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Completed

NCT Number: NCT05445466

Causal Lesion Network Guided Treatment of Bipolar Mania With Transcranial Electrical Stimulation

Mania is a core symptom of bipolar disorder involving periods of euphoria. Decreased inhibitory control, increased risk-taking behaviors, and aberrant reward processing are some of the more recognized symptoms of bipolar disorder and are included in the diagnostic criteria for mania. Current drug therapies for mania are frequently intolerable, ineffective, and carry significant risk for side effects. Presently there are no neurobiologically informed therapies that treat or prevent mania. However, using a newly validated technique termed lesion network mapping, researchers demonstrated that focal brain lesions having a causal role in the development of mania in people without a psychiatric history can occur in different brain locations, such as the right orbitofrontal cortex (OFC), right dorsolateral prefrontal cortex (DLPFC), and right inferior temporal gyrus (ITG). This lesion network evidence converges with existing cross-sectional and longitudinal observations in bipolar mania that have identified specific disruptions in network communication between the amygdala and ventro-lateral prefrontal cortex. The OFC is associated with inhibitory control, risk-taking behavior, and reward learning which are major components of bipolar mania. Thus, the association between OFC with mania symptoms, inhibitory control, risk-taking behavior, and reward processing suggests that this region could be targeted using non-invasive brain stimulation.

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Key information

Conditions

Bipolar Disorder Bipolar and Related Disorders Mania Mental Disorders Mood Disorders Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Pathological Conditions, Signs and Symptoms Psychotic Disorders Schizo Affective Disorder Schizophrenia Spectrum and Other Psychotic Disorders Signs and Symptoms

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

About this study

Mania is a core symptom of bipolar disorder involving periods of euphoria, delusions, and overactivity. Mania occurs in multiple medical and psychiatric illnesses and can be refractory to existing treatments. Two recent studies using brain lesion mapping of psychiatrically healthy individuals presenting with mania identified causal locations in the brain, including the orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), and inferior temporal gyrus (ITG), that were associated with new onset mania symptoms. Moreover, these identified brain regions have also been implicated in bipolar mania with specific disruption in network communication between the amygdala and ventro-lateral prefrontal cortex. The OFC is of particular interest because it is a brain structure that is associated with inhibitory control, risk-taking behavior and reward, which are major behavioral components of mania. Thus, the association between OFC with mania symptoms, inhibitory control, risk-taking behavior and reward suggests that this region could be targeted using noninvasive brain stimulation. While several studies have non-invasively targeted the DLPFC for mania, no study to date has non-invasively stimulated the OFC with either transcranial direct current stimulation (tDCS) or alternating current (tACS) in bipolar disorder and examined its effects on mania, inhibitory control, or risk-taking behavior. However, a study in healthy volunteers showed that cathodal stimulation to the OFC enhanced inhibitory control and decreased risk-taking behavior. Recently, researches have showed that targeting the OFC with tACS, personalized to the individual's intrinsic beta-gamma frequency of the reward network, that individuals showed rapid, reversible, frequency-specific modulation of reward-guided choice behavior and learning. Here we aim to answer the question of whether noninvasive brain stimulation when optimally targeted and personalized to an individual's beta-gamma frequency to the OFC can improve emotional cognitive processing and mania symptoms compared to tDCS or sham targeting. The knowledge gained from this study will provide a marker for clinical response and allow personalized treatment for patients with bipolar disorder.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Aged 18-65 years of age
  • Proficient in English
  • Able to give informed consent
  • Meet diagnostic criteria for bipolar disorder or schizoaffective disorder, bipolar type as verified by the SCID
  • History of mania ( >1 lifetime episode)
  • Experiencing mild to moderate symptoms of mania
  • No changes to mood stabilizing medications for a period of 2 weeks prior to participation
  • Has not recently participated in tES/TMS treatments

Exclusion criteria

  • Substance abuse or dependence (w/in past 6 months)
  • Those who are pregnant/breastfeeding
  • History of head injury with > 15 minutes of loss of consciousness/mal sequelae
  • DSM-V intellectual disability
  • Having a non-removable ferromagnetic metal within the body (particularly in the head)
  • History of seizures

Treatment and study plan

High-Definition Transcranial Electrical-Current Stimulation

Device

Non-frequency dependent transcranial electrical stimulation condition for 5 days of twice a day treatment

Other names: Soterix Medical, GTEN 200

High-Definition Transcranial Alternate-Current Stimulation

Device

Active-control stimulation condition will target alpha (10 Hz) for 5 days of twice a day treatment

Other names: Soterix Medical, GTEN 200

High-Definition Personalized Beta-Gamma Electrical Stimulation

Device

Personalized beta-gamma electrical stimulation for 5 days of twice a day treatment

