Doenças neurológicas

As convulsões são o problema neurológico mais comum nos animais de companhia. Convulsão é o quadro clínico gerado por descargas elétricas paroxísticas, descontroladas e transitórias nos neurónios do encéfalo, levando a alterações da consciência, atividade motora, funções viscerais, perceção sensorial, conduta e memória. A anamnese é muito importante para o diagnóstico, pois é o proprietário quem na maioria das vezes presencia o evento e, os dados obtidos podem auxiliar no plano de diagnóstico e terapêutico. É importante reconhecer, no entanto, que esta informação é coadjuvante ao exame neurológico. As convulsões podem ter causas extracranianas (ex: metabólicas e toxicas), intracranianas (ex: traumatismos, enfermidades infeciosas, malformações congénitas) e idiopáticas (epilepsia idiopática). É fundamental tentar identificar a causa das convulsões através da realização do exame clínico e neurológico, com atenção especial aos sistemas cardio-circulatório, respiratório, digestivo e urinário. Devem ser realizados exames complementares adequados (hemograma, urianálise, enzimas hepáticas, ureia, creatinina, glicemia, sorologias, reação em cadeia de polimerase, radiografias torácicas, ultrassonografia, tomografia computorizada e ressonância magnética quando disponíveis). O objetivo do tratamento antiepilético é controlar as convulsões sem efeitos adversos, no entanto, o clínico apenas pode tentar reduzir a frequência e severidade das convulsões a um nível que não comprometa substancialmente a qualidade de vida do animal e dos proprietários, evitando efeitos secundários.

Effect of body position on transient evoked accoustic emissions: The clinical perspective

The present study investigated body position effects on transient evoked otoacoustic emission (TEOAE) recordings of clinical significance. Sixty adults (30 males, 30 females) were assessed using the Otodynamics ILO88 Analyzer in three positions (sitting, supine, and side-lying). Results indicated significant positional effects on the TEOAE parameters of A-B difference, noise, whole wave reproducibility, and response levels. These differences included higher noise levels in supine and side-lying positions in comparison to the upright sitting position. Lower whole wave reproducibility measurements, and higher response amplitudes, in the side-lying position compared with supine and seated positions were also observed. No significant effects were evident for signal-to-noise ratio or band reproducibility. Given the lack of significant body position effects on these latter parameters and the infrequent clinical use of the other parameters in isolation, there was no evidence to suggest the future need for major review of current pass/fail criteria or of the standard test protocol.

Smoking and elevated blood pressure are the most important risk factors for subarachnoid hemorrhage in the Asia-Pacific region - An overview of 26 cohorts involving 306,620 participants

Background and Purpose - The cause of subarachnoid hemorrhage ( SAH) is poorly understood and there are few large cohort studies of risk factors for SAH. We investigated the risk of SAH mortality and morbidity associated with common cardiovascular risk factors in the Asia-Pacific region and examined whether the strengths of these associations were different in Asian and Australasian ( predominantly white) populations. Methods - Cohort studies were identified from Internet electronic databases, searches of proceedings of meetings, and personal communication. Hazard ratios (HRs) for systolic blood pressure (SBP), current smoking, total serum cholesterol, body mass index (BMI), and alcohol drinking were calculated from Cox models that were stratified by sex and cohort and adjusted for age at risk. Results - Individual participant data from 26 prospective cohort studies ( total number of participants 306 620) that reported incident cases of SAH ( fatal and/or nonfatal) were available for analysis. During the median follow-up period of 8.2 years, a total of 236 incident cases of SAH were observed. Current smoking (HR, 2.4; 95% CI, 1.8 to 3.4) and SBP > 140 mm Hg ( HR, 2.0; 95% CI, 1.5 to 2.7) were significant and independent risk factors for SAH. Attributable risks of SAH associated with current smoking and elevated SBP ( similar to 140 mm Hg) were 29% and 19%, respectively. There were no significant associations between the risk of SAH and cholesterol, BMI, or drinking alcohol. The strength of the associations of the common cardiovascular risk factors with the risk of SAH did not differ much between Asian and Australasian regions. Conclusions - Cigarette smoking and SBP are the most important risk factors for SAH in the Asia-Pacific region.

