Impulsive prepotent actions and tics in Tourette disorder underpinned by a common neural network.

Tourette disorder (TD), which is characterized by motor and vocal tics, is not in general considered as a product of impulsivity, despite a frequent association with attention deficit hyperactivity disorder and impulse control disorders. It is unclear which type of impulsivity, if any, is intrinsically related to TD and specifically to the severity of tics. The waiting type of motor impulsivity, defined as the difficulty to withhold a specific action, shares some common features with tics. In a large group of adult TD patients compared to healthy controls, we assessed waiting motor impulsivity using a behavioral task, as well as structural and functional underpinnings of waiting impulsivity and tics using multi-modal neuroimaging protocol. We found that unmedicated TD patients showed increased waiting impulsivity compared to controls, which was independent of comorbid conditions, but correlated with the severity of tics. Tic severity did not account directly for waiting impulsivity, but this effect was mediated by connectivity between the right orbito-frontal cortex with caudate nucleus bilaterally. Waiting impulsivity in unmedicated patients with TD also correlated with a higher gray matter signal in deep limbic structures, as well as connectivity with cortical and with cerebellar regions on a functional level. Neither behavioral performance nor structural or functional correlates were related to a psychometric measure of impulsivity or impulsive behaviors in general. Overall, the results suggest that waiting impulsivity in TD was related to tic severity, to functional connectivity of orbito-frontal cortex with caudate nucleus and to structural changes within limbic areas

Cerebellar and basal ganglia structural connections in humans: Effect of aging and relation with memory and learning

IntroductionThe cerebellum and basal ganglia were initially considered anatomically distinct regions, each connected via thalamic relays which project to the same cerebral cortical targets, such as the motor cortex. In the last two decades, transneuronal viral transport studies in non-human primates showed bidirectional connections between the cerebellum and basal ganglia at the subcortical level, without involving the cerebral cortical motor areas. These findings have significant implications for our understanding of neurodevelopmental and neurodegenerative diseases. While these subcortical connections were established in smaller studies on humans, their evolution with natural aging is less understood.MethodsIn this study, we validated and expanded the previous findings of the structural connectivity within the cerebellum-basal ganglia subcortical network, in a larger dataset of 64 subjects, across different age ranges. Tractography and fixel-based analysis were performed on the 3 T diffusion-weighted dataset using Mrtrix3 software, considering fiber density and cross-section as indicators of axonal integrity. Tractography of the well-established cerebello-thalamo-cortical tract was conducted as a control. We tested the relationship between the structural white matter integrity of these connections with aging and with the performance in different domains of Addenbrooke’s Cognitive Examination.ResultsTractography analysis isolated connections from the dentate nucleus to the contralateral putamen via the thalamus, and reciprocal tracts from the subthalamic nucleus to the contralateral cerebellar cortex via the pontine nuclei. Control tracts of cerebello-thalamo-cortical tracts were also isolated, including associative cerebello-prefrontal tracts. A negative linear relationship was found between the fiber density of both the ascending and descending cerebellum-basal ganglia tracts and age. Considering the cognitive assessments, the fiber density values of cerebello-thalamo-putaminal tracts correlated with the registration/learning domain scores. In addition, the fiber density values of cerebello-frontal and subthalamo-cerebellar (Crus II) tracts correlated with the cognitive assessment scores from the memory domain.ConclusionWe validated the structural connectivity within the cerebellum-basal ganglia reciprocal network, in a larger dataset of human subjects, across wider age range. The structural features of the subcortical cerebello-basal ganglia tracts in human subjects display age-related neurodegeneration. Individual morphological variability of cerebellar tracts to the striatum and prefrontal cortex was associated with different cognitive functions, suggesting a functional contribution of cerebellar tracts to cognitive decline with aging. This study offers new perspectives to consider the functional role of these pathways in motor learning and the pathophysiology of movement disorders involving the cerebellum and striatum

Loss of inhibition in sensorimotor networks in focal hand dystonia.

