The role of the prefrontal cortex in the development of muscle fatigue in Charcot–Marie–Tooth 1A patients

This study aimed at comparing both peripheral and central mechanisms of muscle fatigue between Charcot–Marie–Tooth 1A patients and healthy individuals during a fatiguing voluntary task by simultaneous electromyographic and electroencephalographic recordings. Six Charcot–Marie–Tooth 1A patients (3 females, 40 ± 11 years) and 6-matched healthy individuals performed four blocks of sub-maximal isometric knee extensions. At the beginning of the session and after each block, electrically-evoked maximal single-twitch, maximal voluntary contraction and surface-electromyography of the vastus lateralis muscle were measured. The movement-related-cortical potentials were averaged in early (block 1–2) and late (block 3–4) stages of fatigue. The effect of fatigue was demonstrated at peripheral level by the decline of maximal voluntary contraction, maximal twitch and surface electromyography amplitude and at central level by the larger amplitude of movement-related-cortical-potentials during late than early stage of fatiguing sub-maximal contractions. Charcot–Marie–Tooth 1A patients showed lower motor cortex activity during motor planning, with earlier onset and larger prefrontal cortex activity during the late stage of the fatiguing task than healthy controls. These data demonstrate the key role of the prefrontal cortex in the development of fatigue in Charcot–Marie–Tooth 1A patients, which may be activated as a compensatory mechanism for the low motor cortex activation, thus reflecting high awareness of movement complexity.     

Electrophysiological properties of hippocampal–cortical neural networks,role in the processes of learning and memory in rats

The recording of hippocampal and cortical long-term potentiation (LTP) in rats in vivo is an appropriate and commonly used method to describe changes in cellular mechanisms underlying synaptic plasticity. Recently, we introduced a method for the simultaneous recording of LTP in bilateral CA1 regions and parietal association cortex (PtA), and observed differences between the Schaffer collateral–CA1 pathway (SC), Schaffer collateral/associational commissural pathway (SAC) and Schaffer collateral/associational commissural–cortex pathway (SACC). In this study, we found that (1) synaptic transmission of the SAC and SACC pathways depended on hippocampal commissural fibers [dorsal and ventral hippocampal commissural fibers, the medial septum (MS) and hippocampal CA3 commissural fibers], (2) nerve conduction velocity of the SACC pathway might be higher than that of the SAC pathway, (3) the input/output (I/O) curve of the SC pathway was shifted to the left side, compared to that of the SAC and SACC pathways, (4) all three pathways could induce stable LTP; however, LTP of the SAC and SACC pathways was much stronger than that of the SC pathway, (5) the degree of paired-pulse facilitation (PPF) was weaker in the SC pathway than that in the SAC and SACC pathways, (6) after cutting off the corpus callosum and commissural fibers, spatial learning and memory were impaired, and the ability to explore the novel environment and spontaneous locomotor activity were weakened. Taken together, our results suggested that hippocampal commissural fibers were very important for exchanging information between hemispheres, and basic differences in electrophysiological properties of hippocampal–cortical neural networks play a vital role in the processes of learning and memory.     

Retaliation or selfishness? An rTMS investigation of the role of the dorsolateral prefrontal cortex in prosocial motives

Equity, fairness and cooperative behavior are crucial for everyday social interactions. Recent neuroimaging studies suggest that the dorsolateral prefrontal cortex (DLPFC) is involved in the evaluation of violations of fairness rules, though difficulties remain to determine its role in implementing retaliating or forgiving responses to unfairness. Accordingly, we applied repetitive transcranial magnetic stimulation (rTMS) to the left and right DLPFC and investigated the impact of the DLPFC on retaliation and selfishness using a sequential neuroeconomic task establishing a role reversal. That is, participants first played an Ultimatum Game (in the role of a recipient) against fair or unfair proposers, followed by a Dictator Game in the role of a proposer. Following inhibition of the right DLPFC, subjects showed an increased punishment rate regarding previously unfair opponents. Surprisingly, previously fair opponents were also treated less fairly after rTMS to the right DLPFC, but not after left or sham rTMS. Previous work suggests that the right DLPFC provides “top-down” cognitive control over prepotent emotional responses to unfairness. Our results indicate, however, that the right DLPFC may be involved in controlling selfish behavior and that its suppression leads to maximization of one’s own benefit, regardless of another’s fairness or unfairness in previous encounters.     

