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Our knowledge on temporal lobe epilepsy (TLE) with hippocampal sclerosis has evolved towards the view that this syndrome affects widespread brain networks. Diffusion weighted imaging studies have shown alterations of large white matter tracts, most notably in left temporal lobe epilepsy, but the degree of altered connections between cortical and subcortical structures remains to be clarified. We performed a whole brain connectome analysis in 39 patients with refractory temporal lobe epilepsy and unilateral hippocampal sclerosis (20 right and 19 left) and 28 healthy subjects. We performed whole-brain probabilistic fiber tracking using MRtrix and segmented 164 cortical and subcortical structures with Freesurfer. Individual structural connectivity graphs based on these 164 nodes were computed by mapping the mean fractional anisotropy (FA) onto each tract. Connectomes were then compared using two complementary methods: permutation tests for pair-wise connections and Network Based Statistics to probe for differences in large network components. Comparison of pair-wise connections revealed a marked reduction of connectivity between left TLE patients and controls, which was strongly lateralized to the ipsilateral temporal lobe. Specifically, infero-lateral cortex and temporal pole were strongly affected, and so was the perisylvian cortex. In contrast, for right TLE, focal connectivity loss was much less pronounced and restricted to bilateral limbic structures and right temporal cortex. Analysis of large network components revealed furthermore that both left and right hippocampal sclerosis affected diffuse global and interhemispheric connectivity. Thus, left temporal lobe epilepsy was associated with a much more pronounced pattern of reduced FA, that included major landmarks of perisylvian language circuitry. These distinct patterns of connectivity associated with unilateral hippocampal sclerosis show how a focal pathology influences global network architecture, and how left or right-sided lesions may have differential and specific impacts on cerebral connectivity. •We computed the structural network of 39 temporal lobe epilepsy (TLE) patients.•Two strategies, pairwise connection analysis and network based statistics, were used.•Widespread disconnections were found in TLE patients with respect to controls.•Left TLE patients were much more affected than right TLE patients.•Left TLE showed a strongly lateralized fronto-temporal disconnection pattern.

Rationale: Face expertise is a pivotal social skill. Developmental prosopagnosia (DP), i.e., the inability to recognize faces without a history of brain damage, affects about 2% of the general population, and is a renowned model system of the face-processing network. Within this network, the right Fusiform Face Area (FFA), is particularly involved in face identity processing and may therefore be a key element in DP. Neural representations within the FFA have been examined with Representational Similarity Analysis (RSA), a data-analytical framework in which multi-unit measures of brain activity are assessed with correlation analysis. Objectives: Our study intended to scrutinize modifications of FFA-activation during face encoding and maintenance based on RSA. Methods: Thirteen participants with DP (23–70 years) and 12 healthy control subjects (19–62 years) participated in a functional MRI study, including morphological MRI, a functional FFA-localizer and a modified Sternberg paradigm probing face memory encoding and maintenance. Memory maintenance of one, two, or four faces represented low, medium, and high memory load. We examined conventional activation differences in response to working memory load and applied RSA to compute individual correlation-matrices on the voxel level. Group correlation-matrices were compared via Donsker’s random walk analysis. Results: On the functional level, increased memory load entailed both a higher absolute FFA-activation level and a higher degree of correlation between activated voxels. Both aspects were deficient in DP. Interestingly, control participants showed a homogeneous degree of correlation for successful trials during the experiment. In DP-participants, correlation levels between FFA-voxels were significantly lower and were less sustained during the experiment. In behavioral terms, DP-participants performed poorer and had longer reaction times in relation to DP-severity. Furthermore, correlation levels were negatively correlated with reaction times for the most demanding high load condition. Conclusion: We suggest that participants with DP fail to generate robust and maintained neural representations in the FFA during face encoding and maintenance, in line with poorer task performance and prolonged reaction times. In DP, alterations of neural coding in the FFA might therefore explain curtailing in working memory and contribute to impaired long-term memory and mental imagery.

To the Editor: In the HYBERNATUS (Hypothermia for Brain Enhancement Recovery by Neuroprotective and Anticonvulsivant Action after Convulsive Status Epilepticus) trial, Legriel et al. (Dec. 22 issue) 1 did not find a beneficial effect of induced hypothermia on functional outcomes at 90 days among patients with convulsive status epilepticus. These results should be revisited with regard to the three potential benefits of induced hypothermia: neuroprotection, seizure treatment, 2 and lowering of intracranial pressure. 3 The neuroprotective effect of hypothermia was not significant, but the trial showed a clear antiepileptic benefit, in that hypothermia lowered the rate of progression to electroencephalogram (EEG)–confirmed status epilepticus. . . .

