 ms (the standard interval), a 1s delay, then a comparison pair of tones. The time interval of the second tone pair will be either equal to (E-condition), longer than (L-condition), or shorter than (S-condition) that of the first pair. Participants are asked to indicate using a keyboard whether the second time interval is equal, longer, or shorter than the first. The tones for all conditions were 700Hz in frequency, 50ms in duration, and presented binaurally via headphones. Participants completed 15 trials during each pre- or post-TMS session for a total of up to 90 total trials across the three study visits. Prior to each IDT session, participants performed a practice run consisting of six trials. The primary outcome for this task was overall accuracy (proportion of correct responses).
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Population: Cross-over design in which patients were assigned to 3 sessions of cerebellar TBS: one session each of iTBS, cTBS, and sham TBS. Analyses were conducted for all participants (patients who completed at least one study visit; n=26) as well as for completers only (patients who completed all 3 study visits; n=20; results not reported here). The fields for overall number of participants analyzed (above) indicate all participants who completed each of the sessions (iTBS, cTBS, sham TBS).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intermittent TBS (iTBS) | Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS | Post-TBS | .479 accuracy (proportion correct) | Standard Deviation 0.128 |
| Intermittent TBS (iTBS) | Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS | Pre-TBS | .503 accuracy (proportion correct) | Standard Deviation 0.156 |
| Intermittent TBS (iTBS) | Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS | Change in accuracy (post-pre) | -.024 accuracy (proportion correct) | Standard Deviation 0.175 |
| Continuous TBS (cTBS) | Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS | Post-TBS | .514 accuracy (proportion correct) | Standard Deviation 0.145 |
| Continuous TBS (cTBS) | Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS | Pre-TBS | .521 accuracy (proportion correct) | Standard Deviation 0.183 |
| Continuous TBS (cTBS) | Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS | Change in accuracy (post-pre) | -.006 accuracy (proportion correct) | Standard Deviation 0.163 |
| Sham TBS | Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS | Pre-TBS | .456 accuracy (proportion correct) | Standard Deviation 0.141 |
| Sham TBS | Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS | Change in accuracy (post-pre) | .069 accuracy (proportion correct) | Standard Deviation 0.198 |
| Sham TBS | Change (Δ) in Accuracy of Time Interval Discrimination Pre- and Post-TMS | Post-TBS | .525 accuracy (proportion correct) | Standard Deviation 0.174 |
Comparison: Conducted a mixed effects analysis, with IDT accuracy as the dependent variable and time (pre, post), condition (iTBS vs. sham, cTBS vs. sham), and the interaction of time x condition (time x iTBS, time x cTBS) as the independent variables. P-value here is for the iTBS (vs. sham) x time interaction.p-value: 0.5195% CI: [-0.1989, 0.0002]Mixed Models Analysis
Comparison: Conducted a mixed effects analysis, with IDT accuracy as the dependent variable and time (pre, post), condition (iTBS vs. sham, cTBS vs. sham), and the interaction of time x condition (time x iTBS, time x cTBS) as the independent variables. P-value here is for the cTBS (vs. sham) x time interaction.p-value: 0.14395% CI: [-0.177, 0.0256]Mixed Models Analysis
Primary
Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS
Participants are presented with a series of words or numbers and prompted to indicate as quickly as possible whether the currently presented stimulus is the same as the one presented n-stimuli previously. For example, in a 2-back task a subject would be asked to indicate whether the current stimulus was identical to that presented 2 stimuli before. To increase the likelihood of detecting change in task performance with each TMS condition (and minimize potential ceiling or floor effects), the difficulty level was individualized so that each participant performed at approximately 80% accuracy; during the pre session of the first study visit, a trial session established the difficulty level, i.e., how many presentations back (n-stimuli) at which the task would start. After the trial session, a session with 50 presentations was carried out and recorded whether the response was correct (accuracy) and the time from presentation to response (reaction time).
