Changes in thresholds for intracortical excitability in chronic stroke: More than just altered intracortical inhibition

Abstract

Purpose: The purpose of the present study was to assess changes in thresholds for the onset of short intracortical inhibition (SICI) and intracortical facilitation (ICF) in individuals with chronic stroke compared to age-matched healthy adults and evaluate the relationship between these thresholds and motor function in the chronic stroke group. Methods: Paired-pulse transcranial magnetic stimulation was used to derive thresholds for the onset of SICI and ICF in 12 neurologically healthy and 12 individuals with chronic stroke. Motor evoked potentials were elicited by a test stimulus of fixed intensity preceded by a conditioning stimulus ranging from 0%-125% of active motor threshold to generate recruitment curves. Regression functions were fit to these recruitment curves to identify thresholds for the onset of SICI and ICF. Mixed measures analysis of variance was used to compare thresholds for each hemisphere within and between groups. Results: Results showed a significant three-way interaction between Group (stroke, healthy), Hemisphere (ipsilesional, contralesional) and Stimulus interval (2 ms, 12 ms). Significant differences in the thresholds for the onset of both SICI and ICF were present in individuals with chronic stroke, with no between hemisphere differences for the control group. When compared to age-matched controls, comparisons revealed significant reductions in ipsilesional, but not contralesional thresholds for the onset of ICF, and significant reductions in contralesional, but not ipsilesional, thresholds for the onset of SICI in individuals with chronic stroke. In addition, as thresholds for ICF and SICI in stroke patients approached the level of healthy adults, higher function on the Wolf Motor Function Test was observed. Conclusions: Reduced thresholds for the onset of SICI and ICF observed in the present study indicate that both inhibitory and facilitatory systems mediate changes in cortical excitability in chronic stroke patients. The association between higher onset thresholds and motor function in the stroke group also suggests that these thresholds have potential utility for tracking functional 694 J.D. Edwards et al. / Intracortical thresholds in chronic strokemotor improvements in patients with chronic stroke. This study provides new insights to further characterize changes in intracortical neurotransmission that play an important role in modulating neuroplasticity and the potential relationship between inhibitory and facilitatory networks and motor function post-stroke.

Selectivity of conventional electrodes for recording motor evoked potentials: An investigation with high‐density surface electromyography

“…Changes in MEP amplitude are difficult to interpret when there is crosstalk from other muscles. For instance, TMS is commonly used to assess corticospinal excitability in clinical populations and in association with interventions . Thus, it is possible that, when the excitability of the target muscle is comparable between conditions, but other muscles are facilitated or inhibited, MEPs collected with conventional EMG may erroneously indicate that the corticospinal excitability of the target muscle was increased or decreased.…”

“…This phenomenon, referred to as crosstalk, could influence the amplitude of motor evoked potentials (MEPs) elicited by TMS. Importantly, stimulation parameters, such as localization of the “hotspot” in the primary motor cortex (M1), motor threshold, and stimulation intensity, are routinely based on the amplitude of the MEP, and hence they depend on whether the EMG recording reflects the activation of the target muscle. As the representation of individual muscles may overlap extensively in M1, non‐target muscles can also be stimulated.…”

Opportunities for concurrent transcranial magnetic stimulation and electroencephalography to characterize cortical activity in stroke

“…Levels of intracortical excitability can be evaluated using paired-pulse TMS (ppTMS) paradigms (Kujirai et al, 1993 ; Nakamura et al, 1997 ). Using ppTMS, altered levels of intracortical inhibition and facilitation in both the ipsilesional and contralesional hemispheres in acute and chronic stroke have been demonstrated (Liepert et al, 2000 ; Manganotti et al, 2002 ; Bütefisch et al, 2003 ; Edwards et al, 2013 ). TMS has also been used to assess interhemispheric interactions in chronic stroke patients (Murase et al, 2004 ; Takeuchi et al, 2010 ).…”

Intracortical Circuits in the Contralesional Primary Motor Cortex in Patients With Chronic Stroke After Botulinum Toxin Type A Injection: Case Studies

“…P1 and P2 did not show any level of ICF at baseline but similar levels of ICF were recorded in the other two participants (P3 and P4) despite the difference in age. Edwards et al (2013) assessed changes in the onset thresholds for SICI and ICF in stroke patients compared to age-matched healthy adults in both ipsi-and contralesional hemisphere (Edwards et al, 2013) and reported significant reductions in onset thresholds for SICI in the contralesional hemisphere and significant reductions in onset thresholds for ICF in the ipsilesional hemisphere in patients with chronic stroke (Edwards et al, 2013). One possible reason that ICF was not recorded for P1 and P2 could be because of changes in the onset threshold for ICF in these patients and the possibility that the stimulus intensity used in this study was insufficient to activate the facilitatory networks in these patients.…”