Spatiotemporal Correlations of Mesoscale Neocortical Activities in Patients with Focal Epilepsy

Brain function is reflected in both the action potentials of individual neurons and interactions through e.g. synaptic currents reflected in widespread, slow fluctuations of the local field potential (LFP). We analyzed microelectrode array data to determine state-dependent correlations between action potential and LFP during seizure events as well as interictally in patients with focal epilepsy. We also examined activity in two different cortical network territories: the seizure core and surrounding penumbra (Schevon et al., 2012). The cross-correlation of spiking activity in the core showed an association of the ictal action potentials with the global oscillatory aspect of the seizure activity and indicated local failure of inhibitory restraint surrounding the ictal spike. These patterns were not observed in the penumbra. Our analyses from clinical recordings and a model of a single ictal spike in the core revealed that both the temporal and spatial components of the network's cross-correlation can be approximated by a sine cardinal (sinc) function. The biological interpretation of these findings is that important functional differences across the neocortical network exist, with a critical role of the millimeter-range excitatory connections within the grey matter. Therefore, localized intervention that prevents escape of hyperactivity from the seizure core may be considered as a therapeutic strategy.

A Review of Accelerated Long-Term Forgetting in Epilepsy

Accelerated long-term forgetting (ALF) is a memory disorder that manifests by a distinct pattern of normal memory for up to an hour after learning, but an increased rate of forgetting during the subsequent hours and days. The topic of ALF has gained much attention in group studies with epilepsy patients and the phenomenon has been shown to have contradictory associations with seizures, epileptiform activity, imaging data, sleep, and antiepileptic medication. The aim of this review was to explore how clinical and imaging data could help determine the topographic and physiological substrate of ALF, and what is the possible use of this information in the clinical setting. We have reviewed 51 group studies in English to provide a synthesis of the existing findings concerning ALF in epilepsy. Analysis of recently reported data among patients with temporal lobe epilepsy, transient epileptic amnesia, and generalized and extratemporal epilepsies provided further indication that ALF is likely a disorder of late memory consolidation. The spatial substrate of ALF might be located along the parts of the hippocampal–neocortical network and novel studies reveal the increasingly possible importance of damage in extrahippocampal sites. Further research is needed to explore the mechanisms of cellular impairment in ALF and to develop effective methods of care for patients with the disorder.

A Theory for the Emergence of Neocortical Network Architecture

Developmental programs that guide neurons and their neurites into specific subvolumes of the mammalian neocortex give rise to lifelong constraints for the formation of synaptic connections. To what degree do these constraints affect cortical wiring diagrams? Here we introduce an inverse modeling approach to show how cortical networks would appear if they were solely due to the spatial distributions of neurons and neurites. We find that neurite packing density and morphological diversity will inevitably translate into non-random pairwise and higher-order connectivity statistics. More importantly, we show that these non-random wiring properties are not arbitrary, but instead reflect the specific structural organization of the underlying neuropil. Our predictions are consistent with the empirically observed wiring specificity from subcellular to network scales. Thus, independent from learning and genetically encoded wiring rules, many of the properties that define the neocortex’ characteristic network architecture may emerge as a result of neuron and neurite development.

Pattern similarity and connectivity of hippocampal-neocortical regions support empathy for pain

Empathy is thought to engage mental simulation, which in turn is known to rely on hippocampal-neocortical processing. Here, we tested how hippocampal-neocortical pattern similarity and connectivity contributed to pain empathy. Using this approach, we analyzed a data set of 102 human participants who underwent functional MRI while painful and non-painful electrical stimulation was delivered to themselves or to a confederate. As hypothesized, results revealed increased pattern similarity between fist-hand pain and pain empathy (compared to non-painful control conditions) within the hippocampus, retrosplenial cortex, the temporo-parietal junction and anterior insula. While representations in these regions were unaffected by confederate similarity, pattern similarity in the dorsal MPFC was increased the more dissimilar the other individual was perceived. Moreover, hippocampal connectivity with regions engaged in first-hand pain was also increased during pain empathy, during which hippocampal coupling with the fusiform gyrus positively scaled with self-report measures of individual perspective taking skills. These findings highlight that shared representations and interactions within a hippocampal-neocortical network support pain empathy. This potentially reflects memory-based mental simulation processes, which seem partially modulated by personality traits and the perceived similarity of the other individual in pain.

Fascial neuromodulation: an emerging concept linking acupuncture, fasciology, osteopathy and neuroscience

According to Traditional Chinese Medicine “acupuncture is believed to restore the balance between Yin and Yang” and this can be understood in the Western medicine terminology as a “modulation of the equilibrium between parasympathetic and sympathetic activity”. The vast majority of studies concerning the mechanisms of action of acupuncture have been conducted on its influence on pain, and it has been proposed that acupuncture may indirectly relieve chronic pain by its effects on autonomic nervous system function. Several studies have shown that acupuncture recruits brain networks involved in the integration of multiple other brain functions: for example, the limbic-paralimbic-neocortical network, which plays a major role in modulating the affective dimensions of pain processing and the integration of emotional, sensorimotor, autonomic and immunological functions. It has been recently proposed that mechanical signaling through the connective tissue, along with transmission of the matrix deformation through the fascial system network, can explain the therapeutic effect of acupuncture. This model of acupunture, which involves the transduction of mechanical signals through the connective planes and produces a secondary involvement of neurophysiological mechanism, appears to fit very closely to the ancient model. It is also compatible with the proposed neurophysiological explanation. Furthermore, it appears to be fruitful also in manual therapy approaches. Drawing on the basis of the “Fascial network hypothesis of meridians”, in which there is an overlap between the channels network described by Traditional Chinese Medicine and the newly-defined fascial system, I propose an intervention through a combination of acupoints that have been selected due to their relationship between “extraordinary acupuncture channels”, the myofascial sequences described by Stecco, and the emotional and adaptive function as contemplated by a psychosomatic model used in posturology. This intervention is aimed at treating both stress and postural imbalance.

Cross-scale effects of neural interactions during human neocortical seizure activity

Small-scale neuronal networks may impose widespread effects on large network dynamics. To unravel this relationship, we analyzed eight multiscale recordings of spontaneous seizures from four patients with epilepsy. During seizures, multiunit spike activity organizes into a submillimeter-sized wavefront, and this activity correlates significantly with low-frequency rhythms from electrocorticographic recordings across a 10-cm-sized neocortical network. Notably, this correlation effect is specific to the ictal wavefront and is absent interictally or from action potential activity outside the wavefront territory. To examine the multiscale interactions, we created a model using a multiscale, nonlinear system and found evidence for a dual role for feedforward inhibition in seizures: while inhibition at the wavefront fails, allowing seizure propagation, feedforward inhibition of the surrounding centimeter-scale networks is activated via long-range excitatory connections. Bifurcation analysis revealed that distinct dynamical pathways for seizure termination depend on the surrounding inhibition strength. Using our model, we found that the mesoscopic, local wavefront acts as the forcing term of the ictal process, while the macroscopic, centimeter-sized network modulates the oscillatory seizure activity.