Other names: Soterix Medical, GTEN 200

Primary outcomes

  1. Young Mania Rating Scale (YMRS)

    Time frame: Change from baseline to 5 Day follow-up

    Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms

  2. Young Mania Rating Scale (YMRS)

    Time frame: Change from baseline to 1-month follow-up

    Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms

  3. Young Mania Rating Scale (YMRS)

    Time frame: Change from baseline to 3-month follow-up

    Measuring total Mania scores; 11 items used to access severity of mania (total score 0-60); higher scores represent higher severity of symptoms

  4. Altman Self-Rating Mania Scale (ASRM)

    Time frame: Change from baseline to 5 Day follow-up

    The ASRM is a 5-item self rating mania scale, assessing the presence and severity of manic symptoms. The scores for all five items are added together, resulting in a total score that can range from 0 to 20. A score of 6 or higher indicates a high probability of a manic or hypomanic condition.

  5. Altman Self-Rating Mania Scale (ASRM)

    Time frame: Change from baseline to 1-month follow-up

    The ASRM is a 5-item self rating mania scale, assessing the presence and severity of manic symptoms. The scores for all five items are added together, resulting in a total score that can range from 0 to 20. A score of 6 or higher indicates a high probability of a manic or hypomanic condition.

  6. Altman Self-Rating Mania Scale (ASRM)

    Time frame: Change from baseline to 3-month follow-up

    The ASRM is a 5-item self rating mania scale, assessing the presence and severity of manic symptoms. The scores for all five items are added together, resulting in a total score that can range from 0 to 20. A score of 6 or higher indicates a high probability of a manic or hypomanic condition.

  7. Psychiatric Hospitalizations for Mania Post Study Entry

    Time frame: Cumulative count of hospitalizations for mania from baseline to end of study

    Psychiatric hospitalization for mania. Count of hospitalizations from baseline to end of study period assessed at Day 5, 1 Month & 3 Month.

Secondary outcomes

  1. Balloon Analogue Risk Task (BART)

    Time frame: Change from baseline to 5 Day follow-up

    The BART is a computerized task the measures risk-taking behavior. Participants are tasked with inflating the virtual balloon. The number of pumps a participant chooses to make on each balloon is used as a measure of their risk-taking behavior. More pumps generally indicate a higher tolerance for risk. The balloon bursts at a given point if the participant overfills it. Number of popped balloons reported for a given trial.

  2. Balloon Analogue Risk Task (BART)

    Time frame: Change from baseline to 1-month follow-up

    The BART is a computerized task the measures risk-taking behavior. Participants are tasked with inflating the virtual balloon. The number of pumps a participant chooses to make on each balloon is used as a measure of their risk-taking behavior. More pumps generally indicate a higher tolerance for risk. The balloon bursts at a given point if the participant overfills it. Number of popped balloons reported for a given trial.

  3. Balloon Analogue Risk Task (BART)

    Time frame: Change from baseline to 3-month follow-up

    The BART is a computerized task the measures risk-taking behavior. Participants are tasked with inflating the virtual balloon. The number of pumps a participant chooses to make on each balloon is used as a measure of their risk-taking behavior. More pumps generally indicate a higher tolerance for risk. The balloon bursts at a given point if the participant overfills it. Number of popped balloons reported for a given trial.

  4. The Go/No Go Task

    Time frame: Change from baseline to 5 Day follow-up

    The Go/No Go Task is a computerized task that measures impulsiveness. Participants presented with Go (to respond) and no Go (when not to respond) instructions. Two trials are performed. The first trial consist of two distinct auditory stimuli (both Go stimuli) where the participant is asked to respond with a different number of mouse clicks to the stimuli respectively. The second trial, has a no Go stimuli (where the participant is suppose to withhold a response) and a go stimuli. Reaction time for correct trials only for the entire task are reported in milliseconds.

  5. The Go/No Go Task

    Time frame: Change from baseline to 1-month follow-up

    The Go/No Go Task is a computerized task that measures impulsiveness. Participants presented with Go (to respond) and no Go (when not to respond) instructions. Two trials are performed. The first trial consist of two distinct auditory stimuli (both Go stimuli) where the participant is asked to respond with a different number of mouse clicks to the stimuli respectively. The second trial, has a no Go stimuli (where the participant is suppose to withhold a response) and a go stimuli. Reaction time for correct trials only for the entire task are reported in milliseconds.

  6. The Go/No Go Task

    Time frame: Change from baseline to 3-month follow-up

    The Go/No Go Task is a computerized task that measures impulsiveness. Participants presented with Go (to respond) and no Go (when not to respond) instructions. Two trials are performed. The first trial consist of two distinct auditory stimuli (both Go stimuli) where the participant is asked to respond with a different number of mouse clicks to the stimuli respectively. The second trial, has a no Go stimuli (where the participant is suppose to withhold a response) and a go stimuli. Reaction time for correct trials only for the entire task are reported in milliseconds.