A novel conotoxin inhibitor of Kv1.6 channel and nAChR subtypes defines a new superfamily of conotoxins

Using assay-directed fractionation of the venom from the vermivorous cone snail Conus planorbis, we isolated a new conotoxin, designated p114a, with potent activity at both nicotinic acetylcholine receptors and a voltage-gated potassium channel subtype. p114a contains 25 amino acid residues with an amidated C-terminus, an elongated N-terminal tail (six residues), and two disulfide bonds (1-3, 2-4 connectivity) in a novel framework distinct from other conotoxins. The peptide was chemically synthesized, and its three-dimensional structure was demonstrated to be well-defined, with an R-helix and two 3(10)-helices present. Analysis of a cDNA clone encoding the prepropeptide precursor of p114a revealed a novel signal sequence, indicating that p114a belongs to a new gene superfamily, the J-conotoxin superfamily. Five additional peptides in the J-superfamily were identified. Intracranial injection of p114a in mice elicited excitatory symptoms that included shaking, rapid circling, barrel rolling, and seizures. Using the oocyte heterologous expression system, p114a was shown to inhibit both a K+ channel subtype (Kv1.6, IC50) 1.59 mu M) and neuronal (IC50 = 8.7 mu M for alpha 3 beta 4) and neuromuscular (IC50 = 0.54 mu M for alpha 1 beta 1 is an element of delta) subtypes of the nicotinic acetylcholine receptor ( nAChR). Similarities in sequence and structure are apparent between the middle loop of p114a and the second loop of a number of alpha-conotoxins. This is the first conotoxin shown to affect the activity of both voltage-gated and ligand-gated ion channels.

Idiopathic sclerosing orbital inflammation

Objective: To perform a multicenter review of the clinical features and treatment of 31 patients with idiopathic sclerosing orbital inflammation. Methods: We included all patients with histologically confirmed idiopathic sclerosing orbital inflammation from 5 regional orbital centers. We reviewed the case notes to determine the clinical presentation, diagnostic features, and response to treatment. The main outcome measures were duration and nature of symptoms, anatomical location of disease, histopathological findings, treatment modalities, treatment efficacy and adverse effects, and final clinical status. Results: We included 13 male and 18 female patients ranging in age from 7 to 83 years. The average duration of symptoms at presentation was 13.4 months. There was a predilection for the lateral and superior quadrants. Thirteen patients had apical disease, and 4 had extraorbital involvement. Histopathological findings invariably showed sclerosis associated with a sparse mixed cellular infiltrate. Twenty- seven patients were treated with oral prednisolone, response to which was good in 9 patients, partial in 11, and poor in 7. Six patients were treated with a second- line immunosuppressive agent, and 6 received radiotherapy. The response to radiotherapy was generally poor. Conclusions: Idiopathic sclerosing orbital inflammation is a rare condition that can be difficult to diagnose and manage. Early intervention with immunosuppression in the form of corticosteroids combinedwith secondline agents can result in control and even regression of the disease.

