Chronic administration of methylphenidate produces neurophysiological and behavioral sensitization.

The electrophysiological properties of acute and chronic methylphenidate (MPD) on neurons of the prefrontal cortex (PFC) and caudate nucleus (CN) have not been studied in awake, freely behaving animals. The present study was designed to investigate the dose-response effects of MPD on sensory evoked potentials recorded from the PFC and CN in freely behaving rats previously implanted with permanent electrodes, as well as their behavioral (locomotor) activities. On experimental day 1, locomotor behavior of rats was recorded for 2 h post-saline injection, and sensory evoked field potentials were recorded before and after saline and 0.6, 2.5, and 10 mg/kg, i.p., MPD administration. Animals were injected for the next five days with daily 2.5 mg/kg MPD to elicit behavioral sensitization. Locomotor recording was resumed on experimental days 2 and 6 after the MPD maintenance dose followed by 3 days of washout. On experimental day 10, rats were connected again to the electrophysiological recording system and rechallenged with saline and the identical MPD doses as on experimental day 1. On experimental day 11, rat's locomotor recording was resumed before and after 2.5 mg/kg MPD administration. Behavioral results showed that repeated administration of MPD induced behavioral sensitization. Challenge doses (0.6, 2.5, and 10.0 mg/kg) of MPD on experimental day 1 elicited dose-response attenuation in the response amplitude of the average sensory evoked field potential components recorded from the PFC and CN. Chronic MPD administration resulted in attenuation of the PFC's baseline recorded on experimental day 10, while the same treatment did not modulate the baseline recorded from the CN. Treatment of MPD on experimental day 10 resulted in further decrease of the average sensory evoked response compared to that obtained on experimental day 1. This observation of further decrease in the electrophysiological responses after chronic administration of MPD suggests that the sensory evoked responses on experimental day 10 represent neurophysiological sensitization. Moreover, two different response patterns were obtained from PFC and CN following chronic methylphenidate administration. In PFC, the baseline and effect of methylphenidate expressed electrophysiological sensitization on experimental day 10, while recording from CN did not exhibit any electrophysiological sensitization.

Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1.

Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have shown that transgenic mice expressing R192Q or S218L FHM1 mutations have increased SD frequency and propagation speed; enhanced corticostriatal propagation; and, similar to the human FHM1 phenotype, more severe and prolonged post-SD neurological deficits. The susceptibility to SD and neurological deficits is affected by allele dosage and is higher in S218L than R192Q mutants. Further, female S218L and R192Q mutant mice were more susceptible to SD and neurological deficits than males. This sex difference was abrogated by ovariectomy and senescence and was partially restored by estrogen replacement, implicating ovarian hormones in the observed sex differences in humans with FHM1. These findings demonstrate that genetic and hormonal factors modulate susceptibility to SD and neurological deficits in FHM1 mutant mice, providing a potential mechanism for the phenotypic diversity of human migraine and aura.

Minimized extracorporeal circulation does not impair cognitive brain function after coronary artery bypass grafting

OBJECTIVES Objective evaluation of the impact of minimized extracorporeal circulation (MECC) on perioperative cognitive brain function in coronary artery bypass grafting (CABG) by electroencephalogram P300 wave event-related potentials and number connection test (NCT) as metrics of cognitive function. METHODS Cognitive brain function was assessed in 31 patients in 2013 with a mean age of 65 years [standard deviation (SD) 10] undergoing CABG by the use of MECC with P300 auditory evoked potentials (peak latencies in milliseconds) directly prior to intervention, 7 days after and 3 months later. Number connection test, serving as method of control, was performed simultaneously in all patients. RESULTS Seven days following CABG, cognitive P300 evoked potentials were comparable with preoperative baseline values [vertex (Cz) 376 (SD 11) ms vs 378 (18) ms, P = 0.39; frontal (Fz) 377 (11) vs 379 (21) ms, P = 0.53]. Cognitive brain function at 3 months was compared with baseline values [(Cz) 376 (11) ms vs 371 (14 ms) P = 0.09; (Fz) 377 (11) ms vs 371 (15) ms, P = 0.04]. Between the first postoperative measurement and 3 months later, significant improvement was observed [(Cz) 378 (18) ms vs 371 (14) ms, P = 0.03; (Fz) 379 (21) vs 371 (15) ms, P = 0.02]. Similar clearly corresponding patterns could be obtained via the number connection test. Results could be confirmed in repeated measures analysis of variance for Cz (P = 0.05) and (Fz) results (P = 0.04). CONCLUSIONS MECC does not adversely affect cognitive brain function after CABG. Additionally, these patients experience a substantial significant cognitive improvement after 3 months, evidentiary proving that the concept of MECC ensures safety and outcome in terms of brain function.

