Beta-band intermuscular coherence: a novel biomarker of upper motor neuron dysfunction in motor neuron disease

Abstract

In motor neuron disease, the focus of therapy is to prevent or slow neuronal degeneration with neuroprotective pharmacological agents; early diagnosis and treatment are thus essential. Incorporation of needle electromyographic evidence of lower motor neuron degeneration into diagnostic criteria has undoubtedly advanced diagnosis, but even earlier diagnosis might be possible by including tests of subclinical upper motor neuron disease. We hypothesized that beta-band (15–30 Hz) intermuscular coherence could be used as an electrophysiological marker of upper motor neuron integrity in such patients. We measured intermuscular coherence in eight patients who conformed to established diagnostic criteria for primary lateral sclerosis and six patients with progressive muscular atrophy, together with 16 age-matched controls. In the primary lateral sclerosis variant of motor neuron disease, there is selective destruction of motor cortical layer V pyramidal neurons and degeneration of the corticospinal tract, without involvement of anterior horn cells. In progressive muscular atrophy, there is selective degeneration of anterior horn cells but a normal corticospinal tract. All patients with primary lateral sclerosis had abnormal motor-evoked potentials as assessed using transcranial magnetic stimulation, whereas these were similar to controls in progressive muscular atrophy. Upper and lower limb intermuscular coherence was measured during a precision grip and an ankle dorsiflexion task, respectively. Significant beta-band coherence was observed in all control subjects and all patients with progressive muscular atrophy tested, but not in the patients with primary lateral sclerosis. We conclude that intermuscular coherence in the 15–30 Hz range is dependent on an intact corticospinal tract but persists in the face of selective anterior horn cell destruction. Based on the distributions of coherence values measured from patients with primary lateral sclerosis and control subjects, we estimated the likelihood that a given measurement reflects corticospinal tract degeneration. Therefore, intermuscular coherence has potential as a quantitative test of subclinical upper motor neuron involvement in motor neuron disease.

High-Frequency Intermuscular Coherence between Arm Muscles during Robot-Mediated Motor Adaptation

“…It would be interesting to test whether changes in IMC become substantiated and robust in longer term motor adaptation protocols and follow the “savings” measured in follow-up adaptation sessions on future days/weeks (Haith et al, 2015; Huberdeau et al, 2015). Evidence of high frequency activity may give crucial physiological insight into mechanisms of functional recovery and, following the examples found in the literature (Nishimura et al, 2009; Kisiel-Sajewicz et al, 2011; Fisher et al, 2012; Bravo-Esteban et al, 2014), we suggest high frequency IMC (40–100 Hz) should be further investigated in long term neurological conditions such as stroke.…”

“…IMC has been used for the evaluation of coherent activation in muscle pairs during isometric contraction tasks (Baker et al, 1999; Kilner et al, 1999; Poston et al, 2010; Semmler et al, 2013; Jesunathadas et al, 2013), tremor (Halliday et al, 2000; van Rootselaar et al, 2006; van der Stouwe et al, 2015), and more recently in rhythmic movement such as pedaling (De Marchis et al, 2015) and stepping (Chang et al, 2012). Changes in different frequency bands of coherence may confer information on the changes in descending neural signals (grip task, IMC in 0–35 Hz range, Danna-Dos Santos et al, 2010; precision grip and ankle dorsiflexion task, IMC in 15–30 Hz range Fisher et al, 2012; precision grip tasks during sustained extension/flexion of elbow joint, IMC in 13–25 Hz range, Lee et al, 2014), on the status of functional recovery of neural structures after injury (force-tracking precision grip task, IMC in 30–46 Hz range, Nishimura et al, 2009) or of impaired motor skills (reaching, IMC in 0–11 Hz range, Kisiel-Sajewicz et al, 2011). IMC has been also recently shown to increase between muscles pairs that are more strongly coordinated during specific motor tasks (bimanual coordination, de Vries et al, 2016; upper-limb isometric contractions to control a myoelectric cursor, Nazarpour et al, 2012), experimentally supporting the hypothesis that multiple muscles coordination may be the result of a neural synchronization strategy of cortical origins (Farmer, 1998).…”

Beta Band Corticomuscular Drive Reflects Muscle Coordination Strategies

“…While fully understanding the neurophysiology and task-dependence of cortico-motor oscillations requires further study, our results justify such future work and provide a springboard for more focused investigations into the relationship between the physical requirements of a task and neural control strategies necessary to satisfy them. Finally, such insights into the origin and modulation of cortico-motor oscillations would not only clarify fundamental mechanism for sensorimotor control, but perhaps provide well-founded tasks and analyses directly translatable to clinical measures and diagnostic tests (Norton and Gorassini, 2006; Hammond et al, 2007; Pogosyan et al, 2009; Fisher et al, 2012; Ko et al, 2016). …”

Transcranial magnetic stimulation and amyotrophic lateral sclerosis: pathophysiological insights

“…Of further relevance, subclinical UMN dysfunction has been reported in progressive muscular atrophy (PMA),101–103 suggesting that PMA may be a phenotype of ALS. While corticomotoneuronal integrity was recently reported to be intact in PMA using a β-band intermuscular coherence technique,104 assessment of cortical function with TMS techniques may be of diagnostic utility, especially in light of presence of subclinical UMN pathology in PMA 102 103…”