Monitoring Infants By Automatic Video Processing

This work has, as its objective, the development of non-invasive and low-cost systems for monitoring and automatic diagnosing specific neonatal diseases by means of the analysis of suitable video signals. We focus on monitoring infants potentially at risk of diseases characterized by the presence or absence of rhythmic movements of one or more body parts. Seizures and respiratory diseases are specifically considered, but the approach is general. Seizures are defined as sudden neurological and behavioural alterations. They are age-dependent phenomena and the most common sign of central nervous system dysfunction. Neonatal seizures have onset within the 28th day of life in newborns at term and within the 44th week of conceptional age in preterm infants. Their main causes are hypoxic-ischaemic encephalopathy, intracranial haemorrhage, and sepsis. Studies indicate an incidence rate of neonatal seizures of 0.2% live births, 1.1% for preterm neonates, and 1.3% for infants weighing less than 2500 g at birth. Neonatal seizures can be classified into four main categories: clonic, tonic, myoclonic, and subtle. Seizures in newborns have to be promptly and accurately recognized in order to establish timely treatments that could avoid an increase of the underlying brain damage. Respiratory diseases related to the occurrence of apnoea episodes may be caused by cerebrovascular events. Among the wide range of causes of apnoea, besides seizures, a relevant one is Congenital Central Hypoventilation Syndrome (CCHS) \cite{Healy}. With a reported prevalence of 1 in 200,000 live births, CCHS, formerly known as Ondine's curse, is a rare life-threatening disorder characterized by a failure of the automatic control of breathing, caused by mutations in a gene classified as PHOX2B. CCHS manifests itself, in the neonatal period, with episodes of cyanosis or apnoea, especially during quiet sleep. The reported mortality rates range from 8% to 38% of newborn with genetically confirmed CCHS. Nowadays, CCHS is considered a disorder of autonomic regulation, with related risk of sudden infant death syndrome (SIDS). Currently, the standard method of diagnosis, for both diseases, is based on polysomnography, a set of sensors such as ElectroEncephaloGram (EEG) sensors, ElectroMyoGraphy (EMG) sensors, ElectroCardioGraphy (ECG) sensors, elastic belt sensors, pulse-oximeter and nasal flow-meters. This monitoring system is very expensive, time-consuming, moderately invasive and requires particularly skilled medical personnel, not always available in a Neonatal Intensive Care Unit (NICU). Therefore, automatic, real-time and non-invasive monitoring equipments able to reliably recognize these diseases would be of significant value in the NICU. A very appealing monitoring tool to automatically detect neonatal seizures or breathing disorders may be based on acquiring, through a network of sensors, e.g., a set of video cameras, the movements of the newborn's body (e.g., limbs, chest) and properly processing the relevant signals. An automatic multi-sensor system could be used to permanently monitor every patient in the NICU or specific patients at home. Furthermore, a wire-free technique may be more user-friendly and highly desirable when used with infants, in particular with newborns. This work has focused on a reliable method to estimate the periodicity in pathological movements based on the use of the Maximum Likelihood (ML) criterion. In particular, average differential luminance signals from multiple Red, Green and Blue (RGB) cameras or depth-sensor devices are extracted and the presence or absence of a significant periodicity is analysed in order to detect possible pathological conditions. The efficacy of this monitoring system has been measured on the basis of video recordings provided by the Department of Neurosciences of the University of Parma. Concerning clonic seizures, a kinematic analysis was performed to establish a relationship between neonatal seizures and human inborn pattern of quadrupedal locomotion. Moreover, we have decided to realize simulators able to replicate the symptomatic movements characteristic of the diseases under consideration. The reasons is, essentially, the opportunity to have, at any time, a 'subject' on which to test the continuously evolving detection algorithms. Finally, we have developed a smartphone App, called 'Smartphone based contactless epilepsy detector' (SmartCED), able to detect neonatal clonic seizures and warn the user about the occurrence in real-time.

Avaliação cefalométrica de valores angulares em telerradiografias laterais e estimadas em posição natural da cabeça de indivíduos com má oclusão

