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The corticospinal and rubrospinal tracts are the predominant tracts for controlling skilled hand function. Injuries to these tracts impair grasping but not gross motor functions such as overground locomotion. The aim of the present study was to determine whether or not, after damage to both the corticospinal and rubrospinal tracts, other spared subcortical motor pathway can mediate the recovery of skilled hand function. Adult rats received a bilateral injury to the corticospinal tract at the level of the medullar pyramids and a bilateral ablation of the rubrospinal axons at C4. One group of rats received, acutely after injury, two injections of chondroitinase-ABC at C7, and starting at 7days post-injury were enrolled in daily reaching and grasping rehabilitation (CHASE group, n=5). A second group of rats received analogous injections of ubiquitous penicillinase, and did not undergo rehabilitation (PEN group, n=5). Compared to rats in the PEN group, CHASE rats gradually recovered the ability to reach and grasp over 42days after injury. Overground locomotion was mildly affected after injury and both groups followed similar recovery. Since the reticulospinal tract plays a predominant role in motor control, we further investigated whether or not plasticity of this pathway could contribute to the animal's recovery. Reticulospinal axons were anterogradely traced in both groups of rats. The density of reticulospinal processes in both the normal and ectopic areas of the grey ventral matter of the caudal segments of the cervical spinal cord was greater in the CHASE than PEN group. The results indicate that after damage to spinal tracts that normally mediate the control of reaching and grasping in rats other complementary spinal tracts can acquire the role of those damaged tracts and promote task-specific recovery.

Objective: To explore the microstructural damage of extrapyramidal system gray matter nuclei in Parkinson disease (PD) using diffusion kurtosis imaging (DKI).Materials and Methods: We enrolled 35 clinically confirmed PD patients and 23 healthy volunteers. All patients underwent MR examination with conventional MRI scan sequences and an additional DKI sequence. We subsequently reconstructed the DKI raw images and analyzed the data. A radiologist in our hospital collected the Mini-Mental State Examination (MMSE) score of all subjects.Results: In the PD group, the mean kurtosis and axial kurtosis level decreased in the red nucleus (RN) and thalamus; the radial kurtosis increased in the substantia nigra (SN) and globus pallidus (GP). Fractional anisotropy decreased in the putamen. The largest area under the ROC curve of mean diffusion in GP was 0.811. Most kurtosis parameters demonstrated a positive correlation with the MMSE score, while several diffusion parameters showed a negative correlation with the same.Conclusion: DKI can qualitatively distinguish PD from healthy controls; furthermore, DKI-derived parameters can quantitatively evaluate the modifications of microstructures in extrapyramidal system gray matter nucleus in PD.

Objective: To explore the microstructural damage of extrapyramidal system gray matter nuclei in Parkinson disease (PD) using diffusion kurtosis imaging (DKI). Materials and Methods: We enrolled 35 clinically confirmed PD patients and 23 healthy volunteers. All patients underwent MR examination with conventional MRI scan sequences and an additional DKI sequence. We subsequently reconstructed the DKI raw images and analyzed the data. A radiologist in our hospital collected the Mini-Mental State Examination (MMSE) score of all subjects. Results: In the PD group, the mean kurtosis and axial kurtosis level decreased in the red nucleus (RN) and thalamus; the radial kurtosis increased in the substantia nigra (SN) and globus pallidus (GP). Fractional anisotropy decreased in the putamen. The largest area under the ROC curve of mean diffusion in GP was 0.811. Most kurtosis parameters demonstrated a positive correlation with the MMSE score, while several diffusion parameters showed a negative correlation with the same. Conclusion: DKI can qualitatively distinguish PD from healthy controls; furthermore, DKI-derived parameters can quantitatively evaluate the modifications of microstructures in extrapyramidal system gray matter nucleus in PD. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the safety of 3-monthly paliperidone palmitate (PP3M) vs once-monthly paliperidone palmitate (PP1M) treatment with regard to extrapyramidal symptom (EPS)-related treatment-emergent adverse events (TEAEs) in patients with schizophrenia, previously stabilized on PP1M treatment.Patients and methods: Data on overall incidence, time to onset (TTO), and time to resolution (TTR) of EPS-related TEAEs (overall, subclasses such as dyskinesia, dystonia, hyperkinesia, parkinsonism, and tremor) from a randomized double-blind (DB) non-inferiority study were compared between PP3M and PP1M. Subgroup analysis was performed by age (18–25, 26–50, and 50+ years) and final open-label (OL) dose (50/75, 100, and 150 mg eq.).Results: Overall incidence of spontaneously reported EPS-related TEAEs decreased from 12.6% (PP1M) in OL phase to 8.3% (PP3M) and 7.4% (PP1M) in the DB phase; overall median TTO and TTR values were comparable between both groups. Among patients with reported EPS-related TEAEs, the median TTO for all EPS-related TEAEs was 17 days (PP1M) in OL phase and 115 days (PP3M) and 98.5 days (PP1M) in DB phase; median TTR was 36.5 days (PP1M) in OL phase and 91 days (PP3M) and 85.5 days (PP1M) in DB phase. No clear dose- or age-related differences in TTO and TTR of EPS-related TEAEs were noted.Conclusion: Despite differences in apparent half-life and pharmacokinetic profiles (peak plasma exposure of PP3M formulation is 70% higher than that of PP1M formulation), both PP3M and PP1M formulations exhibited comparable incidence of EPS-related TEAEs, TTO, and TTR in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Objective: Frameless stereotactic aspiration of a hematoma can be the one of the treatment options for spontaneous intracerebral hemorrhage in the basal ganglia. Postoperative hematoma enlargement, however, can be a serious complication of intracranial surgery that frequently results in severe neurological deficit and even death. Therefore, it is important to identify the risk factors of postoperative hematoma growth. Methods: During a 13-year period, 101 patients underwent minimally invasive frameless stereotactic aspiration for basal ganglia hematoma. Patients were classified into two groups according to whether or not they had postoperative hematoma enlargement in a computed tomography scan. Baseline demographic data and several risk factors, such as hypertension, preoperative hematoma growth, antiplatelet medication, presence of concomitant intraventricular hemorrhage (IVH), were analysed via a univariate statistical study. Results: Nine of 101 patients (8.9%) showed hematoma enlargement after frameless stereotactic aspiration. Among the various risk factors, concomitant IVH and antiplatelet medication were found to be significantly associated with postoperative enlargement of hematomas. Conclusion: In conclusion, our study revealed that aspirin use and concomitant IVH are factors associated with hematoma enlargement subsequent to frameless stereotactic aspiration for basal ganglia hematoma. [ABSTRACT FROM AUTHOR]

