NCT04309370

Interactions of Fronto-Parietal High Frequency rTMS on Anterior Cingulate Cortex Activation in Schizophrenia

Interactions of Fronto-Parietal High Frequency Repetitive Transcranial Magnetic Stimulation on Anterior Cingulate Cortex Activation in Schizophrenia

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: Indiana University · Academic / Other
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Not accepted

Summary

This will be a single site pilot study. 20 subjects with EPP (Early Phase Psychosis), defined as medical record documentation of the onset of clinically significant psychotic symptoms within the past 10 years, will be enrolled. Prior to randomization subjects will undergo fMRI (Functional Magnetic Resonance Imaging) during CC (Cognitive Control) task (Stroop Color-Word paradigm) and resting-state paradigms. This baseline scan will also include a high-resolution structural sequence for neuronavigation purposes. Then, on two separate days, each occurring one-week apart, subjects will receive one session of excitatory (20 Hz) (Hertz) rTMS (Repetitive Transcranial Magnetic Stimulation) targeting the LDLPFC (Left Dorsolateral Prefrontal Cortex) and one session targeting the LSPC (Left Superior Parietal Cortex). The order of stimulation sites will be randomized and counter-balanced. Immediately following each session, subjects will undergo repeat fMRI during CC and RS (Resting State) paradigms. Investigators will also examine the effect of rTMS on CC performance.

Detailed description

In spite of existing work studying rTMS as a treatment modality in schizophrenia, there are no studies that have examined the effects of rTMS targeting superficial CCN (Cognitive Control Network) structures (LDLPFC and LSPC) on ACC (Anterior Cingulate Cortex) activity or CCN connectivity in schizophrenia. It is also important to note that the vast majority of studies using rTMS in schizophrenia have examined chronic populations where confounds associated with prolonged duration of illness may be present. EPP is a desirable population to study because these individuals tend to have fewer psychiatric and physical comorbidities and less antipsychotic drug exposure, all of which are factors that may confound investigations of new treatment interventions for this illness. In light of the significant unmet medical need associated with schizophrenia and the grave clinical effect of disrupted CC in the illness, rTMS modulating the ACC, and potentially CCN circuitry, represents an unexplored and novel potential treatment option. The goal of this project is to utilize HF (20 Hz) rTMS, in conjunction with functional magnetic resonance imaging (fMRI), to provide evidence that rTMS targeting superficial CCN structures (LDLPFC and LSPC) modulates: 1) activation in the ACC during in-scanner CC task performance and 2) functional connectivity between the CCN structures during in-scanner CC task performance. This study will provide vital preliminary data on target engagement informing future clinical trials seeking to investigate rTMS as a novel treatment for CC impairment in schizophrenia. This study will also seek to refine the understanding of the brain circuitry that mediates the potential pro-CC effects of rTMS through the use of fMRI at baseline and following the course of rTMS administration.

Conditions

• Schizophrenia

Interventions

Type	Name	Description
DEVICE	20 Hz rTMS	Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that received FDA clearance for use in treatment resistant major depressive disorder in 2008. rTMS utilizes the application of a repetitively pulsed magnetic field over the scalp to induce an electric field within a discrete area of the cerebral cortex. This electric field results in altered ion flow across the neuronal cellular membrane and ultimately changes in neuronal polarization. rTMS modulates cortical activation depending on the stimulation parameters used. Physiological studies have provided evidence that suggests that high-frequency (HF) rTMS produces an increase in local cortical excitability. Studies have also demonstrated that rTMS may increase or decrease functional connectivity between separate but related cortical structures, utilizing high and low frequency stimulation, respectively.

Timeline

• Start date: 2020-03-12
• Primary completion: 2022-04-15
• Completion: 2022-04-15
• First posted: 2020-03-16
• Last updated: 2023-08-03
• Results posted: 2023-08-03

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated device study