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Cook D.G.,Geriatric Research Education and Clinical Center | D'Ambrosio R.,Regional Epilepsy Center | D'Ambrosio R.,University of Washington | D'Ambrosio R.,Harborview Medical Center
Journal of Neurophysiology | Year: 2010

Astrocytic inwardly rectifying K+ currents (IIRK) have an important role in extracellular K+ homeostasis, which influences neuronal excitability, and serum extravasation has been linked to impaired KIR-mediated K+ buffering and chronic hyperexcitability. Head injury induces acute impairment in astroglial membrane IKIR and impaired K+ buffering in the rat hippocampus, but chronic spontaneous seizures appear in the perilesional neocortex- not the hippocampus-in the early weeks to months after injury. Thus we examined astrocytic KIR channel pathophysiology in both neocortex and hippocampus after rostral parasaggital fluid percussion injury (rpFPI). rpFPI induced greater acute serum extravasation and metabolic impairment in the perilesional neocortex than in the underlying hippocampus, and in situ whole cell recordings showed a greater acute loss of astrocytic IKIR in neocortex than hippocampus. IKIR loss persisted through 1 mo after injury only in the neocortical epileptic focus, but fully recovered in the hippocampus that did not generate chronic seizures. Neocortical cell-attached recordings showed no loss or an increase of IIRK in astrocytic somata. Confocal imaging showed depletion of KIR 4.1 immunoreactivity especially in processes-not somata-of neocortical astrocytes, whereas hippocampal astrocytes appeared normal. In naïve animals, intracortical infusion of serum, devoid of coagulation-mediating thrombin activity, reproduces the effects of rpFPI both in vivo and at the cellular level. In vivo serum infusion induces partial seizures similar to those induced by rpFPI, whereas bath-applied serum, but not dialyzed albumin, rapidly silenced astrocytic KIR membrane currents in whole cell and cellattached patch-clamp recordings in situ. Thus both acute impairment in astrocytic IKIR and chronic spontaneous seizures typical of rpFPI are reproduced by serum extravasation, whereas the chronic impairment in astroglial IKIR is specific to the neocortex that develops the epileptic focus. Copyright © 2010 The American Physiological Society. Source


Labate A.,University of Catanzaro | Labate A.,National Research Council Italy | Cerasa A.,National Research Council Italy | Aguglia U.,Regional Epilepsy Center | And 5 more authors.
Epilepsia | Year: 2010

Purpose: In refractory temporal lobe epilepsy (rTLE), gray matter (GM) abnormalities are not confined to the hippocampus but also are found in extrahippocampal structures. Very recently we observed in mild TLE (mTLE) with or without mesiotemporal sclerosis (MTS), GM reductions in regions outside the presumed epileptogenic focus. To date, there are no studies that directly investigate whether whole-brain GM volume differs between rTLE and mTLE. Herein, we used optimized voxel-based morphometry (VBM) to identify GM abnormalities beyond the hippocampus in both rTLE and mTLE with evidence of MTS. Methods: Brain magnetic resonance imaging (MRI) and optimized VBM were performed in 19 unrelated patients with mTLE, 19 patients with rTLE, and 37 healthy controls. MRI diagnosis of MTS was based on the atrophy of the hippocampal formation and/or mesiotemporal hyper-intensity on fluid-attenuated inversion recovery (FLAIR) or T2 images, or both. Results: No patients (rTLE and mTLE) had generalized tonic-clonic or complex partial seizures for at least 3 weeks before scanning. Both mTLE and rTLE patients showed GM volume reduction of the bilateral thalamus, left hippocampus, and sensorimotor cortex compared with controls. No significant GM difference was found between rTLE and mTLE groups. Discussion: In both rTLE and mTLE, VBM shows GM reductions not confined to the hippocampus involving mainly the thalamus bilaterally. This finding together with the lack of significant GM differences between the two TLE groups supports the hypothesis that mTLE and rTLE might lie along a biologic continuum, suggesting a pathophysiologic role of the thalamus in partial epilepsy. © 2009 International League Against Epilepsy. Source


Prete G.,University of Chieti Pescara | Laeng B.,University of Oslo | Fabri M.,Marche Polytechnic University | Foschi N.,Regional Epilepsy Center | Tommasi L.,University of Chieti Pescara
Neuropsychologia | Year: 2015

