Controlling a mobile robot with a biological brain

The intelligent controlling mechanism of a typical mobile robot is usually a computer system. Some recent research is ongoing in which biological neurons are being cultured and trained to act as the brain of an interactive real world robot�thereby either completely replacing, or operating in a cooperative fashion with, a computer system. Studying such hybrid systems can provide distinct insights into the operation of biological neural structures, and therefore, such research has immediate medical implications as well as enormous potential in robotics. The main aim of the research is to assess the computational and learning capacity of dissociated cultured neuronal networks. A hybrid system incorporating closed-loop control of a mobile robot by a dissociated culture of neurons has been created. The system is flexible and allows for closed-loop operation, either with hardware robot or its software simulation. The paper provides an overview of the problem area, gives an idea of the breadth of present ongoing research, establises a new system architecture and, as an example, reports on the results of conducted experiments with real-life robots.

Neurokinin B is a paracrine vasodilator in the human fetal placental circulation

Neurokinin (NK) B is a member of the tachykinin family of neurotransmitters, exerting hypotensive or hypertensive effects in the mammalian vasculature through synaptic release from peripheral neurons, according to either NK1 and NK2 or NK3 receptor subtype expression, respectively. There is recent evidence that NKB is expressed by the syncytiotrophoblast of the human placenta, an organ that is not innervated. We hypothesized that NKB is a paracrine modulator of tone in the fetal placental circulation. We tested this hypothesis using the in vitro perfused human placental cotyledon. Our data show that NKB is a dilator of the fetal vasculature, causing a maximal 25.1+/-4.5% (mean+/-SEM; n=5) decrease in fetal-side arterial hydrostatic pressure (5-muM NKB bolus; effective concentration in the circulation, 1.89 nM) after preconstriction with U-46619. RT-PCR demonstrated the presence of mRNA for NK1 and NK2 tachykinin receptors in the placenta. Using selective receptor antagonists, we found that NKB-induced vasodilation is through the NK1 receptor subtype. We found no evidence for the involvement of either nitric oxide or prostacyclin in this response. This study demonstrates a paracrine role for NKB in the regulation of fetal placental vascular tone.

Flavonoids and brain health: multiple effects underpinned by common mechanisms

The neuroprotective actions of dietary flavonoids involve a number of effects within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. This multiplicity of effects appears to be underpinned by two processes. Firstly, they interact with important neuronal signalling cascades leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and differentiation. These interactions include selective actions on a number of protein kinase and lipid kinase signalling cascades, most notably the PI3K/Akt and MAP kinase pathways which regulate pro-survival transcription factors and gene expression. Secondly, they induce peripheral and cerebral vascular blood flow in a manner which may lead to the induction of angiogenesis, and new nerve cell growth in the hippocampus. Therefore, the consumption of flavonoid-rich foods, such as berries and cocoa, throughout life holds a potential to limit the neurodegeneration associated with a variety of neurological disorders and to prevent or reverse normal or abnormal deteriorations in cognitive performance.

Effect of apoE genotype and vitamin E on biomarkers of oxidative stress in cultured neuronal cells and the brain of targeted replacement mice

The aetiology of apoE4 genotype-Alzheimer's disease (AD) association are complex. The current study emphasizes the impact of apoE genotype and potential beneficial effects of vitamin E (VE) in relation to oxidative stress. Agonist induced neuronal cell death was examined 1) in the presence of conditioned media containing equal amounts of apoE3 or apoE4 obtained from stably transfected macrophages, and 2) after pretreatment with alpha- and gamma-tocopherol, and -tocotrienol. ApoE3 and apoE4 transgenic mice were fed a diet poor or rich in VE to study the interplay of both apoE genotype and VE status, on membrane lipid peroxidation, antioxidative enzyme activity and glutathione levels in the brain. Cytotoxicity of hydrogen peroxide and glutamate was higher in neuronal cells cultured with apoE4 than apoE3 conditioned media. VE pre-treatment of neurons counteracted the cytotoxicity of a peroxide challenge but not of nitric oxide. No significant effects of apoE genotype or VE supplementation were observed on lipid peroxidation or antioxidative status in the brain of apoE3 and apoE4 mice. VE protects against oxidative insults in vitro, however, no differences in brain oxidative status were observed in mice. Unlike in cultured cells, apoE4 may not contribute to higher neuronal oxidative stress in the brain of young targeted replacement mice.

