Schizophrenia, Traumatic Brain Injury
Conditions
Keywords
Schizophrenia, Traumatic Brain Injury, Neuroplasticity, EEG
Brief summary
This proposal will examine measures of neuroplasticity (the brain's ability to alter its function or structure in response to changes in the environment or novel experiences) in Veterans with schizophrenia or traumatic brain injury (TBI). Both conditions are associated with impaired cognition (for example, attention, memory, learning), which is in turn associated with poor community functioning and integration. However, the two disorders differ in their origins: schizophrenia is a neurodevelopmental disorder appearing usually in late adolescence while TBI is an acquired disorder as the result of an injury to the head. Understanding of the root causes of complex cognitive impairments associated with these disorders remains limited. Neuroplasticity is a fundamental brain process that underlies cognitive functioning and may give insight into the causes of cognitive dysfunction in TBI and schizophrenia. Neuroplasticity will be measured using electroencephalography (EEG) by placing small electrodes on the scalp that record the brain's electrical activity. Participants will listen to simple auditory tones and view simple visual patterns while their EEG is recorded. Additionally, participants will have measures of cognition and clinical interviews for diagnosis of a disorder as well as any current levels of symptoms.
Detailed description
EEG recording: In this procedure, the participant's brain function will be recorded while listening to auditory tones or viewing simple visual stimuli. Participants will respond with a button press to specific tones or images. Participants will have all tasks clearly described to them and will practice each task prior to beginning the experiments. While performing these tasks, the brain's electrical activity (commonly referred to as brain waves) will be recording using electroencephalography (EEG). Participant's will wear a cap that contains several electrodes (small, metal discs that are able to pick up electrical activity). A small amount of gel will be applied to the scalp underneath each electrode. These electrodes simply rest on the surface of the scalp and above and below the left eye. It takes approximately 15 minutes to place and prepare the electrodes. The entire recording session will last approximately 90 minutes (including setup). Before having EEG recorded it is important to wash the hair and scalp and not use conditioners or products in the hair as these may interfere with the electrical signal. The gel used is simply washed out of the hair with running water. During the auditory task, participants will listen to a series of tones while watching a silent movie. Participants do not need to pay attention to the tones. During the visual task, participants will view a series of images on a computer screen that consist of a checkerboard pattern. Periodically, they will be asked to respond with a button press if one of the images is different than the others. Interviews: There will be interviews conducted by trained staff that ask questions about participants' demographics (age, gender, education). A clinical interview will be given to all participants to determine if participants have either schizophrenia, a history of a traumatic brain injury, or have no psychiatric illness. All participants will be asked questions about how they are feeling. In addition, participants will answer questions about their family and friends and how they have been getting along with people in their lives. Behavioral testing: Participants will have measures of cognition assessed using various computer-based tasks and pen-and-pencil questionnaires. These tests assess aspects of cognition including memory, attention, language, and motor skills. Participants will also be asked to view a series of pictures of faces and identify the emotion depicted on the face. Finally, participants will be asked to view a series of short videos consisting of a person telling a personal story. Participants will continuously rate how they think that person in the video is feeling (happy, sad, angry, etc.) while telling their story. Additional Information: It may sometimes be necessary to contact a participant's physician to inquire about their medical history or diagnosis. Permission will be sought from participant's in order for contact to be made with their physician.
Interventions
The investigators will use EEG combined with measures of cognition and clinical interviews to explore connections between these measures and electrical activity in the brain in Veterans with a diagnosis of schizophrenia or TBI, and healthy controls.
Sponsors
Study design
Intervention model description
All participants will have the same tasks delivered in the same manner.
