Chelatable zinc modulates excitability and seizure duration in the amygdala rapid kindling model

Zinc is present in high concentration in many structures of the limbic circuitry, however the role of zinc as a neuromodulator in such synapses is stilt uncertain. In this work, we verified the effects of zinc chelation in an animal model of epileptogenesis induced by amygdala rapid kindling. The basolateral. amygdala was electrically stimulated ten times per day for 2 days. A single stimulus was applied on the third day. Stimulated animals received injections of PBS or the zinc chelator diethildythiocarbamate acid (DEDTC) before each stimulus series. Animals were monitored with video-EEG and were perfused 3 h after the last stimulus for subsequent neo-Timm and Ftuoro-Jade B analysis. Zinc chelation decreased the duration of both behavioral seizures and electrical after-discharges, and also decreased the EEG spikes frequency, without changing the progression of behavioral seizure severity. These results indicate that the zinc ion may have a facilitatory role during kindling progression. (c) 2008 Elsevier B.V. All rights reserved.

Neurobiology of panic disorder: From animal models to brain neuroimaging

Evidence from animal models of anxiety has led to the hypothesis that serotonin enhances inhibitory avoidance (related to anxiety) in the forebrain, but inhibits one-way escape (panic) in the midbrain periaqueductal gray (PAG). Stressing the difference between these emotions, neuroendocrinological results indicate that the hypothalamic-pituitary-adrenal axis is activated by anticipatory anxiety, but not by panic attack nor by electrical stimulation of the rat PAG. Functional neuroimaging has shown activation of the insula and upper brain stem (including PAG), as well as deactivation of the anterior cingulated cortex (ACC) during experimental panic attacks. Voxel-based morphometric analysis of brain magnetic resonance images has shown a grey matter volume increase in the insula and upper brain stem, and a decrease in the ACC of panic patients at rest, as compared to healthy controls. The insula and the ACC detect interoceptive stimuli, which are overestimated by panic patients. It is suggested that these brain areas and the PAG are involved in the pathophysiology of panic disorder. (C) 2008 Elsevier Ltd. All rights reserved.

Dendritic branching patterns of pyramidal cells in the visual cortex of the new world marmoset monkey, with comparative notes on the old world macaque monkey

The basal dendritic arbors of 442 supragranular pyramidal cells in visual cortex of the marmoset monkey were compared by fractal analyses. As detailed in a previous study,(1) individual cells were injected with Lucifer Yellow and processed for a DAB reaction product. The basal dendritic arbors were drawn, in the tangential plane, and the fractal dimension (D) determined by the dilation method. The fractal dimensions were compared between cells in ten cortical areas containing cells involved in visual processing, including the primary visual area (Vi), the second visual area (V2), the dorsoanterior area (DA), the dorsomedial area (DM), the dorsolateral. area (DL), the middle temporal area (MT), the posterior parietal area (PP), the fundus of the superior temporal area (FST) and the caudal and rostral subdivisions of inferotemporal cortex (ITc and ITr, respectively). Of 45 pairwise interareal comparisons of the fractal dimension of neurones, 20 were significantly different. Moreover, comparison of data according to previously published visual processing pathways revealed a trend for cells with greater fractal dimensions in higher cortical areas. Comparison of the present results with those in homologous cortical areas in the macaque monkey(2) revealed some similarities between the two species. The similarity in the trends of D values of cells in both species may reflect developmental features which, result in different functional attributes.

Brain activity during the encoding, retention, and retrieval of stimulus representations

Studies of delayed nonmatching-to-sample (DNMS) performance following lesions of the monkey cortex have revealed a critical circuit of brain regions involved in forming memories and retaining and retrieving stimulus representations. Using event-related functional magnetic resonance imaging (fMRI), we measured brain activity in 10 healthy human participants during performance of a trial-unique visual DNMS task using novel barcode stimuli. The event-related design enabled the identification of activity during the different phases of the task (encoding, retention, and retrieval). Several brain regions identified by monkey studies as being important for successful DNMS performance showed selective activity during the different phases, including the mediodorsal thalamic nucleus (encoding), ventrolateral prefrontal cortex (retention), and perirhinal cortex (retrieval). Regions showing sustained activity within trials included the ventromedial and dorsal prefrontal cortices and occipital cortex. The present study shows the utility of investigating performance on tasks derived from animal models to assist in the identification of brain regions involved in human recognition memory.

