F. Tecchio

A contralesional EEG power increase mediated by interhemispheric disconnection provides negative prognosis in acute stroke

BACKGROUND AND PURPOSEnDespite similar clinical onset, recovery from stroke can be largely variable. We searched for electrophysiological prognostic indices, believing that they can guide future neuromodulation treatments boosting clinical recovery.nnnMETHODSn19-channels resting electroencephalogram (EEG) was collected in 42 patients after 4-10 days (t0) from a unilateral ischemic stroke in the middle cerebral artery (MCA) territory and 20 controls. National Health Institute Stroke Scale (NIHSS) was collected at t0 and 6 months later (t1). Standard spectral band powers and interhemispheric coherences between homologous MCA regions were calculated in both hemispheres.nnnRESULTSnTotal spectral, delta and theta band powers were higher bilaterally in patients than in controls and directly correlated with NIHSSt0 in both hemispheres. A linear regression model including each EEG patients variable differing from those of controls and correlating with effective recovery [ER = (NIHSSt0-NIHSSt1)/(NIHSSt0-NIHSS in healthy conditions)] showed contralesional delta power as the only valid predictor of ER. A further regression model including also NIHSSt0 confirmed that contralesional delta power can add prognostic information to acute clinical impairment. Contralesional delta activity increase was best explained, in addition to the increasing ipsilesional delta activity, by a reduction of interhemispheric functional coupling--which did not explain a significantly portion of effective recovery variability by itself.nnnCONCLUSIONSnContralesional EEG delta activity retains relevant negative prognostic information in acute stroke patients. Present results point to the interhemispheric interplay as a decisive target in setting up enriched rehabilitations.

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.

A neurally-interfaced hand prosthesis tuned inter-hemispheric communication

PURPOSEnThis work investigates how a direct bidirectional connection between brain and hand prosthesis modifies the bi-hemispheric sensorimotor system devoted to the movement control of the lost limb. Hand prostheses are often unable to satisfy users expectations, mostly due to the poor performance of their interfacing system. Neural Interfaces implanted inside nerves of the stump offer the advantage of using the bidirectional neural pathways naturally dispatching signals to control proper hand actions and feed-back sensations. Learning to control a neurally-interfaced hand prosthesis and decode sensory information was previously observed to reduce the inter-hemispheric asymmetry of cortical motor maps and the clinical symptoms of phantom limb syndrome.nnnMETHODSnElectroencephalographic (EEG) data was analysed using Functional Source Separation (FSS), a semi-blind method that incorporates prior knowledge about the signal of interest into data decomposition to give access to cortical patch activities.nnnRESULTSnBi-hemispheric cortices showed normalization of their activity (topographical and spectral patterns) and of functional connectivity between homologous hand controlling areas, during the delivery of the motor command to the cybernetic prosthesis.nnnCONCLUSIONSnThe re-establishment of central-peripheral communication with the lost limb induced by a neurally-interfaced hand prosthesis produces beneficial plastic reorganization, not only restructuring contralateral directly-connected control areas, but also their functional balance within the bi-hemispheric system necessary for motor control.

Sensorimotor integration in focal task-specific hand dystonia: A magnetoencephalographic assessment

To obtain a direct sensorimotor integration assessment in primary hand cortical areas (M1) of patients suffering from focal task-specific hand dystonia, magnetoencephalographic (MEG) and opponens pollicis electromyographic (EMG) activities were acquired during a motor task expressly chosen not to induce dystonic movements in our patients, to disentangle abnormalities indicating a possible substrate on which dystonia develops. A simple isometric contraction was performed either alone or in combination with median nerve stimulation, i.e. when a non-physiological sensory inflow was overlapping with the physiological feedback. As control condition, median nerve stimulation was also performed at rest. The task was performed bilaterally both in eight patients and in 16 healthy volunteers. In comparison with results in controls we found that in dystonic patients: i) MEG-EMG coherence was higher; ii) it reduced much less during galvanic stimulation in the hemisphere contralateral to the dystonic arm, simultaneously with iii) stronger inhibition of the sensory areas responsiveness due to movement; iv) the cortical component including contributions from sensory inhibitory and motor structures was reduced and v) much more inhibited during movement. It is documented that a simultaneous cortico-muscular coherence increase occurs in presence of a reduced M1 responsiveness to the inflow from the sensory regions. This could indicate an unbalance of the fronto-parietal functional impact on M1, with a weakening of the parietal components. Concurrently, signs of a less differentiated sensory hand representation--possibly due to impaired inhibitory mechanisms efficiency--and signs of a reduced repertoire of voluntary motor control strategies were found.

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

INTRODUCTIONnDue 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.nnnMETHODnMagnetoencephalographic 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.nnnRESULTSnNo 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.nnnDISCUSSIONnBecause 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.

Sensorimotor Cortex Reorganization in Alzheimer's Disease and Metal Dysfunction: A MEG Study.

Objective. To verify whether systemic biometals dysfunctions affect neurotransmission in living Alzheimers disease (AD) patients. Methods. We performed a case-control study using magnetoencephalography to detect sensorimotor fields of AD patients, at rest and during median nerve stimulation. We analyzed position and amount of neurons synchronously activated by the stimulation in both hemispheres to investigate the capability of the primary somatosensory cortex to reorganize its circuitry disrupted by the disease. We also assessed systemic levels of copper, ceruloplasmin, non-Cp copper (i.e., copper not bound to ceruloplasmin), peroxides, transferrin, and total antioxidant capacity. Results. Patients sensorimotor generators appeared spatially shifted, despite no change of latency and strength, while spontaneous activity sources appeared unchanged. Neuronal reorganization was greater in moderately ill patients, while delta activity increased in severe patients. Non-Cp copper was the only biological variable appearing to be associated with patient sensorimotor transmission. Conclusions. Our data strengthen the notion that non-Cp copper, not copper in general, affects neuronal activity in AD. Significance. High plasticity in the disease early stages in regions controlling more commonly used body parts strengthens the notion that physical and cognitive activities are protective factors against progression of dementia.