The present study aimed to observe the structural changes of the extracorticospinal tract in Parkinson's disease (PD) using susceptibility-weighted imaging (SWI) and diffusion tensor imaging (DTI) magnetic resonance (MR) scans. The association of DTI parameters and brain-iron accumulation with PD was examined and imaging signs useful in the diagnosis of PD were explored. The study included 30 patients with PD and 30 age- and gender-matched healthy controls who underwent routine MR, SWI and DTI scans. The corrected phase (CP) values of the substantia nigra (SN), red nucleus (RN), globus pallidus (GP) and putamen (PUT) were measured, and fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained. Significant differences were found in the CP values between the PD and control groups in the SN, RN and PUT, but there were no differences in other regions of interest (ROIs). The FA values of the SN and PUT in the PD group were significantly decreased compared with those of the control group, but there was no significant difference in the FA values of the GP. Furthermore, there was no significant inter-group difference in the ADC values of any ROIs. In conclusion, SWI is a method useful for evaluating brain-iron deposition in PD. Increasing iron storage levels have previously been shown to be associated with PD pathogenesis but not with the degree of PD severity. FA values may be useful for diagnosing PD, and DTI may offer some insight into PD pathomechanisms and clinical diagnosis. [ABSTRACT FROM AUTHOR]

OBJETIVO: A presença de síndromes psiquiátricas, incluindo demência, associada a distúrbios motores tem sido cada vez mais reconhecida durante a última década, com destaque para o prejuízo cognitivo na doença de Parkinson idiopática. Esta revisão enfocará a epidemiologia, os aspectos clínicos, diagnósticos diferenciais, mecanismos subjacentes e o tratamento da demência na doença de Parkinson idiopática. MÉTODO: Uma revisão da literatura dos estudos que investigaram a demência da doença de Parkinson idiopática foi realizada. RESULTADOS: A demência é altamente prevalente na doença de Parkinson idiopática. O protótipo da demência na doença de Parkinson idiopática consiste numa síndrome disexecutiva com comprometimento da atenção, funções executivas e, secundariamente, a memória. Neuroquimicamente, o déficit mais significativo parece ser colinérgico; a demência se correlaciona com a presença de corpos de Lewy corticais e límbicos. Evidências preliminares sugerem que os anticolinesterásicos podem ser efetivos na demência da doença de Parkinson idiopática. CONCLUSÕES: O prejuízo cognitivo na doença de Parkinson idiopática é associado a características próprias e é responsável por importante incapacidade nestes pacientes.OBJECTIVE: The concomitant presence of psychiatric syndromes, including dementia, with motor disturbance has been increasingly recognized during the last decade, with emphasis on cognitive impairment in idiopatic Parkinson's disease. This review will focus on the epidemiology, clinical aspects, differential diagnosis, underlying mechanisms and treatment of dementia in Parkinson's disease. METHOD: A literature review of the studies that investigated the dementia in Parkinson's disease was performed. RESULTS: Dementia is highly prevalent in Parkinson's disease. The prototype of dementia in Parkinson's disease is a dysexecutive syndrome with impaired attention, executive functions and secondarily impaired memory. Neurochemically the most significant deficit seems to be cholinergic; dementia seems to correlate best with cortical and limbic Lewy bodies. Preliminary evidence suggests that cholinesterase inhibitors may be effective in Parkinson's disease dementia. CONCLUSIONS: Cognitive impairment in Parkinson's disease is associated to specific features and is responsible for substantial disability in these patients.

The author presents insights on the function of claustrum in information processing in the visual system. Topics discussed include the intrinsic excitatory connectivity of claustrum, the structural discontinuities in the anatomical structure of the claustrum, and how the brain operates in perception and cognition.

Background: The use of antipsychotic drugs, particularly quetiapine, has increased at an unprecedented rate in the last decade, primarily in relation to nonpsychotic indications. This increased use is concerning because of the high rates of metabolic and extrapyramidal side effects and inadequate monitoring of these complications. The purpose of this study was to measure the use of quetiapine and other second-generation antipsychotics by primary care physicians and psychiatrists and the most common diagnoses associated with quetiapine recommendations. Methods: We analyzed data on antipsychotic use from the IMS Brogan Canadian CompuScript Database and the Canadian Disease and Treatment Index, with a focus on quetiapine. We looked at the number of dispensed prescriptions for second-generation antipsychotics written by primary care physicians and psychiatrists and the diagnoses associated with recommendations for quetiapine from 2005 to 2012. Results: Between 2005 and 2012, there was a 300% increase in dispensed prescriptions for quetiapine ordered by family physicians: from 1.04 million in 2005 to 4.17 million in 2012. In comparison, dispensed prescriptions from family physicians for risperidone increased 37.4%: from 1.39 million in 2005 to 1.91 million in 2012; those for olanzapine increased 37.1%, from 0.97 million in 2005 to 1.33 million in 2012. Dispensed prescriptions for quetiapine ordered by psychiatrists increased 141.6%: from 0.87 million in 2005 to 2.11 million in 2012. The top 4 diagnoses associated with quetiapine in 2012 were mood disorders, psychotic disorders, anxiety disorders and sleep disturbances. A 10-fold increase in quetiapine recommendations for sleep disturbances was seen over the study period, with almost all coming from family physicians. Interpretation: These findings indicate a preferential increase in the use of quetiapine over other antipsychotic drugs and show that most of the increased use is a result of off-label prescribing by family physicians. [ABSTRACT FROM AUTHOR]

Goal-directed decision making in biological systems is broadly based on associations between conditional and unconditional stimuli. This can be further classified as classical conditioning (correlation-based learning) and operant conditioning (reward-based learning). A number of computational and experimental studies have well established the role of the basal ganglia in reward-based learning, where as the cerebellum plays an important role in developing specific conditioned responses. Although viewed as distinct learning systems, recent animal experiments point toward their complementary role in behavioral learning, and also show the existence of substantial two-way communication between these two brain structures. Based on this notion of co-operative learning, in this paper we hypothesize that the basal ganglia and cerebellar learning systems work in parallel and interact with each other. We envision that such an interaction is influenced by reward modulated heterosynaptic plasticity (RMHP) rule at the thalamus, guiding the overall goal directed behavior. Using a recurrent neural network actor-critic model of the basal ganglia and a feed-forward correlation-based learning model of the cerebellum, we demonstrate that the RMHP rule can effectively balance the outcomes of the two learning systems. This is tested using simulated environments of increasing complexity with a four-wheeled robot in a foraging task in both static and dynamic configurations. Although modeled with a simplified level of biological abstraction, we clearly demonstrate that such a RMHP induced combinatorial learning mechanism, leads to stabler and faster learning of goal-directed behaviors, in comparison to the individual systems. Thus, in this paper we provide a computational model for adaptive combination of the basal ganglia and cerebellum learning systems by way of neuromodulated plasticity for goal-directed decision making in biological and bio-mimetic organisms. [ABSTRACT FROM AUTHOR]

Electrophysiology studies routinely investigate the relationship between neural oscillations and task performance. However, the sluggish nature of the BOLD response means that few researchers have investigated the spectral properties of the BOLD signal in a similar manner. For the first time we have applied group ICA to fMRI data collected during a standard working memory task (delayed match-to-sample) and using a multivariate analysis,we investigate the relationship between working memory performance (accuracy and reaction time) and BOLD spectral power within functional networks. Our results indicate that BOLD spectral power within specific networks (visual, temporal-parietal, posterior default-mode network, salience network, basal ganglia) correlated with task accuracy. Multivariate analyses show that the relationship between task accuracy and BOLD spectral power is stronger than the relationship between BOLD spectral power and other variables (age, gender, head movement, and neuropsychological measures). A traditional General Linear Model (GLM) analysis found no significant group differences, or regions that covaried in signal intensity with task accuracy, suggesting that BOLD spectral power holds unique information that is lost in a standard GLM approach. We suggest that the combination of ICA and BOLD spectral power is a useful novel index of cognitive performance that may be more sensitive to brain-behavior relationships than traditional approaches. [ABSTRACT FROM AUTHOR]

