Neuroscience

Epilepsy is a chronic neurological disorder characterized by spontaneous recurrent seizures (SRS) and comorbidities. Kindling through repetitive brief stimulation of a limbic structure is a commonly used model of temporal lobe epilepsy. Particularly, extended kindling over a period up to a few months can induce SRS, which may simulate slowly evolving epileptogenesis of temporal lobe epilepsy. Currently, electroencephalographic (EEG) features of SRS in rodent models of extended kindling remain to be detailed. We explored this using a mouse model of extended hippocampal kindling. Intracranial EEG recordings were made from the kindled hippocampus and unstimulated hippocampal, neocortical, piriform, entorhinal, or thalamic area in individual mice. Spontaneous EEG discharges with concurrent low-voltage fast onsets were observed from the two corresponding areas in nearly all SRS detected, irrespective of associated motor seizures. Examined in brain slices, epileptiform discharges were ind...

Temporal lobe epilepsy is the most common and often drug-resistant type of epilepsy in the adult and aging populations and has great diversity in etiology, electro-clinical manifestations, and comorbidities. Kindling through repeated brief stimulation of limbic structures is a commonly used model of temporal lobe epilepsy. Particularly, extended kindling can induce spontaneous recurrent seizures in several animal species. However, kindling studies in middle-aged, aging, or aged animals remain scarce, and currently, little is known about kindling-induced behavioral changes in middle-aged/aging animals. We therefore attempted to provide more information in this area using a mouse model of extended hippocampal kindling. We conducted experiments in middle-aged mice (C57BL/6, male, 12-14 months of age) to model new-onset epilepsy in adult/aging populations. Mice experienced twice daily hippocampal stimulations or handling manipulations for 60-70 days and then underwent continuous electroencephalogram (EEG)-video monitoring to detect spontaneous recurrent seizures. Extended kindled mice consistently exhibited spontaneous recurrent seizures with mean incidences of 6-7 events per day, and these seizures featured EEG discharges and corresponding convulsions. The handling control mice showed neither seizure nor aberrant EEG activity. The two groups of mice underwent the Morris water maze test of spatial learning and memory 1-2 weeks after termination of the kindling stimulation or handling manipulation. During visible platform trials, the kindled mice took a longer distance and required more time than the control mice to find the platform. During hidden platform trials, the kindled mice showed no improvement over 5-day trials in finding the platform whereas the control mice improved significantly. During probe tests in which the hidden platform was removed, the kindled mice spent less time than the controls searching in the correct platform location. There were no significant differences between the kindled and control mice with respect to swim speed or total locomotor activity in an open-field test. Together, these observations indicate that the extended kindled mice with spontaneous recurrent seizures are impaired in spatial learning and memory as assessed by the Morris water maze test. We postulate that

Introducción: La obtención de cultivos celulares epiteliales corneales humanos podría ser de gran utilidad tanto para la investigación básica como para su aplicación clínica en el tratamiento de diversas enfermedades corneales. Material y Métodos: Muestras de limbo esclerocorneal procedentes de donante humano cadáver se pusieron en cultivo con medios específicos para células epiteliales con distintos factores de crecimiento. En la mitad de los cultivos se utilizaron células alimentadoras 3T3. Resultados: Se obtuvieron cultivos primarios de células epiteliales corneales con un alto grado de proliferación, sin importar si el crecimiento se dio sobre células 3T3 o no. La tasa de contaminación de los cultivos fue menor en aquellos donde sí se encontraban estas células alimentadoras. Discusión: La obtención de células epiteliales corneales es posible en el laboratorio a partir de pequeñas biopsias del limbo esclerocorneal tras su expansión en cultivo, utilizando una técnica de cultivo estándar, fácilmente reproducible. Palabras clave: limbo esclerocorneal, ingeniería tisular, epitelio corneal, cultivos celulares. El limbo esclerocorneal es una zona de transición entre la córnea y la esclerótica. Histológicamente, el epitelio del limbo es la zona que separa el epitelio columnar conjuntival del epitelio escamoso estratificado

Multivariate measurements of human brain white matter (WM) with diffusion MRI (dMRI) provide information about the role of WM in a variety of cognitive functions and in brain health. Statistical models take advantage of the regularities in these data to make inferences about individual differences. For example, dMRI data provide the basis for accurate brain-age models – models that predict the chronological age of participants from WM tissue properties. Deep learning (DL) models are powerful machine learning models, which have been shown to provide benefits in many multivariate analysis settings. We investigated whether DL would provide substantial improvements for brain-age models based on dMRI measurements of WM in a large sample of children and adolescents. We found that some DL models fit the data better than a linear baseline, but the differences are small. In particular, recurrent neural network architectures provide up to ∼6% improvement in accuracy. This suggests that inform...

Objective: There is limited research on the use of telerehabilitation platforms in service delivery for people with acquired brain injury (ABI), especially technologies that support delivery of services into the home. This qualitative study aimed to explore the perspectives of rehabilitation coordinators, individuals with ABI and family caregivers on the usability and acceptability of videoconferencing in community-based rehabilitation. Participants' experiences and perceptions of telerehabilitation and their impressions of a particular videoconferencing system were investigated. Method: Guided by the Technology Acceptance Model (Davis, 1989), semi-structured interviews were conducted with 30 participants from a community-based ABI service, including 13 multidisciplinary rehabilitation coordinators, 9 individuals with ABI and 8 family caregivers. During the interview they were shown a paper prototype of a telehealth portal for videoconferencing that was available for use. Interview transcripts were coded by two researchers and analysed thematically. Results: Videoconferencing was used on average for 2% of client consultations. Four major themes depicted factors influencing the uptake of videoconferencing platforms; namely, the context or impetus for use, perceived benefits, potential problems and parameters around use, and balancing the service and user needs. Participants identified beneficial uses of videoconferencing in service delivery and strategies for promoting a positive user experience. Conclusions: Perceptions of the usability of videoconferencing to provide services in the home were largely positive; however, consideration of use on a case-by-case basis and a trial implementation was recommended to enhance successful uptake into service delivery.