Neste estudo o objetivo foi determinar a variável dos valores cefalométricos angulares entre linhas intracranianas com relação à linha de referência M, por meio de telerradiografias em norma lateral realizadas com o PF paralelo ao solo, em indivíduos com má oclusão de Classe I, Classe II (divisão 1 e 2) e Classe III de Angle, e estimar os valores obtidos em telerradiografia lateral com a cabeça na posição natural (PNC). A amostra consistiu de 240 telerradiografias em norma lateral direita, sendo 120 de indivíduos do sexo masculino e 120 do feminino, classificadas em três faixas etárias: 12 à 15 anos; 15 anos e um mês à 17 anos e 11 meses; 18 anos à 21 anos e 11 meses; e um grupo controle com 61 telerradiografias em norma lateral direita em PNC sendo 24 indivíduos do sexo masculino e 37 do sexo feminino, na faixa etária entre 12 anos e 5 meses à 21 anos e 5 meses e portadores de oclusão normal natural. Em todas as telerradiografias foram traçadas as linhas intracranianas Sela-Násio (SN), Básio-Násio (BaN), Pório-Orbitário (PoOr) e Linha M, para que estes ângulos tivessem os seus valores estimados em PNC. As variáveis idade e sexo foram correlacionadas com os ângulos, reais e estimados, nos grupos experimentais. Após a análise estatística dos resultados pode-se concluir que: 1) Os valores cefalométricos angulares médios, reais e estimados obtidos nos quatro grupos experimentais foram: Grupo I Reais: M.SN =102,58°; M.BaN = 121,39°; M.PoOr = 94,08°. Estimados: HV.SN = 8,24° (sexo feminino) e 3,44° (sexo masculino); HV.BaN = 24,65°; HV.PoOr = -2,47°. Grupo II Reais: M.SN = 102,59°; M.BaN = 121,29°; M.PoOr = 93,13°. Estimados: HV.SN = 5,86°; HV.BaN = 24,55°; HV.PoOr = -3,43°. Grupo III Reais: M.SN = 104,38°; M.BaN = 122,25°; M.PoOr = 95,99°. Estimados: HV.SN = 7,65°; HV.BaN = 25,51°; HV.PoOr = -0,56°. Grupo IV Reais: M.SN = 104,63°; M.BaN = 123,63°; M.PoOr = 94,80°. Estimados: HV.SN = 10,14° (sexo feminino) e 5,66° (sexo masculino); HV.BaN = 26,88°; HV.PoOr = - 1,75°. 2) Não houve relação estatisticamente significante entre os valores angulares cefalométricos com relação à faixa etária; 3) Em relação ao sexo, somente o ângulo HV.SN apresentou diferenças estatisticamente significantes, nos Grupos I e IV, sendo para o Grupo I: 8,24° para o sexo feminino e 3,44° para o masculino; e Grupo IV: 10,14° para o sexo feminino e 5,66° para o masculino).

AVALIAÇÃO DO ESPAÇO DISPONÍVEL PARA ERUPÇÃO DOS SEGUNDOS E TERCEIROS MOLARES SUPERIORES PERMANENTES APÓS A DISTALIZAÇÃO DOS PRIMEIROS MOLARES SUPERIORES PERMANENTES

A presente pesquisa tem como objetivo avaliar cefalometricamente, o espaço e po-sicionamento das coroas dos segundos e terceiros molares superiores permanentes não erupcionados na região da tuberosidade maxilar durante a distalização dos pri-meiros molares superiores, além de verificar a correlação entre estas duas variáveis. A amostra foi constituída de 38 telerradiografias em norma lateral direita, obtidas de 19 pacientes, jovens brasileiros, leucodermas e melanodermas, sendo 6 do sexo masculino e 13 do sexo feminino, com idade média de 9 anos 5 meses 13 dias. A metodologia constou inicialmente da divisão dos tempos (T1) inicial, e após a distali-zação do primeiro molar superior permanente em (T2) por um período médio de 10 meses e 23 dias. Para avaliação do espaço e angulação das coroas existente utili-zou-se uma Linha referencial intracraniana (Linha M) sendo esta demarcada, a partir de dois pontos, o ponto SE localizado na sutura esfenoetmoidal, e o ponto Pt locali-zado na parte anterior da fossa pterigopalatina. Esta linha referencial foi transferida até o ponto F, (Linha M ) ponto este localizado na região mais posterio-inferior da tuberosidade maxilar. O espaço avaliado compreendeu entre a Linha M , até a face distal do primeiro molar superior permanente. Na análise estatística usou-se o teste t (Teste t Student) , e na correlação entre espaço e angulação foi utilizado o coefi-ciente de correlação de Pearson. Concluímos que o espaço correspondente entre a distal dos primeiros molares superiores permanentes e extremidade da tuberosidade maxilar, na fase inicial e após a movimentação distal, não é suficiente para a erup-ção dos segundos e terceiros molares superiores permanentes. A angulação das coroas na fase inicial e após a movimentação distal posicionam-se com angulações mais para distal. Quanto à correlação das angulações das coroas dos segundos e terceiros molares superiores permanentes e o espaço para erupção verificamos que quanto maior a angulação das coroas para distal, menor os espaços oferecidos para a erupção.(AU)

