Involvement of the contralateral hippocampus in ictal-like but not interictal epileptic activities in the kainate mouse model of temporal lobe epilepsy.

OBJECTIVE: Animal and human studies have shown that the seizure-generating region is vastly dependent on distant neuronal hubs that can decrease duration and propagation of ongoing seizures. However, we still lack a comprehensive understanding of the impact of distant brain areas on specific interictal and ictal epileptic activities (e.g., isolated spikes, spike trains, seizures). Such knowledge is critically needed, because all kinds of epileptic activities are not equivalent in terms of clinical expression and impact on the progression of the disease. METHODS: We used surface high-density electroencephalography and multisite intracortical recordings, combined with pharmacological silencing of specific brain regions in the well-known kainate mouse model of temporal lobe epilepsy. We tested the impact of selective regional silencing on the generation of epileptic activities within a continuum ranging from very transient to more sustained and long-lasting discharges reminiscent of seizures. RESULTS: Silencing the contralateral hippocampus completely suppresses sustained ictal activities in the focus, as efficiently as silencing the focus itself, but whereas focus silencing abolishes all focus activities, contralateral silencing fails to control transient spikes. In parallel, we observed that sustained focus epileptiform discharges in the focus are preceded by contralateral firing and more strongly phase-locked to bihippocampal delta/theta oscillations than transient spiking activities, reinforcing the presumed dominant role of the contralateral hippocampus in promoting long-lasting, but not transient, epileptic activities. SIGNIFICANCE: Altogether, our work provides suggestive evidence that the contralateral hippocampus is necessary for the interictal to ictal state transition and proposes that crosstalk between contralateral neuronal activity and ipsilateral delta/theta oscillation could be a candidate mechanism underlying the progression from short- to long-lasting epileptic activities.

Alterations in gamma frequency oscillations correlate with cortical tau deposition in Alzheimer's disease.

We assessed the relationship of gamma oscillations with tau deposition in Alzheimer's disease (AD) and other cognitive diseases, as both are altered during the disease course and relate to neurodegeneration. We retrospectively analyzed data from 7 AD, tau positive patients and 9 tau negative patients, who underwent cerebral amyloid PET and tau PET, and EEG within 12 months. Relative gamma power was higher in tau positive (AD) patients than in tau negative patients (p < .05). In tau positive AD patients, tau burden was associated with a linear increase in gamma power (p < .05), while no association was present in the tau negative group nor with amyloid-ß burden in either group. Thus, increase in the gamma power might represent a novel biomarker for tau driven neurodegeneration.

High-density electroencephalographic functional networks in genetic generalized epilepsy: Preserved whole-brain topology hides local reorganization.

OBJECTIVE: Genetic generalized epilepsy (GGE) accounts for approximately 20% of adult epilepsy cases and is considered a disorder of large brain networks, involving both hemispheres. Most studies have not shown any difference in functional whole-brain network topology when compared to healthy controls. Our objective was to examine whether this preserved global network topology could hide local reorganizations that balance out at the global network level. METHODS: We recorded high-density electroencephalograms from 20 patients and 20 controls, and reconstructed the activity of 118 regions. We computed functional connectivity in windows free of interictal epileptiform discharges in broad, delta, theta, alpha, and beta frequency bands, characterized the network topology, and used the Hub Disruption Index (HDI) to quantify the topological reorganization. We examined the generalizability of our results by reproducing a 25-electrode clinical system. RESULTS: Our study did not reveal any significant change in whole-brain network topology among GGE patients. However, the HDI was significantly different between patients and controls in all frequency bands except alpha (p < .01, false discovery rate [FDR] corrected, d < -1), and accompanied by an increase in connectivity in the prefrontal regions and default mode network. This reorganization suggests that regions that are important in transferring the information in controls were less so in patients. Inversely, the crucial regions in patients are less so in controls. These findings were also found in delta and theta frequency bands when using 25 electrodes (p < .001, FDR corrected, d < -1). SIGNIFICANCE: In GGE patients, the overall network topology is similar to that of healthy controls but presents a balanced local topological reorganization. This reorganization causes the prefrontal areas and default mode network to be more integrated and segregated, which may explain executive impairment associated with GGE. Additionally, the reorganization distinguishes patients from controls even when using 25 electrodes, suggesting its potential use as a diagnostic tool.

Reproducible network changes occur in a mouse model of temporal lobe epilepsy but do not correlate with disease severity.

