Table 1. Summary of investigational TMS approaches in schizophrenia.
| TMS paradigm | Definition | Putative neurophysiology | Findings in SZ | |
|---|---|---|---|---|
| Consistent | Emerging | |||
| Cortical excitability | ||||
| Resting motor threshold (RMT) | The minimal stimulator intensity that produces a motor evoked potential of ≥ 50 μV in 5 of 10 trials in a relaxed muscle | Neuronal membrane activity regulated by voltage-gated Na+ channels & ionotropic non-NMDA glutamate receptors | ≈ * | – |
| Motor evoked potential (MEP) amplitude | The mean amplitude of hand muscle contraction evoked by a series of pulses applied at a consistent TMS intensity | Neuronal membrane activity governed by the excitation/inhibition balance through various neurotransmitter systems | ≈ * | – |
| Intracortical facilitation (ICF) | The % of MEP facilitation relative to suprathreshold test pulse MEP, elicited by pairing a subthreshold conditioning pulse (80% of RMT) 7-20 ms before the test pulse | NMDA-glutamate receptor-mediated excitability | ≈ * | – |
| Cortical inhibition | ||||
| Short-interval intracortical inhibition (SICI) | The % of MEP inhibition relative to suprathreshold test pulse MEP, elicited by pairing a subthreshold conditioning pulse (80% of RMT) 1-5 ms before the test pulse | GABAA receptor-mediated inhibitory neurotransmission | ↓ * | Non-specific to SZ, but related to cognitive dysfunction |
| Long-interval intracortical inhibition (LICI) | The % of MEP inhibition relative to suprathreshold test pulse MEP, elicited by pairing a suprathreshold conditioning pulse 50-200 ms before the test pulse | GABAB receptor-mediated inhibitory neurotransmission | ≈ * | ↑ LICI in mania—differential biomarker |
| Cortical silent period (CSP) | Time from MEP offset to the return of any voluntary EMG activity when a suprathreshold pulse is delivered to the motor cortex contralateral to a voluntarily contracted hand muscle | First 50 ms of the silent period is mediated by spinal mechanisms; the later part is mediated by GABAB receptor-driven motor cortical inhibition | ≈ * | Increases with clozapine treatment |
| Putative MNS activity Motor resonance |
The degree of motor cortical reactivity facilitation during action observation, relative to static image viewing | Driven by premotor MNS activity, possibly through premotor-motor connections | ↓ in untreated SZ, related to social cognition deficits | ↑ in untreated mania, modulated by context, but less so in SZ |
| Cortical connectivity | ||||
| Ipsilateral silent period (ISP) | Time from MEP offset to the return of any voluntary EMG activity when a suprathreshold pulse is delivered to the motor cortex ipsilateral to a voluntarily contracted hand muscle | Corpus callosum functional integrity | ↓ | – |
| Transcallosal inhibition (TCI) | The % of MEP inhibition relative to suprathreshold test pulse MEP from one hemisphere, when a suprathreshold conditioning pulse is delivered over the contralateral hemisphere 7-20 ms before the test pulse | Corpus callosum functional integrity | ↓ | – |
| Transcallosal facilitation (TCF) | The % of MEP facilitation relative to suprathreshold test pulse MEP from one hemisphere, when a low-intensity conditioning pulse is delivered over the contralateral hemisphere 4-5 ms before the test pulse | Corpus callosum functional integrity | ≈ | – |
| Parieto-motor connectivity | A subthreshold conditioning pulse applied to the posterior parietal cortex 4 and 15 ms prior facilitates the MEP obtained by administering a test pulse to the motor hand area on the same side | Superior longitudinal fasciculus functional integrity | – | ↓ |
| Premotor-motor connectivity | A subthreshold conditioning stimulus to the premotor cortex (8 ms prior) facilitates the MEP elicited by a suprathreshold test pulse in the contralateralmotor cortex | Transcallosal premotor-motor connectivity | – | ↓ |
| Cerebellar-cortical connectivity | A subthreshold conditioning stimulus to the cerebellum 5-15 ms prior to a suprathreshold test stimulus to the contralateral motor cortex inhibits the output of the test stimulus | Inhibitory influence of the cerebellum on the motor cortex through the cerebello-thalamo cortical connectivity | ↓ | |
| Cortical plasticity | ||||
| Motor cortical plasticity | The degree of facilitation or inhibition of cortical reactivity (most often measured as the MEP amplitude) with TMS/TES perturbation protocols | Long-term potentiation/depression (LTP/LTD)-like experience-dependent synaptic plasticity | ↓ LTP- and LTD-like plasticity* | – |
| Non-motor cortical reactivity and connectivity | ||||
| TMS-evoked potential (TEP) | ATMS pulse when administered to the cortex elicits an immediate response of positive and negative deflections visible on EEG | Cortical reactivity | – | ↓ prefrontal reactivity |
| Cortical connectivity | ATMS pulse when administered to the cortex elicits a delayed intra- and interhemispheric spread of activation that follows in spatial, temporal, and frequency domains | Effective connectivity | ↓ prefrontal connectivity | |
μV microvolts, ms milliseconds, NMDA N-methyl-D-aspartate, SZ schizophrenia, MNS mirror neuron system, TMS transcranial magnetic stimulation, TES transcranial electrical stimulation, EEG electroencephalography, EMG electromyography
*
Consistent findings are highlighted if data is available from meta-analyses (if available) or from at least two studies; emerging findings reflect more recent findings that are not replicated
≈
Not different from healthy
↓
Diminished as compared to healthy)
↑
Enhanced as compared to healthy