Background: Producing sounds by a musical instrument can lead to audiomotor coupling, i.e. the joint activation of the auditory and motor system, even when only one modality is probed. The sonification of otherwise mute movements by sounds based on kinematic parameters of the movement has been shown to improve motor performance and perception of movements. Results: Here we demonstrate in a group of healthy young non-athletes that congruently (sounds match visual movement kinematics) vs. incongruently (no match) sonified breaststroke movements of a human avatar lead to better perceptual judgement of small differences in movement velocity. Moreover, functional magnetic resonance imaging revealed enhanced activity in superior and medial posterior temporal regions including the superior temporal sulcus, known as an important multisensory integration site, as well as the insula bilaterally and the precentral gyrus on the right side. Functional connectivity analysis revealed pronounced connectivity of the STS with the basal ganglia and thalamus as well as frontal motor regions for the congruent stimuli. This was not seen to the same extent for the incongruent stimuli. Conclusions: We conclude that sonification of movements amplifies the activity of the human action observation system including subcortical structures of the motor loop. Sonification may thus be an important method to enhance training and therapy effects in sports science and neurological rehabilitation. [ABSTRACT FROM AUTHOR]

Background Patients with obsessive-compulsive disorder (OCD) have highly idiosyncratic triggers. To fully understand which role this idiosyncrasy plays in the neurobiological mechanisms behind OCD, it is necessary to elucidate the impact of individualization regarding the applied investigation methods. This functional magnetic resonance imaging (fMRI) study explores the neural correlates of contamination/washing-related OCD with a highly individualized symptom provocation paradigm. Additionally, it is the first study to directly compare individualized and standardized symptom provocation. Methods Nineteen patients with washing compulsions created individual OCD hierarchies, which later served as instructions to photograph their own individualized stimulus sets. The patients and 19 case-by-case matched healthy controls participated in a symptom provocation fMRI experiment with individualized and standardized stimulus sets created for each patient. Results OCD patients compared to healthy controls displayed stronger activation in the basal ganglia (nucleus accumbens, nucleus caudatus, pallidum) for individualized symptom provocation. Using standardized symptom provocation, this group comparison led to stronger activation in the nucleus caudatus. The direct comparison of between-group effects for both symptom provocation approaches revealed stronger activation of the orbitofronto-striatal network for individualized symptom provocation. Conclusions The present study provides insight into the differential impact of individualized and standardized symptom provocation on the orbitofronto-striatal network of OCD washers. Behavioral and neural responses imply a higher symptom-specificity of individualized symptom provocation. [ABSTRACT FROM AUTHOR]

Phenytoin is one of the commonly used antiepileptic drugs. The common dose dependent and reversible neurological side effects of phenytoin are nystagmus, diplopia, dysarthria, ataxia, incoordination, chorioathetosis, orofacial dyskinesias and drowsiness. Persistent cerebellar dysfunction with cerebellar atrophy is a well known complication of long term phenytoin use. There are several mechanisms proposed including hypoxia due to frequent seizures or toxic effects of phenytoin on cerebellar Purkinje cells. However, irreversible cerebellar dysfunction following acute phenytoin intoxication is rare. We report a 20 year old female who presented with nystagmus, dysarthria, limb and truncal ataxia with orofacial dyskinesias and chorea. She also had cognitive and affective symptoms in the form of reduced attention, slow responses, lalling speech, blunting of affect, inappropriate laughter, reduced self care and executive dysfunction. The symptoms started 2 weeks following the initiation of phenytoin 300mg/ day, given prophylactically following left basal ganglia bleed. Her serum phenytoin was in toxic range, hence phenytoin was stopped. Her PET scan revealed bilateral cerebellar hypometabolism. At 6 months follow up, she had persistent ataxia with cognitive and affective dysfunction and follow up MRI showed diffuse cerebellar atrophy. The clinical and radiological findings suggest that acute phenytoin intoxication is responsible for persistent ataxia and cerebellar cognitive affective syndrome. [ABSTRACT FROM AUTHOR]

Key points The excitatory afferents to the striatum from the cortex and thalamus are critical in the expression of basal ganglia function., Thalamostriatal afferents are markedly heterogeneous and arise in different subnuclei of the intralaminar thalamus., We used an optogenetic approach, to isolate and selectively activate thalamostriatal afferents arising in the central lateral or parafascicular thalamic nuclei, and to study the properties of their synapses with principal striatal neurons, the medium-spiny neurons., Thalamostriatal synapses differ in many aspects and our data suggest that inputs from the central lateral nucleus are efficient drivers of medium-spiny neuron action potential firing, whereas inputs from the parafascicular nucleus are likely to be modulatory., These results suggest distinct roles for thalamostriatal inputs from different subnuclei of the thalamus and will help us understand how the striatal circuit operates in health and disease., Abstract To understand the principles of operation of the striatum it is critical to elucidate the properties of the main excitatory inputs from cortex and thalamus, as well as their ability to activate the main neurons of the striatum, the medium spiny neurons (MSNs). As the thalamostriatal projection is heterogeneous, we set out to isolate and study the thalamic afferent inputs to MSNs using small localized injections of adeno-associated virus carrying fusion genes for channelrhodopsin-2 and YFP, in either the rostral or caudal regions of the intralaminar thalamic nuclei (i.e. the central lateral or parafascicular nucleus). This enabled optical activation of specific thalamic afferents combined with whole-cell, patch-clamp recordings of MSNs and electrical stimulation of cortical afferents, in adult mice. We found that thalamostriatal synapses differ significantly in their peak amplitude responses, short-term dynamics and expression of ionotropic glutamate receptor subtypes. Our results suggest that central lateral synapses are most efficient in driving MSNs to depolarization, particularly those of the direct pathway, as they exhibit large amplitude responses, short-term facilitation and predominantly express postsynaptic AMPA receptors. In contrast, parafascicular synapses exhibit small amplitude responses, short-term depression and predominantly express postsynaptic NMDA receptors, suggesting a modulatory role, e.g. facilitating Ca2+-dependent processes. Indeed, pairing parafascicular, but not central lateral, presynaptic stimulation with action potentials in MSNs, leads to NMDA receptor- and Ca2+-dependent long-term depression at these synapses. We conclude that the main excitatory thalamostriatal afferents differ in many of their characteristics and suggest that they each contribute differentially to striatal information processing. [ABSTRACT FROM AUTHOR]

Small protein fragments, and not just residues, can be used as basic building blocks to reconstruct networks of coevolved amino acids in proteins. Fragments often enter in physical contact one with the other and play a major biological role in the protein. The nature of these interactions might be multiple and spans beyond binding specificity, allosteric regulation and folding constraints. Indeed, coevolving fragments are indicators of important information explaining folding intermediates, peptide assembly, key mutations with known roles in genetic diseases, distinguished subfamily-dependent motifs and differentiated evolutionary pressures on protein regions. Coevolution analysis detects networks of fragments interaction and highlights a high order organization of fragments demonstrating the importance of studying at a deeper level this structure. We demonstrate that it can be applied to protein families that are highly conserved or represented by few sequences, enlarging in this manner, the class of proteins where coevolution analysis can be performed and making large-scale coevolution studies a feasible goal. [ABSTRACT FROM AUTHOR]