Minimized Extracorporeal Circulation does not impair cognitive brain function after coronary artery bypass grafting

Gebiet: Chirurgie Abstract: Minimized Extracorporeal Circulation does not impair cognitive brain function after coronary artery bypass grafting – – Objectives – Objective evaluation of the impact of minimized extracorporeal circulation (MECC) on perioperative cognitive brain function in coronary bypass grafting (CABG) by Electroencephalogram (EEG) P 300 wave event related potentials (ERP) and number connection test ( NCT) as metrics of cognitive function. – – Methods – Cognitive brain function was assessed in 31 patients with a mean age of 65y (Standard Deviation/SD 10) undergoing coronary artery bypass grafting (CABG) by the use of MECC with P300 auditory evoked potentials (peak latencies in milliseconds [ms]) directly prior to intervention, 7 days after and 3 month later. Number connection test (NCT), serving as method of control, was performed simultaneously in all patients. – – Results – Seven days following CABG, cognitive P300 evoked potentials were comparable to preoperative baseline values (vertex [Cz] 376 (SD 11) ms vs. 378 (18) ms, p=0.39, frontal [Fz] 377 (11) vs. 379 (21) ms, p=0.53). Cognitive brain function showed at 3 months compared to baseline values ([Cz] 376 (11) ms vs. 371 (14 ms) p=0.09, [Fz] 377 (11) ms vs. 371 (15) ms, p=0.04. Between the first postoperative measurement and 3 months later, significant improvement was observed ([Cz] 378 (18) ms vs. 371 (14) ms, p=0.03, [Fz] 379 (21) vs. 371 (15) ms, p=0.02). Similar clearly corresponding patterns could be obtained via number connection test. Results could be confirmed in repeated measures analysis of variance for Cz (p = 0.05) and (Fz) results (p = 0.04). – – Conclusions

Balanced bilinguals favor lexical processing in their opaque language and conversion system in their shallow language

Referred to as orthographic depth, the degree of consistency of grapheme/phoneme correspondences varies across languages from high in shallow orthographies to low in deep orthographies. The present study investigates the impact of orthographic depth on reading route by analyzing evoked potentials to words in a deep (French) and shallow (German) language presented to highly proficient bilinguals. ERP analyses to German and French words revealed significant topographic modulations 240-280ms post-stimulus onset, indicative of distinct brain networks engaged in reading over this time window. Source estimations revealed that these effects stemmed from modulations of left insular, inferior frontal and dorsolateral regions (German>French) previously associated to phonological processing. Our results show that reading in a shallow language was associated to a stronger engagement of phonological pathways than reading in a deep language. Thus, the lexical pathways favored in word reading are reinforced by phonological networks more strongly in the shallow than deep orthography.

Prevention of ischemic complications during aneurysm surgery

Ischemic complications during aneurysm surgery are a frequent cause of postoperative infarctions and new neurological deficits. In this article, we discuss imaging and neurophysiological tools that may help the surgeon to detect intraoperative ischemia. The strength of intraoperative digital subtraction angiography (DSA) is the full view of the arterial and venous vessel. DSA is the gold standard in complex and giant aneurysms, but due to certain disadvantages, it cannot be considered standard of care. Microvascular Doppler sonography is probably the fastest diagnostic tool and can quickly aid diagnosis of large vessel occlusions. Intraoperative indocyanine green videoangiography is the best tool to assess flow in perforating and larger arteries, as well as occlusion of the aneurysm sac. Intraoperative neurophysiological monitoring with somatosensory and motor evoked potentials indirectly measures blood flow by recording neuronal function. It covers all causes of intraoperative ischemia, provided that ischemia occurs in the brain areas under surveillance. However, every method has advantages and disadvantages. No single method is superior to the others in every aspect. Therefore, it is very important for the neurosurgeon to know the strengths and weaknesses of each tool in order to have them available, to know how to use them for each individual situation, and to be ready to apply them within the time window for reversible cerebral ischemia.

