Abstract Stereo-electroencephalography (SEEG) is the gold standard to delineate surgical targets in focal drug-resistant epilepsy. SEEG uses electrodes placed directly into the brain to identify the ...seizure-onset zone (SOZ). However, its major constraint is limited brain coverage, potentially leading to misidentification of the ‘true’ SOZ. Here, we propose a framework to assess adequate SEEG sampling by coupling epileptic biomarkers with their spatial distribution and measuring the system’s response to a perturbation of this coupling. We demonstrate that the system’s response is strongest in well-sampled patients when virtually removing the measured SOZ. We then introduce the spatial perturbation map, a tool that enables qualitative assessment of the implantation coverage. Probability modelling reveals a higher likelihood of well-implanted SOZs in seizure-free patients or non-seizure free patients with incomplete SOZ resections, compared to non-seizure-free patients with complete resections. This highlights the framework’s value in sparing patients from unsuccessful surgeries resulting from poor SEEG coverage.
Single-pulse direct electrical stimulation of cortical regions in patients suffering from focal drug-resistant epilepsy who are explored using intracranial electrodes induces cortico-cortical ...potentials that can be used to infer functional and anatomical connectivity. Here, we describe a neuroimaging framework that allows development of a new probabilistic atlas of functional tractography of the human cortex from those responses. This atlas is unique because it allows inference in vivo of the directionality and latency of cortico-cortical connectivity, which are still largely unknown at the human brain level. In this technical note, we include 1535 stimulation runs performed in 35 adult patients. We use a case of frontal lobe epilepsy to illustrate the asymmetrical connectivity between the posterior hippocampal gyrus and the orbitofrontal cortex. In addition, as a proof of concept for group studies, we study the probabilistic functional tractography between the posterior superior temporal gyrus and the inferior frontal gyrus. In the near future, the atlas database will be continuously increased, and the methods will be improved in parallel, for more accurate estimation of features of interest. Generated probabilistic maps will be freely distributed to the community because they provide critical information for further understanding and modelling of large-scale brain networks.
•New atlas of functional tractography of the human cortex based on stimulations•Probabilistic approach to infer directionality and latency of connectivity in vivo•Connectivity maps freely available to develop large scale models of the brain•Many applications in neuroimaging as well as theoretical, cognitive and clinical neuroscience
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
Reinforcement-based adaptive decision-making is believed to recruit fronto-striatal circuits. A critical node of the fronto-striatal circuit is the thalamus. However, direct evidence of its ...involvement in human reinforcement learning is lacking. We address this gap by analyzing intra-thalamic electrophysiological recordings from eight participants while they performed a reinforcement learning task. We found that in both the anterior thalamus (ATN) and dorsomedial thalamus (DMTN), low frequency oscillations (LFO, 4-12 Hz) correlated positively with expected value estimated from computational modeling during reward-based learning (after outcome delivery) or punishment-based learning (during the choice process). Furthermore, LFO recorded from ATN/DMTN were also negatively correlated with outcomes so that both components of reward prediction errors were signaled in the human thalamus. The observed differences in the prediction signals between rewarding and punishing conditions shed light on the neural mechanisms underlying action inhibition in punishment avoidance learning. Our results provide insight into the role of thalamus in reinforcement-based decision-making in humans.
Purpose: To report three patients with drug‐resistant nocturnal hypermotor seizures (NHSs), no detectable brain lesion, and clinically defined nocturnal frontal lobe epilepsy (NFLE) or autosomal ...dominant NLFE (ADNFLE), whose intracerebral EEG ictal onset primarily involved the insula, rather than the mesial or orbital frontal cortex.
Methods: Fourteen to 15 intracerebral electrodes were implanted in each patient, primarily sampling the frontal lobes with 80 to 91 recording leads covering the most likely side of seizure onset, and two to six leads placed within the ipsilateral insula. Electrical stimulation was used to test the epileptic threshold of frontal and insular brain regions at the various recording sites.
