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Tobulėjanti pavienių nervinių ląstelių parametrų matavimo technika suteikia milžiniškus kiekius informacijos. Kad apdoroti tokias gausias duomenų apimtis, būtina taikyti sudėtingus duomenų apdorojimo metodus pasitelkiant galingas skaičiavimo priemones ir algoritmus. Šio darbo tikslas - nustatyti optimalią interneuronų tiesioginio sklidimo slopinančių sinapsių mokymosi taisyklę, kuri leistų išsaugoti įėjimo signalų aukštą laikinę skiriamąją gebą, kuomet žadinančių sinapsių svorių koeficientai keičiami pagal nuo įėjimų laiko priklausančią sinapsių plastiškumo (angl. spike-timing dependent synaptic plasticity, (STDP)) taisyklę. Vykstant žadinančių sinapsių ilgalaikei potenciacijai, įėjimų signalų integravimo langas išauga. Siekiant išsaugoti integravimo langą siaurą, reikalingas ir tiesioginio sklidimo slopinančių sinapsių plastiškumas. / Plentiful results are coming from advances in single cell recordings. All these data have to be treated in complex ways implementing powerful computational techniques. Goal of this study was to identify the optimal learning rule of feedforward inhibitory interneurons that preserves high temporal precision of input discrimination while excitatory synapses undergo synaptic modifications according to the asymmetric spike-timing dependent plasticity rule. Temporal integration of inputs is enhanced if excitatory synapses undergo long term potentiation. To preserve narrow temporal integration window, feedforward inhibitory synapses must be plastic as well.

INTRODUÇÃO: O ultrassom transcraniano colorido (UTC) é um eficiente método para avaliação da circulação intracraniana e do fluxo sanguíneo cerebral em diversas condições clínicas incluindo o acidente vascular isquêmico agudo. Uma das principais limitação deste método reside na incapacidade de insonação intracraniana adequada através da janela transtemporal em até 20% dos pacientes. Neste contexto, surge a necessidade do desenvolvimento de uma metodologia estruturada que permitisse caracterizar a qualidade da janela transtemporal de forma mais detalhada e objetiva. No presente estudo, objetivamos: determinar a frequência de visualização dos principais marcos anatômicos pela insonação com UCT utilizando-se a janela transtemporal em pacientes com AVCI agudo; classificar o grau de dificuldade na visualização da primeira porção da artéria cerebral média (ACM) ipsilateral ao lado insonado; determinar a influência da idade, sexo, etnia no na qualidade da janela transtemporal pelo UTC. METODOLOGIA: Avaliamos prospectivamente todos os pacientes adultos, consecutivos, com o primeiro e único episódio de acidente vascular isquêmico no período de julho de 2014 a janeiro de 2015 com um exame de UTC (modo B e Doppler colorido). Dois examinadores classificaram a qualidade da janela transtemporal pelo modo B utilizando uma escore baseado na qualidade da visualização de referencias anatômicas (osso temporal contralateral, asa menor do esfenoide ipsilateral e mesencéfalo) variando de 0 (janela ausente) a 9 (excelente janela). Os preditores independentes de uma boa visualização do sinal da ACM ao UTC foram identificados através de um modelo de regressão logística multivariada selecionado pelo método backward. A acurácia do escore do modo B foi avaliada através dos parâmetro de sensibilidade, especificidade e estatística C (curva ROC). RESULTADOS: entre os 200 paciente incluídos no estudo (55% do sexo masculino e com idade média de 61,17 ± 15,22 anos) o osso temporal contralateral não foi visualizado em 48,5% dos casos, o mesencéfalo foi visualizado em 65% e a asa menor do esfenoide foi visualizada em 66%. A porção proximal da artéria cerebral media (M1) foi visualizada em 62% dos casos. Na análise multivariada, a idade (OR: 0,95; IC95%:0,92 - 0,99; p=0,011) e a pontuação no escore do modo B (OR: 2,97; IC95%:1,93- 4,55; p<0,001) foram preditores independentes de visualização do sinal da ACM ao UTC. A pontuação no escore do modo B mostrou um preditor acudado para subsequente visualização da artéria cerebral médica pelo Doppler colorido com uma área sob a curva ROC de 0,896 (p<0,001). O escore de 2 apresentou uma sensibilidade e especificidade de 80 e 87% para este fim, respectivamente. CONCLUSÃO: O escore do modo B baseado na visualização de referência anatômicas intracranianas pelo modo B do UTC é uma ferramenta útil com boa acurácia para capacidade de visualização do fluxo da artéria cerebral media ipsilateral ao UTC. Este escore permite descrever de forma mais detalhada a qualidade de janela transtemporal ao UTC, em suas diferentes