Utility of threshold tracking transcranial magnetic stimulation in ALS

Vucic, Steve; Bos, Mehdi van den; Menon, Parvathi; Howells, James; Dharmadasa, Thanuja; Kiernan, Matthew C.

doi:10.1016/j.cnp.2018.10.002

Cited by 60 publications

(70 citation statements)

References 144 publications

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“…In Experiment 1, based on the corresponding literature, the hunting-threshold was defined as the TS intensity (expressed in percentage of the maximal stimulator output (%MSO)) required to elicit a MEPtarget in the relaxed FDI of 0.2 mV in peak-to-peak amplitude. This fixed MEP value lies in the middle of the steepest portion of the stimulus response curve plotted on a logarithmic scale (Fisher et al, 2002;Vucic et al, 2006Vucic et al, , 2018. In the current study, the TS intensity required to elicit the MEPtarget at rest corresponded on average to 109% rMT (range 103-118 % rMT).…”

Section: Adaptive Threshold-hunting Techniquementioning

confidence: 52%

“…The aim of the present study was to unravel the SICI modulation observed during MI through a methodological and conceptual reconsideration of: (i) the importance of CS intensity and (ii) the inhibitory process within M1 as an inherent feature of MI. To do so, we designed a pair of experiments in which we varied the CS intensity and determined the TS intensity required to maintain a fixed MEP amplitude for each condition using an adaptive threshold hunting technique (Awiszus et al, 1999;Fisher et al, 2002;Awiszus, 2003;Samusyte et al, 2018;Vucic et al, 2018). This method has been recently developed in order to overcome the potential limitations of conventional paired-pulse TMS protocols, such as large variability in MEP amplitude and a "floor/ceiling effect" when the observed inhibition leads to complete MEP suppression Cirillo et al, 2018;Van den Bos et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Unravelling the modulation of intracortical inhibition during motor imagery: An adaptive threshold-hunting study

Neige

Rannaud-Monany

Stinear

et al. 2019

Preprint

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Motor imagery (MI) is the mental simulation of an action without any apparent muscular contraction. By means of transcranial magnetic stimulation, few studies revealed a decrease of short-interval intracortical inhibition (SICI) within the primary motor cortex. However, this decrease is ambiguous, as one would expect greater inhibition during MI to prevent overt motor output. The current study investigated the extent of SICI modulation during MI through a methodological and a conceptual reconsideration of i) the importance of parameters to assess SICI (Exp.1) and ii) the inhibitory process within the primary motor cortex as an inherent feature of MI (Exp.2). Participants performed two tasks: 1) rest and 2) imagery of isometric abduction of the right index finger. Using transcranial magnetic stimulation, motor evoked potentials were elicited in the right first dorsal interosseous muscle. An adaptive threshold-hunting paradigm was used, where the stimulus intensity required to maintain a fixed motor evoked potential amplitude was quantified.To test SICI, we conditioned the test stimulus with a conditioning stimulus (CS) of different intensities. Results revealed an Intensity by Task interaction showing that SICI decreased during MI as compared to rest only for the higher CS intensity (Exp.1). At the lowest CS intensities, a Task main effect revealed that SICI increased during MI (Exp.2). SICI modulation during MI depends critically on the CS intensity. By optimising CS intensity, we have shown that SICI circuits may increase during MI, revealing a potential mechanism to prevent the production of a movement while the motor system is activated.

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Section: Adaptive Threshold-hunting Techniquementioning

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Unravelling the modulation of intracortical inhibition during motor imagery: An adaptive threshold-hunting study

Neige

Rannaud-Monany

Stinear

et al. 2019

Preprint

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“…Cortical hyperexcitability appears to be an important pathogenic and diagnostic biomarker of ALS, mediated by an imbalance of inhibitory and facilitatory cortical circuit activity along with increased cortical neuronal excitability 1,3,8 . The evolution of cortical excitability changes with disease progression in ALS remains to be fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…The pathophysiological processes underlying ALS development are complex and heterogenous, although the extent to which each neuronal populations are affected varies across individuals and disease sages 2 . Cortical hyperexcitability appears to be an important pathophysiological process in ALS, contributing to neurodegeneration via an anterograde glutamatergic excitotoxic process 1,3 . Support for this hypothesis is provided by transcranial magnetic stimulation (TMS) studies disclosing that cortical hyperexcitability is a specific and early feature of ALS, which precedes onset of muscle weakness, underlies development of clinical signs such as the split hand phenomenon, contributes to disease progression, and correlates with greater functional disability 4–8 .…”