It is now clear that non-consciously perceived stimuli can bias our decisions. Although previous researches highlighted the importance of automatic and unconscious processes involved in voluntary action, the neural correlates of such processes remain unclear. Basal ganglia dysfunctions have long been associated with impairment in automatic motor control. In addition, a key role of the medial frontal cortex has been suggested by administrating a subliminal masked prime task to a patient with a small lesion restricted to the supplementary motor area (SMA). In this task, invisible masked arrows stimuli were followed by visible arrow targets for a left or right hand response at different interstimuli intervals (ISI), producing a traditional facilitation effect for compatible trials at short ISI and a reversal inhibitory effect at longer ISI. Here, by using fast event-related fMRI and a weighted parametric analysis, we showed BOLD related activity changes in a cortico-subcortical network, especially in the SMA and the striatum, directly linked to the individual behavioral pattern. This new imaging result corroborates previous works on subliminal priming using lesional approaches. This finding implies that one of the roles of these regions was to suppress a partially activated movement below the threshold of awareness. [ABSTRACT FROM AUTHOR]

Background: Reports of neuroleptic malignant syndrome (NMS) induced by second-generation antipsychotic drugs highlight a propensity for atypical clinical presentations.Aims: To systematically compare the clinical profile of NMS induced by first- (1G-NMS) and second-generation antipsychotic drugs (2G-NMS).Method: The Australian Adverse Drug Reaction Advisory Committee (ADRAC) database was searched to identify individuals with NMS reported between April 1994 and September 2010. The clinical characteristics of 208 people with NMS induced by monotherapy with first- or second-generation antipsychotic drugs, as well as presenting features of NMS, were compared.Results: The individuals with 2G-NMS were younger and more likely to have a psychotic disorder diagnosis. The features of NMS in the two groups were very similar, except that people with 2G-NMS were less likely to present with rigidity or extrapyramidal signs compared with those with 1G-NMS. This difference was due to the lower rates of rigidity in those with clozapine-induced NMS. Mortality was considerably lower for those with 2G-NMS (3.0%) compared with 1G-NMS (16.3%), and the former were more likely to have received supportive treatment.Conclusions: The clinical profile of 2G-NMS is largely similar to 1G-NMS, with clozapine-induced NMS being differentiated by the relative lack of rigidity as a feature. Mortality is lower for 2G-NMS. [ABSTRACT FROM AUTHOR]

Background: The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. Both mechanisms rely on a dorsal frontoparietal network, while focalization additionally involves a ventral frontoparietal network. The role of subcortical structures in attention is less clear, despite the fact that the striatum interacts significantly with the frontal cortex via frontostriatal loops. One means of investigating the basal ganglia's contributions to attention is to examine the features of P300 components (i.e. amplitude, latency, and generators) in patients with basal ganglia damage (such as in Parkinson's disease (PD), in which attention is often impaired). Three-stimulus oddball paradigms can be used to study distracter-elicited and target-elicited P300 subcomponents. Methodology/Principal Findings: In order to compare distracter- and target-elicited P300 components, high-density (128-channel) electroencephalograms were recorded during a three-stimulus visual oddball paradigm in 15 patients with early PD and 15 matched healthy controls. For each subject, the P300 sources were localized using standardized weighted low-resolution electromagnetic tomography (swLORETA). Comparative analyses (one-sample and two-sample t-tests) were performed using SPM5® software. The swLORETA analyses showed that PD patients displayed fewer dorsolateral prefrontal (DLPF) distracter-P300 generators but no significant differences in target-elicited P300 sources; this suggests dysfunction of the DLPF cortex when the executive frontostriatal loop is disrupted by basal ganglia damage. Conclusions/Significance: Our results suggest that the cortical attention frontoparietal networks (mainly the dorsal one) are modulated by the basal ganglia. Disruption of this network in PD impairs resistance to distracters, which results in attention disorders. [ABSTRACT FROM AUTHOR]

In basal ganglia a significant subset of GABAergic medium spiny neurons (MSNs) coexpress D1 and D2 receptors (D1R and D2R) along with the neuropeptides dynorphin (DYN) and enkephalin (ENK). These coexpressing neurons have been recently shown to have a region-specific distribution throughout the mesolimbic and basal ganglia circuits. While the functional relevance of these MSNs remains relatively unexplored, they have been shown to exhibit the unique property of expressing the dopamine D1-D2 receptor heteromer, a novel receptor complex with distinct pharmacology and cell signaling properties. Here we showed that MSNs coexpressing the D1R and D2R also exhibited a dual GABA/glutamate phenotype. Activation of the D1R-D2R heteromer in these neurons resulted in the simultaneous, but differential regulation of proteins involved in GABA and glutamate production or vesicular uptake in the nucleus accumbens (NAc), ventral tegmental area (VTA), caudate putamen and substantia nigra (SN). Additionally, activation of the D1R-D2R heteromer in NAc shell, but not NAc core, differentially altered protein expression in VTA and SN, regions rich in dopamine cell bodies. The identification of a MSN with dual inhibitory and excitatory intrinsic functions provides new insights into the neuroanatomy of the basal ganglia and demonstrates a novel source of glutamate in this circuit. Furthermore, the demonstration of a dopamine receptor complex with the potential to differentially regulate the expression of proteins directly involved in GABAergic inhibitory or glutamatergic excitatory activation in VTA and SN may potentially provide new insights into the regulation of dopamine neuron activity. This could have broad implications in understanding how dysregulation of neurotransmission within basal ganglia contributes to dopamine neuronal dysfunction. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) and basal ganglia dysfunction impair movement timing, which leads to gait instability and falls. Parkinsonian gait consists of random, disconnected stride times-rather than the 1/f structure observed in healthy gait- and this randomness of stride times (low fractal scaling) predicts falling. Walking with fixed-tempo Rhythmic Auditory Stimulation (RAS) can improve many aspects of gait timing; however, it lowers fractal scaling (away from healthy 1/f structure) and requires attention. Here we show that interactive rhythmic auditory stimulation reestablishes healthy gait dynamics in PD patients. In the experiment, PD patients and healthy participants walked with a) no auditory stimulation, b) fixed-tempo RAS, and c) interactive rhythmic auditory stimulation. The interactive system used foot sensors and nonlinear oscillators to track and mutually entrain with the human's step timing. Patients consistently synchronized with the interactive system, their fractal scaling returned to levels of healthy participants, and their gait felt more stable to them. Patients and healthy participants rarely synchronized with fixed-tempo RAS, and when they did synchronize their fractal scaling declined from healthy 1/f levels. Five minutes after removing the interactive rhythmic stimulation, the PD patients' gait retained high fractal scaling, suggesting that the interaction stabilized the internal rhythm generating system and reintegrated timing networks. The experiment demonstrates that complex interaction is important in the (re)emergence of 1/f structure in human behavior and that interactive rhythmic auditory stimulation is a promising therapeutic tool for improving gait of PD patients. [ABSTRACT FROM AUTHOR]