Preprocessing and time-frequency analysis of newborn EEG seizures

Neurological disease or dysfunction in newborn infants is often first manifested by seizures. Prolonged seizures can result in impaired neurodevelopment or even death. In adults, the clinical signs of seizures are well defined and easily recognized. In newborns, however, the clinical signs are subtle and may be absent or easily missed without constant close observation. This article describes the use of adaptive signal processing techniques for removing artifacts from newborn electroencephalogram (EEG) signals. Three adaptive algorithms have been designed in the context of EEG signals. This preprocessing is necessary before attempting a fine time-frequency analysis of EEG rhythmical activities, such as electrical seizures, corrupted by high amplitude signals. After an overview of newborn EEG signals, the authors describe the data acquisition set-up. They then introduce the basic physiological concepts related to normal and abnormal newborn EEGs and discuss the three adaptive algorithms for artifact removal. They also present time-frequency representations (TFRs) of seizure signals and discuss the estimation and modeling of the instantaneous frequency related to the main ridge of the TFR.

MR image-based measurement of rates of change in volumes of brain structures. Part II: Application to a study of Alzheimer's disease and normal aging

We present global and regional rates of brain atrophy measured on serially acquired T1-weighted brain MR images for a group of Alzheimer's disease (AD) patients and age-matched normal control (NC) subjects using the analysis procedure described in Part I. Three rates of brain atrophy: the rate of atrophy in the cerebrum, the rate of lateral ventricular enlargement and the rate of atrophy in the region of temporal lobes, were evaluated for 14 AD patients and 14 age-matched NC subjects. All three rates showed significant differences between the two groups, However, the greatest separation of the two groups was obtained when the regional rates were combined. This application has demonstrated that rates of brain atrophy, especially in specific regions of the brain, based on MR images can provide sensitive measures for evaluating the progression of AD. These measures will be useful for the evaluation of therapeutic effects of novel therapies for AD. (C) 2002 Elsevier Science Inc. All rights reserved.

Minor physical anomalies and quantitative measures of the head and face in patients with psychosis

Background: The aim of this study was to examine minor physical anomalies and quantitative measures of the head and face in patients with psychosis vs healthy controls. Methods: Based on a comprehensive prevalence study of psychosis, we recruited 310 individuals with psychosis and 303 controls. From this sample, we matched 180 case-control pairs for age and sex. Individual minor physical anomalies and quantitative measures related to head size and facial height and depth were compared within the matched pairs. Based on all subjects, we examined the specificity of the findings by comparing craniofacial summary scores in patients with nonaffective or affective psychosis and controls. Results: The odds of having a psychotic disorder were increased in those with wider skull bases (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.02-1.17), smaller lower-facial heights (glabella to subnasal) (OR, 0.57; 95% CI, 0.44-0.75), protruding ears (OR, 1.72; 95% CI, 1.05-2.82), and shorter (OR, 2.29; 95% CI, 1.37-3.82) and wider (OR, 2.28; 95% CI, 1.43-3.65) palates. Compared with controls, those with psychotic disorder had skulls that were more brachycephalic. These differences were found to distinguish patients with nonaffective and affective psychoses from controls. Conclusions: Several of the features that differentiate patients from controls relate to the development of the neuro-basicranial complex and the adjacent temporal and frontal lobes. Future research should examine both the temporal lobe and the middle cranial fossa to reconcile our anthropomorphic findings and the literature showing smaller temporal lobes in patients with schizophrenia. Closer attention to the skull base may provide clues to the nature and timing of altered brain development in patients with psychosis.

