Exploration of the neural correlates of cerebral palsy for sensorimotor BCI control

Cerebral palsy (CP) includes a broad range of disorders, which can result in impairment of posture and movement control. Brain-computer interfaces (BCIs) have been proposed as assistive devices for individuals with CP. Better understanding of the neural processing underlying motor control in affected individuals could lead to more targeted BCI rehabilitation and treatment options. We have explored well-known neural correlates of movement, including event-related desynchronization (ERD), phase synchrony, and a recently-introduced measure of phase dynamics, in participants with CP and healthy control participants. Although present, significantly less ERD and phase locking were found in the group with CP. Additionally, inter-group differences in phase dynamics were also significant. Taken together these findings suggest that users with CP exhibit lower levels of motor cortex activation during motor imagery, as reflected in lower levels of ongoing mu suppression and less functional connectivity. These differences indicate that development of BCIs for individuals with CP may pose additional challenges beyond those faced in providing BCIs to healthy individuals.

Striatum brain-derived neurotrophic factor levels are decreased in dystrophin-deficient mice

Brain dystrophin is enriched in the postsynaptic densities of pyramidal neurons specialized regions of the subsynaptic cytoskeletal network, which are critical for synaptic transmission and plasticity. Lack of dystrophin in brain structures have been involved with impaired cognitive functions. The brain-derived neurotrophic factor (BDNF) is a regulator of neuronal survival, fast synaptic transmission, and activity-dependent synaptic plasticity. The present study investigated BDNF protein levels by Elisa analysis in prefrontal cortex, cerebellum, hippocampus, striatum and cortex tissues from male dystrophic mdx (n = 5) and normal C57BL10 mouse (n = 5). We observed that the mdx mouse display diminution in BDNF levels in striatum (t = 6.073; df = 6; p = 0.001), while a tendency of decrease in BDNF levels was observed in the prefrontal cortex region (t = 1.962; df = 6; p = 0.096). The cerebellum (t = 1.258; df = 7; p = 0.249), hippocampus (t = 0.631; df = 7; p = 0.548) and cortex (t = 0.572; df = 7; p = 0.586) showed no significant alterations as compared to wt mouse. In conclusion, we demonstrate that only striatum decreased BDNF levels compared with wild-type (wt) mouse, differently to the other areas of the brain. This dystrophin deficiency may be affecting BDNF levels in striatum and contributing, in part, in memory storage and restoring. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

A Substrate Trapping Mutant Form of Striatal-Enriched Protein Tyrosine Phosphatase Prevents Amphetamine-Induced Stereotypies and Long-Term Potentiation in the Striatum

Background: Chronic, intermittent exposure to psychostimulant drugs results in striatal neuroadaptations leading to an increase in an array of behavioral responses on subsequent challenge days. A brain-specific striatal-enriched tyrosine phosphatase (STEP) regulates synaptic strengthening by dephosphorylating and inactivating several key synaptic proteins. This study tests the hypothesis that a substrate-trapping form of STEP will prevent the development of amphetamine-induced stereotypies. Methods: A substrate-trapping STEP protein, TAT-STEP (C-S), was infused into the ventrolateral striatum on each of 5 consecutive exposure days and I hour before amphetamine injection. Animals were challenged to see whether sensitization to the stereotypy-producing effects of amphetamine developed. The same TAT-STEP (C-S) protein was used on acute striatal slices to determine the impact on long-term potentiation and depression. Results: Infusion of TAT-STEP (C-S) blocks the increase of amphetamine-induced stereotypies when given during the 5-day period of sensitization. The TAT-STEP (C-S) has no effect if only infused on the challenge day. Treatment of acute striatal slices with TAT-STEP (C-S) blocks the induction of long-term potentiation and potentates long-term depression. Conclusions: A substrate trapping form of STEP blocks the induction of amphetamine-induced neuroplasticity within the ventrolateral striatum and supports the hypothesis that STEP functions as a tonic break on synaptic strengthening.

The indirect amygdala-dorsal striatum pathway mediates conditioned freezing: Insights on emotional memory networks