aplicações. / INTRODUCTION: Transcranial Color-Coded Sonography (TCCS) is an widely-used method to assess the intracranial circulation and cerebral blood flow in several clinical conditions including acute ischemic stroke. One of the main limitations of this technic is related to the quality of the transtemporal window, which is poor in about 20% of cases. In this context, it is important to develop an structured approach to better define the quality of the transtemporal window. In this study we aimed to evaluate how frequently the main anatomic landmarks can be adequately visualized by TCCS in acute stroke patients using the transtemporal window; to assess the proportion of patients in which the ipsilateral middle cerebral artery of visualized by TCCS; and to identify the main predictors of a poor transtemporal window on TCCS. METHODS: We examined 200 consecutive acute ischemic stroke (AIS) patients, from July 2014 to January 2015. All patients underwent prospective TCCS evaluation. Visualization of the contralateral temporal bone (CTB), midbrain (MB) and lesser sphenoid wing (LSW) was scored on B-mode images. The resulting B-Mode Score varied from 0 (poor visualization) to 9 (perfect window). A multivariate logistic regression model (backward selection) was used to identify the independent predictors of visualization of the MCA signal by TCCS. The relationship between these B-Mode Score and visualization of the proximal portion of the ipsilateral MCA was assessed in terms of sensitivity, specificity, ROC curve and C statistics. RESULTS: Among 200 AIS patients (male 55%; mean age, 61.17 ± 15,22 years), CTB was invisible\' in 48,5%, the MB was visualized in 65%; and the LSW was seen in 66%. The M1 segment of the MCA was detected in 62% of cases. After multivariate analysis, age (OR: 0.95; 95CI%:0.92-0.99; p=0.011) and B-Mode score (OR: 2.97;95CI%:1.93-4.55; p<0.001) were independente predictors of visualization of MCA signal by TCCS. The BMode Score show good accuracy for the prediction of MCA visualization with an AUC of 0,896. (p<0,001) on the respective ROC curve. A cut-off of 2 on the B-mode score showed a sensitivity of 80% and a specificity of 87% for adequate MCA visualization by TCCS. CONCLUSION: The B-mode Score, which is based on the visualization of intracranial anatomical landmarks on B-Mode, appears to be a reliable way to characterize the quality of the transtemporal window, with a good accuracy as predictor for visualization of the ipsilateral MCA on TCCS. This score may allow more detailed characterization of the transtemporal window for different clinical applications of TCCS.

The human central auditory system can automatically extract abstract regularities from a variant auditory input. To this end, temporarily separated events need to be related. This study tested whether the timing between events, falling either within or outside the temporal window of integration (~350 ms), impacts the extraction of abstract feature relations. We utilized tone pairs for which tones within but not across pairs revealed a constant pitch relation (e.g., pitch of second tone of a pair higher than pitch of first tone, while absolute pitch values varied across pairs). We measured the mismatch negativity (MMN; the brain’s error signal to auditory regularity violations) to second tones that rarely violated the pitch relation (e.g., pitch of second tone lower). A Short condition in which tone duration (90 ms) and stimulus onset asynchrony between the tones of a pair were short (110 ms) was compared to two conditions, where this onset asynchrony was long (510 ms). In the Long Gap condition, the tone durations were identical to Short (90 ms), but the silent interval was prolonged by 400 ms. In Long Tone, the duration of the first tone was prolonged by 400 ms, while the silent interval was comparable to Short (20 ms). Results show a frontocentral MMN of comparable amplitude in all conditions. Thus, abstract pitch relations can be extracted even when the within-pair timing exceeds the integration period. Source analyses indicate MMN generators in the supratemporal cortex. Interestingly, they were located more anterior in Long Gap than in Short and Long Tone. Moreover, frontal generator activity was found for Long Gap and Long Tone. Thus, the way in which the system automatically registers irregular abstract pitch relations depends on the timing of the events to be linked. Pending that the current MMN data mirror established abstract rule representations coding the regular pitch relation, neural processes building these templates vary with timing.