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Population: Cross-over design in which patients were assigned to 3 sessions of cerebellar TBS: one session each of iTBS, cTBS, and sham TBS. Analyses were conducted for all participants (patients who completed at least one study visit; n=26) as well as for completers only (patients who completed all 3 study visits; n=20; results not reported here). The fields for overall number of participants analyzed (above) indicate all participants who completed each of the sessions (iTBS, cTBS, sham TBS).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Intermittent TBS (iTBS) | Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS | Post-TBS | 817 ms | Standard Error 10.66 |
| Intermittent TBS (iTBS) | Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS | Pre-TBS | 831 ms | Standard Error 13.29 |
| Intermittent TBS (iTBS) | Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS | Change in RT (post-pre) | -14 ms | Standard Error 8.9 |
| Continuous TBS (cTBS) | Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS | Post-TBS | 886 ms | Standard Error 10.8 |
| Continuous TBS (cTBS) | Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS | Pre-TBS | 862 ms | Standard Error 14.62 |
| Continuous TBS (cTBS) | Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS | Change in RT (post-pre) | 24.0 ms | Standard Error 11.46 |
| Sham TBS | Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS | Pre-TBS | 901 ms | Standard Error 11.63 |
| Sham TBS | Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS | Change in RT (post-pre) | -23.8 ms | Standard Error 7.41 |
| Sham TBS | Change (Δ) in Reaction Time (RT) of N-back Working Memory Task Pre- and Post-TMS | Post-TBS | 877 ms | Standard Error 9.16 |
Comparison: Conducted a generalized linear mixed model fit by maximum likelihood (Laplace Approximation) \['glmerMod' in R\] with gamma distribution.~N-back reaction time (RT) was the dependent variable. Time (pre vs. post), condition (iTBS vs. sham, cTBS vs. sham), and the interaction of time x condition (time x iTBS, time x cTBS) were the independent variables. P-value here is for the iTBS (vs. sham) x time interaction.p-value: 0.1118Mixed Models Analysis
Comparison: Conducted a generalized linear mixed model fit by maximum likelihood (Laplace Approximation) \['glmerMod' in R\] with gamma distribution.~N-back reaction time (RT) was the dependent variable. Time (pre vs. post), condition (iTBS vs. sham, cTBS vs. sham), and the interaction of time x condition (time x iTBS, time x cTBS) were the independent variables. P-value here is for the cTBS (vs. sham) x time interaction.p-value: 9e-8Mixed Models Analysis
Primary
Change (Δ) in Symptoms (Anxiety)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Population: Cross-over design in which patients were assigned to 3 sessions of cerebellar TBS: one session each of iTBS, cTBS, and sham TBS. Analyses were conducted for all participants (patients who completed at least one study visit; n=26) as well as for completers only (patients who completed all 3 study visits; n=20; results not reported here). The fields for overall number of participants analyzed (above) indicate all participants who completed each of the sessions (iTBS, cTBS, sham TBS).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Anxiety) | Post-TBS | 4 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Anxiety) | Pre-TBS | 22 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Anxiety) | Change in VAS score (post-pre) | -2.5 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Anxiety) | Post-TBS | 30 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Anxiety) | Pre-TBS | 50 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Anxiety) | Change in VAS score (post-pre) | -1 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Anxiety) | Pre-TBS | 23 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Anxiety) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Anxiety) | Post-TBS | 5 score on a scale |
p-value: 0.83Friedman test
Comparison: We explored the association between interval discrimination task (IDT) performance (accuracy) and each symptom self-rating (here, anxiety). We conducted a mixed effects regression analysis to test the null hypothesis of no association. Model included time (pre, post) and condition (iTBS vs. sham, cTBS vs. sham) in addition to symptom rating as independent variables, and IDT performance accuracy as the dependent variable.p-value: 0.28495% CI: [-0.00179, 0.00052]Mixed Models Analysis
Primary
Change (Δ) in Symptoms (Auditory Hallucinations)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Population: Cross-over design in which patients were assigned to 3 sessions of cerebellar TBS: one session each of iTBS, cTBS, and sham TBS. Analyses were conducted for all participants (patients who completed at least one study visit; n=26) as well as for completers only (patients who completed all 3 study visits; n=20; results not reported here). The fields for overall number of participants analyzed (above) indicate all participants who completed each of the sessions (iTBS, cTBS, sham TBS).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Auditory Hallucinations) | Post-TBS | 0 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Auditory Hallucinations) | Pre-TBS | 0 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Auditory Hallucinations) | Change in VAS score (post-pre) | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Auditory Hallucinations) | Post-TBS | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Auditory Hallucinations) | Pre-TBS | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Auditory Hallucinations) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Auditory Hallucinations) | Pre-TBS | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Auditory Hallucinations) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Auditory Hallucinations) | Post-TBS | 0 score on a scale |
p-value: 0.035Friedman test
Comparison: We explored the association between interval discrimination task (IDT) performance (accuracy) and each symptom self-rating (here, auditory hallucinations). We conducted a mixed effects regression analysis to test the null hypothesis of no association. Model included time (pre, post) and condition (iTBS vs. sham, cTBS vs. sham) in addition to symptom rating as independent variables, and IDT performance accuracy as the dependent variable.p-value: 0.02895% CI: [0.00021, 0.00369]Mixed Models Analysis