Phenotype of arylsulfatase A-deficient mice: Relationship to human metachromatic leukodystrophy

Metachromatic leukodystrophy is a lysosomal sphingolipid storage disorder caused by the deficiency of arylsulfatase A. The disease is characterized by progressive demyelination, causing various neurologic symptoms. Since no naturally occurring animal model of the disease is available, we have generated arylsulfatase A-deficient mice. Deficient animals store the sphingolipid cerebroside-3-sulfate in various neuronal and nonneuronal tissues. The storage pattern is comparable to that of affected humans, but gross defects of white matter were not observed up to the age of 2 years. A reduction of axonal cross-sectional area and an astrogliosis were observed in 1-year-old mice; activation of microglia started at 1 year and was generalized at 2 years. Purkinje cell dendrites show an altered morphology. In the acoustic ganglion numbers of neurons and myelinated fibers are severely decreased, which is accompanied by a loss of brainstem auditory-evoked potentials. Neurologic examination reveals significant impairment of neuromotor coordination.

Intracortical and corticothalamic coherency of fast spontaneous oscillations.

We report that fast (mainly 30- to 40-Hz) coherent electric field oscillations appear spontaneously during brain activation, as expressed by electroencephalogram (EEG) rhythms, and they outlast the stimulation of mesopontine cholinergic nuclei in acutely prepared cats. The fast oscillations also appear during the sleep-like EEG patterns of ketamine/xylazine anesthesia, but they are selectively suppressed during the prolonged phase of the slow (<1-Hz) sleep oscillation that is associated with hyperpolarization of cortical neurons. The fast (30- to 40-Hz) rhythms are synchronized intracortically within vertical columns, among closely located cortical foci, and through reciprocal corticothalamic networks. The fast oscillations do not reverse throughout the depth of the cortex. This aspect stands in contrast with the conventional depth profile of evoked potentials and slow sleep oscillations that display opposite polarity at the surface and midlayers. Current-source-density analyses reveal that the fast oscillations are associated with alternating microsinks and microsources across the cortex, while the evoked potentials and the slow oscillation display a massive current sink in midlayers, confined by two sources in superficial and deep layers. The synchronization of fast rhythms and their high amplitudes indicate that the term "EEG desynchronization," used to designate brain-aroused states, is incorrect and should be replaced with the original term, "EEG activation" [Moruzzi, G. & Magoun, H.W. (1949) Electroencephalogr. Clin. Neurophysiol. 1, 455-473].

Caracterização do potencial evocado auditivo cortical P1-N1-P2 em crianças com estimulação bimodal

Introdução: O implante coclear (IC) amplamente aceito como forma de intervenção e (re) habilitação nas perdas auditivas severas e profundas nas diversas faixas etárias. Contudo observa-se no usuário do IC unilateral queixas como localização e compreensão sonora em meio ao ruído, gerado pelo padrão anormal de estimulação sensorial. A fim de fornecer os benefícios da audição binaural, é preconizado a estimulação bilateral, seja por meio do IC bilateral ou com a adaptação de um aparelho de amplificação sonora individual (AASI) contralateralmente ao IC. Esta última condição é referida como estimulação bimodal, quando temos, concomitantemente dois modos de estimulação: Elétrica (IC) e acústica (AASI). Não há dados suficientes na literatura voltados à população infantil que esclareça ou demonstre o desenvolvimento do córtex auditivo na audição bimodal. Ressalta-se que não foram encontrados estudos em crianças. Objetivo: Caracterizar o PEAC complexo P1, N1 P2 em usuários da estimulação bimodal e verificar se há correlação com testes de percepção de fala. Metodologia: Estudo descritivo de séries de casos, com a realização do PEAC em cinco crianças usuárias da estimulação bimodal, a partir da metodologia proposta por Ventura (2008) utilizando o sistema Smart EP USB Jr da Intelligent Hearing Systems. Foi utilizado o som de fala /da/, apresentado em campo livre. O exame será realizado em três situações: Somente IC, IC e AASI e somente AASI. A análise dos dados dos potenciais corticais foi realizada após a marcação da presença ou ausência dos componentes do complexo P1-N1-P2 por dois juízes com experiência em potenciais evocados. Resultados: Foi obtida a captação do PEAC em todas as crianças em todas as situações de teste, além do que foi possível observar a correlação destes com os testes de percepção auditiva da fala. Foi possível verificar que o registro dos PEAC é um procedimento viável para a avaliação da criança com estimulação bimodal, porém, ainda não há dados suficientes quanto a utilização deste para a avaliação e indicação do IC bilateral.