Who comes first? The role of the prefrontal and parietal cortex in cognitive control

Cognitive control processes enable us to adjust our behavior to changing environmental demands. Although neuropsychological studies suggest that the critical cortical region for cognitive control is the prefrontal cortex, neuro-imaging studies have emphasized the interplay of prefrontal and parietal cortices. This raises the fundamental question about the different contributions of prefrontal and parietal areas in cognitive control. It was assumed that the prefrontal cortex biases processing in posterior brain regions. This assumption leads to the hypothesis that neural activity in the prefrontal cortex should precede parietal activity in cognitive control. The present study tested this assumption by combining results from functional magnetic resonance imaging (fMRI) providing high spatial resolution and event-related potentials (ERPs) to gain high temporal resolution. We collected ERP data using a modified task-switching paradigm. In this paradigm, a situation where the same task was indicated by two different cues was compared with a situation where two cues indicated different tasks. Only the latter condition required updating of the task set. Task-set updating was associated with a midline negative ERP deflection peaking around 470 msec. We placed dipoles in regions activated in a previous fMRI study that used the same paradigm (left inferior frontal junction, right inferior frontal gyrus, right parietal cortex) and fitted their directions and magnitudes to the ERP effect. The frontal dipoles contributed to the ERP effect earlier than the parietal dipole, providing support for the view that the prefrontal cortex is involved in updating of general task representations and biases relevant stimulus-response associations in the parietal cortex.     

Spinal fMRI demonstrates segmental organisation of functionally connected networks in the cervical spinal cord: A test–retest reliability study

Resting functional magnetic resonance imaging (fMRI) studies have identified intrinsic spinal cord activity, which forms organised motor (ventral) and sensory (dorsal) resting-state networks. However, to facilitate the use of spinal fMRI in, for example, clinical studies, it is crucial to first assess the reliability of the method, particularly given the unique anatomical, physiological, and methodological challenges associated with acquiring the data. Here, we characterise functional connectivity relationships in the cervical cord and assess their between-session test–retest reliability in 23 young healthy volunteers. Resting-state networks were estimated in two ways (1) by estimating seed-to-voxel connectivity maps and (2) by calculating seed-to-seed correlations. Seed regions corresponded to the four grey matter horns (ventral/dorsal and left/right) of C5–C8 segmental levels. Test–retest reliability was assessed using the intraclass correlation coefficient. Spatial overlap of clusters derived from seed-to-voxel analysis between sessions was examined using Dice coefficients. Following seed-to-voxel analysis, we observed distinct unilateral dorsal and ventral organisation of cervical spinal resting-state networks that was largely confined in the rostro–caudal extent to each spinal segmental level, with more sparse connections observed between segments. Additionally, strongest correlations were observed between within-segment ipsilateral dorsal–ventral connections, followed by within-segment dorso–dorsal and ventro–ventral connections. Test–retest reliability of these networks was mixed. Reliability was poor when assessed on a voxelwise level, with more promising indications of reliability when examining the average signal within clusters. Reliability of correlation strength between seeds was highly variable, with the highest reliability achieved in ipsilateral dorsal–ventral and dorso-dorsal/ventro–ventral connectivity. However, the spatial overlap of networks between sessions was excellent. We demonstrate that while test–retest reliability of cervical spinal resting-state networks is mixed, their spatial extent is similar across sessions, suggesting that these networks are characterised by a consistent spatial representation over time.     