Eligibility
Inclusion criteria
* Veterans with a diagnosis of schizophrenia or a history of mild or moderate traumatic brain injury (TBI) * Veterans without a psychiatric diagnosis and no history of TBI (healthy control participants) will also be recruited * No other neurological or medical condition interfering with providing informed consent or valid assessment * No current depression based on the Structured Clinical Interview for DSM-5 (SCID-I) or depressive symptoms rated moderate or higher * a rating of 13 or higher on the Hamilton Depression Rating Scale * No DSM-V substance use disorder greater than mild severity in the past 3 months * No form of cognitive remediation in the 6 months prior to testing * An 8th grade reading level assessed with the Wide Range Achievement Test (WRAT) * Normal or corrected-to-normal vision and hearing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mismatch Negativity (MMN) Amplitudes in Microvolts | 1 Day | Electroencephalography (EEG) measures the brain's activity while viewing simple visual stimuli or listening to simple auditory tones. MMN is measured while listening to a series of auditory tones, and is derived as the difference in responses to common stimuli minus rare stimuli (e.g., stimuli presented 90% of the time minus stimuli presented 10% of the time). A more negative value indicates stronger MMN, a more positive value indicates a stronger Repetition Positivity (RP) to the Standard stimuli, and a more negative value indicates a stronger Deviant Negativity (DN) to the Deviant stimuli. The investigators examined the deviant negativity, repetition positivity, and the MMN (which is defined as the difference between the standard-deviant), at three different standard tone repetition sequences (2, 6, or 36). In each case, the RP, DN, and MMN get stronger (i.e., larger amplitude) as the number of standard repetitions (2, 6, 36) increase. |
| Visual Long-Term Potentiation (LTP) Task | 1 Day | This LTP task compares visual evoked potentials (VEPs) derived from the EEG before and after a period of extended visual stimulation (tetanization). We measured VEP amplitudes to two different checkerboard patterns before (pre-) and at three time points after (post-) a 10-minute prolonged tetanization checkerboard. VEPs were measured to tetanized (i.e., the same stimuli used in the 10-minute tetanization) or not tetanized (a different checkerboard pattern than the one used in tetanization) stimuli, prior to baseline (pre-), and at 5- (Post 1), 10- (Post 2), and 15- (Post 3) minutes after tetanization. This resulted in 4 VEP measurements for each tetanized and non-tetanized checkerboard. We focused on relative changes from baseline for evidence of plasticity and input specificity (i.e., tetanized vs. non-tetanized stimuli) at each of the 3 post-tetanization time points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurocognition | 1 Day | The MATRICS Consensus Cognitive Battery (MCCB) measures cognition in seven different domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition) and provides a SINGLE summary t-score (age and gender corrected) of overall cognitive functioning. The range of T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better overall cognitive functioning. |
| Empathic Accuracy | 1 Day | Participants watch 9, short video clips of a person recounting a personal story. The participant must continuously rate how the person in the video is feeling while telling the story. The participant's ratings are then correlated with the ratings of the person who was in the video rating how they felt recounting their story. The average correlation for the 9 videos is the dependent variable, with higher positive correlations indicating higher empathic accuracy. |
| Community Integration | 1 Day | Community integration will be assessed by administering the Community Integration Questionnaire, which has 3 sub-scores (home, social, and activities). A higher score indicates better community integration. |
| Ekman Facial Affect Identification | 1 Day | Participants view a series of 56 faces depicting one of seven different emotions (happy, sad, surprised, angry, afraid, disgusted, and neutral). The total number correctly identified faces is the outcome measure, with higher scores indicating better performance. Scores range from 0-56, with 56 indicating 100% accurate facial affect identification. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| People With Schizophrenia People who have been diagnosed with schizophrenia and meet the investigators' research criteria for symptoms indicative of schizophrenia within their lifetime.
Electroencephalography: The investigators will use EEG combined with measures of cognition and clinical interviews to explore connections between these measures and electrical activity in the brain in Veterans with a diagnosis of schizophrenia or TBI, and healthy controls. | 26 |
| People With TBI People who have been diagnosed with a mild or moderate traumatic brain injury (TBI) and meet research criteria indicative of TBI within their lifetime.
Electroencephalography: The investigators will use EEG combined with measures of cognition and clinical interviews to explore connections between these measures and electrical activity in the brain in Veterans with a diagnosis of schizophrenia or TBI, and healthy controls. | 23 |
| Healthy Controls People without a history of psychiatric illness or TBI and who do not meet research criteria for a psychiatric illness or TBI.