A series of N,N-disubstituted piperazines were synthesized containing the structural elements of both methylenedioxybenzylpiperazine (MDBP) and trifluoromethylphenylpiperazine (TFMPP) in a single molecule. These six potential designer drug molecules having a regioisomeric relationship were compared in gas chromatography-mass spectrometry (GC-MS), gas chromatography-infrared spectroscopy and serotonin receptor affinity studies. These compounds were separated by capillary gas chromatography on an Rxi Ò -17Sil MS stationary phase film and the elution order appears to be determined by the position of aromatic ring substitution. The majority of electron ionization mass spectral fragment ions occur via processes initiated by one of the two nitrogen atoms of the piperazine ring. The major electron ionization mass spectrometry (EI-MS) fragment ions observed in all six of these regioisomeric substances occur at m/z = 364, 229, 163 and 135. The relative intensity of the various fragment ions is also equivalent in each of the six EI-MS spectra. The vapour phase infrared spectra provide a number of absorption bands to differentiate among the six individual compounds on this regioisomeric set. Thus, the mass spectra place these compounds into a single group and the vapour phase infrared spectra differentiate among the six regioisomeric possibilities. All of the TFMPP-MDBP regioisomers displayed significant binding to 5-HT 2B receptors and in contrast to 3-TFMPP, most of these TFMPP-MDBP isomers did not show significant binding at 5-HT 1 receptor subtypes. Only the 3-TFMPP-3,4-MDBP (Compound 5) isomer displayed affinity comparable to 3-TFMPP at 5-HT 1A receptors (K i = 188 nmol/L).

The robust Indian textile industry results in prodigious consumption followed by equivalent waste, leading to environmental deterioration. The solution is circular textile production/products (CTPs), but their existence is almost absent in the Indian market due to a lack of focus on consumers’ acceptance of CTPs. To bridge the literature gap, the TPB model was extended to explore the antecedents that directly and indirectly influence consumers’ attitudes and purchase intentions towards CTPs. The PLS-SEM (using Smart-PLS) was used to assess the structural model with the 409 samples collected through an online survey from the NCR of India. The findings revealed that personal benefits, environmental consciousness (except risk perception), perceived behavioral control, and subjective norms significantly and directly influence consumers’ attitudes and purchase intentions towards CTPs. In addition, attitude significantly and indirectly mediates the relationship between “environmental cons...

Epilepsy is estimated by the World Health Organization to affect 0.8% of the world's population. Although epilepsy is a relatively common neurological disorder, its etiology and pathophysiology continue to be elusive in many cases. In recent years, an increasing body of evidence has indicated that there is a complex relationship between epilepsy and the immune system. Abnormalities in expression of cytokines and immune cells have been observed in patients with epilepsy and in animal models. Moreover, the immune system and its associated inflammatory reactions seem to play an important role in epileptogenesis. Data in this field implicate cytokines as mediators of spontaneous seizures. This review provides an overview on the current knowledge of the relationship between cytokines and epilepsy and focus on the most commonly studied cytokines IL-1b, IL-6, and TNFa.

Epilepsy is estimated by the World Health Organization to affect 0.8% of the world's population. Although epilepsy is a relatively common neurological disorder, its etiology and pathophysiology continue to be elusive in many cases. In recent years, an increasing body of evidence has indicated that there is a complex relationship between epilepsy and the immune system. Abnormalities in expression of cytokines and immune cells have been observed in patients with epilepsy and in animal models. Moreover, the immune system and its associated inflammatory reactions seem to play an important role in epileptogenesis. Data in this field implicate cytokines as mediators of spontaneous seizures. This review provides an overview on the current knowledge of the relationship between cytokines and epilepsy and focus on the most commonly studied cytokines IL-1b, IL-6, and TNFa.

Population transmembrane currents and neuronal firing in different layers of the human entorhinal cortex (ER) were recorded during semantic and episodic memory processes using a linear array of 24 laminar microelectrodes . Both measures, as well as local broadband spectral power, increased during retrieval of newly-learned characteristics, especially in superficial layers. No differences were observed in the activity evoked by remembering people as compared to places. Semantic retrieval evoked similar activity. In contrast, intentional encoding of declarative memory evoked relatively little activity. A double-dissociation of these responses with simultaneously recorded lateral inferotemporal recordings suggests that entorhinal cortex may be specifically engaged during retrieval, across multiple memory types and materials.

The purpose of this study is to assess the clinical value of spatiotemporal source analysis for analyzing ictal magnetoencephalography (MEG). Ictal MEG and simultaneous scalp EEG was recorded in five patients with medically intractable frontal lobe epilepsy. Dynamic statistical parametric maps (dSPMs) were calculated at the peak of early ictal spikes for the purpose of estimating the spatiotemporal cortical source distribution. DSPM solutions were mapped onto a cortical surface, which was derived from each patient's MRI. Equivalent current dipoles (ECDs) were calculated using a single-dipole model for comparison with dSPMs. In all patients, dSPMs tended to have a localized activation, consistent with the clinically determined ictal onset zone, whereas most ECDs were considered to be inappropriate sources according to their goodness-of-fit values. Analyzing ictal MEG spikes by using dSPMs may provide useful information in presurgical evaluation of epilepsy.