A further update on the role of excitotoxicity in the pathogenesis of Parkinson’s disease

Increased levels of extracellular glutamate and hyperactivation of glutamatergic receptors in the basal ganglia trigger a critical cascade of events involving both intracellular pathways and cell-to-cell interactions that affect cell viability and promote neuronal death. The ensemble of these glutamate-triggered events is responsible for excitotoxicity, a phenomenon involved in several pathological conditions affecting the central nervous system, including a neurodegenerative disease such as Parkinson’s disease (PD). PD is an age-related disorder caused by the degeneration of dopaminergic neurons within the substantia nigra pars compacta, with a miscellaneous pathogenic background. Glutamate-mediated excitotoxicity may be involved in a lethal vicious cycle, which critically contributes to the exacerbation of nigrostriatal degeneration in PD. Since excitotoxicity is a glutamate-receptor-mediated phenomenon, growing interest and work have been dedicated to the research for modulators of glutamate neurotransmission that might enable new therapeutic interventions to slow down the neurodegenerative process and ameliorate PD motor symptoms.     

Stimulation of α(2A)-adrenoceptors promotes the maturation of dendritic spines in cultured neurons of the medial prefrontal cortex

Dendritic spines are tiny protrusions along dendrites that receive excitatory synaptic inputs and compartmentalize postsynaptic responses in the mature brain. It is known that change in spine morphology is associated with brain functions such as learning and memory. α_2A-Adrenoceptors (α_2A-ARs) are highly expressed in cortical neurons and play important roles in neuronal differentiation, growth and neurotrophy. However, little is known about the role of α_2A-ARs in the maturation of dendritic spines. Here, we report that stimulation of α_2A-ARs promotes the maturation of dendritic spines in cultured neurons of the medial prefrontal cortex of rodents. Our results show that, stimulation of α_2A-ARs by guanfacine induced significantly more stubby or mushroom spines in cultured mPFC neurons, with an enlargement of the spine head size. In parallel, the expression of PSD95 (a postsynaptic protein) in guanfacine-treated neurons was enhanced, while that of synapsin (a pre-synaptic protein) kept unchanged. These effects of guanfacine were blocked by co-administered yohimbine, a non-selective α₂-AR antagonist. The present results implicate a prominent role of α_2A-ARs in regulating the maturation of dendritic spines in the mPFC.     

Vertical nystagmus in Wernicke’s encephalopathy: pathogenesis and role of central processing of information from the otoliths

Patients with Wernicke’s encephalopathy (WE) often have unusual patterns of vertical nystagmus. Initially there is often a spontaneous upbeating nystagmus that may change to downbeat nystagmus with a change in the direction of gaze, convergence or with vestibular stimuli. Patients also often show a profound loss of the horizontal but not the vertical vestibulo-ocular reflex (VOR). Furthermore, the acute upbeat nystagmus may change to a chronic downbeat nystagmus. We present hypotheses for these features based on (1) the location of vertical gaze-holding networks near the area postrema of the dorsomedial medulla where the blood–brain barrier is located, which we suggest becomes compromised in WE, (2) the location of the vestibular nuclei in the brainstem, medially for the horizontal VOR, and laterally for the vertical VOR, (3) neuronal circuits differ in susceptibility to and in the ability to recover from thiamine deficiency, and (4) impaired processing of otolith information in WE, normally used to modulate translational vestibulo-ocular reflexes, leads to some of the characteristics of the spontaneous vertical nystagmus including the peculiar reversal in its direction with a change in gaze or convergence.

     

Metagenomic next-generation sequencing of viruses,bacteria, and fungi in the epineurium of the facial nerve with Bell’s palsy patients

Journal of NeuroVirology - Bell’s palsy (BP) represents a major cause leading to facial paralysis in the world. The etiology of BP is still unknown, and virology is the prevailing theory. The...     

Is there “neural efficiency” during the processing of visuo-spatial information in male humans? An EEG study