O efeito da estimulação top-down e bottom-up no potencial evocado auditivo de tronco encefálico com estímulo complexo

Introdução: Crianças com transtorno fonológico (TF) apresentam dificuldade na percepção de fala, em processar estímulos acústicos quando apresentados de forma rápida e em sequência. A percepção dos sons complexos da fala, dependem da integridade no processo de codificação analisado pelo Sistema Nervoso Auditivo. Por meio do Potencial Evocado Auditivo de Tronco Encefálico com estímulo complexo (PEATEc) é possível investigar a representação neural dos sons em níveis corticais e obter informações diretas sobre como a estrutura do som da sílaba falada é codificada no sistema auditivo. Porém, acredita-se que esse potencial sofre interferências tanto de processos bottom-up quanto top-down, o que não se sabe é quanto e como cada um desses processos modifica as respostas do PEATEc. Uma das formas de investigar a real influência dos aspectos top-down e bottom-up nos resultados do PEATEc é estimulando separadamente esses dois processos por meio do treinamento auditivo e da terapia fonoaudiológica. Objetivo: Verificar o impacto da estimulação sensorial (processamento bottom-up) e cognitiva (processamento top-down), separadamente, nos diferentes domínios da resposta eletrofisiológica do PEATEc. Método: Participaram deste estudo 11 crianças diagnosticadas com TF, com idades entre 7 e 10:11, submetidas a avaliação comportamental e eletrofisiológica e então dividas nos grupos Bottom-up (B-U) (N=6) e Top-down T-D (N=5). A estimulação bottom-up foi voltada ao treinamento das habilidades sensoriais, através de softwares de computador. A estimulação top-down foi realizada por meio de tarefas para estimular as habilidades cognitiva por meio do Programa de Estimulação Fonoaudiológica (PEF). Ambas as estimulações foram aplicadas uma vez por semana, num período de aproximadamente 45 minutos por 12 semanas. Resultados: O grupo B-U apresentou melhoras em relação aos domínios onset e harmônicos e no valor da pontuação do escore após ser submetido à estimulação bottom-up. Por sua vez, após serem submetidos à estimulação top-down, o grupo T-D apresentou melhoras em relação aos domínios onset, espectro-temporal, fronteiras do envelope e harmônicos e para os valores da pontuação do escore. Conclusão: Diante dos resultados obtidos neste estudo, foi possível observar que a estimulação sensorial (processamento bottom-up) e a estimulação cognitiva (processamento top-down) mostraram impactar de forma diferente a resposta eletrofisiológica do PEATEc

Automated Analysis of the Auditory Brainstem Response Using Derivative Estimation Wavelets

In this paper, we describe an algorithm that automatically detects and labels peaks I - VII of the normal, suprathreshold auditory brainstem response (ABR). The algorithm proceeds in three stages, with the option of a fourth: ( 1) all candidate peaks and troughs in the ABR waveform are identified using zero crossings of the first derivative, ( 2) peaks I - VII are identified from these candidate peaks based on their latency and morphology, ( 3) if required, peaks II and IV are identified as points of inflection using zero crossings of the second derivative and ( 4) interpeak troughs are identified before peak latencies and amplitudes are measured. The performance of the algorithm was estimated on a set of 240 normal ABR waveforms recorded using a stimulus intensity of 90 dBnHL. When compared to an expert audiologist, the algorithm correctly identified the major ABR peaks ( I, III and V) in 96 - 98% of the waveforms and the minor ABR peaks ( II, IV, VI and VII) in 45 - 83% of waveforms. Whilst peak II was correctly identified in only 83% and peak IV in 77% of waveforms, it was shown that 5% of the peak II identifications and 31% of the peak IV identifications came as a direct result of allowing these peaks to be found as points of inflection. Copyright (C) 2005 S. Karger AG, Basel.

