The use of event-related potentials in the investigation of cognitive performance in people with Multiple Sclerosis: Systematic review.

A biomarker of cognition in Multiple Sclerosis (MS) that is independent from the response of people with MS (PwMS) to test questions would provide a more holistic assessment of cognitive decline. One suggested method involves event-related potentials (ERPs). This systematic review tried to answer five questions about the use of ERPs in distinguishing PwMS from controls: which stimulus modality, which experimental paradigm, which electrodes, and which ERP components are most discriminatory, and whether amplitude or latency is a better measure. Our results show larger pooled effect sizes for visual stimuli than auditory stimuli, and larger pooled effect sizes for latency measurements than amplitude measurements. We observed great heterogeneity in methods and suggest that future research would benefit from more uniformity in methods and that results should be reported for the individual subtypes of PwMS. With more standardised methods, ERPs have the potential to be developed into a clinical tool in MS.

Evidence for a Window of Enhanced Plasticity in the Human Motor Cortex Following Ischemic Stroke.

BACKGROUND: In preclinical models, behavioral training early after stroke produces larger gains compared with delayed training. The effects are thought to be mediated by increased and widespread reorganization of synaptic connections in the brain. It is viewed as a period of spontaneous biological recovery during which synaptic plasticity is increased. OBJECTIVE: To look for evidence of a similar change in synaptic plasticity in the human brain in the weeks and months after ischemic stroke. METHODS: We used continuous theta burst stimulation (cTBS) to activate synapses repeatedly in the motor cortex. This initiates early stages of synaptic plasticity that temporarily reduces cortical excitability and motor-evoked potential amplitude. Thus, the greater the effect of cTBS on the motor-evoked potential, the greater the inferred level of synaptic plasticity. Data were collected from separate cohorts (Australia and UK). In each cohort, serial measurements were made in the weeks to months following stroke. Data were obtained for the ipsilesional motor cortex in 31 stroke survivors (Australia, 66.6 ± 17.8 years) over 12 months and the contralesional motor cortex in 29 stroke survivors (UK, 68.2 ± 9.8 years) over 6 months. RESULTS: Depression of cortical excitability by cTBS was most prominent shortly after stroke in the contralesional hemisphere and diminished over subsequent sessions (P = .030). cTBS response did not differ across the 12-month follow-up period in the ipsilesional hemisphere (P = .903). CONCLUSIONS: Our results provide the first neurophysiological evidence consistent with a period of enhanced synaptic plasticity in the human brain after stroke. Behavioral training given during this period may be especially effective in supporting poststroke recovery.

Exploratory Randomized Double-Blind Placebo-Controlled Trial of Botulinum Therapy on Grasp Release After Stroke (PrOMBiS).

Background. OnabotulinumtoxinA injections improve upper-limb spasticity after stroke, but their effect on arm function remains uncertain. Objective. To determine whether a single treatment with onabotulinumtoxinA injections combined with upper-limb physiotherapy improves grasp release compared with physiotherapy alone after stroke. Methods. A total of 28 patients, at least 1 month poststroke, were randomized to receive either onabotulinumtoxinA or placebo injections to the affected upper limb followed by standardized upper-limb physiotherapy (10 sessions over 4 weeks). The primary outcome was time to release grasp during a functionally relevant standardized task. Secondary outcomes included measures of wrist and finger spasticity and strength using a customized servomotor, clinical assessments of stiffness (modified Ashworth Scale), arm function (Action Research Arm Test [ARAT], Nine Hole Peg Test), arm use (Arm Measure of Activity), Goal Attainment Scale, and quality of life (EQ5D). Results. There was no significant difference between treatment groups in grasp release time 5 weeks post injection (placebo median = 3.0 s, treatment median = 2.0 s; t(24) = 1.20; P = .24; treatment effect = -0.44, 95% CI = -1.19 to 0.31). None of the secondary measures passed significance after correcting for multiple comparisons. Both groups achieved their treatment goals (placebo = 65%; treatment = 71%), and made improvements on the ARAT (placebo +3, treatment +5) and in active wrist extension (placebo +9°, treatment +11°). Conclusions. In this group of stroke patients with mild to moderate spastic hemiparesis, a single treatment with onabotulinumtoxinA did not augment the improvements seen in grasp release time after a standardized upper-limb physiotherapy program.

Non-invasive brain stimulation as a tool to study cerebellar-M1 interactions in humans.

The recent development of non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) has allowed the non-invasive assessment of cerebellar function in humans. Early studies showed that cerebellar activity, as reflected in the excitability of the dentate-thalamo-cortical pathway, can be assessed with paired stimulation of the cerebellum and the primary motor cortex (M1) (cerebellar inhibition of motor cortex, CBI). Following this, many attempts have been made, using techniques such as repetitive TMS and transcranial electrical stimulation (TES), to modulate the activity of the cerebellum and the dentate-thalamo-cortical output, and measure their impact on M1 activity. The present article reviews literature concerned with the impact of non-invasive stimulation of cerebellum on M1 measures of excitability and "plasticity" in both healthy and clinical populations. The main conclusion from the 27 reviewed articles is that the effects of cerebellar "plasticity" protocols on M1 activity are generally inconsistent. Nevertheless, two measurements showed relatively reproducible effects in healthy individuals: reduced response of M1 to sensorimotor "plasticity" (paired-associative stimulation, PAS) and reduced CBI following repetitive TMS and TES. We discuss current challenges, such as the low power of reviewed studies, variability in stimulation parameters employed and lack of understanding of physiological mechanisms underlying CBI.