Positive feedback plays a key role in the ability of signaling molecules to form highly localized clusters in the membrane or cytosol of cells. Such clustering can occur in the absence of localizing mechanisms such as pre-existing spatial cues, diffusional barriers, or molecular cross-linking. What prevents positive feedback from amplifying inevitable biological noise when an un-clustered "off" state is desired? And, what limits the spread of clusters when an "on" state is desired? Here, we show that a minimal positive feedback circuit provides the general principle for both suppressing and amplifying noise: below a critical density of signaling molecules, clustering switches off; above this threshold, highly localized clusters are recurrently generated. Clustering occurs only in the stochastic regime, suggesting that finite sizes of molecular populations cannot be ignored in signal transduction networks. The emergence of a dominant cluster for finite numbers of molecules is partly a phenomenon of random sampling, analogous to the fixation or loss of neutral mutations in finite populations. We refer to our model as the "neutral drift polarity model." Regulating the density of signaling molecules provides a simple mechanism for a positive feedback circuit to robustly switch between clustered and un-clustered states. The intrinsic ability of positive feedback both to create and suppress clustering is a general mechanism that could operate within diverse biological networks to create dynamic spatial organization. [ABSTRACT FROM AUTHOR]

The striatum is the main input station of the basal ganglia and is strongly associated with motor and cognitive functions. Anatomical evidence suggests that individual striatal neurons are unlikely to share their inputs from the cortex. Using a biologically realistic large-scale network model of striatum and cortico-striatal projections, we provide a functional interpretation of the special anatomical structure of these projections. Specifically, we show that weak pairwise correlation within the pool of inputs to individual striatal neurons enhances the saliency of signal representation in the striatum. By contrast, correlations among the input pools of different striatal neurons render the signal representation less distinct from background activity. We suggest that for the network architecture of the striatum, there is a preferred cortico-striatal input configuration for optimal signal representation. It is further enhanced by the low-rate asynchronous background activity in striatum, supported by the balance between feedforward and feedback inhibitions in the striatal network. Thus, an appropriate combination of rates and correlations in the striatal input sets the stage for action selection presumably implemented in the basal ganglia. [ABSTRACT FROM AUTHOR]

Inhibitory motor control is a core function of cognitive control. Evidence from diverse experimental approaches has linked this function to a mostly right-lateralized network of cortical and subcortical areas, wherein a signal from the frontal cortex to the basal ganglia is believed to trigger motor-response cancellation. Recently, however, it has been recognized that in the context of typical motor-control paradigms those processes related to actual response inhibition and those related to the attentional processing of the relevant stimuli are highly interrelated and thus difficult to distinguish. Here, we used fMRI and a modified Stop-signal task to specifically examine the role of perceptual and attentional processes triggered by the different stimuli in such tasks, thus seeking to further distinguish other cognitive processes that may precede or otherwise accompany the implementation of response inhibition. In order to establish which brain areas respond to sensory stimulation differences by rare Stop-stimuli, as well as to the associated attentional capture that these may trigger irrespective of their task-relevance, we compared brain activity evoked by Stop-trials to that evoked by Go-trials in task blocks where Stop-stimuli were to be ignored. In addition, region-of-interest analyses comparing the responses to these task-irrelevant Stop-trials, with those to typical relevant Stop-trials, identified separable activity profiles as a function of the task-relevance of the Stop-signal. While occipital areas were mostly blind to the task-relevance of Stop-stimuli, activity in temporo-parietal areas dissociated between task-irrelevant and task-relevant ones. Activity profiles in frontal areas, in turn, were activated mainly by task-relevant Stop-trials, presumably reflecting a combination of triggered top-down attentional influences and inhibitory motor-control processes. [ABSTRACT FROM AUTHOR]

Structural, neurochemical, and functional abnormalities have been identified in the brains of individuals with bipolar disorder, including in key brain structures implicated in postural control, i.e. the cerebellum, brainstem, and basal ganglia. Given these findings, we tested the hypothesis that postural control deficits are present in individuals with bipolar disorder. Sixteen participants with bipolar disorder (BD) and 16 age-matched non-psychiatric healthy controls were asked to stand as still as possible on a force platform for 2 minutes under 4 conditions: (1) eyes open-open base; (2) eyes closed-open base; (3) eyes open-closed base; and (4) eyes closed-closed base. Postural sway data were submitted to conventional quantitative analyses of the magnitude of sway area using the center of pressure measurement. In addition, data were submitted to detrended fluctuation analysis, a nonlinear dynamical systems analytic technique that measures complexity of a time-series, on both the anterior-posterior and medio-lateral directions. The bipolar disorder group had increased sway area, indicative of reduced postural control. Decreased complexity in the medio-lateral direction was also observed for the bipolar disorder group, suggesting both a reduction in dynamic range available to them for postural control, and that their postural corrections were primarily dominated by longer time-scales. On both of these measures, significant interactions between diagnostic group and visual condition were also observed, suggesting that the BD participants were impaired in their ability to make corrections to their sway pattern when no visual information was available. Greater sway magnitude and reduced complexity suggest that individuals with bipolar disorder have deficits in sensorimotor integration and a reduced range of timescales available on which to make postural corrections. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted to identify neurological reasons for migraine disease. It has been stated that for the study, brain functions and morphology of patients with very low frequency of migraine attacks and patients with very high frequency of migraine attacks have been compared. It has been stated that study results showed significant role of the basal ganglia in the pathophysiology of the episodic migraine.

Machado-Joseph Disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), represents the most common form of SCA worldwide. MJD is an autosomal dominant neurodegenerative disorder of late onset, involving predominantly the cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems; although sharing features with other SCAs, the identification of minor, but more specific signs, facilitates its differential diagnosis. MJD presents strong phenotypic heterogeneity, which has justified the classification of patients into three main clinical types. Main pathological lesions are observed in the spinocerebellar system, as well as in the cerebellar dentate nucleus. MJD's causative mutation consists in an expansion of an unstable CAG tract in exon 10 of the ATXN3 gene, located at 14q32.1. Haplotype-based studies have suggested that two main founder mutations may explain the present global distribution of the disease; the ancestral haplotype is of Asian origin, and has an estimated age of around 5,800 years, while the second mutational event has occurred about 1,400 years ago. The ATXN3 gene encodes for ataxin-3, which is ubiquitously expressed in neuronal and non-neuronal tissues, and, among other functions, is thought to participate in cellular protein quality control pathways. Mutated ATXN3 alleles consensually present about 61 to 87 CAG repeats, resulting in an expanded polyglutamine tract in ataxin-3. This altered protein gains a neurotoxic function, through yet unclear mechanisms. Clinical variability of MJD is only partially explained by the size of the CAG tract, which leaves a residual variance that should be explained by still unknown additional factors. Several genetic tests are available for MJD, and Genetic Counseling Programs have been created to better assist the affected families, namely on what concerns the possibility of pre-symptomatic testing. The main goal of this review was to bring together updated knowledge on MJD, covering several aspects from its initial descriptions and clinical presentation, through the discovery of the causative mutation, its origin and dispersion, as well as molecular genetics aspects considered essential for a better understanding of its neuropathology. Issues related with molecular testing and Genetic Counseling, as well as recent progresses and perspectives on genetic therapy, are also addressed. [ABSTRACT FROM AUTHOR]