The valence hypothesis and the right hemisphere hypothesis in emotion processing have been alternatively supported. To better disentangle the two accounts, we carried out two studies, presenting healthy participants and an anterior callosotomized patient with 'hybrid faces', stimuli created by superimposing the low spatial frequencies of an emotional face to the high spatial frequencies of the same face in a neutral expression. In both studies we asked participants to judge the friendliness level of stimuli, which is an indirect measure of the processing of emotional information, despite this remaining "invisible". In Experiment 1 we presented hybrid faces in a divided visual field paradigm using different tachistoscopic presentation times; in Experiment 2 we presented hybrid chimeric faces in canonical view and upside-down. In Experiments 3 and 4 we tested a callosotomized patient, with spared splenium, in similar paradigms as those used in Experiments 1 and 2. Results from Experiments 1 and 3 were consistent with the valence hypothesis, whereas results of Experiments 2 and 4 were consistent with the right hemisphere hypothesis. This study confirms that the low spatial frequencies of emotional faces influence the social judgments of observers, even when seen for 28. ms (Experiment 1), possibly by means of configural analysis (Experiment 2). The possible roles of the cortical and subcortical emotional routes in these tasks are discussed in the light of the results obtained in the callosotomized patient. We propose that the right hemisphere and the valence accounts are not mutually exclusive, at least in the case of subliminal emotion processing. © 2015 Elsevier Ltd. Source


Labate A.,University of Catanzaro | Labate A.,National Research Council Italy | Cerasa A.,National Research Council Italy | Aguglia U.,University of Catanzaro | And 6 more authors.
Epilepsia | Year: 2011

Purpose: In refractory mesial temporal lobe epilepsy (MTLE) extrahippocampal and neocortical abnormalities have been described in patients with or without mesial temporal sclerosis (MTS). Recently we observed gray matter reductions in regions outside the hippocampus in benign MTLE with or without MTS. Cortical thickness has been proposed as a viable methodologic alternative for assessment of neuropathologic changes in extratemporal regions. Herein, we aimed to use this technique to describe cortical abnormalities in patients with benign TLE. Methods: Whole-brain cortical thickness analysis (FreeSurfer) was performed in 32 unrelated patients with benign TLE [16 patients with signs of MTS on magnetic resonance imaging (MRI), pMTLE; 16 without, nMTLE] and 44 healthy controls. Key Findings: In the pMTLE group, the most significant thinning was found in the sensorimotor cortex bilaterally but was more extensive in the left hemisphere (false discovery rate, p < 0.05). Other areas were localized in the occipital cortex, left supramarginal gyrus, left superior parietal gyrus, left paracentral sulcus, left inferior/middle/superior frontal gyrus, left inferior frontal sulcus, right cingulate cortex, right superior frontal gyrus, right inferior parietal gyrus, right fusiform gyrus, and cuneus/precuneus. In the nMTLE, a similar neurodegenerative pattern was detected, although not surviving correction for multiple comparisons. Direct comparison between pMTLE and nMTLE did not reveal significant changes. Significance: Patients with either benign pMTLE or nMTLE showed comparable cortical thinning, mainly confined to the sensorimotor cortex. This finding that is not appreciated on routine MRI supports the hypothesis that similar to refractory MTLE, even in benign MTLE, pathology in neocortical regions maybe implicated in the pathophysiology of this syndrome. © Wiley Periodicals, Inc. 2011 International League Against Epilepsy. Source


Prete G.,University of Chieti Pescara | Marzoli D.,University of Chieti Pescara | Brancucci A.,University of Chieti Pescara | Fabri M.,Marche Polytechnic University | And 2 more authors.
Behavioural Brain Research | Year: 2014

Hemispheric asymmetries have been widely explored in both the visual and the auditory domain, but little is known about hemispheric asymmetries in audio-visual integration. We compared the performance of a partially callosotomized patient, a total split-brain patient and a control group during the evaluation of the emotional valence of chimeric faces and dichotic syllables (an emotional syllable in one ear and white noise in the other ear) presented unimodally (only faces or only syllables) or bimodally (faces and syllables presented simultaneously). Stimuli could convey happy and sad expressions and participants were asked to evaluate the emotional content of each presentation, using a 5-point Likert scale (from very sad to very happy). In unimodal presentations, the partially callosotomized patient's judgments depended on the emotional valence of the stimuli processed by the right hemisphere, whereas those of the total split-brain patient showed the opposite lateralization; in these conditions, the control group did not show asymmetries. Moreover, in bimodal presentations, results provided support for the valence hypothesis (i.e., left asymmetry for positive emotions and vice versa) in both the control group and the partially callosotomized patient, whereas the total split-brain patient showed a tendency to evaluate the emotional content of the right hemiface even when asked to focus on the acoustic modality. We conclude that partial and total hemispheric disconnections reveal opposite patterns of hemispheric asymmetry in auditory, visual and audio-visual emotion processing. These results are discussed in the light of the right-hemisphere hypothesis and the valence hypothesis. © 2014 Elsevier B.V. Source

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