More intelligent persons (high IQ) typically present a higher cortical activity during tasks requiring the encoding of visuo-spatial information, namely higher alpha (about 10 Hz) event-related desynchronization (ERD; Doppelmayr et al., 2005 [23]). The opposite is true (“neural efficiency”) during the retrieval of the encoded information, as revealed by both lower alpha ERD and/or lower theta (about 5 Hz) event-related synchronization (ERS; Grabner et al., 2004 [19]). To reconcile these contrasting results, here we evaluated the working hypothesis that more intelligent male subjects are characterized by a high cortical activity during the encoding phase. This deep encoding would explain the relatively low cortical activity for the retrieval of the encoded information. To test this hypothesis, electroencephalographic (EEG) data were recorded in 22 healthy young male volunteers during visuo-spatial information processing (encoding) and short-term retrieval of the encoded information. Cortical activity was indexed by theta ERS and alpha ERD. It was found that the higher the subjects’ total IQ, the stronger the frontal theta ERS during the encoding task. Furthermore, the higher the subjects’ total IQ, the lower the frontal high-frequency alpha ERD (about 10–12 Hz) during the retrieval task. This was not true for parietal counterpart of these EEG rhythms. These results reconcile previous contrasting evidence confirming that more intelligent persons do not ever show event-related cortical responses compatible with “neural efficiency” hypothesis. Rather, their cortical activity would depend on flexible and task-adapting features of frontal activation.     

A role for cannabinoids in the treatment of myotonia? Report of compassionate use in a small cohort of patients

Journal of Neurology - The symptomatic treatment of myotonia and myalgia in patients with dystrophic and non-dystrophic myotonias is often not satisfactory. Some patients anecdotally report...     

"Brain is to thought as stomach is to ??": investigating the role of rostrolateral prefrontal cortex in relational reasoning

Brain imaging studies suggest that the rostrolateral prefrontal cortex (RLPFC), is involved in relational reasoning. Functional magnetic resonance imaging (fMRI) studies involving Raven's Progressive Matrices or verbal propositional analogies indicate that the RLPFC is engaged by tasks that require integration across multiple relational structures. Several studies have shown that the RLPFC is more active when people must evaluate an analogy (e.g., Is shoe to foot as glove is to hand?) than when they must simply evaluate two individual semantic relationships, consistent with the hypothesis that this region is important for relational integration. The current fMRI investigation further explores the role of the RLPFC in reasoning and relational integration by comparing RLPFC activation across four different propositional analogy conditions. Each of the four conditions required either relation completion (e.g., Shoe is to foot as glove is to WHAT? --> "hand") or relation comparison (e.g., Is shoe to foot as glove is to hand? --> "yes"). The RLPFC was engaged more strongly by the comparison subtask relative to completion, suggesting that the RLPFC is particularly involved in comparing relational structures.     

A tale of two factors: What determines the rate of progression in Huntington's disease? A longitudinal MRI study

Over the past several years, increased attention has been devoted to understanding regionally selective brain changes that occur in Huntington's disease and their relationships to phenotypic variability. Clinical progression is also heterogeneous, and although CAG repeat length influences age of onset, its role, if any, in progression has been less clear. We evaluated progression in Huntington's disease using a novel longitudinal magnetic resonance imaging analysis. Our hypothesis was that the rate of brain atrophy is influenced by the age of onset of Huntington's disease. We scanned 22 patients with Huntington's disease at approximately 1‐year intervals; individuals were divided into 1 of 3 groups, determined by the relative age of onset. We found significant differences in the rates of atrophy of cortex, white matter, and subcortical structures; patients who developed symptoms earlier demonstrated the most rapid rates of atrophy compared with those who developed symptoms during middle age or more advanced age. Rates of cortical atrophy were topologically variable, with the most rapid changes occurring in sensorimotor, posterior frontal, and portions of the parietal cortex. There were no significant differences in the rates of atrophy in basal ganglia structures. Although both CAG repeat length and age influenced the rate of change in some regions, there was no significant correlation in many regions. Rates of regional brain atrophy seem to be influenced by the age of onset of Huntington's disease symptoms and are only partially explained by CAG repeat length. These findings suggest that other genetic, epigenetic, and environmental factors play important roles in neurodegeneration in Huntington's disease. © 2011 Movement Disorder Society     

Lack of NMDA–AMPA interaction in antidepressant-like effect of CGP 37849, an antagonist of NMDA receptor,in the forced swim test

The NMDA receptor antagonist, CGP 37849-induced reduction in immobility time in the forced swim test in mice was not antagonized by pre-treatment with the AMPA receptor antagonist NBQX. This is the first demonstration of the antidepressant effect of the NMDA antagonist not being dependent on the AMPA transmission.