Summary:  Purpose: To examine whether magnetoencephalography (MEG) can be used to determine patterns of brain activity underlying widespread paroxysms of epilepsy patients, thereby extending the applicability of MEG to a larger population of epilepsy patients. Methods: We studied two children with symptomatic localization‐related epilepsy. Case 1 had widespread spikes in EEG with an operation scar from a resection of a brain tumor; Case 2 had hemispheric slow‐wave activity in EEG with sensory auras. MEG was collected with a 204‐channel helmet‐shaped sensor array. Dynamic statistical parametric maps (dSPMs) were constructed to estimate the cortical distribution of interictal discharges for these patients. Equivalent current dipoles (ECDs) also were calculated for comparison with the results of dSPM. Results: In case 1 with widespread spikes, dSPM presented the major activity at the vicinity of the operation scar in the left frontal lobe at the peak of the spikes, and some activities ...

It is unclear whether focal epilepsies chronically influence the processing of cortex distant to the epileptogenic zone. Therefore, motor cortex excitability was analysed in patients with temporal and extratemporal epilepsies whose epileptogenic zones did not include the primary motor area. Single and paired-pulse transcranial magnetic stimulation (TMS) was applied to the primary motor cortex in 20 healthy controls and 23 patients with focal epilepsy (39.4 6 13.2 years; 12 left, 11 right; 14 temporal, nine extratemporal: six frontal, three parieto-occipital) ipsi-and contralateral to the epileptogenic zone. In all patients, the epileptogenic zone did not include the primary motor cortex. The resting motor threshold (RMT), the cortical silent period (CSP), the intracortical inhibition [ICI; combined interstimulus intervals (ISI) 2 and 3 ms] and the intracortical facilitation (ICF; combined ISI 10 and 15 ms) were determined. The measures obtained ipsilateral to the epileptogenic zone were compared with those elicited in contralateral hemispheres and, in exploratory analyses, with controls using non-parametric tests, including Hodges-Lehmann estimates of median differences (HLE) with 95% confidence intervals (CI). In the patient group, the CSP elicited in the ipsilateral motor cortex (median 162.3 ms) was shortened compared with the contralateral CSP (median 174.6 ms; HLE 15.9 ms; CI 6.2, 27.0 ms; P = 0.002). This interhemispheric difference was more pronounced in extratemporal epilepsies (HLE 23.4 ms; CI À3.2, 67.6 ms) compared with temporal epilepsies (HLE 14.3 ms; CI 4.7, 26.2 ms). Patients with parieto-occipital epilepsies showed the greatest interhemispheric differences in CSP (HLE 33.5 ms) and patients with mesial temporal epilepsies the smallest (HLE 9.9 ms). No significant differences were found between ipsi-and contralateral RMT, ICI or ICF. In analyses of subgroups, the CSP was shorter in epileptic hemispheres of patients with extratemporal epilepsies (141.4 ms) than in controls (173.4 ms; HLE 40.0 ms; CI 3.2, 83.4 ms; P = 0.029). ICF was increased in epileptic hemispheres of extratemporal epilepsies (147.6%) compared with temporal epilepsies (114.6%; HLE 33.0%; CI 4.1, 68.3%; P = 0.038). The results suggest that focal epilepsies influence chronically distant cortex, leading to decreased inhibition and increased facilitation in the ipsilateral motor cortex even when the epileptogenic zone is apart from it. This alteration may be due to synaptic reorganization and appears to be more pronounced in extratemporal and neocortical temporal than in mesial temporal epilepsies. This may have diagnostic implications.

En el presente trabajo se estudia el proceso de friction stir spot welding de planchuelas de aleación de aluminio AA6082 utilizando dos métodos de cálculo sucesivos. En una primera etapa se modela la inserción del perno en el material a soldar como un problema unidimensional axisimétrico no estacionario.De este caso se extrae el campo de temperaturas que es utilizado como campo de condiciones térmicas iniciales al momento de modelar el proceso de permanencia en el paso siguiente. Esta segunda etapa del proceso se realiza mediante un modelo bidimensional axisimétrico considerando al material constitutivamenteviscoplástico y, consecuentemente, resolviendo un problema de flujo de Stokes con viscosidades no lineales. Como resultados de este caso se obtienen los campos de velocidades, temperaturas y tensiones para todo el continuo. Las estimaciones realizadas se comparan con resultados experimentales de soldaduras de punto por fricción agitación.In this work, the friction stir spot weldi...

The purpose of the study has been an analysis of Polish students’ cued translation of Polish (L1) and English or French (L2) sentences into Portuguese (third or additional language in De Angelis’s (2007) terminology). In particular, the study investigates cross-linguistic interaction (Herdina and Jessner’s (2002) term) in multilingual processing involved in L3 production. In fact, translation constitutes a special case of production because, on the one hand, the content is already contained in the L1 or L2 source sentences, but at the same time, this is not necessarily a facilitation, as the cues may require the use of words or structures the participants might not use in free production. The article is based on two studies carried out with thirty and forty-two students of Portuguese philology respectively. As the results show, cross-linguistic interaction in various directions was observed, not only from L2 (English or French), L3 (in those participants for whom Portuguese was an L...