Causality and synchronisation in complex systems with applications to neuroscience

This thesis presents an investigation, of synchronisation and causality, motivated by problems in computational neuroscience. The thesis addresses both theoretical and practical signal processing issues regarding the estimation of interdependence from a set of multivariate data generated by a complex underlying dynamical system. This topic is driven by a series of problems in neuroscience, which represents the principal background motive behind the material in this work. The underlying system is the human brain and the generative process of the data is based on modern electromagnetic neuroimaging methods . In this thesis, the underlying functional of the brain mechanisms are derived from the recent mathematical formalism of dynamical systems in complex networks. This is justified principally on the grounds of the complex hierarchical and multiscale nature of the brain and it offers new methods of analysis to model its emergent phenomena. A fundamental approach to study the neural activity is to investigate the connectivity pattern developed by the brain’s complex network. Three types of connectivity are important to study: 1) anatomical connectivity refering to the physical links forming the topology of the brain network; 2) effective connectivity concerning with the way the neural elements communicate with each other using the brain’s anatomical structure, through phenomena of synchronisation and information transfer; 3) functional connectivity, presenting an epistemic concept which alludes to the interdependence between data measured from the brain network. The main contribution of this thesis is to present, apply and discuss novel algorithms of functional connectivities, which are designed to extract different specific aspects of interaction between the underlying generators of the data. Firstly, a univariate statistic is developed to allow for indirect assessment of synchronisation in the local network from a single time series. This approach is useful in inferring the coupling as in a local cortical area as observed by a single measurement electrode. Secondly, different existing methods of phase synchronisation are considered from the perspective of experimental data analysis and inference of coupling from observed data. These methods are designed to address the estimation of medium to long range connectivity and their differences are particularly relevant in the context of volume conduction, that is known to produce spurious detections of connectivity. Finally, an asymmetric temporal metric is introduced in order to detect the direction of the coupling between different regions of the brain. The method developed in this thesis is based on a machine learning extensions of the well known concept of Granger causality. The thesis discussion is developed alongside examples of synthetic and experimental real data. The synthetic data are simulations of complex dynamical systems with the intention to mimic the behaviour of simple cortical neural assemblies. They are helpful to test the techniques developed in this thesis. The real datasets are provided to illustrate the problem of brain connectivity in the case of important neurological disorders such as Epilepsy and Parkinson’s disease. The methods of functional connectivity in this thesis are applied to intracranial EEG recordings in order to extract features, which characterize underlying spatiotemporal dynamics before during and after an epileptic seizure and predict seizure location and onset prior to conventional electrographic signs. The methodology is also applied to a MEG dataset containing healthy, Parkinson’s and dementia subjects with the scope of distinguishing patterns of pathological from physiological connectivity.