The dorsal striatum (DS) is involved in various forms of learning and memory such as procedural learning, habit learning, reward-association and emotional learning. We have previously reported that bilateral DS lesions disrupt tone fear conditioning (TFC), but not contextual fear conditioning (CFC) [Ferreira TL, Moreira KM, Ikeda DC, Bueno OFA, Oliveira MGM (2003) Effects of dorsal striatum lesions in tone fear conditioning and contextual fear conditioning. Brain Res 987:17-24]. To further elucidate the participation of DS in emotional learning, in the present study, we investigated the effects of bilateral pretest (postraining) electrolytic DS lesions on TFC. Given the well-acknowledged role of the amygdala in emotional learning, we also examined a possible cooperation between DS and the amygdala in TFC, by using asymmetrical electrolytic lesions, consisting of a unilateral lesion of the central amygdaloid nucleus (CeA) combined to a contralateral DS lesion. The results show that pre-test bilateral DS lesions disrupt TFC responses, suggesting that DS plays a role in the expression of TFC. More importantly, rats with asymmetrical pre-training lesions were impaired in TFC, but not in CFC tasks. This result was confirmed with muscimol asymmetrical microinjections in DS and CeA, which reversibly inactivate these structures. On the other hand, similar pretest lesions as well as unilateral electrolytic lesions of CeA and DS in the same hemisphere did not affect TFC. Possible anatomical substrates underlying the observed effects are proposed. Overall, the present results underscore that other routes, aside from the well-established CeA projections to the periaqueductal gray, may contribute to the acquisition/consolidation of the freezing response associated to a TFC task. It is suggested that CeA may presumably influence DS processing via a synaptic relay on dopaminergic neurons of the substantia nigra compacta and retrorubral nucleus. The present observations are also in line with other studies showing that TFC and CFC responses are mediated by different anatomical networks. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

Role of glutathione in schizophrenia? The effect of brain glutathione depletion on prepulse inhibition (PPI) in rats and mice

Reductions in brain glutathione (GSH) levels have been reported in schizophrenia. We investigated the effects of brain GSH depletion on prepulse inhibition (PPI), a model of sensorimotor gating which is disrupted in individuals with schizophrenia. It was hypothesized that GSH depletion would lead to disruption of PPI similar to that seen in schizophrenia and enhance the effect of increased dopamine release by amphetamine. Sprague-Dawley rats and C57Bl/6 mice were treated with saline or 2-cyclohexene-1-one (CHX, 75 mg/kg and 120 mg/kg respectively) to deplete brain GSH. 225 minutes later the animals were injected with amphetamine (2.5 mg/kg in rats and 25 mg/kg in mice). Total brain GSH levels were measured using an enzymatic recycling assay. Surprisingly, in rats CHX treatment prevented the disruption of PPI by amphetamine. Thus, while there was the expected disruption of PPI caused by amphetamine on its own (average %PPI reduced from 58 ± 5 to 44 ± 4), in combination with CHX, amphetamine had no significant effect (67 ± 4 vs. 63 ± 3, respectively). In contrast to rats, in mice CHX had no effect on PPI. Thus, amphetamine similarly disrupted PPI after saline (41 ± 5 vs. 28 ± 5) and CHX pretreatment (45 ± 6 vs. 26 ± 5). There were significant 40-63% depletions of GSH in frontal cortex and striatum of CHX-treated rats and mice. These data show that GSH depletion in the brain by CHX treatment did not induce the expected decrease in PPI. Because the levels of GSH depletion in this study were similar to those found in schizophrenia, these results cast doubt on a direct interaction between brain GSH levels and PPI disruption in this illness. In rats, CHX treatment prevented the disruption of PPI caused by amphetamine. We have observed that resting levels of GSH are lower in rats than in mice. It is plausible that some oxidative damage may occur after amphetamine treatment alone, which induces marked release of the electroactive species, dopamine. In mice with their higher levels of GSH (either with or without CHX treatment) and in control rats, this does not cause functional effects. However, in CHX-treated rats GSH levels are reduced to a point where amphetamine-induced dopamine release may cause increased metabolism and lipid peroxidation inducing a decrease in postsynaptic dopamine receptor function and consequently leading to an apparent inhibition of the disruption of PPI. In conclusion, while individuals with schizophrenia show disruption of PPI and reduced brain GSH levels, in rats and mice brain GSH depletion alone does not impact on PPI. In combination with a hyperdopaminergic state, functional effects on PPI regulation were found. These effects warrant further investigation.

Hippeastrum vittatum (L'Hér.) Herbert e hippeastrum striatum (Lam.) Moore : análise química e avaliação biológica dos alcalóides isolados