In imaging studies of neonates, particularly in the clinical setting, diffusion tensor imaging-based tractography is typically unreliable due to the use of fast acquisition protocols that yield low resolution and signal-to-noise ratio (SNR). These image acquisition protocols are implemented with the aim of reducing displacement artifacts that may be produced by the movement of the neonate's head during the scanning session. 1 In addition, axons are not yet fully myelinated in neonates. As a result, the water molecule's movements are not as constrained as in older brains, making it even more difficult to define structure by means of diffusion profiles. Here, we introduce a post-processing method that overcomes some of the difficulties described above, allowing the determination of reliable tracts in newborns. We test our method using neonatal data and in particular, we successfully extract a limbic and some association and commisural fibers, all of which are typically difficult to obtain by direct tractography. The method is further validated through visual inspection by expert pediatric neuroradiologists.

Many children born preterm exhibit frontal executive dysfunction, behavioral problems including attentional deficit/ hyperactivity disorder and attention related learning disabilities. Anomalies in regional specificity of cortico-striato-thalamocortical circuits may underlie deficits in these disorders. Nonspecific volumetric deficits of striatal structures have been documented in these subjects, but little is known about surface deformation in these structures. For the first time, here we found regional surface morphological differences in the preterm neonatal ventral striatum. We performed regional group comparisons of the surface anatomy of the striatum (putamen and globus pallidus) between 17 preterm and 19 term-born neonates at term-equivalent age. We reconstructed striatal surfaces from manually segmented brain magnetic resonance images and analyzed them using our in-house conformal mapping program. All surfaces were registered to a template with a new surface fluid registration method. Vertex-based statistical comparisons between the two groups were performed via four methods: univariate and multivariate tensor-based morphometry, the commonly used medial axis distance, and a combination of the last two statistics. We found statistically significant differences in regional morphology between the two groups that are consistent across statistics, but more extensive for multivariate measures. Differences were localized to the ventral aspect of the striatum. In particular, we found abnormalities in the preterm anterior/inferior putamen, which is interconnected with the medial orbital/prefrontal cortex and the midline thalamic nuclei including the medial dorsal nucleus and pulvinar. These findings support the hypothesis that the ventral striatum is vulnerable, within the cortico-stiatothalamo-cortical neural circuitry, which may underlie the risk for long-term development of frontal executive dysfunction, attention deficit hyperactivity disorder and attention-related learning disabilities in preterm neonates.

Background: Acute post-anoxic myoclonus (PAM) can be divided into an unfavorable (generalized/subcortical) and more favorable ((multi)focal/cortical) outcome group that could support prognostication in post-anoxic encephalopathy; however, the inter-rater variability of clinically assessing these PAM subtypes is unknown. Methods: We prospectively examined PAM patients using a standardized video protocol. Videos were rated by three neurologists who classified PAM phenotype (generalized/(multi)focal), stimulus sensitivity, localization (proximal/distal/both), and severity (Clinical Global Impression-Severity Scale (CGI-S) and Unified Myoclonus Rating Scale (UMRS)). Results: Poor inter-rater agreement was found for phenotype and stimulus sensitivity (k5-0.05), moderate agreement for localization (k50.46). Substantial agreement was obtained for the CGI-S (intraclass correlation coefficient (ICC)50.64) and almost perfect agreement for the UMRS (ICC50.82). Discussion: Clinical assessment of PAM is not reproducible between physicians, and should therefore not be used for prognostication. PAM severity measured by the UMRS appears to be reliable; however, the relation between PAM severity and outcome is unknown.

The purpose of this review is to critically examine phosphene induction and saccadic eye movement generation by electrical microstimulation of striate cortex (area V1) in humans and monkeys. The following issues are addressed: 1) Properties of electrical stimulation as they pertain to the activation of V1 elements; 2) the induction of phosphenes in sighted and blind human subjects elicited by electrical stimulation using various stimulation parameters and electrode types; 3) the induction of phosphenes with electrical microstimulation of V1 in monkeys; 4) the generation of saccadic eye movements with electrical microstimulation of V1 in monkeys; and 5) the tasks involved for the development of a cortical visual prosthesis for the blind. In this review it is concluded that electrical microstimulation of area V1 in trained monkeys can be used to accelerate the development of an effective prosthetic device for the blind.

This study aimed to ascertain students' mental models while learning about salt hydrolysis through augmented reality (AR). The study comprised 36 participants from Public High School 51 in Jakarta. A descriptive qualitative approach was adopted for this research, employing various data collection methods such as written drawings, interviews, classroom observations, teacher notes, student worksheets, and final tests. In categorizing students' mental models, three main types emerged: scientific, synthetic, and initial mental models. The findings revealed that 7.20% of students fell into the initial mental model category, 53.90% exhibited synthetic mental models, and 38.90% demonstrated scientific mental models. Notably, incorporating AR into salt hydrolysis learning predominantly influenced the development of synthetic mental models. The study's results also indicated that the utilization of AR positively enhanced students' spatial abilities in understanding submicroscopic representations.

From one-way communication to two-way communication, text-based to multimedia, unencrypted to end-to-end encrypted chats, computer, computer-to-human chats have evolved over the years to more sophisticated chatbots, mimicking natural human language based on predefined algorithms. ChatGPT is one of the most recent of such tools and, due to its capabilities has grown tremendously in use. Despite the numerous benefits of ChatGPT, some users have raised

Behavioral studies indicate that adverse childhood experiences (ACE) are associated with altered empathic responding, but the neural mechanisms underlying this relationship remain unclear. Given the significance of empathy in contexts marred by historical conflict and systemic inequality, work on these mechanisms is particularly important in such contexts. The current study extends previous work by (1) examining associations of different dimensions of ACE with volumetric change in empathy-related circuitry, (2) distinguishing between trait and state empathy, and (3) including perceived discrimination as an additional psychosocial stressor. Thirty-nine healthy South African adults from the general population (M age = 40.6 years) underwent 3 T MRI. FreeSurfer v6.0 was used to extract predefined volumes subserving empathy. Results showed that childhood abuse and perceived discrimination were associated with reduced state empathic concern, whereas childhood neglect was associated with reduced trait cognitive empathy. Childhood abuse was furthermore associated with volumetric increases in frontolimbic (hippocampus, anterior cingulate cortex (ACC)) and neocortical (superior frontal and temporal) regions subserving affective and cognitive empathy, and uniquely mediated the relationship between ACC volume and perceived discrimination. The association of ACE with altered empathic responding may thus be underpinned by specific circuitry reflective of adversity type, with childhood abuse contributing to heightened responsivity to socioemotional cues.