Nonlinearity in all-night sleep EEG recorded with foramen ovale electrodes in a patient with temporal lobe epilepsy

Objective: It is investigated to which extent measures of nonlinearity derived from surrogate data analysis are capable to quantify the changes of epileptic activity related to varying vigilance levels. Methods: Surface and intracranial EEG from foramen ovale (FO-)electrodes was recorded from a patient with temporal lobe epilepsy under presurgical evaluation over one night. Different measures of nonlinearity were estimated for non-overlapping 30-s segments for selected channels from surface and intracranial EEG. Additionally spectral measures were calculated. Sleep stages were scored according to Rechtschaffen/Kales and epileptic transients were counted and classified by visual inspection. Results: In the intracranial recordings stronger nonlinearity was found ipsilateral to the epileptogenic focus, more pronounced in NREM sleep, weaker in REM sleep. The dynamics within the NREM episodes varied with the different nonlinearity measures. Some nonlinearity measures showed variations with the sleep cycle also in the intracranial recordings contralateral to the epileptic focus and in the surface EEG. It is shown that the nonlinearity is correlated with short-term fluctuations of the delta power. The higher frequency of occurrence of clinical relevant epileptic spikes in the first NREM episode was not clearly reflected in the nonlinearity measures. Conclusions: It was confirmed that epileptic activity renders the EEG nonlinear. However, it was shown that the sleep dynamics itself also effects the nonlinearity measures. Therefore, at the present stage it is not possible to establish a unique connection between the studied nonlinearity measures and specific types of epileptic activity in sleep EEG recordings.

The value of magnetoencephalography to guide electrode implantation in epilepsy

To investigate if Magnetoencephalography (MEG) can add non-redundant information to guide implantation sites for intracranial recordings (IR). The contribution of MEG to intracranial recording planning was evaluated in 12 consecutive patients assessed pre-surgically with MEG followed by IR. Primary outcome measures were the identification of focal seizure onset in IR and favorable surgical outcome. Outcome measures were compared to those of 12 patients matched for implantation type in whom non-invasive pre-surgical assessment suggested clear hypotheses for implantation (non-MEG group). In the MEG group, non-invasive assessment without MEG was inconclusive, and MEG was then used to further help identify implantation sites. In all MEG patients, at least one virtual MEG electrode generated suitable hypotheses for the location of implantations. No differences in outcome measures were found between non-MEG and MEG groups. Although the MEG group included more complex patients, it showed similar percentage of successful implantations as the non-MEG group. This suggests that MEG can contribute to identify implantation sites where standard methods failed. © 2013 Springer Science+Business Media New York.

Magnetoencephalography in epilepsy

Magnetoencephalographic (MEG) signals, like electroencephalographic (EEG) measures, are the direct extracranial manifestations of neuronal activation. The two techniques can detect time-varying changes in electromagnetic activity with a sub-millisecond time resolution. Extra-cranial electromagnetic measures are the cornerstone of the non-invasive diagnostic armamentarium in patients with epilepsy. Their extremely high temporal resolution – comparable to intracranial recordings – is the basis for a precise definition of onset and propagation of ictal and interictal abnormalities. Given the cost of the infrastructure and equipment, MEG has yet to develop into a routinely applicable diagnostic tool in clinical settings. However, in recent years, an increasing number of patients with epilepsy have been investigated – usually in the context of presurgical evaluation of refractory epilepsies – and initial encouraging results have been reported. We will briefly review the principles and the technology behind MEG and its contribution in the diagnostic work-up of patients with epilepsy.