Electroencephalography: The investigators will use EEG combined with measures of cognition and clinical interviews to explore connections between these measures and electrical activity in the brain in Veterans with a diagnosis of schizophrenia or TBI, and healthy controls. | 26 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Did not meet inclusion criteria | 1 | 6 | 3 |
| Overall Study | Lost to Follow-up | 1 | 4 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | People With Schizophrenia | Total | Healthy Controls | People With TBI |
|---|---|---|---|---|
| Age, Continuous | 52.5 years STANDARD_DEVIATION 9.8 | 48.4 years STANDARD_DEVIATION 12.4 | 49.1 years STANDARD_DEVIATION 12.9 | 42.9 years STANDARD_DEVIATION 12.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 19 Participants | 7 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 56 Participants | 19 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 36 Participants | 15 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 4 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 31 Participants | 8 Participants | 11 Participants |
| Region of Enrollment United States | 26 Participants | 75 Participants | 26 Participants | 23 Participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 20 Participants | 68 Participants | 25 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 23 | 0 / 26 |
| other Total, other adverse events | 0 / 26 | 0 / 23 | 0 / 26 |
| serious Total, serious adverse events | 0 / 26 | 0 / 23 | 0 / 26 |
Outcome results
Mismatch Negativity (MMN) Amplitudes in Microvolts
Electroencephalography (EEG) measures the brain's activity while viewing simple visual stimuli or listening to simple auditory tones. MMN is measured while listening to a series of auditory tones, and is derived as the difference in responses to common stimuli minus rare stimuli (e.g., stimuli presented 90% of the time minus stimuli presented 10% of the time). A more negative value indicates stronger MMN, a more positive value indicates a stronger Repetition Positivity (RP) to the Standard stimuli, and a more negative value indicates a stronger Deviant Negativity (DN) to the Deviant stimuli. The investigators examined the deviant negativity, repetition positivity, and the MMN (which is defined as the difference between the standard-deviant), at three different standard tone repetition sequences (2, 6, or 36). In each case, the RP, DN, and MMN get stronger (i.e., larger amplitude) as the number of standard repetitions (2, 6, 36) increase.
Time frame: 1 Day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| People With Schizophrenia | Mismatch Negativity (MMN) Amplitudes in Microvolts | Standard2 | 0.04 microvolts | Standard Deviation 1.53 |
| People With Schizophrenia | Mismatch Negativity (MMN) Amplitudes in Microvolts | Deviant36 | -0.98 microvolts | Standard Deviation 1.69 |
| People With Schizophrenia | Mismatch Negativity (MMN) Amplitudes in Microvolts | Standard36 | 0.16 microvolts | Standard Deviation 1.02 |
| People With Schizophrenia | Mismatch Negativity (MMN) Amplitudes in Microvolts | Standard6 | -0.15 microvolts | Standard Deviation 1.39 |
| People With Schizophrenia | Mismatch Negativity (MMN) Amplitudes in Microvolts | MMN2 | -0.59 microvolts | Standard Deviation 2.38 |
| People With Schizophrenia | Mismatch Negativity (MMN) Amplitudes in Microvolts | Deviant6 | -0.80 microvolts | Standard Deviation 1.44 |
| People With Schizophrenia | Mismatch Negativity (MMN) Amplitudes in Microvolts | MMN36 | -1.14 microvolts | Standard Deviation 1.92 |
| People With Schizophrenia | Mismatch Negativity (MMN) Amplitudes in Microvolts | MMN6 | -0.65 microvolts | Standard Deviation 2.01 |
| People With Schizophrenia | Mismatch Negativity (MMN) Amplitudes in Microvolts | Deviant2 | -0.54 microvolts | Standard Deviation 1.82 |
| People With TBI | Mismatch Negativity (MMN) Amplitudes in Microvolts | Standard6 | -0.40 microvolts | Standard Deviation 1.23 |
| People With TBI | Mismatch Negativity (MMN) Amplitudes in Microvolts | MMN2 | -1.19 microvolts | Standard Deviation 1.88 |
| People With TBI | Mismatch Negativity (MMN) Amplitudes in Microvolts | MMN6 | -1.87 microvolts | Standard Deviation 1.98 |
| People With TBI | Mismatch Negativity (MMN) Amplitudes in Microvolts | MMN36 | -3.13 microvolts | Standard Deviation 2.42 |
| People With TBI | Mismatch Negativity (MMN) Amplitudes in Microvolts | Standard2 | -0.46 microvolts | Standard Deviation 1.43 |
| People With TBI | Mismatch Negativity (MMN) Amplitudes in Microvolts | Standard36 | 0.08 microvolts | Standard Deviation 1.34 |
