Repetitive Transcranial Magnetic Stimulation as a Therapeutic and Probe in Schizophrenia: Examining the Role of Neuroimaging and Future Directions

Abstract

Schizophrenia is a complex condition associated with perceptual disturbances, decreased motivation and affect, and disrupted cognition. Individuals living with schizophrenia may experience myriad poor outcomes, including impairment in independent living and function as well as decreased life expectancy. Though existing treatments may offer benefit, many individuals still experience treatment resistant and disabling symptoms. In light of the negative outcomes associated with schizophrenia and the limitations in currently available treatments, there is a significant need for novel therapeutic interventions. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can modulate the activity of discrete cortical regions, allowing direct manipulation of local brain activation and indirect manipulation of the target's associated neural networks. rTMS has been studied in schizophrenia for the treatment of auditory hallucinations, negative symptoms, and cognitive deficits, with mixed results. The field's inability to arrive at a consensus on the use rTMS in schizophrenia has stemmed from a variety of issues, perhaps most notably the significant heterogeneity amongst existing trials. In addition, it is likely that factors specific to schizophrenia, rather than the rTMS itself, have presented barriers to the interpretation of existing results. However, advances in approaches to rTMS as a biologic probe and therapeutic, many of which include the integration of neuroimaging with rTMS, offer hope that this technology may still play a role in improving the understanding and treatment of schizophrenia.

Keywords: MRI; Repetitive transcranial magnetic stimulation; Schizophrenia; fMRI.

Fig. 1

During repetitive transcranial magnetic stimulation (rTMS), an electric current is used to create a repetitively pulsed magnetic field. When applied over the scalp, this induces an electric current within a discrete area of the brain with resultant changes in neuronal polarization. The end result is altered neuronal activity in the area where the rTMS is applied

Fig. 2

fMRI-guided rTMS. Neuronavigated rTMS targeting (A) episodic memory (EM) circuitry and (B) cognitive control in early-phase psychosis. Here, rTMS is applied to the precuneus and left dorsolateral prefrontal cortex, respectively. Baseline fMRI during task performance allows for identification of the point of maximal BOLD signal change during EM retrieval and cognitive control tasks, enabling individualized stimulation for each subject. In both sets of images, the motor strip has been highlighted for use during motor threshold determination