Transcranial magnetic stimulation: a neuroscientific probe of cortical function in schizophrenia

Abstract

Transcranial magnetic stimulation (TMS) is a neuropsychiatric tool that can serve as a useful method to better understand the neurobiology of cognitive function, behavior, and emotional processing. The purpose of this article is to examine the utility of TMS as a means to measure neocortical function in neuropsychiatric disorders in general, and schizophrenia in particular, for the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative. When incorporating TMS paradigms in research studies, methodologic considerations include technical aspects of TMS, cohort selection and confounding factors, and subject safety. Available evidence suggests benefits of TMS alone or in combination with neurophysiologic and neuroimaging methods, including positron emission tomography, single photon emission computed tomography, magnetic resonance imaging, functional magnetic resonance imaging, functional near infrared spectroscopy, magnetoencephalography, and electroencephalography, to explore neocortical function. With the multiple TMS techniques including single-pulse, paired-pulse, paired associative stimulation, and repetitive TMS and theta burst stimulation, combined with neurophysiologic and neuroimaging methods, there exists a plethora of TMS experimental paradigms to modulate neocortical physiologic processes. Specifically, TMS can measure cortical excitability, intracortical inhibitory and excitatory mechanisms, and local and network cortical plasticity. Coupled with functional and electrophysiologic modalities, TMS can provide insight into the mechanisms underlying healthy neurodevelopment and aging, as well as neuropsychiatric pathology. Thus, TMS could be a useful tool in the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia armamentarium of biomarker methods. Future investigations are warranted to optimize TMS methodologies for this purpose.

Figure 1

Mechanism of action of transcranial magnetic stimulation (TMS). TMS uses magnetic fields that enter cortical tissue and with varied intensities can result in neuronal depolarization, intracortical inhibition or facilitation, or the releasing of endogenous neurotransmitters that results in transsynaptic action.

Figure 2

Combined transcranial magnetic stimulation (TMS) with electrophysiological and neuroimaging methods to develop biomarkers of disease. A: TMS can be safely combined with imaging techniques, such as functional magnetic resonance imaging (fMRI), or neocortical recording methods, such as electroencephalography (EEG), to comprehensively study behavior and develop useful biomarkers; B: The eXimia Neuronavigation Brain Stimulation system by Nexstim, and schematic plots of acquired TMS-EEG data on motor and prefrontal cortices.

Figure 3

Schematic representation of TMS measures of motor cortical reactivity and plasticity. A: Single-pulse TMS and motor evoked potential; B: Cortical silent period; C: Paired-pulse TMS to assess intracortical inhibition and intracortical facilitation; D: Paired-pulse TMS to assess transcallosal inhibition; E: Paired associative stimulation [schematics A-D from (21); schematic E from (57)].

Figure 4

Results from study of plasticity mechanisms in five early-onset, first-episode, antipsychotic-naïve schizophrenia patients. A: Summary of individual results: on the x axis, red dots represent the schizophrenia (SCZ) patients and blue dots the age-matched healthy controls (HC); values on the Y axis represent the time to return to baseline levels following continuous theta burst stimulation (cTBS). All subjects in the schizophrenia group show shorter duration of the modulatory effects of cTBS on cortical reactivity than their matched controls, with the exception of one patient whose effects returned to baseline at the same time as his matched control; B: Average baseline-corrected MEP amplitude for the schizophrenia group (in red) and control group (in blue), at all time-points assessed (5 to 120 minutes post-cTBS). In both graphs, error bars indicate standard error of the mean for each time point. Values are represented as proportion of baseline amplitude with a line at 1.0 representing baseline amplitude.