Atypical amygdala function and connectivity have reliably been associated with psychopathy. However, the amygdala is not a unitary structure. To examine how psychopathic traits in a nonforensic sample are linked to amygdala response to violence, this study used probabilistic tractography to classify amygdala subnuclei based on anatomical projections to and from amygdala subnuclei in a group of 43 male participants. The segmentation identified the basolateral complex (BLA; lateral, basal, and accessory basal subnuclei) and the central subnucleus (CE), which were used as seeds in a functional connectivity analysis to identify differences in neuronal coupling specific to observed violence. While a full amygdala seed showed significant connectivity only to right middle occipital gyrus, subnuclei seeds revealed unique connectivity patterns. BLA showed enhanced coupling with anterior cingulate and prefrontal regions, while CE showed increased connectivity with the brainstem, but reduced c...

Morality is a fundamental component of human cultures and has been defined as prescriptive norms regarding how people should treat one another, including concepts such as justice, fairness, and rights. Using fMRI, the current study examined the extent to which dispositions in justice sensitivity (i.e., how individuals react to experiences of injustice and unfairness) predict behavioral ratings of praise and blame and how they modulate the online neural response and functional connectivity when participants evaluate morally laden (good and bad) everyday actions. Justice sensitivity did not impact the neuro-hemodynamic response in the action-observation network but instead influenced higher-order computational nodes in the right temporoparietal junction (rTPJ), right dorsolateral and dorsomedial prefrontal cortex (rdlPFC, dmPFC) that process mental states understanding and maintain goal representations. Activity in these regions predicted praise and blame ratings. Further, the hemodyn...

Accumulating evidence demonstrates that similar neural circuits are activated during the first-hand experience of pain and the observation of pain in others. However, most functional MRI studies did not detect signal change in the primary somatosensory cortex during pain empathy. To test if the perception of pain in others involves the primary somatosensory cortex, neuromagnetic oscillatory activity was recorded from the primary somatosensory cortex in 16 participants while they observed static pictures depicting body parts in painful and nonpainful situations. The left median nerve was stimulated at the wrist, and the poststimulus rebounds of the ~10-Hz somatosensory cortical oscillations were quantified. Compared to the baseline condition, the level of the ~10-Hz oscillations was suppressed during both of the observational situations, indicating the activation of the primary somatosensory cortex. Importantly, watching painful compared to nonpainful situations suppressed somatosensory oscillations to a significant stronger degree. In addition, the suppression caused by perceiving others in the painful relative to the non-painful situations correlated with the perspective taking subscale of the interpersonal reaction index. These results, consistent with the mirror-neuron system, demonstrate that the perception of pain in others modulates neural activity in primary somatosensory cortex and supports the idea that the perception of pain in others elicits subtle somatosensory activity that may be difficult to detect by fMRI techniques.

Perceiving the pain of others activates a large part of the pain matrix in the observer . Because this shared neural representation can lead to empathy or personal distress , regulatory mechanisms must operate in people who inflict painful procedures in their practice with patient populations in order to prevent their distress from impairing their ability to be of assistance. In this functional magnetic resonance imaging MRI study, physicians who practice acupuncture were compared to naive participants while observing animated visual stimuli depicting needles being inserted into different body parts, including the mouth region, hands, and feet. Results indicate that the anterior insula somatosensory cortex, periaqueducal gray, and anterior cingulate cortex were significantly activated in the control group, but not in the expert group, who instead showed activation of the medial and superior prefrontal cortices and the temporoparietal junction, involved in emotion regulation and theory of mind.

Brain signal recordings with epidural microarrays constitute a low-invasive approach for recording distributed neuronal signals. Epidural field potentials (EFPs) may serve as a safe and highly beneficial signal source for a variety of research questions arising from both basic and applied neuroscience. A wider use of these signals, however, is constrained by a lack of data on their specific information content. Here, we make use of the high spatial resolution and the columnar organization of macaque primary visual cortex (V1) to investigate whether and to what extent EFP signals preserve information about various visual stimulus features. Two monkeys were presented with different feature combinations of location, size, shape, and color, yielding a total of 375 stimulus conditions. Visual features were chosen to access different spatial levels of functional organization. We found that, besides being highly specific for locational information, EFPs were significantly modulated by small differences in size, shape, and color, allowing for high stimulus classification rates even at the single-trial level. The results support the notion that EFPs constitute a low-invasive, highly beneficial signal source for longer-term recordings for medical and basic research by showing that they convey significant and reliable information about constituent features of activating stimuli.