Primary
Change (Δ) in Symptoms (Delusions of Control)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Population: Cross-over design in which patients were assigned to 3 sessions of cerebellar TBS: one session each of iTBS, cTBS, and sham TBS. Analyses were conducted for all participants (patients who completed at least one study visit; n=26) as well as for completers only (patients who completed all 3 study visits; n=20; results not reported here). The fields for overall number of participants analyzed (above) indicate all participants who completed each of the sessions (iTBS, cTBS, sham TBS).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Delusions of Control) | Post-TBS | 0 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Delusions of Control) | Pre-TBS | 0 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Delusions of Control) | Change in VAS score (post-pre) | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Delusions of Control) | Post-TBS | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Delusions of Control) | Pre-TBS | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Delusions of Control) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Delusions of Control) | Pre-TBS | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Delusions of Control) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Delusions of Control) | Post-TBS | 0 score on a scale |
p-value: 0.33Friedman test
Comparison: We explored the association between interval discrimination task (IDT) performance (accuracy) and each symptom self-rating (here, delusions of control). We conducted a mixed effects regression analysis to test the null hypothesis of no association. Model included time (pre, post) and condition (iTBS vs. sham, cTBS vs. sham) in addition to symptom rating as independent variables, and IDT performance accuracy as the dependent variable.p-value: 0.77795% CI: [-0.00305, 0.00228]Mixed Models Analysis
Primary
Change (Δ) in Symptoms (Depressed Mood)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Population: Cross-over design in which patients were assigned to 3 sessions of cerebellar TBS: one session each of iTBS, cTBS, and sham TBS. Analyses were conducted for all participants (patients who completed at least one study visit; n=26) as well as for completers only (patients who completed all 3 study visits; n=20; results not reported here). The fields for overall number of participants analyzed (above) indicate all participants who completed each of the sessions (iTBS, cTBS, sham TBS).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Depressed Mood) | Post-TBS | 19.5 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Depressed Mood) | Pre-TBS | 22.5 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Depressed Mood) | Change in VAS score (post-pre) | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Depressed Mood) | Post-TBS | 42 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Depressed Mood) | Pre-TBS | 37 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Depressed Mood) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Depressed Mood) | Pre-TBS | 16 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Depressed Mood) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Depressed Mood) | Post-TBS | 4 score on a scale |
p-value: 0.91Friedman test
Comparison: We explored the association between interval discrimination task (IDT) performance (accuracy) and each symptom self-rating (here, depressed mood). We conducted a mixed effects regression analysis to test the null hypothesis of no association. Model included time (pre, post) and condition (iTBS vs. sham, cTBS vs. sham) in addition to symptom rating as independent variables, and IDT performance accuracy as the dependent variable.p-value: 0.24395% CI: [-0.00048, 0.0019]Mixed Models Analysis
Primary
Change (Δ) in Symptoms (Elated Mood)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent/no elation, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. Higher VAS scores for elation indicate more elation (suggestive of mania). The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Population: Cross-over design in which patients were assigned to 3 sessions of cerebellar TBS: one session each of iTBS, cTBS, and sham TBS. Analyses were conducted for all participants (patients who completed at least one study visit; n=26) as well as for completers only (patients who completed all 3 study visits; n=20; results not reported here). The fields for overall number of participants analyzed (above) indicate all participants who completed each of the sessions (iTBS, cTBS, sham TBS).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Elated Mood) | Pre-TBS | 6 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Elated Mood) | Change in VAS score (post-pre) | 0 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Elated Mood) | Post-TBS | 8.5 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Elated Mood) | Pre-TBS | 2 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Elated Mood) | Post-TBS | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Elated Mood) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Elated Mood) | Pre-TBS | 1 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Elated Mood) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Elated Mood) | Post-TBS | 1 score on a scale |
p-value: 0.755Friedman test
Comparison: We explored the association between interval discrimination task (IDT) performance (accuracy) and each symptom self-rating (here, elated mood). We conducted a mixed effects regression analysis to test the null hypothesis of no association. Model included time (pre, post) and condition (iTBS vs. sham, cTBS vs. sham) in addition to symptom rating as independent variables, and IDT performance accuracy as the dependent variable.p-value: 0.31795% CI: [-0.00208, 0.00067]Mixed Models Analysis
Primary