Results: In all three patients, a low‐voltage fast activity was recorded within the anterosuperior aspect of the insula at ictal onset, either in isolation, or extending to the nearby frontal operculum in the ADNFLE patient. The role of the insula was further supported in all three patients either by the presence of high‐amplitude spikes that clearly predominated over that region (n = 2) or by triggering the patient's typical aura or seizure when applying an electrical stimulation at that site, selectively (n = 2).
Conclusions: The anterosuperior portion of the insula might play a pivotal role in generating nocturnal hypermotor seizures in some patients with nonlesional drug‐resistant epilepsy suggesting NFLE or ADNFLE. Whether these patients are amenable to successful surgery remain an open issue.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
How do we choose a particular action among equally valid alternatives? Nonhuman primate findings have shown that decision-making implicates modulations in unit firing rates and local field potentials ...(LFPs) across frontal and parietal cortices. Yet the electrophysiological brain mechanisms that underlie free choice in humans remain ill defined. Here, we address this question using rare intracerebral electroencephalography (EEG) recordings in surgical epilepsy patients performing a delayed oculomotor decision task. We find that the temporal dynamics of high-gamma (HG, 60-140 Hz) neural activity in distinct frontal and parietal brain areas robustly discriminate free choice from instructed saccade planning at the level of single trials. Classification analysis was applied to the LFP signals to isolate decision-related activity from sensory and motor planning processes. Compared with instructed saccades, free-choice trials exhibited delayed and longer-lasting HG activity during the delay period. The temporal dynamics of the decision-specific sustained HG activity indexed the unfolding of a deliberation process, rather than memory maintenance. Taken together, these findings provide the first direct electrophysiological evidence in humans for the role of sustained high-frequency neural activation in frontoparietal cortex in mediating the intrinsically driven process of freely choosing among competing behavioral alternatives.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As you might experience it while reading this sentence, silent reading often involves an imagery speech component: we can hear our own "inner voice" pronouncing words mentally. Recent functional ...magnetic resonance imaging studies have associated that component with increased metabolic activity in the auditory cortex, including voice-selective areas. It remains to be determined, however, whether this activation arises automatically from early bottom-up visual inputs or whether it depends on late top-down control processes modulated by task demands. To answer this question, we collaborated with four epileptic human patients recorded with intracranial electrodes in the auditory cortex for therapeutic purposes, and measured high-frequency (50-150 Hz) "gamma" activity as a proxy of population level spiking activity. Temporal voice-selective areas (TVAs) were identified with an auditory localizer task and monitored as participants viewed words flashed on screen. We compared neural responses depending on whether words were attended or ignored and found a significant increase of neural activity in response to words, strongly enhanced by attention. In one of the patients, we could record that response at 800 ms in TVAs, but also at 700 ms in the primary auditory cortex and at 300 ms in the ventral occipital temporal cortex. Furthermore, single-trial analysis revealed a considerable jitter between activation peaks in visual and auditory cortices. Altogether, our results demonstrate that the multimodal mental experience of reading is in fact a heterogeneous complex of asynchronous neural responses, and that auditory and visual modalities often process distinct temporal frames of our environment at the same time.
Objective
Antiepileptic drugs (AEDs) have cognitive side effects that, particularly in children, may affect intellectual functioning. With the TimeToStop (TTS) study, we showed that timing of AED ...withdrawal does not majorly influence long‐term seizure outcomes. We now aimed to evaluate the effect of AED withdrawal on postoperative intelligence quotient (IQ), and change in IQ (delta IQ) following pediatric epilepsy surgery.
Methods
We collected IQ scores of children from the TTS cohort with both pre‐ and postoperative neuropsychological assessments (NPAs; n = 301) and analyzed whether reduction of AEDs prior to the latest NPA was related to postoperative IQ and delta IQ, using linear regression analyses. Factors previously identified as independently relating to (delta) IQ, and currently identified predictors of (delta) IQ, were considered possible confounders and used for adjustment. Additionally, we adjusted for a compound propensity score that contained previously identified determinants of timing of AED withdrawal.
