L. Tomasevic

Developmental Tuning and Decay in Senescence of Oscillations Linking the Corticospinal System

There is increasing evidence of the importance of synchronous activity within the corticospinal system for motor control. We compared oscillatory activity in the primary sensorimotor cortex [EEG of sensorimotor cortex (SMC-EEG)] and a motor neuronal pool [surface electromyogram of opponens pollicis (OP-EMG)], and their coherence in children (4–12 years of age), young adults (20–35 years of age), and elderly adults (>55 years of age). The ratio between lower (2–13 Hz) and higher (14–32 Hz) frequencies in both SMC-EEG and OP-EMG decreased with age, correlating inversely with motor performance. There was evidence for larger, more distributed cortical networks in the children and elderly compared with young adults. Corticomuscular coherence (CMC) was present in all age groups and shifted between frontal and parietal cortical areas. In children, CMC was smaller and less stationary in amplitude and frequency than in adults. Young adults had single peaks of CMC clustered near the modal frequency (23 Hz); multiple peaks with a broad spread of frequencies occurred in children and the elderly; the further the frequency of the maximum peak CMC was from 23 Hz, the poorer the performance. CMC amplitude was inversely related to performance in young adults but was not modulated in relation to performance in children and the elderly. We propose that progressive fine-tuning of the frequency coding and stabilization of the dynamic properties within and between corticospinal networks occurs during adolescence, refining the capacity for efficient dynamic communication in adulthood. In old age, blurring of the tuning between networks and breakdown in their integration occurs and is likely to contribute to a decrement in motor control.

The myth of the 'unaffected' side after unilateral stroke: Is reorganisation of the non-infarcted corticospinal system to re-establish balance the price for recovery?

Background Bilateral changes in the hemispheric reorganisation have been observed chronically after unilateral stroke. Our hypotheses were that activity dependent competition between the lesioned and non-lesioned corticospinal systems would result in persisting asymmetry and be associated with poor recovery. Methods Eleven subjects (medium 6.5 years after stroke) were compared to 9 age-matched controls. The power spectral density (PSD) of the sensorimotor electroencephalogram (SM1-EEG) and electromyogram (EMG) and corticomuscular coherence (CMC) were studied during rest and isometric contraction of right or left opponens pollicis (OP). Global recovery was assessed using NIH score. Findings There was bilateral loss of beta frequency activity in the SM1-EEGs and OP-EMGs in strokes compared to controls. There was no difference between strokes and controls in symmetry indices estimated between the two corticospinal systems for SM1-EEG, OP-EMG and CMC. Performance correlated with preservation of beta frequency power in OP-EMG in both hands. Symmetry indices for the SM1-EEG, OP-EMG and CMC correlated with recovery. Interpretation Significant changes occurred at both cortical and spinomuscular levels after stroke but to the same degree and in the same direction in both the lesioned and non-lesioned corticospinal systems. Global recovery correlated with the degree of symmetry between corticospinal systems at all three levels — cortical and spinomuscular levels and their connectivity (CMC), but not with the absolute degree of abnormality. Re‐establishing balance between the corticospinal systems may be important for overall motor function, even if it is achieved at the expense of the non-lesioned system.

Cortico-muscular coherence as an index of fatigue in multiple sclerosis

Background: Highly common in multiple sclerosis (MS), fatigue severely impacts patients’ daily lives. Previous findings of altered connectivity patterns led to the hypothesis that the distortion of functional connections within the brain-muscle circuit plays a crucial pathogenic role. Objective: The objective of this paper is to identify markers sensitive to fatigue in multiple sclerosis. Methods: Structural (magnetic resonance imaging with assessment of thalamic volume and cortical thickness of the primary sensorimotor areas) and functional (cortico-muscular coherence (CMC) from simultaneous electroencephalo- and surface electromyographic recordings during a weak handgrip task) measures were used on 20 mildly disabled MS patients (relapsing–remitting course, Expanded Disability Status Scale score ≤ 2) who were recruited in two fatigue-dependent groups according to the Modified Fatigue Index Scale (MFIS) score. Results: The two groups were similar in terms of demographic, clinical and imaging features, as well as task execution accuracy and weariness. In the absence of any fatigue-dependent brain and muscular oscillatory activity alterations, CMC worked at higher frequencies as fatigue increased, explaining 67% of MFIS variance (p=.002). Conclusion: Brain-muscle functional connectivity emerged as a sensitive marker of phenomena related to the origin of MS fatigue, impacting central-peripheral communication well before the appearance of any impairment in the communicating nodes.