OBJECTIVE: To investigate GABA-ergic receptor density and associated brain functional and grey matter changes in focal hand dystonia (FHD). METHODS: 18 patients with FHD of the right hand and 18 age and gender matched healthy volunteers (HV) participated in this study. We measured the density of GABA-A receptors using [11C] Flumazenil and perfusion using [15O] H2O. Anatomical images were also used to measure grey matter volume with voxel-based morphometry (VBM). RESULTS: In FHD patients compared to HV, the vermis VI of the right cerebellum and the left sensorimotor cortex had a decrease of Flumazenil binding potential (FMZ-BP), whereas the striatum and the lateral cerebellum did not show significant change. Bilateral inferior prefrontal cortex had increased FMZ-BP and an increase of perfusion, which correlated negatively with disease duration. Only the left sensorimotor cortex showed a decrease of grey matter volume. INTERPRETATION: Impairments of GABAergic neurotransmission in the cerebellum and the sensorimotor cortical areas could explain different aspects of loss of inhibitory control in FHD, the former being involved in maladaptive plasticity, the latter in surround inhibition. Reorganization of the inferior prefrontal cortices, part of the associative network, might be compensatory for the loss of inhibitory control in sensorimotor circuits. These findings suggest that cerebellar and cerebral GABAergic abnormalities could play a role in the functional imbalance of striato-cerebello-cortical loops in dystonia

The Forward Model: A Unifying Theory for the Role of the Cerebellum in Motor Control and Sense of Agency

International audienceFor more than two decades, there has been converging evidence for an essential role of the cerebellum in non-motor functions. The cerebellum is not only important in learning and sensorimotor processes, some growing evidences show its implication in conditional learning and reward, which allows building our expectations about behavioral outcomes. More recent work has demonstrated that the cerebellum is also required for the sense of agency, a cognitive process that allows recognizing an action as our own, suggesting that the cerebellum might serve as an interface between sensorimotor function and cognition. A unifying model that would explain the role of the cerebellum across these processes has not been fully established. Nonetheless, an important heritage was given by the field of motor control: the forward model theory. This theory stipulates that movements are controlled based on the constant interactions between our organism and its environment through feedforward and feedback loops. Feedforward loops predict what is going to happen, while feedback loops confront the prediction with what happened so that we can react accordingly. From an anatomical point of view, the cerebellum is at an ideal location at the interface between the motor and sensory systems, as it is connected to cerebral, striatal, and spinal entities via parallel loops, so that it can link sensory and motor systems with cognitive processes. Recent findings showing that the cerebellum participates in building the sense of agency as a predictive and comparator system will be reviewed together with past work on motor control within the context of the forward model theory

Functional anatomy of writing with the dominant hand.

While writing performed by any body part is similar in style, indicating a common program, writing with the dominant hand is particularly skilled. We hypothesized that this skill utilizes a special motor network supplementing the motor equivalence areas. Using functional magnetic resonance imaging in 13 normal subjects, we studied nine conditions: writing, zigzagging and tapping, each with the right hand, left hand and right foot. We identified brain regions activated with the right (dominant) hand writing task, exceeding the activation common to right-hand use and the writing program, both identified without right-hand writing itself. Right-hand writing significantly differed from the other tasks. First, we observed stronger activations in the left dorsal prefrontal cortex, left intraparietal sulcus and right cerebellum. Second, the left anterior putamen was required to initiate all the tested tasks, but only showed sustained activation during the right-hand writing condition. Lastly, an exploratory analysis showed clusters in the left ventral premotor cortex and inferior and superior parietal cortices were only significantly active for right-hand writing. The increased activation with right-hand writing cannot be ascribed to increased effort, since this is a well-practiced task much easier to perform than some of the other tasks studied. Because parietal-premotor connections code for particular skills, it would seem that the parietal and premotor regions, together with basal ganglia-sustained activation likely underlie the special skill of handwriting with the dominant hand

Cerebello-Cortical Differences in Effective Connectivity of the Dominant and Non-dominant Hand during a Visuomotor Paradigm of Grip Force Control