Este trabalho foi realizado com o objetivo de isolar e identificar os alcalóides presentes nas espécies H. vittatum e H. striatum, analisar a atividade antitumoral, inibidora da enzima acetilcolinesterase, antioxidante dos extratos e alcalóides obtidos, realizar ensaio de toxicidade para o alcalóide montanina, bem como observar sua atividade em pesquisa básica do comportamento em roedores e verificar comparativamente a modulação da montanina e da galantamina sobre a via de sinalização das proteínas quinases pRaf/pMEK/pERK/pCREB. Método: Fitoquímico: As partes aéreas e subterrâneas das espécies coletadas foram maceradas em etanol e processadas em extração ácido-base para a obtenção dos extratos diclorometano e n-BuOH. Os alcalóides isolados foram identificados com a utilização de métodos cromatográficos, espectrométricos e espectroscópicos. Testes in vitro: Atividade antitumoral: Os extratos e alcalóides obtidos foram avaliados em método in vitro, onde se aplicaram células tumorais biopsiadas de humanos. Inibição da enzima acetilcolinesterase: Os compostos isolados, montanina (Hv1 e Hv2), vitatina (Hv4), pancracina (Hv5) e Hv6 de H. vittatum e a galantamina foram testados em ensaio de bioautografia por cromatografia em camada delgada (CCD) com 1-naftil acetato. Atividade antioxidante: Os compostos anteriormente citados foram testados pelo método que utiliza o difenilpicrilhidrazol (DPPH) em CCD. Testes in vivo: Toxicidade da montanina (24 horas): A montanina foi administrada com doses de 10 a 100 mg/kg i.p. em camundongos e a toxicidade observada por 24 horas comparando-se aos grupos controle. A dose letal mediana foi calculada com método dos probitos. Avaliação da atividade central da montanina: Foram realizados experimentos com camundongos machos em Campo Aberto (CA), Nado Forçado (NF), Labirinto em Cruz Elevado (LCE), Indução do Sono por Pentobarbital (ISP) e sobre a consolidação da memória em ratos (esquiva inibitória passiva). Análise bioquímica da via das MAPKs: Aplicou-se metodologia in vitro em homogenatos (fatias hipocampais) tratados com os alcalóides montanina ou galantamina. A obtenção dos resultados ocorreu a partir da realização de eletroforese de alta voltagem e “Western Blot”. Resultados e Conclusões: A partir dos extratos de alcalóides totais de H. vittatum foram isoladas cinco substâncias: (a) Hv1 (montanina – 0,007%) isolado do extrato diclorometano de folhas, (b) Hv2 (montanina – 0,09%), (c) Hv3 (licorina 0,003%) e (d) Hv4 (vitatina – 0,0003%), isolados do extrato diclorometano de bulbos. Do extrato n-BuOH dos bulbos foram isolados o alcalóide Hv5 (pancracina – 0,0025%) e o composto Hv6 (0,0034%). Da espécie H. striatum foi isolado o alcalóide licorina (Hs3) e dois compostos não identificados (Hs1 e Hs3). O alcalóide vitatina demonstrou inibir moderadamente o crescimento das células tumorais com os valores de IC50 ≤ 29 g/ml. A montanina apresentou o maior efeito antiproliferativo entre os produtos testados. Os valores de IC50 foram menores que 1,0 g/ml para as linhagens testadas. Os extratos diclorometano e n-BuOH de H. vittatum foram considerados antiproliferativos para as células tumorais humanas empregadas, com valores de absorvância 25% menores que o controle. Para as atividades inibidoras da enzima acetilcolinesterase e antioxidante, somente o composto Hv6 apresentou ação. A dose letal mediana para a montanina em camundongos machos foi calculada em 64 mg/kg i.p. A montanina não alterou a locomoção e a atividade exploratória de camundongos quando administrada pela via intraperitoneal (i.p.) nas doses de 10 e 30 mg/kg (CA). Na avaliação da atividade central da montanina administrada por via i.p., observamos atividade ansiolítica (0,1; 1,0; 3,0 mg/kg – LCE), antidepressiva (3,0 mg/kg - NF) e tendência para atividade hipnótica (ISP). No paradigma de memória de esquiva inibitória passiva, a montanina não alterou significativamente o comportamento dos ratos wistar, na via de administração e nas doses testadas. Na investigação comparativa da modulação da via de sinalização das MAPKs (envolvidas com a memória) em fatias hipocampais tratadas (ratos), concluiu-se que a montanina e a galantamina aumentam a fosforilação (atividade) das proteínas testadas. Os resultados obtidos para a galantamina sugerem um possível mecanismo de ação que explique bioquimicamente uma de suas ações que contribuem para a melhora da memória em ratos na esquiva inibitória.