Dynamics of Gray Matter Loss in Alzheimer's Disease

We detected and mapped a dynamically spreading wave of gray matter loss in the brains of patients with Alzheimer's disease (AD). The loss pattern was visualized in four dimensions as it spread over time from temporal and limbic cortices into frontal and occipital brain regions, sparing sensorimotor cortices. The shifting deficits were asymmetric (left hemisphere >right hemisphere) and correlated with progressively declining cognitive status ( p 15% loss). The maps distinguished different phases of AD and differentiated AD from normal aging. Local gray matter loss rates (5.3 +/- 2.3% per year in AD v 0.9 +/- 0.9% per year in controls) were faster in the left hemisphere ( p < 0.029) than the right. Transient barriers to disease progression appeared at limbic/frontal boundaries. This degenerative sequence, observed in vivo as it developed, provides the first quantitative, dynamic visualization of cortical atrophic rates in normal elderly populations and in those with dementia.

Potenciais evocados auditivos de média latência em adultos com epilepsia

Introdução Os potenciais evocados auditivos de média latência (PEAML) reflectem actividade neuronal mesencefáfica, mais precisamente da região tálamo-cortical, dos colículos inferiores e da formação reticular. A epilepsia é caracterizada por variadas manifestações anormais do comportamento cerebral, sendo descrita como uma perturbação da função cerebral, tendo origem numa descarga anómala de um conjunto ou da totalidade dos neurónios do córtice cerebral. Está documentado, que as descargas eléctricas provocadas pelas crises de epilepsia podem levar a perdas neuronais, pelo que poderão existir alterações nos PEAML. Objectivos A escassa existência de literatura sobre o tema e a não investigação na população portuguesa, originou a execução deste estudo, que teve como objectivo investigar e documentar a existência de alterações ou achados nos componentes neuronais de média latência (PEAML), numa amostra de portugueses com epilepsia. Metodologia Foram realizados PEAML a um grupo de controlo (GC) composto por 16 participantes e a um grupo clínico (GCL) de 8 participantes com epilepsia, sendo analisados os componentes Na, Pa e Na-Pa quanto à sua morfologia, latência e amplitude. Resultados A morfologia das ondas e a presença de epilepsia não estão associados, no entanto, contrariamente ao GC que evidenciou latências e amplitudes de Na, Pa e Na-Pa dentro dos padrões de normalidade, a alteração ou ausência de respostas por parte do GCL é significativa na totalidade das medidas investigadas. Conclusão Em epilepsias generalizadas e focais do lobo temporal os PEAML evidenciam alterações, tal achado poderá ser eventualmente justificado pela propagação ascendente e descendente da informação auditiva se encontrar comprometida, devido a sequelas deixadas pelas crises epilépticas nas vias auditivas mesencefálicas. As alterações verificadas foram uma morfologia anómala das ondas ou ausência das mesmas.

Different Electroclinical Manifestations of the Epilepsy Associated with Hamartomas Connecting to the Middle or Posterior Hypothalamus

PURPOSE: The epilepsy associated with hypothalamic hamartomas (HHs) has typical clinical, electrophysiologic, and behavioral manifestations refractory to drug therapy and with unfavorable evolution. It is well known that only sessile lesions produce epilepsy, but no correlation has been established between the different types of sessile hamartomas and the diverse manifestations of the epilepsy. We correlate anatomic details of the hamartoma and the clinical and neurophysiologic manifestations of the associated epilepsy. METHODS: HHs of seven patients with epilepsy (ages 2- 25 years) were classified as to lateralization and connection to the anteroposterior axis of the hypothalamus by using high-resolution brain magnetic resonance imaging. We correlated the anatomic classification with the clinical and neurophysiologic manifestations of the epilepsy as evaluated in long-term (24 h) video-EEG recordings. RESULTS: HHs ranged in size from 0.4 to 2.6 cc, with complete lateralization in six of seven patients. Ictal manifestations showed good correlation with the lobar involvement of ictal/interictal EEGs. These manifestations suggest the existence of two types of cortical involvement, one associated with the temporal lobe, produced by hamartomas connected to the posterior hypothalamus (mamillary bodies), and the other associated with the frontal lobe, seen in lesions connecting to the middle hypothalamus. CONCLUSIONS: A consistent clinical and neurophysiologic pattern of either temporal or frontal lobe cortical secondary involvement was found in the patients of our series. It depends on whether the hamartoma connects to the mamillary bodies (temporal lobe cases) or whether it connects to the medial hypothalamus (frontal lobe cases).