Age-associated changes in protein oxidation and proteasome activities in rat brain: modulation by antioxidants

The free radical theory of ageing postulates that age-associated neurodegeneration is caused by an imbalance between pro-oxidants and antioxidants resulting in oxidative stress. The current study showed regional variation in brain susceptibility to age-associated oxidative stress as shown by increased lipofuscin deposition and protein carbonyl levels in male rats of age 15-16 months compared to control ones (3-5 months). The hippocampus is the area most vulnerable to change compared to the cortex and cerebellum. However, proteasomal enzyme activity was not affected by age in any of the brain regions studied. Treatment with melatonin or coenzyme Q10 for 4 weeks reduced the lipofuscin content of the hippocampus and carbonyl level. However, both melatonin and coenzyme Q10 treatments inhibited beta-glutamyl peptide hydrolase activity. This suggests that these molecules can alter proteasome function independently of their antioxidant actions. (c) 2005 Elsevier Inc. All rights reserved.

Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels

Phytochemical-rich foods have been shown to be effective at reversing age-related deficits in memory in both animals and humans. We show that a supplementation with a blueberry diet (2% w/w) for 12 weeks improves the performance of aged animals in spatial working memory tasks. This improvement emerged within 3 weeks and persisted for the remainder of the testing period. Memory performance correlated well with the activation of cAMP-response element-binding protein (CREB) and increases in both pro- and mature levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. Changes in CREB and BDNF in aged and blueberry-supplemented animals were accompanied by increases in the phosphorylation state of extracellular signal-related kinase (ERK1/2), rather than that of calcium calmodulin kinase (CaMKII and CaMKIV) or protein kinase A. Furthermore, age and blueberry supplementation were linked to changes in the activation state of Akt, mTOR, and the levels of Arc/Arg3.1 in the hippocampus, suggesting that pathways involved in de novo protein synthesis may be involved. Although causal relationships cannot be made among supplementation, behavior, and biochemical parameters, the measurement of anthocyanins and flavanols in the brain following blueberry supplementation may indicate that changes in spatial working memory in aged animals are linked to the effects of flavonoids on the ERK-CREB-BDNF pathway. (c) 2008 Elsevier Inc. All Fights reserved.

Theory of mind in children with traumatic brain injury

Objective: This study was designed to examine the existence of deficits in mentalizing or theory of mind (ToM) in children with traumatic brain injury (TBI). Research design: ToM functioning was assessed in 12 children aged 6-12 years with TBI and documented frontal lobe damage and compared to 12 controls matched for age, sex and verbal ability. Brief measures of attention and memory were also included. Main outcome and results: The TBI group was significantly impaired relative to controls on the advanced ToM measure and a measure of basic emotion recognition. No difference was found in a basic measure of ToM. Conclusion: Traumatic brain damage in childhood may disrupt the developmental acquisition of emotion recognition and advanced ToM skills. The clinical and theoretical importance of these findings is discussed and the implications for the assessment and treatment of children who have experienced TBI are outlined.

fMRI delineation of working memory for emotional prosody in the brain: commonalities with the lexico-semantic emotion network

Decoding emotional prosody is crucial for successful social interactions, and continuous monitoring of emotional intent via prosody requires working memory. It has been proposed by Ross and others that emotional prosody cognitions in the right hemisphere are organized in an analogous fashion to propositional language functions in the left hemisphere. This study aimed to test the applicability of this model in the context of prefrontal cortex working memory functions. BOLD response data were therefore collected during performance of two emotional working memory tasks by participants undergoing fMRI. In the prosody task, participants identified the emotion conveyed in pre-recorded sentences, and working memory load was manipulated in the style of an N-back task. In the matched lexico-semantic task, participants identified the emotion conveyed by sentence content. Block-design neuroimaging data were analyzed parametrically with SPM5. At first, working memory for emotional prosody appeared to be right-lateralized in the PFC, however, further analyses revealed that it shared much bilateral prefrontal functional neuroanatomy with working memory for lexico-semantic emotion. Supplementary separate analyses of males and females suggested that these language functions were less bilateral in females, but their inclusion did not alter the direction of laterality. It is concluded that Ross et al.'s model is not applicable to prefrontal cortex working memory functions, that evidence that working memory cannot be subdivided in prefrontal cortex according to material type is increased, and that incidental working memory demands may explain the frontal lobe involvement in emotional prosody comprehension as revealed by neuroimaging studies. (c) 2007 Elsevier Inc. All rights reserved.