Cocaine is one of the most widely abused drugs all over the world which is associated with the occurrence of ischemic events and bleeding in the central nervous system and cardiovascular system. This is because of various factors including: vasospasm. cerebral vasculitis, increased platelet aggregation, cardioembolism and hypertensive emergencies associated with impaired cerebral autoregulation. We describe a case of a patient who is admitted with acute intoxication due to cocaine and heroin aspiration. Presenting with acute myocardial infarction (AMI) with ST segment elevation in V1, V2 and V3, increased troponin, hypomagnesemia, hyperkalemia, hypocalcemia, mixed acidosis, aspiration pneumonia, depression of consciousness with shallow breathing, cyanosis and withdrawal syndrome which was treated with haloperidol at intensive care unit. Then, the patient presents with extra pyramidalism suggesting the appearance of an adverse event with this treatment. For this reason. haloperidol was suspended and biperidene and bromocriptine were started without total remission of symptoms. Finally, basal ganglia ischemia was evidenced by magnetic resonance imaging. The aim of this report is to describe the clinical manifestations associated with the atypical consumption of these two psychoactive substances that were consumed by this patient as well as a therapeutic approach to the triggered disease. [ABSTRACT FROM AUTHOR]

Transgenic mice expressing eGFP under population specific promoters are widely used in neuroscience to identify specific subsets of neurons in situ and as sensors of neuronal activity in vivo. Mice expressing eGFP from a bacterial artificial chromosome under the Nr4a1 promoter have high expression within the basal ganglia, particularly within the striosome compartments and striatal-like regions of the extended amygdala (bed nucleus of the stria terminalis, striatal fundus, central amygdaloid nucleus and intercalated cells). Grossly, eGFP expression is inverse to the matrix marker calbindin 28K and overlaps with mu-opioid receptor immunoreactivity in the striatum. This pattern of expression is similar to Drd1, but not Drd2, dopamine receptor driven eGFP expression in structures targeted by medium spiny neuron afferents. Striosomal expression is strong developmentally where Nr4a1-eGFP expression overlaps with Drd1, TrkB, tyrosine hydroxylase and phospho-ERK, but not phospho-CREB, immunoreactivity in ''dopamine islands''. Exposure of adolescent mice to methylphenidate resulted in an increase in eGFP in both compartments in the dorsolateral striatum but eGFP expression remained brighter in the striosomes. To address the role of activity in Nr4a1-eGFP expression, primary striatal cultures were prepared from neonatal mice and treated with forskolin, BDNF, SKF-83822 or high extracellular potassium and eGFP was measured fluorometrically in lysates. eGFP was induced in both neurons and contaminating glia in response to forskolin but SKF-83822, brain derived neurotrophic factor and depolarization increased eGFP in neuronal-like cells selectively. High levels of eGFP were primarily associated with Drd1+ neurons in vitro detected by immunofluorescence; however ∼15% of the brightly expressing cells contained punctate met-enkephalin immunoreactivity. The Nr4a1-GFP mouse strain will be a useful model for examining the connectivity, physiology, activity and development of the striosome system. Citation: Davis MI, Puhl HL III (2011) Nr4a1-eGFP Is a Marker of Striosome-Matrix Architecture, Development and Activity in the Extended Striatum [ABSTRACT FROM AUTHOR]

Parkinson's disease is a neurodegenerative disorder manifesting in debilitating motor symptoms. This disorder is characterized by abnormal activity throughout the cortico-basal ganglia loop at both the single neuron and network levels. Previous neurophysiological studies have suggested that the encoding of movement in the parkinsonian state involves correlated activity and synchronized firing patterns. In this study, we used multi-electrode recordings to directly explore the activity of neurons from the globus pallidus of parkinsonian primates during passive limb movements and to determine the extent to which they interact and synchronize. The vast majority (80/103) of the recorded pallidal neurons responded to periodic flexion-extension movements of the elbow. The response pattern was sinusoidal-like and the timing of the peak response of the neurons was uniformly distributed around the movement cycle. The interaction between the neuronal activities was analyzed for 123 simultaneously recorded pairs of neurons. Movement-based signal correlation values were diverse and their mean was not significantly different from zero, demonstrating that the neurons were not activated synchronously in response to movement. Additionally, the difference in the peak responses phase of pairs of neurons was uniformly distributed, showing their independent firing relative to the movement cycle. Our results indicate that despite the widely distributed activity in the globus pallidus of the parkinsonian primate, movement encoding is dispersed and independent rather than correlated and synchronized, thus contradicting current views that posit synchronous activation during Parkinson's disease. [ABSTRACT FROM AUTHOR]

Objectives: In the search for neurobiological correlates of depression, a major finding is hyperactivity in limbic-paralimbic regions. However, results so far have been inconsistent, and the stimuli used are often unspecific to depression. This study explored hemodynamic responses of the brain in patients with depression while processing individualized and clinically derived stimuli. Methods: Eighteen unmedicated patients with recurrent major depressive disorder and 17 never-depressed control subjects took part in standardized clinical interviews from which individualized formulations of core interpersonal dysfunction were derived. In the patient group such formulations reflected core themes relating to the onset and maintenance of depression. In controls, formulations reflected a major source of distress. This material was thereafter presented to subjects during functional magnetic resonance imaging (fMRI) assessment. Results: Increased hemodynamic responses in the anterior cingulate cortex, medial frontal gyrus, fusiform gyrus and occipital lobe were observed in both patients and controls when viewing individualized stimuli. Relative to control subjects, patients with depression showed increased hemodynamic responses in limbic-paralimbic and subcortical regions (e.g. amygdala and basal ganglia) but no signal decrease in prefrontal regions. Conclusions: This study provides the first evidence that individualized stimuli derived from standardized clinical interviewing can lead to hemodynamic responses in regions associated with self-referential and emotional processing in both groups and limbic-paralimbic and subcortical structures in individuals with depression. Although the regions with increased responses in patients have been previously reported, this study enhances the ecological value of fMRI findings by applying stimuli that are of personal relevance to each individual's depression. [ABSTRACT FROM AUTHOR]

The songbird area X is a basal ganglia homolog that contains two pallidal cell types--local neurons that project within the basal ganglia and output neurons that project to the thalamus. Based on these projections, it has been proposed that these classes are structurally homologous to the primate external (GPe) and internal (GPi) pallidal segments. To test the hypothesis that the two area X pallidal types are functionally homologous to GPe and GPi neurons, we recorded from neurons in area X of singing juvenile male zebra finches, and directly compared their firing patterns to neurons recorded in the primate pallidus. In area X,wefound two cell classes that exhibited high firing (HF) rates (>60 Hz) characteristic of pallidal neurons. HF-1 neurons, like most GPe neurons we examined, exhibited large firing rate modulations, including bursts and long pauses. In contrast, HF-2 neurons, like GPi neurons, discharged continuously without bursts or long pauses. To test whether HF-2 neurons were the output neurons that project to the thalamus, we next recorded directly from pallidal axon terminals in thalamic nucleus DLM, and found that all terminals exhibited singing-related firing patterns indistinguishable from HF-2 neurons. Our data show that singing-related neural activity distinguishes two putative pallidal cell types in area X: thalamusprojecting neurons that exhibit activity similar to the primate GPi, and non-thalamus-projecting neurons that exhibit activity similar to the primate GPe. These results suggest that song learning in birds and motor learning in mammals use conserved basal ganglia signaling strategies. [ABSTRACT FROM AUTHOR]

