A Review of Studies Leveraging Multimodal TMS-fMRI Applications in the Pathophysiology and Treatment of Schizophrenia.

Sachin Pradeep Baliga,Urvakhsh Meherwan Mehta

doi:10.3389/fnhum.2021.662976

Abstract

The current review provides an overview of the existing literature on multimodal transcranial magnetic stimulation, and functional magnetic resonance imaging (TMS/fMRI) studies in individuals with schizophrenia and discusses potential future avenues related to the same. Multimodal studies investigating pathophysiology have explored the role of abnormal thalamic reactivity and have provided further evidence supporting the hypothesis of schizophrenia as a disorder of aberrant connectivity and cortical plasticity. Among studies examining treatment, low-frequency rTMS for the management of persistent auditory verbal hallucinations (AVH) was the most studied. While multimodal TMS/fMRI studies have provided evidence of involvement of local speech-related and distal networks on stimulation of the left temporoparietal cortex, current evidence does not suggest the superiority of fMRI based neuronavigation over conventional methods or of active rTMS over sham for treatment of AVH. Apart from these, preliminary findings suggest a role of rTMS in treating deficits in neurocognition, social cognition, and self-agency. However, most of these studies have only examined medication-resistant symptoms and have methodological concerns arising from small sample sizes and short treatment protocols. That being said, combining TMS with fMRI appears to be a promising approach toward elucidating the pathophysiology of schizophrenia and could also open up a possibility toward developing personalized treatment for its persistent and debilitating symptoms.

Highlights

Schizophrenia is a severe mental illness characterized by positive, negative, cognitive symptom clusters
Cortical Connectivity Single-pulse Transcranial magnetic stimulation (TMS) to the precentral gyrus has been utilized with concurrent functional magnetic resonance imaging (fMRI) to measure response in synaptically connected regions in a case-control study (Guller et al, 2012a)
In an extension of the experiment, resting state functional connectivity, white matter (WM) structural connectivity, and gray matter (GM) integrity were assessed in the same subjects using DTI (Guller et al, 2012b)

Summary

Introduction

Schizophrenia is a severe mental illness characterized by positive (such as delusions, hallucinations), negative (anhedonia, asociality), cognitive (such as working memory deficits) symptom clusters. It has a life-time prevalence of around 1% and typically begins in late adolescence or early adulthood, leading to substantial disability, morbidity and mortality. When given repetitively in trains, rTMS can have differential effects by causing excitatory or inhibitory changes depending on the stimulation pattern and the cortical state (Wagner et al, 2007). TMS has limited spatial resolution when used on its own unless combined with an imaging modality (Wagner et al, 2007)

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