INTRODUÇÃO: O ultrassom transcraniano colorido (UTC) é um eficiente método para avaliação da circulação intracraniana e do fluxo sanguíneo cerebral em diversas condições clínicas incluindo o acidente vascular isquêmico agudo. Uma das principais limitação deste método reside na incapacidade de insonação intracraniana adequada através da janela transtemporal em até 20% dos pacientes. Neste contexto, surge a necessidade do desenvolvimento de uma metodologia estruturada que permitisse caracterizar a qualidade da janela transtemporal de forma mais detalhada e objetiva. No presente estudo, objetivamos: determinar a frequência de visualização dos principais marcos anatômicos pela insonação com UCT utilizando-se a janela transtemporal em pacientes com AVCI agudo; classificar o grau de dificuldade na visualização da primeira porção da artéria cerebral média (ACM) ipsilateral ao lado insonado; determinar a influência da idade, sexo, etnia no na qualidade da janela transtemporal pelo UTC. METODOLOGIA: Avaliamos prospectivamente todos os pacientes adultos, consecutivos, com o primeiro e único episódio de acidente vascular isquêmico no período de julho de 2014 a janeiro de 2015 com um exame de UTC (modo B e Doppler colorido). Dois examinadores classificaram a qualidade da janela transtemporal pelo modo B utilizando uma escore baseado na qualidade da visualização de referencias anatômicas (osso temporal contralateral, asa menor do esfenoide ipsilateral e mesencéfalo) variando de 0 (janela ausente) a 9 (excelente janela). Os preditores independentes de uma boa visualização do sinal da ACM ao UTC foram identificados através de um modelo de regressão logística multivariada selecionado pelo método backward. A acurácia do escore do modo B foi avaliada através dos parâmetro de sensibilidade, especificidade e estatística C (curva ROC). RESULTADOS: entre os 200 paciente incluídos no estudo (55% do sexo masculino e com idade média de 61,17 ± 15,22 anos) o osso temporal contralateral não foi visualizado em 48,5% dos casos, o mesencéfalo foi visualizado em 65% e a asa menor do esfenoide foi visualizada em 66%. A porção proximal da artéria cerebral media (M1) foi visualizada em 62% dos casos. Na análise multivariada, a idade (OR: 0,95; IC95%:0,92 - 0,99; p=0,011) e a pontuação no escore do modo B (OR: 2,97; IC95%:1,93- 4,55; p<0,001) foram preditores independentes de visualização do sinal da ACM ao UTC. A pontuação no escore do modo B mostrou um preditor acudado para subsequente visualização da artéria cerebral médica pelo Doppler colorido com uma área sob a curva ROC de 0,896 (p<0,001). O escore de 2 apresentou uma sensibilidade e especificidade de 80 e 87% para este fim, respectivamente. CONCLUSÃO: O escore do modo B baseado na visualização de referência anatômicas intracranianas pelo modo B do UTC é uma ferramenta útil com boa acurácia para capacidade de visualização do fluxo da artéria cerebral media ipsilateral ao UTC. Este escore permite descrever de forma mais detalhada a qualidade de janela transtemporal ao UTC, em suas diferentes aplicações. / INTRODUCTION: Transcranial Color-Coded Sonography (TCCS) is an widely-used method to assess the intracranial circulation and cerebral blood flow in several clinical conditions including acute ischemic stroke. One of the main limitations of this technic is related to the quality of the transtemporal window, which is poor in about 20% of cases. In this context, it is important to develop an structured approach to better define the quality of the transtemporal window. In this study we aimed to evaluate how frequently the main anatomic landmarks can be adequately visualized by TCCS in acute stroke patients using the transtemporal window; to assess the proportion of patients in which the ipsilateral middle cerebral artery of visualized by TCCS; and to identify the main predictors of a poor