  7. Electroencephalography (EEG) Resting State

    Time frame: Change from baseline to 5 Day follow-up

    Measuring neural activity at rest consisting of 5 minutes of eyes-open resting-state EEG (rsEEG) was recorded. Fast Fourier transformations were conducted on data, resulting in 4 frequency bands: delta/theta, alpha, beta, and gamma.

  8. Electroencephalography (EEG) Resting State

    Time frame: Change from baseline to 1-month follow-up

    Measuring neural activity at rest consisting of 5 minutes of eyes-open resting-state EEG (rsEEG) was recorded. Fast Fourier transformations were conducted on data, resulting in 4 frequency bands: delta/theta, alpha, beta, and gamma.

  9. Electroencephalography (EEG) Resting State

    Time frame: Change from baseline to 3-month follow-up

    Measuring neural activity at rest consisting of 5 minutes of eyes-open resting-state EEG (rsEEG) was recorded. Fast Fourier transformations were conducted on data, resulting in 4 frequency bands: delta/theta, alpha, beta, and gamma.

  10. Reinforcement Learning Task

    Time frame: Change from baseline to 5 Day follow-up

    The reinforcement learning task is a monetary based learning tasks that included reward and punishment trails. The task presents multiple trials of stimuli where the participant chooses 1 of 2 stimuli presented at a time (one of which is associated with punishment represented by loss of monetary reward while the other is associated with gain of monetary reward). EEG is record during the task and signal is captured during the participants choose and the feedback received. Reported is the peak beta/gamma range response derived from the EEG during reward feedback. This measurement is used from the baseline assessment to inform the personalized beta-gamma range stimulation for the Personalized Beta-Gamma tACS group.

  11. Reinforcement Learning Task

    Time frame: Change from baseline to 1-month follow-up

    The reinforcement learning task is a monetary based learning tasks that included reward and punishment trails. The task presents multiple trials of stimuli where the participant chooses 1 of 2 stimuli presented at a time (one of which is associated with punishment represented by loss of monetary reward while the other is associated with gain of monetary reward). EEG is record during the task and signal is captured during the participants choose and the feedback received. Reported is the peak beta/gamma range response derived from the EEG during reward feedback. This measurement is used from the baseline assessment to inform the personalized beta-gamma range stimulation for the Personalized Beta-Gamma tACS group.

  12. Reinforcement Learning Task

    Time frame: Change from baseline to 3-month follow-up

    The reinforcement learning task is a monetary based learning tasks that included reward and punishment trails. The task presents multiple trials of stimuli where the participant chooses 1 of 2 stimuli presented at a time (one of which is associated with punishment represented by loss of monetary reward while the other is associated with gain of monetary reward). EEG is record during the task and signal is captured during the participants choose and the feedback received. Reported is the peak beta/gamma range response derived from the EEG during reward feedback. This measurement is used from the baseline assessment to inform the personalized beta-gamma range stimulation for the Personalized Beta-Gamma tACS group.

  13. Social Functioning Scale (SFS)

    Time frame: Change from baseline to 5 Day follow-up

    The SFS a self-report questionnaire initially designed for people diagnosed with Schizophrenia; consists of 79 items designed to reflect the social skills and performances in different areas of life. Subscores are summed together for a total score. Total score of SFS ranges between 0-223 points. Higher scores mean better social functioning.

  14. Social Functioning Scale (SFS)

    Time frame: Change from baseline to 1-month follow-up

    The SFS a self-report questionnaire initially designed for people diagnosed with Schizophrenia; consists of 79 items designed to reflect the social skills and performances in different areas of life. Subscores are summed together for a total score. Total score of SFS ranges between 0-223 points. Higher scores mean better social functioning.

  15. Social Functioning Scale (SFS)

    Time frame: Change from baseline to 3-month follow-up

    The SFS a self-report questionnaire initially designed for people diagnosed with Schizophrenia; consists of 79 items designed to reflect the social skills and performances in different areas of life. Subscores are summed together for a total score. Total score of SFS ranges between 0-223 points. Higher scores mean better social functioning.

  16. Global Assessment of Functioning (GAF)

    Time frame: Change from baseline to 5 Day follow-up

    The GAF measures how symptoms affect individuals day-to-day life; scored from 0 to 100

  17. Global Assessment of Functioning (GAF)

    Time frame: Change from baseline to 1-month follow-up

    The GAF measures how symptoms affect individuals day-to-day life; scored from 0 to 100

  18. Global Assessment of Functioning (GAF)

    Time frame: Change from baseline to 3-month follow-up

    The GAF measures how symptoms affect individuals day-to-day life; scored from 0 to 100

  19. Positive and Negative Syndrome Scale (PANSS)

    Time frame: Change from baseline to 5 Day follow-up

    30 items included in the PANSS measuring positive, negative and general symptoms; 7 related to positive symptoms, 7 for negative symptoms, and 16 for general psychopathology Scale. Ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale. Scores summed for Total Score on scale (30 to 210). Higher scores mean worse clinical symptoms. Total score reported.