Results
Mean interval to the latest NPA was 19.8 ± 18.9 months. Reduction of AEDs at the latest NPA significantly improved postoperative IQ and delta IQ (adjusted regression coefficient RC = 3.4, 95% confidence interval CI = 0.6–6.2, p = 0.018 and RC = 4.5, 95% CI = 1.7–7.4, p = 0.002), as did complete withdrawal (RC = 4.8, 95% CI = 1.4–8.3, p = 0.006 and RC = 5.1, 95% CI = 1.5–8.7, p = 0.006). AED reduction also predicted ≥10‐point IQ increase (p = 0.019). The higher the number of AEDs reduced, the higher was the IQ (gain) after surgery (RC = 2.2, 95% CI = 0.6–3.7, p = 0.007 and RC = 2.6, 95% CI = 1.0–4.2, p = 0.001, IQ points per AED reduced).
Interpretation
Start of AED withdrawal, number of AEDs reduced, and complete AED withdrawal were associated with improved postoperative IQ scores and gain in IQ, independent of other determinants of cognitive outcome. Ann Neurol 2015;78:104–114
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
Cerebral cavernous malformations (CCMs) are well‐defined, mostly singular lesions present in 0.4–0.9% of the population. Epileptic seizures are the most frequent symptom in patients with CCMs ...and have a great impact on social function and quality of life. However, patients with CCM‐related epilepsy (CRE) who undergo surgical resection achieve postoperative seizure freedom in only about 75% of cases. This is frequently because insufficient efforts are made to adequately define and resect the epileptogenic zone. The Surgical Task Force of the Commission on Therapeutics of the International League Against Epilepsy (ILAE) and invited experts reviewed the pertinent literature on CRE. Definitions of definitive and probable CRE are suggested, and recommendations regarding the diagnostic evaluation and etiology‐specific management of patients with CRE are made. Prospective trials are needed to determine when and how surgery should be done and to define the relations of the hemosiderin rim to the epileptogenic zone.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Mechanosensors are emerging players responding to hemodynamic and physical inputs. Their significance in the central nervous system remains relatively uncharted. Using human-derived brain specimens ...or cells and a pre-clinical model of mesio-temporal lobe epilepsy (MTLE), we examined how the mRNA levels of the mechanosensitive channel PIEZO1 adjust to disease-associated pro-inflammatory trajectories.
In brain tissue micro-punches obtained from 18 drug-resistant MTLE patients, PIEZO1 expression positively correlated with pro-inflammatory biomarkers TNFα, IL-1β, and NF-kB in the epileptogenic hippocampus compared to the adjacent amygdala and temporal cortex tissues. In an experimental MTLE model, hippocampal Piezo1 and cytokine expression levels were increased post-status epilepticus (SE) and during epileptogenesis. Piezo1 expression positively correlated with Tnfα, Il1β, and Nf-kb in the hippocampal foci. Next, by combining RNAscope with immunohistochemistry, we identified Piezo1 in glio-vascular cells. Post-SE and during epileptogenesis, ameboid IBA1 microglia, hypertrophic GFAP astrocytes, and damaged NG2DsRed pericytes exhibited time-dependent patterns of increased Piezo1 expression. Digital droplet PCR analysis confirmed the Piezo1 trajectory in isolated hippocampal microvessels in the ipsi and contralateral hippocampi. The combined examinations performed in this model showed Piezo1 expression returning towards basal levels after the epileptogenesis-associated peak inflammation. From these associations, we next asked whether pro-inflammatory players directly regulate PIEZO1 expression. We used human-derived brain cells and confirmed that endothelium, astrocytes, and pericytes expressed PIEZO1. Exposure to human recombinant TNFα or IL1β upregulated NF-kB in all cells. Furthermore, TNFα induced PIEZO1 expression in a dose and time-dependent manner, primarily in astrocytes.
This exploratory study describes a spatiotemporal dialogue between PIEZO1 brain cell-mechanobiology and neuro-inflammatory cell remodeling. The precise functional mechanisms regulating this interplay in disease conditions warrant further investigation.
•Spatiotemporal neuroinflammation correlates with PIEZO1 levels in human and rodent brains.•Glio-vascular cells present trajectories of Piezo1 expression during disease progression.•TNFα induces PIEZO1 expression in human astrocytes.•These events describe an interplay between cell-mechanobiology and neuroinflammation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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