Change (Δ) in Symptoms (Ideas/Delusions of Reference)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Population: Cross-over design in which patients were assigned to 3 sessions of cerebellar TBS: one session each of iTBS, cTBS, and sham TBS. Analyses were conducted for all participants (patients who completed at least one study visit; n=26) as well as for completers only (patients who completed all 3 study visits; n=20; results not reported here). The fields for overall number of participants analyzed (above) indicate all participants who completed each of the sessions (iTBS, cTBS, sham TBS).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Ideas/Delusions of Reference) | Post-TBS | 0 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Ideas/Delusions of Reference) | Pre-TBS | 0 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Ideas/Delusions of Reference) | Change in VAS score (post-pre) | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Ideas/Delusions of Reference) | Post-TBS | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Ideas/Delusions of Reference) | Pre-TBS | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Ideas/Delusions of Reference) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Ideas/Delusions of Reference) | Pre-TBS | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Ideas/Delusions of Reference) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Ideas/Delusions of Reference) | Post-TBS | 0 score on a scale |
p-value: 0.237Friedman test
Comparison: We explored the association between interval discrimination task (IDT) performance (accuracy) and each symptom self-rating (here, ideas/delusions of reference). We conducted a mixed effects regression analysis to test the null hypothesis of no association. Model included time (pre, post) and condition (iTBS vs. sham, cTBS vs. sham) in addition to symptom rating as independent variables, and IDT performance accuracy as the dependent variable.p-value: 0.17895% CI: [-0.0035, 0.00065]Mixed Models Analysis
Primary
Change (Δ) in Symptoms (Paranoid Ideation)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Population: Cross-over design in which patients were assigned to 3 sessions of cerebellar TBS: one session each of iTBS, cTBS, and sham TBS. Analyses were conducted for all participants (patients who completed at least one study visit; n=26) as well as for completers only (patients who completed all 3 study visits; n=20; results not reported here). The fields for overall number of participants analyzed (above) indicate all participants who completed each of the sessions (iTBS, cTBS, sham TBS).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Paranoid Ideation) | Post-TBS | 0 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Paranoid Ideation) | Pre-TBS | 0 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Paranoid Ideation) | Change in VAS score (post-pre) | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Paranoid Ideation) | Post-TBS | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Paranoid Ideation) | Pre-TBS | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Paranoid Ideation) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Paranoid Ideation) | Pre-TBS | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Paranoid Ideation) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Paranoid Ideation) | Post-TBS | 0 score on a scale |
p-value: 0.02Friedman test
Comparison: We explored the association between interval discrimination task (IDT) performance (accuracy) and each symptom self-rating (here, paranoid ideation). We conducted a mixed effects regression analysis to test the null hypothesis of no association. Model included time (pre, post) and condition (iTBS vs. sham, cTBS vs. sham) in addition to symptom rating as independent variables, and IDT performance accuracy as the dependent variable.p-value: 0.59795% CI: [-0.00108, 0.00188]Mixed Models Analysis
Primary
Change (Δ) in Symptoms (Visual Hallucinations)
Participants will take a brief computerized survey pre- and post-TMS, in which they will be presented with visual analogue scales (VAS, range 0-100, 0=absent, 100=most severe) and asked to indicate current levels of depression, anxiety, euphoria, auditory hallucinations, visual hallucinations, paranoia, referential thinking, and delusions of control. The VAS format will allow participants to self-report ratings quickly and easily with simple mouse clicks.
Time frame: In each of the 3 study visits (separated by at least 36h), participants undergo (a) pre-TMS assessments (15-20min), (b) TMS (15min), and (c) post-TMS assessments (15-20min). Approximately 30-45 min separate the pre- and post-TMS task performances.
Population: Cross-over design in which patients were assigned to 3 sessions of cerebellar TBS: one session each of iTBS, cTBS, and sham TBS. Analyses were conducted for all participants (patients who completed at least one study visit; n=26) as well as for completers only (patients who completed all 3 study visits; n=20; results not reported here). The fields for overall number of participants analyzed (above) indicate all participants who completed each of the sessions (iTBS, cTBS, sham TBS).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Visual Hallucinations) | Post-TBS | 0 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Visual Hallucinations) | Pre-TBS | 0 score on a scale |
| Intermittent TBS (iTBS) | Change (Δ) in Symptoms (Visual Hallucinations) | Change in VAS score (post-pre) | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Visual Hallucinations) | Post-TBS | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Visual Hallucinations) | Pre-TBS | 0 score on a scale |
| Continuous TBS (cTBS) | Change (Δ) in Symptoms (Visual Hallucinations) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Visual Hallucinations) | Pre-TBS | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Visual Hallucinations) | Change in VAS score (post-pre) | 0 score on a scale |
| Sham TBS | Change (Δ) in Symptoms (Visual Hallucinations) | Post-TBS | 0 score on a scale |
p-value: 0.748Friedman test
Comparison: We explored the association between interval discrimination task (IDT) performance (accuracy) and each symptom self-rating (here, visual hallucinations). We conducted a mixed effects regression analysis to test the null hypothesis of no association. Model included time (pre, post) and condition (iTBS vs. sham, cTBS vs. sham) in addition to symptom rating as independent variables, and IDT performance accuracy as the dependent variable.p-value: 0.68595% CI: [-0.0023, 0.00151]Mixed Models Analysis