  20. Positive and Negative Syndrome Scale (PANSS)

    Time frame: Change from baseline to 1-month follow-up

    30 items included in the PANSS measuring positive, negative and general symptoms; 7 related to positive symptoms, 7 for negative symptoms, and 16 for general psychopathology Scale. Ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale. Scores summed for Total Score on scale (30 to 210). Higher scores mean worse clinical symptoms. Total score reported.

  21. Positive and Negative Syndrome Scale (PANSS)

    Time frame: Change from baseline to 3-month follow-up

    30 items included in the PANSS measuring positive, negative and general symptoms; 7 related to positive symptoms, 7 for negative symptoms, and 16 for general psychopathology Scale. Ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale. Scores summed for Total Score on scale (30 to 210). Higher scores mean worse clinical symptoms. Total score reported.

  22. Montgomery-Åsberg Depression Rating Scale (MADRS)

    Time frame: Change from baseline to 5 Day follow-up

    The MADRS is designed to measure depression and severity of symptoms; 0 to 6 indicates no depression, 7 to 19 indicates mild depression, 20 to 34 indicates moderate depression, 35 and greater indicates severe depression. Total score reported (0 to 60).

  23. Montgomery-Åsberg Depression Rating Scale (MADRS)

    Time frame: Change from baseline to 1-month follow-up

    The MADRS is designed to measure depression and severity of symptoms; 0 to 6 indicates no depression, 7 to 19 indicates mild depression, 20 to 34 indicates moderate depression, 35 and greater indicates severe depression. Total score reported (0 to 60).

  24. Montgomery-Åsberg Depression Rating Scale (MADRS)

    Time frame: Change from baseline to 3-month follow-up

    The MADRS is designed to measure depression and severity of symptoms; 0 to 6 indicates no depression, 7 to 19 indicates mild depression, 20 to 34 indicates moderate depression, 35 and greater indicates severe depression. Total score reported (0 to 60).

  25. Barratt Impulsiveness Scale-11 (BIS-11)

    Time frame: Change from baseline to 5 Day follow-up

    The BIS-11 is designed to assess the personality/behavioral impulsiveness. The BIS-11 has 30 items and is scored appropriately. Scored to yield a total score, three second-order factors, and six first-order factors. Each question has a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). Higher scores mean more impulsive behavior. Total score reported (30-120).

  26. Barratt Impulsiveness Scale-11 (BIS-11)

    Time frame: Change from baseline to 1-month follow-up

    The BIS-11 is designed to assess the personality/behavioral impulsiveness. The BIS-11 has 30 items and is scored appropriately. Scored to yield a total score, three second-order factors, and six first-order factors. Each question has a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). Higher scores mean more impulsive behavior. Total score reported (30-120).

  27. Barratt Impulsiveness Scale-11 (BIS-11)

    Time frame: Change from baseline to 3-month follow-up

    The BIS-11 is designed to assess the personality/behavioral impulsiveness. The BIS-11 has 30 items and is scored appropriately. Scored to yield a total score, three second-order factors, and six first-order factors. Each question has a 4-point scale ranging from 1 (rarely/never) to 4 (almost always/always). Higher scores mean more impulsive behavior. Total score reported (30-120).

  28. Brief Assessment of Cognition (BACS)

    Time frame: Change from baseline to 5 Day follow-up

    The BACS is designed to assess several domains of cognition; Verbal Memory; Processing Speed; Working Memory; Verbal Fluency; Motor Function; Executive Functioning. Higher scores indicate better cognitive functioning. Total score reported after being transformed into z score based on normative scoring provide by test makers.

  29. Brief Assessment of Cognition (BACS)

    Time frame: Change from baseline to 1-month follow-up

    The BACS is designed to assess several domains of cognition; Verbal Memory; Processing Speed; Working Memory; Verbal Fluency; Motor Function; Executive Functioning. Higher scores indicate better cognitive functioning. Total score reported after being transformed into z score based on normative scoring provide by test makers.

  30. Brief Assessment of Cognition (BACS)

    Time frame: Change from baseline to 3-month follow-up

    The BACS is designed to assess several domains of cognition; Verbal Memory; Processing Speed; Working Memory; Verbal Fluency; Motor Function; Executive Functioning. Higher scores indicate better cognitive functioning. Total score reported after being transformed into z score based on normative scoring provide by test makers.

Sponsors and collaborators

Lead sponsor

Beth Israel Deaconess Medical Center

Other

Registry information

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Jul 6, 2022
Registry last updated
Nov 6, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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