International audienceStructural and functional differences are known to exist within the cortical sensorimotor networks with respect to the dominant vs. non-dominant hand. Similarly, the cerebellum, a key structure in the sensorimotor network with its cerebello-cortical connections, has been reported to respond differently when using the dominant vs. non-dominant hand. Several groups have already investigated causal interactions during diverse motor paradigms using effective connectivity but few have studied the larger visuomotor network, including key structures such as the parietal cortex and the cerebellum, with both hands. Moreover, the effect of force level on such interactions is still unclear. We therefore sought to determine the hemispheric asymmetries in the cerebello-cortical sensorimotor network in right-handers at two force levels (5% and 10% maximum voluntary contraction) for both hands. Cerebello-cortical modulations were investigated in 28 healthy, right-handed volunteers by determining the effective connectivity during a visuomotor task at two force levels under fMRI. A network was built consisting of the left and right primary motor (M1), ventral premotor (PMv) and posterior parietal cortices (PPC), in addition to the supplementary motor area (SMA), and the ipsilateral cerebellum (Cer) to the hand performing the motor task. Task performance (precision of isometric grip force tracking) did not differ between hands, nor did task-related activations in the sensorimotor areas apart from the contralateral primary motor cortex. However, during visuomotor control of the non-dominant hand, connectivity analysis revealed causal modulations between (i) the ipsilateral cerebellum and SMA, and (ii) the ipsilatearl cerebellum and contralateral PPC, which was not the case when using the dominant hand. These cerebello-cortical modulations for the non-dominant hand were Moulton et al. Cerebello-Cortical Effective Connectivity in Right-Handers more present at the higher of the two force levels. We conclude that precision force generation executed with the non-dominant hand, compared to the dominant hand, may require enhanced cerebello-cortical interaction to ensure equivalent left-right task performance

Brain modulation after exergaming training in advanced forms of Parkinson’s disease: a randomized controlled study

Abstract Background Physical activity combined with virtual reality and exergaming has emerged as a new technique to improve engagement and provide clinical benefit for gait and balance disorders in people with Parkinson’s disease (PD). Objective To investigate the effects of a training protocol using a home-based exergaming system on brain volume and resting-state functional connectivity (rs-FC) in persons with PD. Methods A single blind randomized controlled trial was conducted in people with PD with gait and/or balance disorders. The experimental (active) group performed 18 training sessions at home by playing a custom-designed exergame with full body movements, standing in front of a RGB-D Kinect® motion sensor, while the control group played using the computer keyboard. Both groups received the same training program. Clinical scales, gait recordings, and brain MRI were performed before and after training. We assessed the effects of both training on both the grey matter volumes (GVM) and rs-FC, within and between groups. Results Twenty-three patients were enrolled and randomly assigned to either the active (n = 11) or control (n = 12) training groups. Comparing pre- to post-training, the active group showed significant improvements in gait and balance disorders, with decreased rs-FC between the sensorimotor, attentional and basal ganglia networks, but with an increase between the cerebellar and basal ganglia networks. In contrast, the control group showed no significant changes, and rs-FC significantly decreased in the mesolimbic and visuospatial cerebellar and basal ganglia networks. Post-training, the rs-FC was greater in the active relative to the control group between the basal ganglia, motor cortical and cerebellar areas, and bilaterally between the insula and the inferior temporal lobe. Conversely, rs FC was lower in the active relative to the control group between the pedunculopontine nucleus and cerebellar areas, between the temporal inferior lobes and the right thalamus, between the left putamen and dorsolateral prefrontal cortex, and within the default mode network. Conclusions Full-body movement training using a customized exergame induced brain rs-FC changes within the sensorimotor, attentional and cerebellar networks in people with PD. Further research is needed to comprehensively understand the neurophysiological effects of such training approaches. Trial registration ClinicalTrials.gov NCT03560089

Distinct right-hand writing activations – unique significant BOLD response.

<p>Right-hand writing activations, thresholded at p<0.001 FWE corrected, and masked by each of the other tasks, thresholded at p<0.05 FWE corrected. <b>a</b>) Cluster of activations, displayed over coronal and sagittal anatomical images. <b>b</b>) BOLD time courses of each task, for each of the clusters shown in <b>a</b>). PMv = ventral premotor cortex; IFS = inferior frontal sulcus; IPL = inferior parietal lobule; SPL = superior parietal lobule.</p

Exclusive activation for writing.

<p>Areas significantly activated for writing versus tapping (p<0.05, FWE corrected) with exclusive mask for zigzagging-tapping (p<0.001 uncorrected). <b>a).</b> Sagittal and coronal view of clusters (SMA = supplementary motor area; PMd = dorsal premotor cortex; SPC = superior parietal cortex; IPC = inferior parietal cortex; PMv = ventral premotor cortex). <b>b</b>). Time courses extracted from SMA (sphere centered on [−8 2 50]; see detailed statistics in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0067931#pone-0067931-t003" target="_blank">Table 3</a>) during the nine tasks (RH = right hand; LH = left hand; RF = right foot; w = writing; t = tapping; z = zigzagging).</p