Background: Although studies have indicated that the frontal lobe plays an important role in performance on the Wisconsin Card Sorting Test (WCST) and that basal ganglia play a specific role in frontal lobe function, the role of striatal dopamine (DA) activity In performance on the WCST remains unclear. Methods: We assessed the relation between the availability of striatal dopamine transporters (DATs) and performance on the WCST as a measure of executive function in healthy individuals. We approximated the availability of DATs in 53 healthy volunteers aged 19-61 years by use of single photon emission computed tomography with technetium-99m (99mTc)- TRODAT-1 as the ligand. The WCST was administered to all participants. Results: The availability of DAT was significantly negatively correlated with perseverative errors on the WCST, both before and after adjustment for body mass index (rbefore = -0.39, p = 0.004; rother = -0.39, p = 0.005). Limitations: This was an association study; thus, a causal relation between DAT availability and performance cannot be confirmed. Conciusion: Our results suggest that striatal DAT availability may play a role in executive function as measured by the WCST. [ABSTRACT FROM AUTHOR]

Many voxel-based morphometry (VBM) studies have found abnormalities in gray matter density (GMD) in obsessive–compulsive disorder (OCD). Here, we performed a quantitative meta-analysis of VBM studies contrasting OCD patients with healthy controls (HC). A literature search identified 10 articles that included 343 OCD patients and 318 HC. Anatomic likelihood estimation meta-analyses were performed to assess GMD changes in OCD patients relative to HC. GMD was smaller in parieto-frontal cortical regions, including the supramarginal gyrus, the dorsolateral prefrontal cortex, and the orbitofrontal cortex, and greater in the basal ganglia (putamen) and the anterior prefrontal cortex in OCD patients relative to HC. No significant differences were found between children and adults. Our findings indicate differences in GMD in parieto-frontal areas and the basal ganglia between OCD patients and HC. We conclude that structural abnormalities within the prefrontal-basal ganglia network are involved in OCD pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Trial by trial variability during motor learning is a feature encoded by the basal ganglia of both humans and songbirds, and is important for reinforcement of optimal motor patterns, including those that produce speech and birdsong. Given the many parallels between these behaviors, songbirds provide a useful model to investigate neural mechanisms underlying vocal learning. In juvenile and adult male zebra finches, endogenous levels of FoxP2, a molecule critical for language, decrease two hours after morning song onset within area X, part of the basal ganglia-forebrain pathway dedicated to song. In juveniles, experimental 'knockdown' of area X FoxP2 results in abnormally variable song in adulthood. These findings motivated our hypothesis that low FoxP2 levels increase vocal variability, enabling vocal motor exploration in normal birds. Methodology/Principal Findings: After two hours in either singing or non-singing conditions (previously shown to produce differential area X FoxP2 levels), phonological and sequential features of the subsequent songs were compared across conditions in the same bird. In line with our prediction, analysis of songs sung by 75 day (75d) birds revealed that syllable structure was more variable and sequence stereotypy was reduced following two hours of continuous practice compared to these features following two hours of non-singing. Similar trends in song were observed in these birds at 65d, despite higher overall within-condition variability at this age. Conclusions/Significance: Together with previous work, these findings point to the importance of behaviorally-driven acute periods during song learning that allow for both refinement and reinforcement of motor patterns. Future work is aimed at testing the observation that not only does vocal practice influence expression of molecular networks, but that these networks then influence subsequent variability in these skills. [ABSTRACT FROM AUTHOR]

Objective: Bilateral basal ganglia calcification is a rare disease with symmetrical and bilateral deposition of calcium and other minerals in the basal ganglia, cerebellum, dentate nucleus, and white matter. Clinical findings are variable and can present with psychiatric symptoms, epileptic seizures, cerebellar features, extrapyramidal dysfunction, and dementia. Parathyroid pathologies as well as other metabolic disorders are the main etiologic causes of bilateral basal ganglia calcification. Patients and Methods: In this article, we retrospectively analyzed the etiologic and clinical findings of 17 (nine famale, eight male) patients diagnosed with bilateral basal ganglia calcification between 2002 and 2008 in Gaziantep University, Faculty of Medicine, Department of Neurology outpatient clinic. Results: Clinical features were variable. Four patients had headache, six seizures, five speech disorder, four movement disorders, and four forgetfulness and psychiatric problems. Nine of 17 patients had hypoparathyroidism in the etiology of bilateral basal ganglia calcification. The involvements of basal ganglia and the thalamus were the most frequent findings in cranial imagings. Conclusion: Hypoparathyroidism and thalamus involvement were found frequently. The detection of bilateral basal ganglia calcification on imaging may be helpful in the diagnosis and treatment of underlying diseases and thus can be considered an important finding. [ABSTRACT FROM AUTHOR]

Objective: The concomitant presence of psychiatric syndromes, including dementia, with motor disturbance has been increasingly recognized during the last decade, with emphasis on cognitive impairment in idiopatic Parkinson's disease. This review will focus on the epidemiology, clinical aspects, differential diagnosis, underlying mechanisms and treatment of dementia in Parkinson's disease. Method: A literature review of the studies that investigated the dementia in Parkinson's disease was performed. Results: Dementia is highly prevalent in Parkinson's disease. The prototype of dementia in Parkinson's disease is a dysexecutive syndrome with impaired attention, executive functions and secondarily impaired memory. Neurochemically the most significant deficit seems to be cholinergic; dementia seems to correlate best with cortical and limbic Lewy bodies. Preliminary evidence suggests that cholinesterase inhibitors may be effective in Parkinson's disease dementia. Conclusions: Cognitive impairment in Parkinson's disease is associated to specific features and is responsible for substantial disability in these patients. [ABSTRACT FROM AUTHOR]