Source localization methods

One of the most pressing demands on electrophysiology applied to the diagnosis of epilepsy is the non-invasive localization of the neuronal generators responsible for brain electrical and magnetic fields (the so-called inverse problem). These neuronal generators produce primary currents in the brain, which together with passive currents give rise to the EEG signal. Unfortunately, the signal we measure on the scalp surface doesn't directly indicate the location of the active neuronal assemblies. This is the expression of the ambiguity of the underlying static electromagnetic inverse problem, partly due to the relatively limited number of independent measures available. A given electric potential distribution recorded at the scalp can be explained by the activity of infinite different configurations of intracranial sources. In contrast, the forward problem, which consists of computing the potential field at the scalp from known source locations and strengths with known geometry and conductivity properties of the brain and its layers (CSF/meninges, skin and skull), i.e. the head model, has a unique solution. The head models vary from the computationally simpler spherical models (three or four concentric spheres) to the realistic models based on the segmentation of anatomical images obtained using magnetic resonance imaging (MRI). Realistic models – computationally intensive and difficult to implement – can separate different tissues of the head and account for the convoluted geometry of the brain and the significant inter-individual variability. In real-life applications, if the assumptions of the statistical, anatomical or functional properties of the signal and the volume in which it is generated are meaningful, a true three-dimensional tomographic representation of sources of brain electrical activity is possible in spite of the ‘ill-posed’ nature of the inverse problem (Michel et al., 2004). The techniques used to achieve this are now referred to as electrical source imaging (ESI) or magnetic source imaging (MSI). The first issue to influence reconstruction accuracy is spatial sampling, i.e. the number of EEG electrodes. It has been shown that this relationship is not linear, reaching a plateau at about 128 electrodes, provided spatial distribution is uniform. The second factor is related to the different properties of the source localization strategies used with respect to the hypothesized source configuration.

The value of magnetoencephalography to guide electrode implantation in epilepsy

Purpose: To investigate if magnetoencephalography (MEG) can identify implantation sites for intracranial recordings (IR). Method: Two groups of 12 patients assessed for surgery with IR with and without MEG were compared (MEG and control groups). In the control group, non-invasive presurgical assessment without MEG suggested clear hypotheses for implantation. In the MEG group, non-invasive assessment was inconclusive, and MEG was used to identify implantation sites. Both groups were matched for implantation type. The success of implantation was defined by findings in IR: a) Focal seizure onset; b)Unilateral focal abnormal responses to single pulse electrical stimulation(SPES); and c) Concordance between a) and b). Results: In all MEG patients, at least one virtual MEG electrode generated suitable hypotheses for the location of implantations. The proportion of patients showing focal seizure onset restricted to one hemisphere was similar in control and MEG groups (6/12 vs. 11/12, Fisher’s exact test,p = 0.0686). The proportion of patients showing unilateral responses to SPES was lower in the control than in the MEG group (7/12 vs. 12/12,p = 0.0373). Conclusion: The MEG group showed similar or higher incidence of successful implantations than controls.

The functional neuroanatomy of auditory sensory gating and its behavioural implications

Auditory sensory gating (ASG) is the ability in individuals to suppress incoming irrelevant sensory input, indexed by evoked response to paired auditory stimuli. ASG is impaired in psychopathology such as schizophrenia, in which it has been proposed as putative endophenotype. This study aims to characterise electrophysiological properties of the phenomenon using MEG in time and frequency domains as well as to localise putative networks involved in the process at both sensor and source level. We also investigated the relationship between ASG measures and personality profiles in healthy participants in the light of its candidate endophenotype role in psychiatric disorders. Auditory evoked magnetic fields were recorded in twenty seven healthy participants by P50 ‘paired-click’ paradigm presented in pairs (conditioning stimulus S1- testing stimulus S2) at 80dB, separated by 250msec with inter trial interval of 7-10 seconds. Gating ratio in healthy adults ranged from 0.5 to 0.8 suggesting dimensional nature of P50 ASG. The brain regions active during this process were bilateral superior temporal gyrus (STG) and bilateral inferior frontal gyrus (IFG); activation was significantly stronger in IFG during S2 as compared to S1 (at p<0.05). Measures of effective connectivity between these regions using DCM modelling revealed the role of frontal cortex in modulating ASG as suggested by intracranial studies, indicating major role of inhibitory interneuron connections. Findings from this study identified a unique event-related oscillatory pattern for P50 ASG with alpha (STG)-beta (IFG) desynchronization and increase in cortical oscillatory gamma power (IFG) during S2 condition as compared to S1. These findings show that the main generator for P50 response is within temporal lobe and that inhibitory interneurons and gamma oscillations in the frontal cortex contributes substantially towards sensory gating. Our findings also show that ASG is a predictor of personality profiles (introvert vs extrovert dimension).