Remarkable alterations of perception during long-lasting attentional processes have been described in several recent studies. Although these findings have gained much interest, almost nothing is known about the modulation of neuronal responses during sustained attention. Therefore, we investigated the effect of prolonged selective attention on neuronal feature selectivity. Awake macaque monkeys were trained to perform a motion-tracking task that required attending one of two simultaneously presented moving bars for up to 15 sec. Extracellular recordings were obtained from neurons in macaque motion-sensitive middle temporal visual area (MT/V5). Under conditions of attention, we found high and constant direction selectivity over time. This was expressed by a strong and persistent response contrast between presentations of preferred and nonpreferred stimuli in successive motion cycles. With attention directed to another moving bar, neuronal responses to the behaviorally irrelevant stimulus became continuously less specific for the direction of motion. In particular, increasingly higher firing rates for motion in null direction caused a strong reduction of direction selectivity, which further increased with enhanced proximity between target and distracter bar. A passive condition experiment revealed that this reduction occurred only when motion remained the behaviorally relevant feature but disappeared when attention was withdrawn from this feature domain. Thus, sustained attention seems to stabilize direction selectivity of neurons in area MT against a time and competitiondependent degradation, whereas nonattended objects suffer from a reduced neuronal representation.

Selective visual attention is known to be associated with characteristic modulations of neuronal activity in early visual cortex, but there is only rare evidence showing that these neuronal modulations are directly related to attention-dependent behavioral improvements. Here, we describe a strong, transient increase in the response of neurons in the mediotemporal (MT) area to behaviorally relevant speed changes that is not only modulated by attention but also highly correlated with the animal's performance. In trials with fast reaction time (RT), this transient component occurs with short latency, whereas latency increases monotonically with slower RT. Importantly, RTs are related not to the firing rate modulation during sustained attentive tracking of the target prior to the speed change but to the variability of the neuronal response. Our findings suggest a direct link between attention-dependent response modulations in early visual cortex and improved behavioral performance.

In human and nonhuman primates, goal-directed behavior requires the selection of relevant pieces of information from the multitude of simultaneous sensory inputs. Feature-based attention (FBA) plays a crucial role in this selection by improving the neuronal representation of an attended stimulus feature. Of particular interest for understanding the neuronal mechanisms behind FBA is the processing fate of spatially unattended stimuli, either sharing the attended feature attribute or belonging to the attended or to a nonattended feature dimension. Using a wide range of cue/stimulus combinations, we investigated eventrelated potentials from the human brain, recorded under conditions of different feature attention but constant visual stimulation. We found that neural processing of visual stimuli sharing the dimension or the attribute of the attended target is associated with two distinct spatiotemporal processes, particularly prominent during the selection negativity period. Dimension-based modulation of neural signals first emerged over frontal electrode sites, and temporally preceded and accompanied attribute-specific FBA effects at occipital, parieto-occipital, and parietal electrodes. The findings suggest a process of FBA that not only increases responses of those neurons particularly tuned to the attended attribute but also modulates activity in the cortical module that is selective for the feature dimension to which the attended attribute belongs.

Brain signal recordings with epidural microarrays constitute a low-invasive approach for recording distributed neuronal signals. Epidural field potentials (EFPs) may serve as a safe and highly beneficial signal source for a variety of research questions arising from both basic and applied neuroscience. A wider use of these signals, however, is constrained by a lack of data on their specific information content. Here, we make use of the high spatial resolution and the columnar organization of macaque primary visual cortex (V1) to investigate whether and to what extent EFP signals preserve information about various visual stimulus features. Two monkeys were presented with different feature combinations of location, size, shape, and color, yielding a total of 375 stimulus conditions. Visual features were chosen to access different spatial levels of functional organization. We found that, besides being highly specific for locational information, EFPs were significantly modulated by smal...

Sudden changes in visual scenes often indicate important events for behavior. For their quick and reliable detection, the brain must be capable to process these changes as independently as possible from its current activation state. In motion-selective area MT, neurons respond to instantaneous speed changes with pronounced transients, often far exceeding the expected response as derived from their speed tuning profile. We here show that this complex, non-linear behavior emerges from the combined temporal dynamics of excitation and divisive inhibition, and provide a comprehensive mathematical analysis. A central prediction derived from this investigation is that attention increases the steepness of the transient response irrespective of the activation state prior to a stimulus change, and irrespective of the sign of the change (i.e. irrespective of whether the stimulus is accelerating or decelerating). Extracellular recordings of attention-dependent representation of both speed incre...

Eag1 (ether-à-go-go-1), a member of the voltage-dependent potassium channel family, is expressed mainly in the brain, and at low levels in placenta, testis, and adrenal gland, and only transiently in myoblasts. Recently, several studies have suggested that Eag1 is selectively expressed in various tumor tissues. Eag1 plays important roles in tumor proliferation, malignant transformation, invasion, metastasis, recurrence, and prognosis. Therefore, it has become a new molecular target for tumor diagnosis, prognosis evaluation, and tumor-targeted therapy. This review provides information about the current progress in understanding Eag1 structure, electrophysiological characteristics, and role in cancer.

Neurotrophins, such as brain-derived neurotrophic factor (BDNF), are essential for neuronal survival and growth. The signaling cascades initiated by BDNF and its receptor are the key regulators of synaptic plasticity, which plays important role in learning and memory formation. Changes in BDNF levels and signaling pathways have been identified in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, and have been linked with the symptoms and course of these diseases. This review summarizes the current understanding of the role of BDNF in several neurodegenerative diseases, as well as the underlying molecular mechanism. The therapeutic potential of BDNF treatment is also discussed, in the hope of discovering new avenues for the treatment of neurodegenerative diseases.