Section: Introductionmentioning

confidence: 99%

Cortical hyperexcitability evolves with disease progression in ALS

Menon

Higashihara

Bos

et al. 2020

Ann Clin Transl Neurol

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Objective: Cortical hyperexcitability has been established as an early feature of amyotrophic lateral sclerosis (ALS). The evolution of cortical hyperexcitability with ALS progression remains to be fully elucidated. This study aims to investigate changes in cortical function in ALS with disease progression. Methods: Cortical function assessed by threshold tracking transcranial magnetic stimulation (TMS) along with clinical phenotyping was prospectively undertaken on 444 patients presenting with suspected ALS (345 ALS; 99 neuromuscular mimics). Disease stage was defined as follows: (1) King's clinical staging system and (2) proportion of disease duration statistically categorized into tertials. Results: Cortical hyperexcitability was evident across all ALS stages, being more prominent in later stages of ALS as indicated by increased motor-evoked potential amplitude (P < 0.05), as well as longer disease duration as reflected by reduced short-interval intracortical inhibition (P < 0.05). Prolonged central motor conduction time was evident with disease progression. These changes were accompanied by reduction in neurophysiological index (P < 0.001) and compound muscle action potential amplitude (P < 0.01), progressive muscle weakness (P < 0.001), and decline in the ALS functional rating scale (P < 0.001). Interpretation: This study established an increase in cortical hyperexcitability with increased disease duration in ALS, mediated by cortical disinhibition and direct increase in corticomotoneuronal excitability.

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“…In addition to SICI reduction, the MEP amplitude was also significantly increased, albeit only when recording from the hand and lower limb regions. The MEP amplitude reflects the density of corticomotoneuronal projections onto motor neurons 42 as well as the excitability of the local spinal cord circuitry 45 . The increase in MEP amplitude could be explained by cortical hyperexcitability, and is in keeping with previous studies in ALS patients 13,46,47 .…”

Section: Cortical Hyperexcitability and Alsmentioning

confidence: 99%

Regional motor cortex dysfunction in amyotrophic lateral sclerosis

Menon

Yiannikas

Kiernan

et al. 2019

Ann Clin Transl Neurol

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Objective The pathophysiological processes underlying amyotrophic lateral sclerosis (ALS) need to be better understood, although cortical dysfunction has been implicated. Previous transcranial magnetic stimulation (TMS) studies have assessed cortical dysfunction from the hand. The aim of the present study was to determine whether cortical dysfunction was evident across representations of three body regions, and to relate these changes to clinical features of ALS. Methods In this cross‐sectional study, threshold tracking TMS was undertaken in 60 sporadic ALS patients, with motor evoked potential (MEP) responses recorded over the hand (abductor pollicis brevis), lower limb (tibialis anterior), and bulbar (trapezius) regions. The cross‐sectional findings were compared to 28 age‐ and gender‐matched controls. Results Cortical dysfunction was evident across the representation of the three body regions, although the degree and nature of the dysfunction varied. Cortical hyperexcitability, as heralded by reduced short interval intracortical inhibition (SICI), was evident in all cortical regions (hand, P < 0.01; leg, P < 0.05; bulbar, P < 0.05) in ALS patients when compared with healthy control subjects. Importantly, features of cortical hyperexcitability seemed more prominent in clinically affected body regions and correlated with functional disability and muscle weakness. Cortical inexcitability was more prominent in the leg (P < 0.001) and bulbar regions (P < 0.01) when compared with controls. Interpretation The nature of cortical dysfunction varied across the body regions in ALS, with cortical hyperexcitability being more prominent in the upper limbs while cortical inexcitability was more evident in the lower limbs and bulbar regions. The findings suggest a heterogeneity of cortical pathophysiological processes in ALS.

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Utility of threshold tracking transcranial magnetic stimulation in ALS

Abstract: HighlightsThe threshold tracking transcranial magnetic stimulation [TMS] technique provides valuable insights into ALS pathogenesis.Cortical hyperexcitability identifies the disease site origin and subsequent spread.Threshold tracking TMS holds great promise as an ALS biomarker.

Cited by 60 publications

References 144 publications

Unravelling the modulation of intracortical inhibition during motor imagery: An adaptive threshold-hunting study

Unravelling the modulation of intracortical inhibition during motor imagery: An adaptive threshold-hunting study

Cortical hyperexcitability evolves with disease progression in ALS

Regional motor cortex dysfunction in amyotrophic lateral sclerosis

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