Sensorimotor Integration in Dyslexic Children under Different Sensory Stimulations

Dyslexic children, besides difficulties in mastering literacy, also show poor postural control that might be related to how sensory cues coming from different sensory channels are integrated into proper motor activity. Therefore, the aim of this study was to examine the relationship between sensory information and body sway, with visual and somatosensory information manipulated independent and concurrently, in dyslexic children. Thirty dyslexic and 30 non-dyslexic children were asked to stand as still as possible inside of a moving room either with eyes closed or open and either lightly touching a moveable surface or not for 60 seconds under five experimental conditions: (1) no vision and no touch; (2) moving room; (3) moving bar; (4) moving room and stationary touch; and (5) stationary room and moving bar. Body sway magnitude and the relationship between room/bar movement and body sway were examined. Results showed that dyslexic children swayed more than non-dyslexic children in all sensory condition. Moreover, in those trials with conflicting vision and touch manipulation, dyslexic children swayed less coherent with the stimulus manipulation compared to non-dyslexic children. Finally, dyslexic children showed higher body sway variability and applied higher force while touching the bar compared to non-dyslexic children. Based upon these results, we can suggest that dyslexic children are able to use visual and somatosensory information to control their posture and use the same underlying neural control processes as non-dyslexic children. However, dyslexic children show poorer performance and more variability while relating visual and somatosensory information and motor action even during a task that does not require an active cognitive and motor involvement. Further, in sensory conflict conditions, dyslexic children showed less coherent and more variable body sway. These results suggest that dyslexic children have difficulties in multisensory integration because they may suffer from integrating sensory cues coming from multiple sources. © 2013 Viana et al.

Age-related differences in postural control: effects of the complexity of visual manipulation and sensorimotor contribution to postural performance

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sleep deprivation affects sensorimotor coupling in postural control of young adults

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Adaptation of sensorimotor coupling in postural control Is impaired by sleep deprivation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Acute cocaine treatment increases thimet oligopeptidase in the striatum of rat brain

Many studies indicate that thimet oligopeptidase (EC3.4.24.15; TOP) can be implicated in the metabolism of bioactive peptides, including dynorphin 1-8, alpha-neoendorphin, beta-neoendorphin and GnRH. Furthermore, the higher levels of this peptidase are found in neuroendocrine tissue and testis. In the present study, we have evaluated the effect of acute cocaine administration in male rats on TOP specific activity and mRNA levels in prosencephalic brain areas related with the reward circuitry; ventral striatum, hippocampus, and frontal cortex. No significant differences on TOP specific activity were detected in the hippocampus and frontal cortex of cocaine treated animals compared to control vehicle group. However, a significant increase in activity was observed in the ventral striatum of cocaine treated-rats. The increase occurred in both, TOP specific activity and TOP relative mRNA amount determined by real time RT-PCR. As TOP can be implicated in the processing of many neuropeptides, and previous studies have shown that cocaine also alters the gene expression of proenkephalin and prodynorphin in the striatum, the present findings suggest that TOP changes in the brain could play important role in the balance of neuropeptide level correlated with cocaine effects. (C) 2012 Elsevier Inc. All rights reserved.

Both the dorsal hippocampus and the dorsolateral striatum are needed for rat navigation in the Morris water maze

The multiple memory systems theory proposes that the hippocampus and the dorsolateral striatum are the core structures of the spatial/relational and stimulus-response (S-R) memory systems, respectively. This theory is supported by double dissociation studies showing that the spatial and cue (S-R) versions of the Morris water maze are impaired by lesions in the dorsal hippocarnpus and dorsal striatum, respectively. In the present study we further investigated whether adult male Wistar rats bearing double and bilateral electrolytic lesions in the dorsal hippocampus and dorsolateral striatum were as impaired as rats bearing single lesions in just one of these structures in learning both versions of the water maze. Such a prediction, based on the multiple memory systems theory, was not confirmed. Compared to the controls, the animals with double lesions exhibited no improvement at all in the spatial version and learned the cued version very slowly. These results suggest that, instead of independent systems competing for holding control over navigational behaviour, the hippocampus and dorsal striatum both play critical roles in navigation based on spatial or cue-based strategies. (C) 2011 Elsevier B.V. All rights reserved.

Functional coupling of sensorimotor and associative areas during a catching ball task: a qEEG coherence study

Abstract Background Catching an object is a complex movement that involves not only programming but also effective motor coordination. Such behavior is related to the activation and recruitment of cortical regions that participates in the sensorimotor integration process. This study aimed to elucidate the cortical mechanisms involved in anticipatory actions when performing a task of catching an object in free fall. Methods Quantitative electroencephalography (qEEG) was recorded using a 20-channel EEG system in 20 healthy right-handed participants performed the catching ball task. We used the EEG coherence analysis to investigate subdivisions of alpha (8-12 Hz) and beta (12-30 Hz) bands, which are related to cognitive processing and sensory-motor integration. Results Notwithstanding, we found the main effects for the factor block; for alpha-1, coherence decreased from the first to sixth block, and the opposite effect occurred for alpha-2 and beta-2, with coherence increasing along the blocks. Conclusion It was concluded that to perform successfully our task, which involved anticipatory processes (i.e. feedback mechanisms), subjects exhibited a great involvement of sensory-motor and associative areas, possibly due to organization of information to process visuospatial parameters and further catch the falling object.