Regional personalized electrodes to select transcranial current stimulation target

Rationale: Personalizing transcranial stimulations promises to enhance beneficial effects for individual patients. Objective: To stimulate specific cortical regions by developing a procedure to bend and position custom shaped electrodes; to probe the effects on cortical excitability produced when the properly customized electrode is targeting different cortical areas. Method: An ad hoc neuronavigation procedure was developed to accurately shape and place the personalized electrodes on the basis of individual brain magnetic resonance images (MRI) on bilateral primary motor (M1) and somatosensory (S1) cortices. The transcranial alternating current stimulation (tACS) protocol published by Feurra et al. (2011b) was used to test the effects on cortical excitability of the personalized electrode when targeting S1 or M1. Results: Neuronal excitability as evaluated by tACS was different when targeting M1 or S1, with the General Estimating Equation model indicating a clear tCS Effect (p < 0.001), and post hoc comparisons showing solely M1 20 Hz tACS to reduce M1 excitability with respect to baseline and other tACS conditions. Conclusions: The present work indicates that specific cortical regions can be targeted by tCS properly shaping and positioning the stimulating electrode. Significance: Through multimodal brain investigations continuous efforts in understanding the neuronal changes related to specific neurological or psychiatric diseases become more relevant as our ability to build the compensating interventions improves. An important step forward on this path is the ability to target the specific cortical area of interest, as shown in the present pilot work.

Multiple frequency functional connectivity in the hand somatosensory network: An EEG study

OBJECTIVE To investigate the dynamics of communication within the primary somatosensory neuronal network. METHODS Multichannel EEG responses evoked by median nerve stimulation were recorded from six healthy participants. We investigated the directional connectivity of the evoked responses by assessing the Partial Directed Coherence (PDC) among five neuronal nodes (brainstem, thalamus and three in the primary sensorimotor cortex), which had been identified by using the Functional Source Separation (FSS) algorithm. We analyzed directional connectivity separately in the low (1-200 Hz, LF) and high (450-750 Hz, HF) frequency ranges. RESULTS LF forward connectivity showed peaks at 16, 20, 30 and 50 ms post-stimulus. An estimate of the strength of connectivity was modulated by feedback involving cortical and subcortical nodes. In HF, forward connectivity showed peaks at 20, 30 and 50 ms, with no apparent feedback-related strength changes. CONCLUSIONS In this first non-invasive study in humans, we documented directional connectivity across subcortical and cortical somatosensory pathway, discriminating transmission properties within LF and HF ranges. SIGNIFICANCE The combined use of FSS and PDC in a simple protocol such as median nerve stimulation sheds light on how high and low frequency components of the somatosensory evoked response are functionally interrelated in sustaining somatosensory perception in healthy individuals. Thus, these components may potentially be explored as biomarkers of pathological conditions.

INTER-HEMISPHERIC FUNCTIONAL CONNECTIVITY CHANGES WITH CORPUS CALLOSUM MORPHOLOGY IN MULTIPLE SCLEROSIS

Multiple sclerosis (MS) affects myelin sheaths within the central nervous system, concurring to cause brain atrophy and neurodegeneration as well as gradual functional disconnections. To explore early signs of altered connectivity in MS from a structural and functional perspective, the morphology of corpus callosum (CC) was correlated with a dynamic inter-hemispheric connectivity index. Twenty mildly disabled patients affected by a relapsing-remitting (RR) form of MS (EDSS⩽3.5) and 15 healthy subjects underwent structural MRI to measure CC thickness over 100 sections and electroencephalography to assess a spectral coherence index between primary regions devoted to hand control, at rest and during an isometric handgrip. In patients, an overall CC atrophy was associated with increased lesion load. A less efficacious inter-hemispheric coherence (IHCoh) during movement was associated with CC atrophy in sections interconnecting homologous primary motor areas (anterior mid-body). In healthy controls, less efficacious IHCoh at rest was associated with a thinner CC splenium. Our data suggest that in mildly disabled RR-MS patients a covert impairment may be detected in the correlation between the structural (CC thickness) and functional (IHCoh) measures of homologous networks, whereas these two counterparts do not yet differ individually from controls.

The spontaneous fluctuation of the excitability of a single node modulates the internodes connectivity: A TMS-EEG study

Brain effective connectivity can be tracked by cerebral recruitments evoked by transcranial magnetic stimulation (TMS), as measured by simultaneous electroencephalography (TMS‐EEG). When TMS is targeting the primary motor area, motor evoked potentials (MEPs) can be collected from the “target” muscles. The aim of this study was to measure whether or not effective brain connectivity changes with the excitability level of the corticospinal motor pathway (CSMP) as parameterized by MEP amplitude. After averaging two subgroups of EEG‐evoked responses corresponding to high and low MEP amplitudes, we calculated the individual differences between them and submitted the grand average to sLORETA algorithm obtaining localized regions of interest (RoIs). Statistical differences of RoI recruitment strength between low and high CSMP excitation was assessed in single subjects. Preceding the feedback arrival, neural recruitment for stronger CSMP activation were weaker at 6–10 ms of homotopic sensorimotor areas BA3/4/5 of the right nonstimulated hemisphere (trend), weaker at 18–25 ms of left parietal BA2/3/40, and stronger at 26–32 ms of bilateral frontal motor areas BA6/8. The proposed method enables the tracking of brain network connectivity during stimulation of one node by measuring the strength of the connected recruited node activations. Spontaneous increases of the excitation of the node originating the transmission within the hand control network gave rise to dynamic recruitment patterns with opposite behaviors, weaker in homotopic and parietal circuits, stronger in frontal ones. The effective connectivity within bilateral circuits orchestrating hand control appeared dynamically modulated in time even in resting state as probed by TMS. Hum Brain Mapp 35:1740–1749, 2014.

