Brain Stimulation to the Hippocampus in Schizophrenia

Stanford University60 enrolled

Overview

Schizophrenia - marked by delusions, hallucinations, and cognitive deficits - causes the most disability of any mental health condition, but existing treatments have significant side effect burden and are often ineffective. Disordered neural activity in the hippocampus likely contributes to schizophrenia symptoms, but to develop better therapies we need to understand whether hippocampal activity in schizophrenia can be systematically affected by non-invasive brain stimulation techniques like transcranial magnetic stimulation (TMS). This proposal will investigate the use of connectivity-guided theta burst brain stimulation to specifically target hippocampal function in schizophrenia, offering insights into fundamental hippocampal processes, schizophrenia pathophysiology, and potential avenues to use brain stimulation as a therapeutic tool in this devastating illness.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Schizophrenia Disorders Mental Disorder Psychotic Disorder

Interventions

Intracranial electrodesDEVICE

Intracranial electrodes will be used for the delivery of invasive electrical brain stimulation.

TMSDEVICE

TMS will be used for the delivery of noninvasive brain stimulation

TMS shamDEVICE

Sham TMS will be used as a comparator for noninvasive brain stimulation

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Men and women, ages 18 to 65 years * Medically intractable epilepsy requiring phase II monitoring (intracranial EEG arms only) * DSM-V diagnosis of schizophrenia spectrum Axis I disorders including delusional disorder, brief psychotic disorder, schizophreniform disorder, schizophrenia, schizoaffective disorder (non-invasive TMS-EEG arms only). * Must have intellectual capacity to ensure adequate comprehension of the study and potential risks involved in order to provide informed consent * No current or history of major neurological disorders other than epilepsy. Exclusion Criteria: * DSM5 diagnosis of intellectual disability * Significant head injury * Active suicidal ideation or history of suicide attempt within the past 1 year. * Medical illness affecting brain structure or function, or other uncontrolled or unstable medical condition. * Pregnancy or postpartum (\<6 weeks after delivery or miscarriage) * Inability to provide informed consent * Active substance abuse other than alcohol or cannabis within the past 1 year * Psychotic illness with a temporal relation to substance use or head injury * Those with a contraindication for MRIs or TMS (e.g. implanted metal).

Outcomes

Primary Outcomes

Change in intracranial EEG after one TBS session

Change in spontaneous oscillatory EEG power from before to after application of one TBS session, for active and sham stimulation, as measured via intracranial recording electrodes (iEEG).

Time frame: 45 minutes

Change in scalp EEG after one TBS session

Change in spontaneous oscillatory EEG power from before to after application of one TBS session, for active and sham stimulation, as measured via scalp recording electrodes (scalp electroencephalography).

Time frame: 45 minutes

Secondary Outcomes

Change in TMS-provoked EEG power

Change in oscillatory EEG power as provoked by repeated single pulses of TMS, compared from before to after a single session of TBS.

Time frame: 45 minutes

Change in electrical stimulation provoked iEEG power

Change in oscillatory iEEG power as provoked by repeated single pulses of invasive electrical stimulation, compared from before to after a single session of TBS.

Time frame: 45 minutes

Brain Stimulation to the Hippocampus in Schizophrenia

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts