Plasticity Induced in the Human Spinal Cord by Focal Muscle Vibration

The spinal cord spinal cord has in the past been considered a hardwired system which responds to inputs in a stereotyped way. A growing body of data have instead demonstrated its ability to retain information and modify its effector capabilities, showing activity-dependent plasticity. Whereas, plasticity in the spinal cord is well documented after different forms of physical exercise, whether exogenous stimulation can induce similar changes is still a matter of debate. This issue is both of scientific and clinical relevance, since at least one form of stimulation, i.e., focal muscle vibration (fMV), is currently used as a treatment for spasticity. The aim of the present study was to assess whether fMV can induce plasticity at the SC level when applied to different muscles of the upper limb. Changes in different electrophysiological measures, such as H-reflex testing homonymous and heteronymous pathways, reciprocal inhibition and somatosensory evoked potentials were used as outcomes. We found that fMV was able to induce long-term depression-like plasticity in specific spinal cord circuits depending on the muscle vibrated. These findings helped understand the basic mechanisms underlying the effects of fMV and might help to develop more advanced stimulation protocols

Distal Upper Limb Tremor during Walking in Parkinson's Disease

Background: Distal upper limb tremor during walking (TW) is frequently observed in Parkinson's disease (PD) but its clinical features are unknown. Objective: To characterize the occurrence and the clinical features of TW in comparison to the other types of tremors in PD. Methods: Fifty-one PD patients with rest tremor were evaluated off- and on-treatment. Occurrence, body distribution, severity and latency of TW and of other tremor types were assessed. Results: TW was present in 78% of the PD patients examined. TW body distribution and severity were similar to those of rest and re-emergent tremor but different from the postural tremor presented by the same patients. TW latency, observed in 85% of patients, was on average 5.8 s. Dopaminergic treatment significantly improved TW, rest, and re-emergent tremor severity but left TW latency unaffected. Conclusions: TW is a frequent motor sign in PD and is likely a clinical variant of rest tremor

Neurophysiological and clinical biomarkers of secondary progressive multiple sclerosis: A cross-sectional study

Timely diagnosis of secondary progressive multiple sclerosis (SPMS) represents a clinical challenge. The Frailty Index, a quantitative frailty measure, and the Neurophysiological Index, a combined measure of sensorimotor cortex inhibitory mechanism parameters, have recently emerged as promising tools to support SPMS diagnosis. The aim of this study was to explore the possible relationship between these two indices in MS. MS participants underwent a clinical evaluation, Frailty Index administration, and neurophysiological assessment. Frailty and Neurophysiological Index scores were found to be higher in SPMS and correlated with each other, thus suggesting that they may capture similar SPMS-related pathophysiological mechanisms

Motor Cortical Correlates of Paired Associative Stimulation Induced Plasticity: A TMS-EEG Study

Paired associative stimulation (PAS) is a non-invasive brain stimulation technique that modulates synaptic plasticity in the human motor cortex (M1). Since previous studies have primarily used motor-evoked potentials (MEPs) as outcome measure, cortical correlates of PAS-induced plasticity remain unknown. Therefore, the aim of this observational study was to investigate cortical correlates of a standard PAS induced plasticity in the primary motor cortex by using a combined TMS-EEG approach in a cohort of eighteen healthy subjects. In addition to the expected long-lasting facilitatory modulation of MEPs amplitude, PAS intervention also induced a significant increase in transcranial magnetic stimulation-evoked potentials (TEPs) P30 and P60 amplitude. No significant correlation between the magnitude of PAS-induced changes in TEP components and MEP amplitude were observed. However, the linear regression analysis revealed that the combined changes in P30 and P60 component amplitudes significantly predicted the MEP facilitation after PAS. The findings of our study offer novel insight into the neurophysiological changes associated with PAS-induced plasticity at M1 cortical level and suggest a complex relationship between TEPs and MEPs changes following PAS

Cortico-Subcortical White Matter Bundle Changes in Cervical Dystonia and Blepharospasm

Dystonia is thought to be a network disorder due to abnormalities in the basal ganglia-thalamo-cortical circuit. We aimed to investigate the white matter (WM) microstructural damage of bundles connecting pre-defined subcortical and cortical regions in cervical dystonia (CD) and blepharospasm (BSP). Thirty-five patients (17 with CD and 18 with BSP) and 17 healthy subjects underwent MRI, including diffusion tensor imaging (DTI). Probabilistic tractography (BedpostX) was performed to reconstruct WM tracts connecting the globus pallidus, putamen and thalamus with the primary motor, primary sensory and supplementary motor cortices. WM tract integrity was evaluated by deriving their DTI metrics. Significant differences in mean, radial and axial diffusivity between CD and HS and between BSP and HS were found in the majority of the reconstructed WM tracts, while no differences were found between the two groups of patients. The observation of abnormalities in DTI metrics of specific WM tracts suggests a diffuse and extensive loss of WM integrity as a common feature of CD and BSP, aligning with the increasing evidence of microstructural damage of several brain regions belonging to specific circuits, such as the basal ganglia-thalamo-cortical circuit, which likely reflects a common pathophysiological mechanism of focal dystonia

EEG Markers of Treatment Resistance in Idiopathic Generalized Epilepsy: From Standard EEG Findings to Advanced Signal Analysis