transtemporal window on TCCS. METHODS: We examined 200 consecutive acute ischemic stroke (AIS) patients, from July 2014 to January 2015. All patients underwent prospective TCCS evaluation. Visualization of the contralateral temporal bone (CTB), midbrain (MB) and lesser sphenoid wing (LSW) was scored on B-mode images. The resulting B-Mode Score varied from 0 (poor visualization) to 9 (perfect window). A multivariate logistic regression model (backward selection) was used to identify the independent predictors of visualization of the MCA signal by TCCS. The relationship between these B-Mode Score and visualization of the proximal portion of the ipsilateral MCA was assessed in terms of sensitivity, specificity, ROC curve and C statistics. RESULTS: Among 200 AIS patients (male 55%; mean age, 61.17 ± 15,22 years), CTB was invisible\' in 48,5%, the MB was visualized in 65%; and the LSW was seen in 66%. The M1 segment of the MCA was detected in 62% of cases. After multivariate analysis, age (OR: 0.95; 95CI%:0.92-0.99; p=0.011) and B-Mode score (OR: 2.97;95CI%:1.93-4.55; p<0.001) were independente predictors of visualization of MCA signal by TCCS. The BMode Score show good accuracy for the prediction of MCA visualization with an AUC of 0,896. (p<0,001) on the respective ROC curve. A cut-off of 2 on the B-mode score showed a sensitivity of 80% and a specificity of 87% for adequate MCA visualization by TCCS. CONCLUSION: The B-mode Score, which is based on the visualization of intracranial anatomical landmarks on B-Mode, appears to be a reliable way to characterize the quality of the transtemporal window, with a good accuracy as predictor for visualization of the ipsilateral MCA on TCCS. This score may allow more detailed characterization of the transtemporal window for different clinical applications of TCCS.

The human central auditory system can automatically extract abstract regularities from a variant auditory input. To this end, temporarily separated events need to be related. This study tested whether the timing between events, falling either within or outside the temporal window of integration (~350 ms), impacts the extraction of abstract feature relations. We utilized tone pairs for which tones within but not across pairs revealed a constant pitch relation (e.g., pitch of second tone of a pair higher than pitch of first tone, while absolute pitch values varied across pairs). We measured the mismatch negativity (MMN; the brain’s error signal to auditory regularity violations) to second tones that rarely violated the pitch relation (e.g., pitch of second tone lower). A Short condition in which tone duration (90 ms) and stimulus onset asynchrony between the tones of a pair were short (110 ms) was compared to two conditions, where this onset asynchrony was long (510 ms). In the Long Gap condition, the tone durations were identical to Short (90 ms), but the silent interval was prolonged by 400 ms. In Long Tone, the duration of the first tone was prolonged by 400 ms, while the silent interval was comparable to Short (20 ms). Results show a frontocentral MMN of comparable amplitude in all conditions. Thus, abstract pitch relations can be extracted even when the within-pair timing exceeds the integration period. Source analyses indicate MMN generators in the supratemporal cortex. Interestingly, they were located more anterior in Long Gap than in Short and Long Tone. Moreover, frontal generator activity was found for Long Gap and Long Tone. Thus, the way in which the system automatically registers irregular abstract pitch relations depends on the timing of the events to be linked. Pending that the current MMN data mirror established abstract rule representations coding the regular pitch relation, neural processes building these templates vary with timing.:Introduction; Materials and methods; Results; Discussion; Conclusion