How does the brain mediate interpretation of incongruent auditory emotions? The neural response to prosody in the presence of conflicting lexico-semantic cues

We frequently encounter conflicting emotion cues. This study examined how the neural response to emotional prosody differed in the presence of congruent and incongruent lexico-semantic cues. Two hypotheses were assessed: (i) decoding emotional prosody with conflicting lexico-semantic cues would activate brain regions associated with cognitive conflict (anterior cingulate and dorsolateral prefrontal cortex) or (ii) the increased attentional load of incongruent cues would modulate the activity of regions that decode emotional prosody (right lateral temporal cortex). While the participants indicated the emotion conveyed by prosody, functional magnetic resonance imaging data were acquired on a 3T scanner using blood oxygenation level-dependent contrast. Using SPM5, the response to congruent cues was contrasted with that to emotional prosody alone, as was the response to incongruent lexico-semantic cues (for the 'cognitive conflict' hypothesis). The right lateral temporal lobe region of interest analyses examined modulation of activity in this brain region between these two contrasts (for the 'prosody cortex' hypothesis). Dorsolateral prefrontal and anterior cingulate cortex activity was not observed, and neither was attentional modulation of activity in right lateral temporal cortex activity. However, decoding emotional prosody with incongruent lexico-semantic cues was strongly associated with left inferior frontal gyrus activity. This specialist form of conflict is therefore not processed by the brain using the same neural resources as non-affective cognitive conflict and neither can it be handled by associated sensory cortex alone. The recruitment of inferior frontal cortex may indicate increased semantic processing demands but other contributory functions of this region should be explored.

How the brain blinks: towards a neurocognitive model of the attentional blink

When people monitor a visual stream of rapidly presented stimuli for two targets (T1 and T2), they often miss T2 if it falls into a time window of about half a second after T1 onset-the attentional blink (AB). We provide an overview of recent neuroscientific studies devoted to analyze the neural processes underlying the AB and their temporal dynamics. The available evidence points to an attentional network involving temporal, right-parietal and frontal cortex, and suggests that the components of this neural network interact by means of synchronization and stimulus-induced desynchronization in the beta frequency range. We set up a neurocognitive scenario describing how the AB might emerge and why it depends on the presence of masks and the other event(s) the targets are embedded in. The scenario supports the idea that the AB arises from "biased competition", with the top-down bias being generated by parietal-frontal interactions and the competition taking place between stimulus codes in temporal cortex.

Development of multi-electrode array screening for anticonvulsants in acute rat brain slices

The acute hippocampal brain slice preparation is an important in vitro screening tool for potential anticonvulsants. Application of 4-aminopyridine (4-AP) or removal of external Mg2+ ions induces epileptiform bursting in slices which is analogous to electrical brain activity seen in status epilepticus states. We have developed these epileptiform models for use with multi-electrode arrays (MEAs), allowing recording across the hippocampal slice surface from 59 points. We present validation of this novel approach and analyses using two anticonvulsants, felbamate and phenobarbital, the effects of which have already been assessed in these models using conventional extracellular recordings. In addition to assessing drug effects on commonly described parameters (duration, amplitude and frequency), we describe novel methods using the MEA to assess burst propagation speeds and the underlying frequencies that contribute to the epileptiform activity seen. Contour plots are also used as a method of illustrating burst activity. Finally, we describe hitherto unreported properties of epileptiform, bursting induced by 100 mu M 4-AP or removal of external Mg2+ ions. Specifically, we observed decreases over time in burst amplitude and increase over time in burst frequency in the absence of additional pharmacological interventions. These MEA methods enhance the depth, quality and range of data that can be derived from the hippocampal slice preparation compared to conventional extracellular recordings. it may also uncover additional modes of action that contribute to anti-epileptiform drug effects. (C) 2009 Elsevier B.V. All rights reserved.