Abstract
Transcranial magnetic stimulation (TMS) is a non-invasive method used to investigate neurophysiological integrity of the human neuromotor system. We describe in detail, the methodology of a single pulse TMS protocol that was performed in a large cohort of people (n = 110) with multiple sclerosis (MS). The aim was to establish and validate a core-set of TMS variables that predicted typical MS clinical outcomes: walking speed, hand dexterity, fatigue, and cognitive processing speed. We provide a brief and simple methodological pipeline to examine excitatory and inhibitory corticospinal mechanisms in MS that map to clinical status. Delayed and longer ipsilateral silent period (a measure of transcallosal inhibition; the influence of one brain hemisphere’s activity over the other), longer cortical silent period (suggestive of greater corticospinal inhibition via GABA) and higher resting motor threshold (lower corticospinal excitability) most strongly related to clinical outcomes, especially when measured in the hemisphere corresponding to the weaker hand. Greater interhemispheric asymmetry (imbalance between hemispheres) correlated with poorer performance in the greatest number of clinical outcomes. We also show, not surprisingly, that TMS variables related more strongly to motor outcomes than non-motor outcomes. As it was validated in a large sample of patients with varying severities of central nervous system dysfunction, the protocol described herein can be used by investigators and clinicians alike to investigate the role of TMS as a biomarker in MS and other central nervous system disorders.
Highlights
Biological markers (‘biomarkers’) are surrogate markers of disease activity used in the diagnosis, characterization, prognostication, and surveillance of disease throughout its natural history and in response to therapy [1]
When we examined which Transcranial Magnetic Stimulation (TMS) variables were the best predictors of clinical outcomes, measurements from the hemisphere corresponding to the weaker hand—namely motor thresholds, motor evoked potential (MEP) amplitudes, and Cortical Silent Period (CSP) duration—significantly accounted for the most variance in fatigue and cognition (SDMT)
Values derived from the hemisphere corresponding to the weaker hand resulted in the strongest relationships to clinical outcomes, suggesting that, as a minimum, measurements should be taken from this side
Summary
Biological markers (‘biomarkers’) are surrogate markers of disease activity used in the diagnosis, characterization, prognostication, and surveillance of disease throughout its natural history and in response to therapy [1]. Certain biomarkers provide information on neurophysiological processes related to neurologic disease, which allows researchers to predict potential for disease recovery and understand mechanisms of prospective treatments This is critical information needed to determine how neurorehabilitation may alter neuroplasticity in heterogeneous disorders of the central nervous system such as stroke and multiple sclerosis (MS) [2,3,4,5]. Many groups internationally use TMS to probe central nervous system function; methods often vary considerably among laboratories, making it difficult to compare findings across studies. It is not clear which TMS techniques (e.g., single pulse or paired pulse) and which TMS variables are relevant as rehabilitation and neuroplasticity biomarkers
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