Impairment of memory is one of the most frequently reported symptoms during sudden hypoxia exposure in human. Cortical atrophy has been linked to the impaired memory function and is suggested to occur with chronic high-altitude exposure. However, the precise molecular mechanism(s) of hypoxia-induced memory impairment remains an enigma. In this work, we review hypoxia-induced learning and memory deficit in human and rat studies. Based on data from rat studies using different protocols of continuous hypoxia, we try to elicit potential mechanisms of hypobaric hypoxia-induced memory deficit.

Introduction: Increased nociceptive responses were shown in the offspring of prenatally stressed rats. Reports have demonstrated the anti-nociceptive effects of Tualang honey in the rat offspring. The present study was done to determine whether the modulation of nociceptive behaviour by Tualang honey was mediated by modulating changes in the histology, oxidative stress parameters and N-methyl-D-aspartate (NMDA) receptors in the thalamus of the rat offspring. Methods: Eighteen Sprague Dawley pregnant rats were randomly assigned to control (C), stress (S) and stress-treated with Tualang honey (SH) groups. Stress was given in a form of restraint stress.Tualang honey was given to SH group from first day of pregnancy until delivery. Thirty-three adult male offspring were subjected to formalin test before they were sacrificed. Nociceptive behaviour score, number of neurons, level of oxidative stress parameters and NMDA receptors in the thalamus were analysed by using one-way ANOVA. Results: The study demonstrated a significant decrease in mean nociceptive behaviour score (p<0.05) with lower malondialdehyde (MDA, p<0.05) and higher superoxide dismutase SOD and catalase levels in the thalamus of SH group compared to S group (p<0.05). There was also increased Nissl positive neurons in the thalamus of SH group compared to S group. There was no significant difference in NMDA receptor level between S and SH groups. Conclusion: The modulation of nociceptive responses in the prenatally stressed rat offspring by Tualang honey was associated with improvement in oxidative stress parameters and histology of the thalamus in the rat offspring exposed to prenatal stress.

Recent evidence has exhibited dietary influence on the manifestation of depressive-like behaviour induced by stressor tasks. The present study examined the effects of Tualang honey supplement administered with the goal of preventing or attenuating the occurrence of depressive-like behaviour in male rats subjected to noise stress. Forty-eight adult male rats were randomly divided into the following groups: i) nonstressed with placebo, ii) nonstressed with honey, iii) stressed with placebo, and iv) stressed with honey. Tualang honey (200 mg/kg body weight) was administered for 28 days. Stressed rats were subjected to loud noise 100 dB(A) 4 hours daily for 14 days. Forced swimming test was performed to evaluate depressive-like behaviour. Stressed control rats displayed significant increase in depressive-like behaviour, serum adrenocorticotropic hormone (ACTH), corticosterone, and brain oxidative stress markers levels, with significant decrease in antioxidant enzymes activities and tota...

The generation of the most abundant neurons of the cerebellum, the granule cells, relies on a balance between clonal expansion and apoptosis during the first 10 days after birth in the external germinal layer (EGL). The amino acid glutamate controls such critical phases of cell development in other systems through specific receptors such as metabotropic glutamate receptor 5 (mGlu 5 R). However, the function of mGlu 5 Rs on the proliferation and survival of granule cell precursors (GCPs) remains elusive. We found mGlu 5 R mRNA transcripts in EGL using RT-PCR and observed mGlu 5 R-mediated Ca 2+ responses in GCPs in acute slices as early as postnatal day (P) 2-3. Using in vivo injections of the selective non-competitive mGlu 5 R antagonist 2-Methyl-6-(phenylethynyl)pyridine (MPEP) in P7-9 mice, we found a 20% increase in the number of proliferative GCPs labeled at P7 with the S-phase marker bromodeoxyuridine (BrdU), but no increase in cell proliferation examined 2 hours following a BrdU injection. Furthermore, similar treatments led to a significant 70% decrease in the number of apoptotic GCPs in the EGL as determined by TUNEL staining. In contrast, in vivo treatment with the mGlu 5 R agonist (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG) resulted in a ~60% increase in the number of TUNELlabeled GCPs compared to control. These findings identify a unique role for glutamate acting at mGlu 5 Rs as a functional switch regulating GCP survival in the EGL, thus controlling the total number of cerebellar granule cells produced.

The generation of the most abundant neurons of the cerebellum, the granule cells, relies on a balance between clonal expansion and apoptosis during the first 10 days after birth in the external germinal layer (EGL). The amino acid glutamate controls such critical phases of cell development in other systems through specific receptors such as metabotropic glutamate receptor 5 (mGlu 5 R). However, the function of mGlu 5 Rs on the proliferation and survival of granule cell precursors (GCPs) remains elusive. We found mGlu 5 R mRNA transcripts in EGL using RT-PCR and observed mGlu 5 R-mediated Ca 2+ responses in GCPs in acute slices as early as postnatal day (P) 2-3. Using in vivo injections of the selective non-competitive mGlu 5 R antagonist 2-Methyl-6-(phenylethynyl)pyridine (MPEP) in P7-9 mice, we found a 20% increase in the number of proliferative GCPs labeled at P7 with the S-phase marker bromodeoxyuridine (BrdU), but no increase in cell proliferation examined 2 hours following a BrdU injection. Furthermore, similar treatments led to a significant 70% decrease in the number of apoptotic GCPs in the EGL as determined by TUNEL staining. In contrast, in vivo treatment with the mGlu 5 R agonist (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG) resulted in a ~60% increase in the number of TUNELlabeled GCPs compared to control. These findings identify a unique role for glutamate acting at mGlu 5 Rs as a functional switch regulating GCP survival in the EGL, thus controlling the total number of cerebellar granule cells produced.