P 15. Delta waves increase after cortical plasticity induction during wakefulness

Objective Delta waves are the most prominent electroencephalographic (EEG) feature of non-rapid eye movement sleep with cortical origin. Several human studies suggested they are sensor of synaptic weight and possible effectors of sleep-dependent synaptic plasticity. During wakefulness delta waves are almost absent in physiological conditions, but they come out when a subcortical brain lesion occurs. For these reasons delta waves during wakefulness are considered as a lesional sign but no definitive data about its functional significance were provided. Our aim was to verify whether delta waves can be a sign of plastic cortical modifications. Materials and methods 11 young healthy subjects (28xa0±xa03) were enrolled in the study. Intermittent theta burst stimulation (iTBS) was administered on left primary motor cortex to induce enduring cortical motor plasticity. High density scalp EEG (32 channels) was recorded all along the experiment. PSD for standard frequency bands (delta 1–3.5xa0Hz, theta 4–7.5xa0Hz, alpha 8–12xa0Hz, beta 13–22xa0Hz) was calculated in each longitudinal bipolar derivation. 5-min resting opened-eyes EEG was analyzed pre-iTBS (T0) and immediately after iTBS (T1), after 15 (T2) and 30 (T3)xa0min. MEP amplitude and visual analogic scales about sleepiness, alertness, and the Stanford Sleepiness Scale were analyzed at the same time-points to explore motor plasticity induction and alertness status. Results iTBS induced a 9%-increase of MEP amplitude which remained stable until 30xa0min after stimulation (T1vsT0 p xa0=xa00.005; T2vsT1 p xa0=xa00.560; T3vsT2 p xa0=xa00.158). A selective increase (+87.5%) in delta band PSD was evident at T1 vs T0, remaining stable all along the experiment (T1vsT0 p xa0=xa00.019, T2vsT1 p xa0=xa00.724, T3vsT2 p xa0=xa01). Significant changes were bilaterally present only in fronto-central derivations ( p Discussion Our experiment firstly demonstrated a large and enduring increase in EEG delta activity in cortical areas undergoing plasticity induction during wakefulness. Present results may open new scenarios in interpreting scalp EEG slow waves after brain lesions not only as sign of lesion but also as sign of neuronal plastic rearrangement not with a negative value.

A New, High-Efficacy, Noninvasive Transcranial Electric Stimulation Tuned to Local Neurodynamics

In this paper, we pose the following working hypothesis: in humans, transcranial electric stimulation (tES) with a time course that mimics the endogenous activity of its target is capable of altering the targets excitability. In our case, the target was the primary motor cortex (M1). We identified the endogenous neurodynamics of hand M1s subgroups of pyramidal neuronal pools in each of our subjects by applying Functional Source Separation (FSS) to their EEG recordings. We then tested whether the corticospinal excitability of the hand representation under the above described stimulation, which we named transcranial individual neurodynamics stimulation (tIDS), was higher than in the absence of stimulation (baseline). As a check, we compared tIDS with the most efficient noninvasive facilitatory corticospinal tES known so far, which is 20 Hz transcranial alternating current stimulation (tACS). The control conditions were as follows: (1) sham, (2) transcranial random noise stimulation (tRNS) in the same frequency range as tIDS (1–250 Hz), and (3) a low current tIDS (tIDSlow). Corticospinal excitability was measured with motor-evoked potentials under transcranial magnetic stimulation. The mean motor-evoked potential amplitude increase was 31% of the baseline during tIDS (p < 0.001), and it was 15% during tACS (p = 0.096). tRNS, tIDSlow, and sham induced no effects. Whereas tACS did not produce an enhancement in any subject at the individual level, tIDS was successful in producing an enhancement in 8 of the 16 subjects. The results of the present proof-of-principle study showed that proper exploitation of local neurodynamics can enhance the efficacy of personalized tES. SIGNIFICANCE STATEMENT This study demonstrated that, in humans, transcranial individual neurodynamics stimulation (tIDS), which mimics the endogenous dynamics of the target neuronal pools, effectively changes the excitability of these pools. tIDS holds promise for high-efficacy personalized neuromodulations based on individual local neurodynamics.

ID 73 – Cortical parcellation based on local neuronal electrical activity

Brodmann’s pioneering work resulted in the classification of the cortical areas based on their cyto-architecture and topology. Here, we aim at documenting that cortical areas can be also classified by neuronal activities specific to well identifiable structures and to the latter’s networking within the whole brain. We investigated this notion in the primary somatosensory area (S1) and in the primary motor area (M1) in both hemispheres. Our results show that S1 and M1 are topologically differentiated by their respective neuronal activities, which are specific, independent of hemisphere and of subject’s state (i.e., at rest, performing movements or receiving external stimulations). S1 displays higher power than M1 (pxa0=xa0.001) in the beta frequency band, while the opposite occurs in the gamma2 band (pxa0=xa0.034). We also show that the fractal dimensions (FD) emerged from our study as a strong index capable of differentiating the two brain areas in all subject’s states, with S1’s FD smaller than M1’s (pxa0 xa0.00001). The present work intends to be a first step toward the identification and classification of brain cortical areas via the dynamics of their neuronal activity, which we believe will advance our knowledge of the brain’s intimate structural–functional unity.