Paired Associative Stimulation in the Dorsolateral Prefrontal Cortex in Patients With Schizophrenia

NCT01545999 | Active Not Recruiting

• 1 other identifier: #165/2009-04
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to

1. 1.assess the effect of PAS in schizophrenia in the dorsolateral prefrontal cortex (DLPFC)
2. 2.assess the effect of PAS induced long-term potentiation (LTP) on the performance of patients with schizophrenia on a cognitive task related to DLFPC.

Conditions

Schizophrenia

Keywords

Transcranial Magnetic Stimulation (TMS); Dorsolateral Prefrontal Cortex (DLPFC); Schizophrenia; Working Memory; Paired Associative Stimulation (PAS); Electroencephalography (EEG); Cognition

Outcome Measures

Primary Outcomes (1)

• Changes in working memory

  The N-Back is a working memory task where the subject is presented with a sequence of stimuli (letters). The task consists of indicating when the current stimulus matches the one from n steps earlier in the sequence. The load factor n can be adjusted to make the task more or less difficult. Subjects are required to complete the 0, 1, 2 and 3 back at baseline, 1 day post PAS delivery and 7 days post PAS.

  1 day and 7 days post N-back task

Study Arms (2)

PAS 25

ACTIVE COMPARATOR

In humans, paired associative stimulation (PAS-25) is a transcranial magnetic stimulation (TMS) protocol that has been shown to result in LTP-like plasticity (PAS-LTP) in the motor cortex (M1). PAS-LTP has been shown to be dependent on the NMDAR and to correlate significantly with performance on a motor learning task.

Other: Brain Stimulation via Transcranial Magnetic Stimulation

PAS 100

SHAM COMPARATOR

To control for non-specific effects of PAS protocol, the investigators will use a modified PAS protocol (PAS-100) that does not result in any neurophysiologic effects. Patients with schizophrenia and healthy controls will be assessed first with the N-back task and then randomized

Other: Brain Stimulation via Transcranial Magnetic Stimulation

Interventions

Brain Stimulation via Transcranial Magnetic Stimulation OTHER

PAS-25 will consist of 180 PNS delivered to right median nerve, each paired with a single TMS pulse delivered over left DLPFC with an interstimulus interval of 25 ms. This ISI was designed to generate approximately synchronous arrival of both inputs in M1 and was reported to markedly enhance TMS-induced MEP following PAS-25. Patients with schizophrenia will be asked to continue with a 2-week course (5 days/week) of daily PAS-25 or PAS-100 to assess potential of a repetitive course of PAS-25 on enhancing working memory in patients with Schizophrenia. One and seven days after the 2-week course PAS-25 or PAS-100, patients with schizophrenia will be assessed with the N-back task.

PAS 100; PAS 25

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 or above
• All races and ethnicities.
• Females and males.
• Meet DSM-IV TR criteria for a current diagnosis of schizophrenia or schizoaffective disorder.
• Clinically stable as operationalized by (1) either having not been hospitalized within 3 months or having been hospitalized for 3 months or more prior to assessment, and (2) having had no change in antipsychotic medication dosage within the 4 weeks prior to assessment.
• Willingness and ability to speak English
• Willingness to provide informed consent
• Corrected visual ability that enables reading of newspaper headlines and corrected hearing capacity that is adequate to respond to a raised conversational voice.

You may not qualify if:

• Meets criteria for a cognitive disorder secondary to a neurological or other medical disorder affecting the central nervous system (for example, multiple sclerosis, history of traumatic brain injury, stroke, untreated hypothyroidism).
• Mini Mental Status Examination score of 17 and less because a subject with a very low MMSE score is unlikely to be able to compete the NP battery.
• Diagnosis of bipolar disorder or current major depressive episode.
• Meets diagnostic criteria for current alcohol or other drug dependence within 6 months of testing
• Electroconvulsive Therapy (ECT) within 6 months of testing.
• Left handedness.
• Incompetency to consent
• Age 18 or above
• Willingness and ability to speak English
• Willingness to provide informed consent
• Corrected visual ability that enables reading of newspaper headlines and corrected hearing capacity that is adequate to respond to a raised conversational voice.
• DSM IV TR psychiatric diagnosis except for simple phobias or an adjustment disorder.
• Other neurological disorder affecting central nervous system.
• Psychotropic medication except for sedative /hypnotics at a stable dose for at least 4 weeks.
• Family history of a primary psychotic disorder in a first-degree relative.

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR): collaborator
• National Alliance for Research on Schizophrenia and Depression: collaborator
• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H4, Canada

Location

Related Links

• Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching

MeSH Terms

Conditions

Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Tarek K Rajji, MD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 17, 2012
• First Posted: March 7, 2012
• Study Start: March 1, 2012
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)