| People With TBI | Mismatch Negativity (MMN) Amplitudes in Microvolts | Deviant2 | -1.66 microvolts | Standard Deviation 1.36 |
| People With TBI | Mismatch Negativity (MMN) Amplitudes in Microvolts | Deviant6 | -2.26 microvolts | Standard Deviation 1.6 |
| People With TBI | Mismatch Negativity (MMN) Amplitudes in Microvolts | Deviant36 | -3.05 microvolts | Standard Deviation 1.9 |
| Healthy Controls | Mismatch Negativity (MMN) Amplitudes in Microvolts | MMN36 | -2.90 microvolts | Standard Deviation 2.86 |
| Healthy Controls | Mismatch Negativity (MMN) Amplitudes in Microvolts | MMN2 | -0.41 microvolts | Standard Deviation 1.89 |
| Healthy Controls | Mismatch Negativity (MMN) Amplitudes in Microvolts | Deviant2 | -1.32 microvolts | Standard Deviation 1.73 |
| Healthy Controls | Mismatch Negativity (MMN) Amplitudes in Microvolts | MMN6 | -1.75 microvolts | Standard Deviation 2.11 |
| Healthy Controls | Mismatch Negativity (MMN) Amplitudes in Microvolts | Deviant36 | -2.55 microvolts | Standard Deviation 2.19 |
| Healthy Controls | Mismatch Negativity (MMN) Amplitudes in Microvolts | Standard6 | 0.34 microvolts | Standard Deviation 1.15 |
| Healthy Controls | Mismatch Negativity (MMN) Amplitudes in Microvolts | Standard2 | -0.91 microvolts | Standard Deviation 1.27 |
| Healthy Controls | Mismatch Negativity (MMN) Amplitudes in Microvolts | Deviant6 | -1.40 microvolts | Standard Deviation 2 |
| Healthy Controls | Mismatch Negativity (MMN) Amplitudes in Microvolts | Standard36 | 0.35 microvolts | Standard Deviation 1.44 |
Visual Long-Term Potentiation (LTP) Task
This LTP task compares visual evoked potentials (VEPs) derived from the EEG before and after a period of extended visual stimulation (tetanization). We measured VEP amplitudes to two different checkerboard patterns before (pre-) and at three time points after (post-) a 10-minute prolonged tetanization checkerboard. VEPs were measured to tetanized (i.e., the same stimuli used in the 10-minute tetanization) or not tetanized (a different checkerboard pattern than the one used in tetanization) stimuli, prior to baseline (pre-), and at 5- (Post 1), 10- (Post 2), and 15- (Post 3) minutes after tetanization. This resulted in 4 VEP measurements for each tetanized and non-tetanized checkerboard. We focused on relative changes from baseline for evidence of plasticity and input specificity (i.e., tetanized vs. non-tetanized stimuli) at each of the 3 post-tetanization time points.
Time frame: 1 Day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| People With Schizophrenia | Visual Long-Term Potentiation (LTP) Task | Post-NonTetanized 3 | 0.325 microvolt | Standard Deviation 0.857 |
| People With Schizophrenia | Visual Long-Term Potentiation (LTP) Task | Post-tetanization 2 | 0.677 microvolt | Standard Deviation 1.489 |
| People With Schizophrenia | Visual Long-Term Potentiation (LTP) Task | Post-tetanization 3 | 0.475 microvolt | Standard Deviation 1.803 |
| People With Schizophrenia | Visual Long-Term Potentiation (LTP) Task | Post-NonTetanized 2 | 0.465 microvolt | Standard Deviation 0.951 |
| People With Schizophrenia | Visual Long-Term Potentiation (LTP) Task | Post-tetanization 1 | 1.215 microvolt | Standard Deviation 1.601 |
| People With Schizophrenia | Visual Long-Term Potentiation (LTP) Task | Pre-NonTetanized | 0.207 microvolt | Standard Deviation 0.664 |
| People With Schizophrenia | Visual Long-Term Potentiation (LTP) Task | Pre-tetanization | 0.295 microvolt | Standard Deviation 1.758 |
| People With Schizophrenia | Visual Long-Term Potentiation (LTP) Task | Post-NonTetanized 1 | 0.557 microvolt | Standard Deviation 0.978 |
| People With TBI | Visual Long-Term Potentiation (LTP) Task | Post-tetanization 1 | 1.145 microvolt | Standard Deviation 1.217 |
| People With TBI | Visual Long-Term Potentiation (LTP) Task | Post-NonTetanized 1 | 0.197 microvolt | Standard Deviation 1.217 |
| People With TBI | Visual Long-Term Potentiation (LTP) Task | Post-NonTetanized 2 | 0.364 microvolt | Standard Deviation 1.515 |
| People With TBI | Visual Long-Term Potentiation (LTP) Task | Post-NonTetanized 3 | 0.705 microvolt | Standard Deviation 1.303 |
| People With TBI | Visual Long-Term Potentiation (LTP) Task | Pre-tetanization | 0.201 microvolt | Standard Deviation 1.53 |
| People With TBI | Visual Long-Term Potentiation (LTP) Task | Post-tetanization 2 | 0.360 microvolt | Standard Deviation 1.563 |
| People With TBI | Visual Long-Term Potentiation (LTP) Task | Post-tetanization 3 | 0.226 microvolt | Standard Deviation 1.722 |
| People With TBI | Visual Long-Term Potentiation (LTP) Task | Pre-NonTetanized | 0.155 microvolt | Standard Deviation 1.378 |
| Healthy Controls | Visual Long-Term Potentiation (LTP) Task | Post-NonTetanized 3 | 0.142 microvolt | Standard Deviation 1.054 |
| Healthy Controls | Visual Long-Term Potentiation (LTP) Task | Post-NonTetanized 1 | 0.508 microvolt | Standard Deviation 1.271 |
| Healthy Controls | Visual Long-Term Potentiation (LTP) Task | Pre-tetanization | 0.274 microvolt | Standard Deviation 1.554 |
| Healthy Controls | Visual Long-Term Potentiation (LTP) Task | Post-tetanization 1 | 1.149 microvolt | Standard Deviation 1.316 |
| Healthy Controls | Visual Long-Term Potentiation (LTP) Task | Post-tetanization 2 | 0.662 microvolt | Standard Deviation 1.319 |
| Healthy Controls | Visual Long-Term Potentiation (LTP) Task | Post-tetanization 3 | 0.540 microvolt | Standard Deviation 1.508 |
| Healthy Controls | Visual Long-Term Potentiation (LTP) Task | Pre-NonTetanized | 0.049 microvolt | Standard Deviation 1.203 |
| Healthy Controls | Visual Long-Term Potentiation (LTP) Task | Post-NonTetanized 2 | 0.334 microvolt | Standard Deviation 1.408 |
Community Integration
Community integration will be assessed by administering the Community Integration Questionnaire, which has 3 sub-scores (home, social, and activities). A higher score indicates better community integration.
Time frame: 1 Day
Population: A higher score indicates better functioning. CIQ-home ranges from 0-10, CIQ-social ranges from 0-12, and CIQ-activities ranges from 0-17.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| People With Schizophrenia | Community Integration | CIQ-social | 7.24 score on a scale | Standard Error 2.332 |
| People With Schizophrenia | Community Integration | CIQ-home | 5.88 score on a scale | Standard Error 3.046 |
| People With Schizophrenia | Community Integration | CIQ-activities | 3.00 score on a scale | Standard Error 1.581 |
| People With TBI | Community Integration | CIQ-social | 8.45 score on a scale | Standard Error 2.385 |
| People With TBI | Community Integration | CIQ-home | 6.05 score on a scale | Standard Error 2.87 |
| People With TBI | Community Integration | CIQ-activities | 4.36 score on a scale | Standard Error 1.56 |
| Healthy Controls | Community Integration | CIQ-home | 6.67 score on a scale | Standard Error 2.461 |
| Healthy Controls | Community Integration | CIQ-activities | 3.96 score on a scale | Standard Error 1.574 |
| Healthy Controls | Community Integration | CIQ-social | 8.96 score on a scale | Standard Error 2.116 |
Ekman Facial Affect Identification
Participants view a series of 56 faces depicting one of seven different emotions (happy, sad, surprised, angry, afraid, disgusted, and neutral). The total number correctly identified faces is the outcome measure, with higher scores indicating better performance. Scores range from 0-56, with 56 indicating 100% accurate facial affect identification.
Time frame: 1 Day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| People With Schizophrenia | Ekman Facial Affect Identification | 42.4 score on a scale (total out of 56) | Standard Deviation 7.1 |
| People With TBI | Ekman Facial Affect Identification | 46.4 score on a scale (total out of 56) | Standard Deviation 5.9 |
| Healthy Controls | Ekman Facial Affect Identification | 44.6 score on a scale (total out of 56) | Standard Deviation 5.7 |
Empathic Accuracy
Participants watch 9, short video clips of a person recounting a personal story. The participant must continuously rate how the person in the video is feeling while telling the story. The participant's ratings are then correlated with the ratings of the person who was in the video rating how they felt recounting their story. The average correlation for the 9 videos is the dependent variable, with higher positive correlations indicating higher empathic accuracy.
Time frame: 1 Day
Population: We are unable to analyze the data due to an error in the scoring script that is not fixable.
Neurocognition
The MATRICS Consensus Cognitive Battery (MCCB) measures cognition in seven different domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition) and provides a SINGLE summary t-score (age and gender corrected) of overall cognitive functioning. The range of T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better overall cognitive functioning.
Time frame: 1 Day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| People With Schizophrenia | Neurocognition | 35.13 t-score | Standard Deviation 15.18 |
| People With TBI | Neurocognition | 45.32 t-score | Standard Deviation 11.34 |
| Healthy Controls | Neurocognition | 46.29 t-score | Standard Deviation 12.42 |