Study Design:Postal survey.Objectives:To examine if the intensity of pain in persons with spinal cord injury (SCI) varied as a function of pain site, and to identify the patient and SCI characteristics associated with pain location, pain intensity and pain interference in a sample of persons with SCI.Setting:Community sample, United States.Methods:A postal survey including measures of pain intensity, pain interference, other pain, demographic and medical characteristics was completed by 238 adults with SCI.Results:Average pain intensity was moderate and pain was common across the body. Demographic and medical variables, including SCI level, were generally not associated with pain prevalence, intensity and interference. However, persons with higher level injuries were more likely to report upper extremity pain than persons with paraplegic injuries. The lower body was the location of the highest pain ratings.Conclusion:Persons with SCI tend to experience high pain intensity over multiple body locations. Lower body pain was as common as upper extremity pain, but tended to be more intense.Spinal Cord (2008) 46, 451–455; doi:10.1038/sc.2008.5; published online 19 February 2008 [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of spinal lower motoneurons. Gene delivery is a promising strategy to deliver therapeutic molecules to these vulnerable cells. However, definition of an optimal route of delivery capable of accessing neurons over a considerable extent of the neuraxis represents a significant logistical problem. Intramuscular vector injections are not ideal as this approach would involve hundreds of injections to completely treat an ALS patient and also would be dependent on retrograde transport of the viral platform of choice. Alternatively, upper motoneurons could deliver trophic factors over considerable distances by anterograde transport after a relatively localized intracerebral injection. To test this approach, the present study was designed to compare the corticospinal (CST) and rubrospinal (RST) tracts for their ability to transport recombinant adeno-associated virus serotype 5 (rAAV5)-derived green fluorescent protein (GFP) or glial cell line-derived neurotrophic factor (GDNF) to the spinal cord. Unilateral injections of rAAV5-GFP into the red nucleus (RN) or motor cortex of normal rats produced GFP-positive fibers in the appropriate descending tracts extending to the lumbar spinal cord. For both tracts, GFP-positive axonal projections into the spinal gray matter were consistently observed. GDNF immunohistochemistry demonstrated that confirmed RN injections resulted in GDNF-positive fibers projecting into spinal gray matter as seen in the GFP group. In contrast, confirmed cortical rAAV5-GDNF injections resulted in less evident staining in spinal cord. Spinal cord GDNF levels were elevated at distances up to 72 mm from the injection sites, and confirmed that RST-related GDNF transport to spinal cord surpassed CST-associated delivery. [ABSTRACT FROM AUTHOR]

The application of deep brain stimulation (DBS) for the treatment of Parkinson's disease offered a direct "insight" into the human electrical activity in subcortical structures. The analysis of the oscillatory activity [local field potentials (LFPs)] disclosed the importance of rhythms and of interactions between rhythms in the human basal ganglia information processing. The aim of this study was to investigate the existence of possible nonlinear interactions between LFP rhythms characterizing the output structure of the basal ganglia, the globus pallidus internus, by means of bispectral analysis. The results of this study disclosed that the rhythms expressed in the globus pallidus internus of the untreated parkinsonian patient are not independent and, in particular, the low-beta (13-20 Hz) band generates harmonics that are included in the high-beta (20-35 Hz) band. Conversely, in the dystonic globus pallidus, as well as in the parkinsonian globus pallidus after dopaminergic medication (i.e., in the more "normal" condition), the rhythms are substantially independent and characterized by a strong activity in the low-frequency band that generates a second harmonic (4-14 Hz), mostly included in the same band. The interactions between rhythms in the human globus pallidus are therefore different in different pathologies and in different patient's states. The interpretation of these interactions is likely critical for fully understanding the role of LFP rhythms in the pathophysiology of human basal ganglia. [ABSTRACT FROM AUTHOR]

Background: Occupational and chronic exposure to solvents and metals is considered a possible risk factor for Parkinson's disease and essential tremor. While manufacturing dental prostheses, dental technicians are exposed to numerous chemicals that contain toxins known to affect the central nervous system, such as solvents (which contain n-hexane in particular) and metals (which contain mercury, iron, chromium, cobalt and nickel). Methods: We performed an epidemiological and clinical study on all 27 dental technicians working in a school for dental technicians. We asked all the technicians to fill in a self-administered questionnaire on extra-pyramidal symptoms, and the General Health Questionnaire (GHQ), a self-administered screening instrument, to detect any psychiatric disorders. Moreover, we invited all 27 dental technicians to undergo a neurological examination and provide a detailed occupational history in our clinic. Results: Of the 14 subjects who underwent the neurological examination, four had postural tremor and one had a diagnosis of Parkinson's disease. Conclusion: We found a high prevalence of extra-pyramidal signs and symptoms in this group of male dental technicians working in a state technical high school in Rome. We believe that this finding may be due to the presence of toxins in the dental technician's work. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic treatment in schizophrenia is frequently associated with extrapyramidal side effects. Objective behavioural measures to evaluate the severity of extrapyramidal side effects in the clinical setting do not exist. Objectives: This study was designed to investigate grasping movements in five drug naive and 13 medicated subjects with schizophrenia and to compare their performance with that of 18 healthy control subjects. Deficits of grip force performance were correlated with clinical scores of both parkinson-like motor disability and psychiatric symptom severity Methods: Participants performed vertical arm movements with a handheld instrumented object and caught a weight that was dropped into a handheld cup either expectedly from the opposite hand or unexpectedly from the experimenter's hand. The scaling of grip force and the temporospatial coupling between grip and load force profiles was analysed. The psychiatric symptom severity was assessed by the positive and negative symptom score of schizophrenia and the brief psychiatric rating scale. Extrapyramidal symptoms were assessed by the unified Parkinson's disease rating scale. Results: Drug naive subjects with schizophrenia performed similar to healthy controls. In contrast, medicated subjects with schizophrenia exhibited excessive grip force scaling and impaired coupling between grip and load force profiles. These performance deficits were strongly correlated with the severity of both extrapyramidal side effects related to antipsychotic therapy and negative symptoms related to the underlying pathology. Conclusions: These data provide preliminary evidence that deficits of sensorimotor performance in schizophrenia are, at least in part, related to the side effects of antipsychotic treatment. The investigation of grasping movements may provide a sensitive measure to objectively evaluate extrapyramidal side effects related to antipsychotic therapy. [ABSTRACT FROM AUTHOR]

Abstract: The development of methods for mobilizing residual organic liquids trapped in porous media is becoming increasingly important as world demand for oil increases and because of the need to remediate aquifers degraded by slow-dissolving organic contaminants. Low-frequency elastic wave stimulation is one such technique, but until recently the lack of a mechanistic understanding of the effects of vibration on mobilization of oil ganglia has prevented the method from being applied predictably in the field. Recently, a simple capillary-physics mechanism has been developed to explain vibration-induced mobilization of a trapped non-wetting organic phase in porous media. Specific predictions that follow from this hypothesized mechanism are that vibrations will be most effective in mobilizing trapped oil when the acceleration amplitude is within an optimal range of values (that depend on the magnitudes of the capillary forces trapping the ganglia and the imposed static pressure gradients) and for sufficiently low vibration frequencies. In this paper we describe two-dimensional glass micromodel experiments that support these predictions. [Copyright &y& Elsevier]

In this study, we used functional MRI (fMRI) at high field (3T) to track the time course of activation in the entire basal ganglia circuitry, as well as other motor-related structures, during the explicit learning of a sequence of finger movements over a month of training. Fourteen right-handed healthy volunteers had to practice 15 min daily a sequence of eight moves using the left hand. MRI sessions were performed on days 1, 14 and 28. In both putamen, activation decreased with practice in rostrodorsal (associative) regions. In contrast, there was a significant signal increase in more caudoventral (sensorimotor) regions of the putamen. Subsequent correlation analyses between signal variations and behavioral variables showed that the error rate (movement accuracy) was positively correlated with signal changes in areas activated during early learning, whereas reaction time (movement speed) was negatively correlated with signal changes in areas activated during advanced learning stages, including the sensorimotor putamen and globus pallidus. These results suggest the possibility that motor representations shift from the associative to the sensorimotor territories of the striato-pallidal complex during the explicit learning of motor sequences, suggesting that motor skills are stored in the sensorimotor territory of the basal ganglia that supports a speedy performance. [ABSTRACT FROM AUTHOR]