Idiopathic generalized epilepsy (IGE) represents a common form of epilepsy in both adult and pediatric epilepsy units. Although IGE has been long considered a relatively benign epilepsy syndrome, a remarkable proportion of patients could be refractory to treatment. While some clinical prognostic factors have been largely validated among IGE patients, the impact of routine electroencephalography (EEG) findings in predicting drug resistance is still controversial and a growing number of authors highlighted the potential importance of capturing the sleep state in this setting. In addition, the development of advanced computational techniques to analyze EEG data has opened new opportunities in the identification of reliable and reproducible biomarkers of drug resistance in IGE patients. In this manuscript, we summarize the EEG findings associated with treatment resistance in IGE by reviewing the results of studies considering standard EEGs, 24-h EEG recordings, and resting-state protocols. We discuss the role of 24-h EEG recordings in assessing seizure recurrence in light of the potential prognostic relevance of generalized fast discharges occurring during sleep. In addition, we highlight new and promising biomarkers as identified by advanced EEG analysis, including hypothesis-driven functional connectivity measures of background activity and data-driven quantitative findings revealed by machine learning approaches. Finally, we thoroughly discuss the methodological limitations observed in existing studies and briefly outline future directions to identify reliable and replicable EEG biomarkers in IGE patients

The third-stimulus temporal discrimination threshold: focusing on the temporal processing of sensory input within primary somatosensory cortex

The somatosensory temporal discrimination threshold (STDT) has been used in recent years to investigate time processing of sensory information, but little is known about the physiological correlates of somatosensory temporal discrimination. The objective of this study was to investigate whether the time interval required to discriminate between two stimuli varies according to the number of stimuli in the task. We used the third-stimulus temporal discrimination threshold (ThirdDT), defined as the shortest time interval at which an individual distinguishes a third stimulus following a pair of stimuli delivered at the STDT. The STDT and ThirdDT were assessed in 31 healthy subjects. In a subgroup of 10 subjects, we evaluated the effects of the stimuli intensity on the ThirdDT. In a subgroup of 16 subjects, we evaluated the effects of S1 continuous theta-burst stimulation (S1-cTBS) on the STDT and ThirdDT. Results show that ThirdDT is shorter than STDT. We found a positive correlation between STDT and ThirdDT values. As long as the stimulus intensity was within the perceivable and painless range, it did not affect ThirdDT values. S1-cTBS significantly affected both STDT and ThirdDT, although the latter was affected to a greater extent and for a longer period of time. We conclude that the interval needed to discriminate between time-separated tactile stimuli is related to the number of stimuli used in the task. STDT and ThirdDT are encoded in S1, probably by a shared tactile temporal encoding mechanism whose performance rapidly changes during the perception process. ThirdDT is a new method to measure somatosensory temporal discrimination.NEW & NOTEWORTHY To investigate whether the time interval required to discriminate between stimuli varies according to changes in the stimulation pattern, we used the third-stimulus temporal discrimination threshold (ThirdDT). We found that the somatosensory temporal discrimination acuity varies according to the number of stimuli in the task. The ThirdDT is a new method to measure somatosensory temporal discrimination and a possible index of inhibitory activity at the S1 level

Intracortical Inhibition and Surround Inhibition in the Motor Cortex: A TMS-EEG Study

Background: Short-latency intracortical inhibition (SICI) and motor surround inhibition (mSI) are cortical phenomena that have been investigated with transcranial magnetic stimulation (TMS). mSI is believed to be necessary for the execution of fine finger movements, SICI may participate in mSI genesis, and however, the mechanisms underlying both mSI and SICI are not entirely clear. Objective: We explored the cortical physiology of SICI and mSI in healthy subjects by TMS-evoked cortical potentials (TEPs). Methods: Single (sp) and paired-pulse (pp) TMS were delivered on the ADM muscle cortical hotspot while recording EEG and EMG. Three conditions were tested: spTMS and ppTMS at rest, and spTMS at the onset of an index finger movement. SICI and mSI were calculated on the ADM motor evoked potential (MEP) and two groups were defined based on the presence of mSI. Average TEPs were calculated for each condition and for five regions of interest. Results: At movement onset we observed a widespread reduction of the inhibitory late component N100 suggesting cortical facilitation associated with motor performance. At motor cortex level, SICI and mSI are associated with similar modulation of TEPs consisting in a reduction of P30 and an increase of N45 amplitude. Conclusion: Our findings suggest that SICI and mSI modulate cortical excitability with shared inhibitory mechanisms

Corrigendum: Plasticity Induced in the Human Spinal Cord by Focal Muscle Vibration

In the published article, there was an error regarding the affiliation for Giorgio Leodori. As well as having affiliation two, “Department of Human Neurosciences, University of Rome “Sapienza”, Rome, Italy”, he should also have affiliation three, “Department of Clinical Neurophysiology, IRCCS Neuromed Institute, Pozzilli, Italy.” The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated

Myoclonus: An electrophysiological diagnosis

Background Many different movement disorders have similar ‘jerk‐like' phenomenology and can be misconstrued as myoclonus. Different types of myoclonus also share similar phenomenological characteristics which can be difficult to distinguish, solely based on clinical exam. However, they have distinctive physiologic characteristics which can help refine categorization of ‘jerk‐like' movements. Objectives In this review, we briefly summarize the clinical, physiologic and pathophysiologic characteristics of different types of myoclonus. The methodology and technical considerations for electrophysiologic assessment of ‘jerk‐like' movements is reviewed. A simplistic pragmatic approach for classification of myoclonus and other ‘jerk‐like' movements based on objective electrophysiologic characteristics is proposed. Conclusions Clinical neurophysiology is an underutilized tool in the diagnosis and treatment of movement disorders. Various jerk‐like movements have distinguishing physiologic characteristics, differentiated in the milliseconds range which is beyond human capacity. We wish to argue that the categorization of movement disorders as myoclonus can be refined based on objective physiology which can have important prognostic and therapeutic implications