On day (D) 4, clinical deterioration with myoclonus worsening prompted the insertion of a left retrograde jugular catheter for brain oxygenation monitoring which showed profound desaturation (SjvO2 47%) that persisted despite deep sedation and attempts to increase cerebral oxygen delivery with initiation of vasopressors and red blood cells transfusion, consistent with an increased cerebral metabolic rate. Furthermore, focal lesions and substantially higher CSF interleukine-6 level as compared with serum sample argue for an autochthonous brain inflammatory process rather than a toxic encephalopathy induced by passive transfer of proinflammatory cytokines from the systemic compartment [3]. [...]the efficacy of immunomodulation with corticosteroids supports an immunological mechanism. Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The amygdala is a key structure for monitoring the relevance of environmental stimuli. Yet, little is known about the dynamics of its response to primary social cues such as gaze and emotion. Here, we examined evoked amygdala responses to gaze and facial emotion changes in five epileptic patients with intracerebral electrodes. Patients first viewed a neutral face that would then convey social cues: it turned either happy or fearful with or without gaze aversion. This social cue was followed by a laterally presented target, the detection of which was faster if it appeared in a location congruent with the averted gaze direction. First, we observed pronounced evoked amygdala potentials to the initial neutral face. Second, analysis of the evoked responses to the cue showed an early effect of gaze starting at 123 ms in the right amygdala. Differential effects of fearful vs happy valence were individually present but more variable in time and therefore not observed at group-level. Our study is the first to demonstrate such an early effect of gaze in the amygdala, in line with its particular behavioral relevance in the spatial attention task.

Songs constitute a natural combination of lyrics and melodies, but it is unclear whether and how these two song components are integrated during the emergence of a memory trace. Network theories of memory suggest a prominent role of the hippocampus, together with unimodal sensory areas, in the build-up of conjunctive representations. The present study tested the modulatory influence of the hippocampus on neural adaptation to songs in lateral temporal areas. Patients with unilateral hippocampal sclerosis and healthy matched controls were presented with blocks of short songs in which lyrics and/or melodies were varied or repeated in a crossed factorial design. Neural adaptation effects were taken as correlates of incidental emergent memory traces. We hypothesized that hippocampal lesions, particularly in the left hemisphere, would weaken adaptation effects, especially the integration of lyrics and melodies. Results revealed that lateral temporal lobe regions showed weaker adaptation to repeated lyrics as well as a reduced interaction of the adaptation effects for lyrics and melodies in patients with left hippocampal sclerosis. This suggests a deficient build-up of a sensory memory trace for lyrics and a reduced integration of lyrics with melodies, compared to healthy controls. Patients with right hippocampal sclerosis showed a similar profile of results although the effects did not reach significance in this population. We highlight the finding that the integrated representation of lyrics and melodies typically shown in healthy participants is likely tied to the integrity of the left medial temporal lobe. This novel finding provides the first neuroimaging evidence for the role of the hippocampus during repetitive exposure to lyrics and melodies and their integration into a song.

Songs constitute a natural combination of lyrics and melodies, but it is unclear whether and how these two song components are integrated during the emergence of a memory trace. Network theories of memory suggest a prominent role of the hippocampus, together with unimodal sensory areas, in the build-up of conjunctive representations. The present study tested the modulatory influence of the hippocampus on neural adaptation to songs in lateral temporal areas. Patients with unilateral hippocampal sclerosis and healthy matched controls were presented with blocks of short songs in which lyrics and/or melodies were varied or repeated in a crossed factorial design. Neural adaptation effects were taken as correlates of incidental emergent memory traces. We hypothesized that hippocampal lesions, particularly in the left hemisphere, would weaken adaptation effects, especially the integration of lyrics and melodies. Results revealed that lateral temporal lobe regions showed weaker adaptation to repeated lyrics as well as a reduced interaction of the adaptation effects for lyrics and melodies in patients with left hippocampal sclerosis. This suggests a deficient build-up of a sensory memory trace for lyrics and a reduced integration of lyrics with melodies, compared to healthy controls. Patients with right hippocampal sclerosis showed a similar profile of results although the effects did not reach significance in this population. We highlight the finding that the integrated representation of lyrics and melodies typically shown in healthy participants is likely tied to the integrity of the left medial temporal lobe. This novel finding provides the first neuroimaging evidence for the role of the hippocampus during repetitive exposure to lyrics and melodies and their integration into a song.

Occipito-temporal regions within the face network process perceptual and socio-emotional information, but the dynamics and interactions between different nodes within this network remain unknown. Here, we analyzed intracerebral EEG from 11 epileptic patients viewing a stimulus sequence beginning with a neutral face with direct gaze. The gaze could avert or remain direct, while the emotion changed to fearful or happy. N200 field potential peak latencies indicated that face processing begins in inferior occipital cortex and proceeds anteroventrally to fusiform and inferior temporal cortices, in parallel. The superior temporal sulcus responded preferentially to gaze changes with augmented field potential amplitudes for averted versus direct gaze, and large effect sizes relative to other regions of the network. An overlap analysis of posterior white matter tractography endpoints (from 1066 healthy brains) relative to active intracerebral electrodes from the 11 patients showed likely involvement of both dorsal and ventral posterior white matter pathways. The inferior occipital and temporal sulci likely broadcast their information - the former dorsally to intraparietal sulcus, and the latter between fusiform and superior temporal cortex. Overall, our data call for inclusion of inferior temporal cortex in face processing models, and anchor the superior temporal cortex in dynamic gaze processing. Competing Interest Statement The authors have declared no competing interest.