Establishment and characterization of a human model of the blood-brain barrier

Dissertação apresentada para a obtenção do Grau de Mestre em Genética Molecular e Biomedicina, pela Universidade N ova de Lisboa, Faculdade de Ciências e Tecnologia

Past/present and future worries: na fMRI study

For the past decade, numerous imaging techniques gave rise to remarka-ble progresses in the understanding of brain’s structure and function. Amongst the wide variety of studies onto the field of neuroscience, neuropsychiatric re-searches with resource to neuroimaging have attracted increasing attention. The present study will focus on the identification of brain areas recruited while normative subjects read sentences related to past/present or future wor-ries. Our main aim was to accurately characterize these brain areas while providing them with a time-stamp that would hopefully help us understand the implications of past/present memories and future envisioning in worrying episodes. With that purpose, functional magnetic resonance imaging data was collected from ten healthy individuals. The obtained data was processed and statistically treated using the General Linear Model and both Fixed and Ran-dom Effects Analysis for group-level results. Thereafter, a Multi-Voxel Pattern Analysis with Searchlight Mapping was performed in order to find patterns of activation that allow differentiation between conditions. The obtained results indicate higher brain activation while reading sen-tences related to past/present worries when compared to future worry or neu-tral sentences. The main areas include frontal cortex, posterior parietal, occipital and temporal areas. Worrying, per se, was characterized by activation of the medial posterior parietal cortex, left posterior occipital lobe and left central temporal lobe. With the searchlight mapping approach we were able to further identify patterns of distinction between conditions, which were located in the parietal, limbic and frontal lobes.

Association of N-acetylaspartate and cerebrospinal fluid Aβ42 in dementia.

The interplay of amyloid and mitochondrial function is considered crucial in the pathophysiology of Alzheimer's disease (AD). We tested the association of the putative marker of mitochondrial function N-acetylaspartate (NAA) as measured by proton magnetic resonance spectroscopy within the medial temporal lobe and cerebrospinal fluid amyoid-β42 (Aβ42), total Tau and pTau181. 109 patients were recruited in a multicenter study (40 mild AD patients, 14 non-AD dementia patients, 29 mild cognitive impairment (MCI) AD-type patients, 26 MCI of non-AD type patients). NAA correlated with Aβ42 within the AD group. Since the NAA concentration is coupled to neuronal mitochondrial function, the correlation between NAA and Aβ42 may reflect the interaction between disrupted mitochondrial pathways and amyloid production.

IRM opératoire et chirurgie de l'épilepsie [Intraoperative MRI and epilepsy surgery].

Intraoperative imaging, in particular intraoperative MRI, is a developing area in neurosurgery and its role is currently being evaluated. Its role in epilepsy surgery has not been defined yet and its use has been limited. In our experience with a compact and mobile low-field intraoperative MRI system, a few epilepsy surgeries have been performed using this technique. As the integration of imaging and functional data plays an important role in the planning of epilepsy surgery, intraoperative verification of the surgical result may be highly valuable. Therefore, teams that have access to intraoperative MRI should be encouraged to use this technique prospectively to evaluate its current relevance in epilepsy surgery.

GABA receptor subunits in human auditory cortex in normal and stroke cases.

GABA receptors are ubiquitous in the cerebral cortex and play a major role in shaping responses of cortical neurons. GABAA and GABAB receptor subunit expression was visualized by immunohistochemistry in human auditory areas from both hemispheres in 9 normal subjects (aged 43-85 years; time between death and fixation 6-24 hours) and in 4 stroke patients (aged 59-87 years; time between death and fixation 7-24 hours) and analyzed qualitatively for GABAA and semiquantitatively for GABAB receptor subunits. In normal brains, the primary auditory area (TC) and the surrounding areas TB and TA displayed distinct GABAA receptor subunit labeling with differences among cortical layers and areas. In postacute and chronic stroke we found a layer-selective downregulation of the alpha-2 subunit in the anatomically intact cerebral cortex of the intact and of the lesioned hemisphere, whereas the alpha-1, alpha-3 and beta-2/3 subunits maintained normal levels of expression. The GABAB receptors had a distinct laminar pattern in auditory areas and minor differences among areas. Unlike in other pathologies, there is no modulation of the GABAB receptor expression in subacute or chronic stroke.