Studying the development of brain network disruptions in epilepsy is challenged by the paucity of data before epilepsy onset. Here, we used the unilateral, kainate mouse model of hippocampal epilepsy to investigate brain network changes before and after epilepsy onset and their stability across time. Using 32 epicranial electrodes distributed over the mouse hemispheres, we analyzed EEG epochs free from epileptic activity in 15 animals before and 28 days after hippocampal injection (group 1) and in 20 animals on two consecutive days (d28 and d29, group 2). Statistical dependencies between electrodes were characterized with the debiased-weighted phase lag index. We analyzed: a) graph metric changes from baseline to chronic stage (d28) in group 1; b) their reliability across d28 and d29, in group 2; c) their correlation with epileptic activity (EA: seizure, spike and fast-ripple rates), averaged over d28 and d29, in group 2. During the chronic stage, intra-hemispheric connections of the non-injected hemisphere strengthened, yielding an asymmetrical network in low (4-8 Hz) and high theta (8-12 Hz) bands. The contralateral hemisphere also became more integrated and segregated within the high theta band. Both network topology and EEG markers of EA were stable over consecutive days but not correlated with each other. Altogether, we show reproducible large-scale network modifications after the development of focal epilepsy. These modifications are mostly specific to the non-injected hemisphere. The absence of correlation with epileptic activity does not allow to specifically ascribe these network changes to mechanisms supporting EA or rather compensatory inhibition but supports the notion that epilepsy extends beyond the sole repetition of EA and impacts network that might not be involved in EA generation.

Sensorimotor recalibration of postural control strategies occurs after whole body vibration.

Efficient postural control results from an effective interplay between sensory feedbacks integration and muscle modulation and can be affected by ageing and neuromuscular injuries. With this study, we investigated the effect of whole-body vibratory stimulation on postural control strategies employed to maintain an upright posture. We explored both physiological and posturography metrics, through corticomuscular and intramuscular coherence, and muscle networks analyses. The stimulation disrupts balance in the short term, but leads to a greater contribution of cortical activity, necessary to modulate muscle activation via the formation of (new) synergies. We also observed a reconfiguration of muscle recruitment patterns that returned to pre-stimulation levels after few minutes, accompanied by a slight improvement of balance in the anterior-posterior direction. Our results suggest that, in the context of postural control, appropriate mechanical stimulation is capable of triggering a recalibration of the sensorimotor set and might offer new perspectives for motor re-education.

Characterisation of the transient mechanical response and the electromyographical activation of lower leg muscles in whole body vibration training.

The aim of this study is to characterise the transient mechanical response and the neuromuscular activation of lower limb muscles in subjects undergoing Whole Body Vibration (WBV) at different frequencies while holding two static postures, with focus on muscles involved in shaping postural responses. Twenty-five participants underwent WBV at 15, 20, 25 and 30 Hz while in hack squat or on fore feet. Surface electromyography and soft tissue accelerations were collected from Gastrocnemius Lateralis (GL), Soleus (SOL) and Tibialis Anterior (TA) muscles. Estimated displacement at muscle bellies revealed a pattern never highlighted before that differed across frequencies and postures (p < 0.001). After stimulation starts, muscle oscillation peaks, drops and further stabilises, suggesting the occurrence of a neuromuscular activation to reduce the vibration-induced oscillation. The oscillation attenuation at the SOL muscle correlated with its increased activation (rho = 0.29, p < 0.001). Furthermore, only specific WBV settings led to a significant increase in muscle contraction: WBV-induced activation of SOL and GL was maximal in fore-feet (p < 0.05) and in response to higher frequencies (30 Hz vs 15 Hz, p < 0.001). The analysis of the mechanical dynamics of lower leg muscles highlights a resonant response to WBVs, that for the SOL correlates to the increased muscle activation. Despite differing across frequencies and postures, this resonant behaviour seems to discourage the use of dynamic exercises on vibrating platforms. As for the most efficient WBV combination, calf muscle response to WBVs is maximised if those muscles are already pre-contracted and the stimulation frequencies are in the 25-30 Hz range.

Cortical Pathways During Postural Control: New Insights From Functional EEG Source Connectivity.

Postural control is a complex feedback system that relies on vast array of sensory inputs in order to maintain a stable upright stance. The brain cortex plays a crucial role in the processing of this information and in the elaboration of a successful adaptive strategy to external stimulation preventing loss of balance and falls. In the present work, the participants postural control system was challenged by disrupting the upright stance via a mechanical skeletal muscle vibration applied to the calves. The EEG source connectivity method was used to investigate the cortical response to the external stimulation and highlight the brain network primarily involved in high-level coordination of the postural control system. The cortical network reconfiguration was assessed during two experimental conditions of eyes open and eyes closed and the network flexibility (i.e. its dynamic reconfiguration over time) was correlated with the sample entropy of the stabilogram sway. The results highlight two different cortical strategies in the alpha band: the predominance of frontal lobe connections during open eyes and the strengthening of temporal-parietal network connections in the absence of visual cues. Furthermore, a high correlation emerges between the flexibility in the regions surrounding the right temporo-parietal junction and the sample entropy of the CoP sway, suggesting their centrality in the postural control system. These results open the possibility to employ network-based flexibility metrics as markers of a healthy postural control system, with implications in the diagnosis and treatment of postural impairing diseases.