Movement-induced uncoupling of primary sensory and motor areas in focal task-specific hand dystonia

INTRODUCTION Due to growing evidence of sensorimotor integration impairment in focal task-specific hand dystonia, we aimed at describing primary sensory (S1) and primary motor (M1) cortex source activities and their functional cross-talk during a non-dystonia-inducing sensorimotor task free of biases generated by the interfering with the occurrence of dystonic movements. METHOD Magnetoencephalographic brain signals and opponens pollicis (OP) electromyographic activities were acquired at rest and during a simple isometric contraction performed either alone or in combination with median nerve stimulation. The task was performed separately with the right and left hand by eight patients suffering from focal task-specific hand dystonia and by eight healthy volunteers. Through an ad hoc procedure Functional Source Separation (FSS), distinct sources were identified in S1 (FSS1) and M1 (FSM1) devoted to hand control. Spectral properties and functional coupling (coherence) between the two sources were assessed in alpha [8,13]Hz, beta [14,32]Hz and gamma [33,45]Hz frequency bands. RESULTS No differences were found between spectral properties of patients and controls for either FSM1 or FSS1 cerebral sources. Functional coupling between FSM1 and FSS1 (gamma band coherence), while comparable between dystonic patients and healthy controls at rest, was selectively reduced in patients during movement. All findings were present in both hemispheres. DISCUSSION Because previous literature has shown that gamma-band sensory-motor synchronization reflects an efficiency index of sensory-motor integration, our data demonstrate that, in dystonic patients, uncoupling replaces the functional coupling required for efficient sensory-motor control during motor exertion. The presence of bi-hemispheric abnormalities in unilateral hand dystonia supports the presence of an endophenotypic trait.

Functional and structural balances of homologous sensorimotor regions in multiple sclerosis fatigue

Fatigue in multiple sclerosis (MS) is a highly disabling symptom. Among the central mechanisms behind it, an involvement of sensorimotor networks is clearly evident from structural and functional studies. We aimed at assessing whether functional/structural balances of homologous sensorimotor regions—known to be crucial for sensorimotor networks effectiveness—decrease with MS fatigue increase. Functional connectivity measures at rest and during a simple motor task (weak handgrip of either the right or left hand) were derived from primary sensorimotor areas electroencephalographic recordings in 27 mildly disabled MS patients. Structural MRI-derived inter-hemispheric asymmetries included the cortical thickness of Rolandic regions and the volume of thalami. Fatigue symptoms increased together with the functional inter-hemispheric imbalance of sensorimotor homologous areas activities at rest and during movement, in absence of any appreciable parenchymal asymmetries. This finding supports the development of compensative interventions that may revert these neuronal activity imbalances to relieve fatigue in MS.

Slow Activity in Focal Epilepsy During Sleep and Wakefulness

Introduction. We aimed to test differences between healthy subjects and patients with respect to slow wave activity during wakefulness and sleep. Methods. Fifteen patients affected by nonlesional focal epilepsy originating within temporal areas and fourteen matched controls underwent a 24-hour EEG recording. We studied the EEG power spectral density during wakefulness and sleep in delta (1-4 Hz), theta (5-7 Hz), alpha (8-11 Hz), sigma (12-15 Hz), and beta (16-20 Hz) bands. Results. During sleep, patients with focal epilepsy showed higher power from delta to beta frequency bands compared with controls. The effect was widespread for alpha band and above, while localized over the affected hemisphere for delta (sleep cycle 1, P = .006; sleep cycle 2, P = .008; sleep cycle 3, P = .017). The analysis of interhemispheric differences showed that the only frequency band stronger over the affected regions was the delta band during the first 2 sleep cycles (sleep cycle 1, P = .014; sleep cycle 2, P = .002). During wakefulness, patients showed higher delta/theta activity over the affected regions compared with controls. Conclusions. Patients with focal epilepsy showed a pattern of power increases characterized by a selective slow wave activity enhancement over the epileptic regions during daytime and sleep. This phenomenon was stronger and asymmetric during the first sleep cycles.