The relationship between the auditory brain-stem response and its reconstructed waveforms following discrete wavelet transformation

Objective: To examine the relationship between the auditory brain-stem response (ABR) and its reconstructed waveforms following discrete wavelet transformation (DWT), and to comment on the resulting implications for ABR DWT time-frequency analysis. Methods: ABR waveforms were recorded from 120 normal hearing subjects at 90, 70, 50, 30, 10 and 0 dBnHL, decomposed using a 6 level discrete wavelet transformation (DWT), and reconstructed at individual wavelet scales (frequency ranges) A6, D6, D5 and D4. These waveforms were then compared for general correlations, and for patterns of change due to stimulus level, and subject age, gender and test ear. Results: The reconstructed ABR DWT waveforms showed 3 primary components: a large-amplitude waveform in the low-frequency A6 scale (0-266.6 Hz) with its single peak corresponding in latency with ABR waves III and V; a mid-amplitude waveform in the mid-frequency D6 scale (266.6-533.3 Hz) with its first 5 waves corresponding in latency to ABR waves 1, 111, V, VI and VII; and a small-amplitude, multiple-peaked waveform in the high-frequency D5 scale (533.3-1066.6 Hz) with its first 7 waves corresponding in latency to ABR waves 1, 11, 111, IV, V, VI and VII. Comparisons between ABR waves 1, 111 and V and their corresponding reconstructed ABR DWT waves showed strong correlations and similar, reliable, and statistically robust changes due to stimulus level and subject age, gender and test ear groupings. Limiting these findings, however, was the unexplained absence of a small number (2%, or 117/6720) of reconstructed ABR DWT waves, despite their corresponding ABR waves being present. Conclusions: Reconstructed ABR DWT waveforms can be used as valid time-frequency representations of the normal ABR, but with some limitations. In particular, the unexplained absence of a small number of reconstructed ABR DWT waves in some subjects, probably resulting from 'shift invariance' inherent to the DWT process, needs to be addressed. Significance: This is the first report of the relationship between the ABR and its reconstructed ABR DWT waveforms in a large normative sample. (C) 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

On the dual structure of the auditory brainstem response in dogs

Objective: To use the over-complete discrete wavelet transform (OCDWT) to further examine the dual structure of auditory brainstem response (ABR) in the dog. Methods: ABR waveforms recorded from 20 adult dogs at supra-threshold (90 and 70 dBnHL) and threshold (0-15 dBSL) levels were decomposed using a six level OCDWT and reconstructed at individual scales (frequency ranges) A6 (0-391 Hz), D6 (391-781 Hz), and D5 (781-1563 Hz). Results: At supra-threshold stimulus levels, the A6 scale (0-391 Hz) showed a large amplitude waveform with its prominent wave corresponding in latency with ABR waves II/III; the D6 scale (391-781 Hz) showed a small amplitude waveform with its first four waves corresponding in latency to ABR waves I, II/III, V, and VI; and the D5 scale (781-1563 Hz) showed a large amplitude, multiple peaked waveform with its first six waves corresponding in latency to ABR waves I, II, III, IV, V, and VI. At threshold stimulus levels (0-15 dBSL), the A6 scale (0-391 Hz) continued to show a relatively large amplitude waveform, but both the D6 and D5 scales (391781 and 781-1563 Hz, respectively) now showed relatively small amplitude waveforms. Conclusions: A dual structure exists within the ABR of the dog, but its relative structure changes with stimulus level. Significance: The ABR in the dog differs from that in the human both in the relative contributions made by its different frequency components, and the way these components change with stimulus level. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.