Direct videomicroscopic visualization of organ formation and regeneration in toto is a powerful strategy to study cellular processes that often cannot be replicated in vitro. Intravital imaging aims at quantifying changes in tissue architecture or subcellular organization over time during organ development, regeneration or degeneration. A general feature of this approach is its reliance on the optical isolation of defined cell types in the whole animals by transgenic expression of fluorescent markers. Here we describe a simple and robust method to analyze sensory hair-cell development and regeneration in the zebrafish lateral line by high-resolution intravital imaging using laser-scanning confocal microscopy (LSCM) and selective plane illumination microscopy (SPIM). The main advantage of studying hair-cell regeneration in the lateral line is that it occurs throughout the life of the animal, which allows its study in the most natural context. We detail protocols to achieve continuous videomicroscopy for up to 68 hours, enabling direct observation of cellular behavior, which can provide a sensitive assay for the quantitative classification of cellular phenotypes and cell-lineage reconstruction. Modifications to this protocol should facilitate pharmacogenetic assays to identify or validate otoprotective or reparative drugs for future clinical strategies aimed at preserving aural function in humans.

Repetitive motor behaviors are common in neurodevelopmental, psychiatric, and neurological disorders. Despite their prevalence in certain clinical populations, our understanding of the neurobiological cause of repetitive behavior is lacking. Likewise, not knowing the pathophysiology has precluded efforts to find effective drug treatments. Our comparisons between mouse strains that differ in their expression of repetitive behavior revealed an important role of the subthalamic nucleus. In mice with high rates of repetitive behavior, we found significant differences in dendritic spine density, gene expression, and neuronal activation in the subthalamic nucleus. Taken together, these data demonstrate a hypoglutamatergic state. Furthermore, by using environmental enrichment to reduce repetitive behavior, we found evidence of increased glutamatergic tone in the subthalamic nucleus with our measures of spine density and gene expression. These results suggest the subthalamic nucleus is a major contributor to repetitive behavior expression and highlight the potential of drugs that increase subthalamic nucleus function to reduce repetitive behavior in clinical populations.

Repetitive motor behaviors are observed in many neurodevelopmental and neurological disorders (e.g. autism spectrum disorders, Tourette syndrome, fronto-temporal dementia). Despite their clinical importance, the neurobiology underlying these highly stereotyped, apparently functionless behaviors is poorly understood. Identification of mechanisms that mediate the development of repetitive behaviors will aid in the discovery of new therapeutic targets and treatment development. Using a deer mouse model, we have shown that decreased indirect basal ganglia pathway activity is associated with high levels of repetitive behavior. Environmental enrichment (EE) markedly attenuates the development of such aberrant behaviors in mice, although mechanisms driving this effect are unknown. We hypothesized that EE would reduce repetitive motor behaviors by increasing indirect basal ganglia pathway function. We assessed neuronal activation and dendritic spine density in basal ganglia of adult deer mi...

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that involves cognitive decline and dementia. To model the hippocampal neurodegeneration and memory-related behavioral impairment that occurs in FTLD and other tau and TDP-43 proteinopathy diseases, we used an adeno-associated virus serotype 9 (AAV9) vector to induce bilateral expression of either microtubule-associated protein tau or transactive response DNA binding protein 43 kDa (TDP-43) in adult rat dorsal hippocampus. Human wild-type forms of tau or TDP-43 were expressed. The vectors/doses were designed for moderate expression levels within neurons. Rats were evaluated for acquisition and retention in the Morris water task over 12 weeks after gene transfer. Neither vector altered acquisition performance compared to controls. In measurements of retention, there was impairment in the TDP-43 group. Histological examination revealed specific loss of dentate gyrus granule cells and concomitant gliosis proximal to the injection site in the TDP-43 group, with shrinkage of the dorsal hippocampus. Despite specific tau pathology, the tau gene transfer surprisingly did not cause obvious neuronal loss or behavioral impairment. The data demonstrate that TDP-43 produced mild behavioral impairment and hippocampal neurodegeneration in rats, whereas tau did not. The models could be of value for studying mechanisms of FTLD and other diseases with tau and TDP-43 pathology in the hippocampus including Alzheimer's disease, with relevance to early stage mild impairment.

Tauopathy in the hippocampus is one of the earliest cardinal features of Alzheimer's disease (AD), a condition characterized by progressive memory impairments. In fact, density of tau neurofibrillary tangles (NFTs) in the hippocampus strongly correlates with severity of cognitive impairments in AD. In the present study, we employed a somatic cell gene transfer technique to create a rodent model of tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the hippocampus of adult rats. The P301L mutation is causal for frontotemporal dementia with parkinsonism-17 (FTDP-17), but it has been used for studying memory effects characteristic of AD in transgenic mice. To ascertain if P301L-induced mnemonic deficits are persistent, animals were tested for 6 months. It was hypothesized that adultonset, spatially restricted tau expression in the hippocampus would produce progressive spatial working memory deficits on a learned alternation task. Rats injected with the tau vector exhibited persistent impairments on the hippocampal-dependent task beginning at about 6 weeks posttransduction compared to rats injected with a green fluorescent protein vector. Histological analysis of brains for expression of human tau revealed hyperphosphorylated human tau and NFTs in the hippocampus in experimental animals only. Thus, adult-onset, vector-induced tauopathy spatially restricted to the hippocampus progressively impaired spatial working memory in rats. We conclude that the model faithfully reproduces histological and behavioral findings characteristic of dementing tauopathies. The rapid onset of sustained memory impairment establishes a preclinical model particularly suited to the development of potential tauopathy therapeutics.