Control Of Motor Behavior Research Articles

Potentiation of active locomotor state by spinal-projecting serotonergic neurons.

Animals produce diverse motor actions that enable expression of context-appropriate behaviors. Neuromodulators facilitate behavioral flexibility by altering the temporal dynamics and output of neural circuits. Discrete populations of serotonergic (5-HT) neurons target circuits in the brainstem and spinal cord, but their role in the control of motor behavior is unclear. Here we define the pre- and post-synaptic organization of the spinal-projecting serotonergic system and define a role in locomotor control. We show that while forebrain-targeting 5-HT neurons decrease their activity during locomotion, subpopulations of spinal projecting neurons increase their activity in a context-dependent manner. Optogenetic activation of ventrally projecting 5-HT neurons does not trigger initiation of movement, but rather enhances the speed and duration of ongoing locomotion over extended time scales. These findings indicate that the descending serotonergic system potentiates locomotor output and demonstrate a role for serotonergic neurons in modulating the temporal dynamics of motor circuits.

Performing a Motor Action Enhances Social Reward Processing and Modulates the Neural Processing of Predictive Cues.

Associative learning affects many areas of human behavior. Recently, we showed that the neural response to monetary reward is enhanced by performing an action, suggesting interactions between neural systems controlling motor behavior and reward processing. Given that many psychiatric disorders are associated with social anhedonia, a key open question is whether such effects generalize to social rewards, and in how far they affect associative learning. We developed a novel task in which participants (n = 66) received social reward feedback and social punishment either by pressing a button or waiting. Predictive cues were linked to feedback valence with 80% accuracy. Using EEG, we measured the neural response to both predictive cues and social feedback. We found enhanced reward positivity for social reward preceded by an action, and an enhanced N2 for cues predicting negative feedback. Cue-locked P3 amplitude was reduced for cues associated with negative feedback in passive trials only, showing a modulation of outcome anticipation by performing a motor action. This was supported by connectivity analyses showing stronger directed theta synchronization, in line with increased top-down modulation of attention, in active compared with passive trials. These findings suggest that actively obtaining social feedback enhances reward sensitivity and modulates outcome anticipation.

Ultrasound-Assisted CRISPRi-Exosome for Epigenetic Modification of α-Synuclein Gene in a Mouse Model of Parkinson's Disease.

Currently, there is a lack of effective treatment for Parkinson's disease (PD). In PD patients, aberrant methylation of SNCA (α-synuclein gene) has been reported and may be a potential therapeutic target. In this study, we established an epigenetic regulation platform based on an exosomal CRISPR intervention system. With the assist of focused ultrasound (FUS) opening the blood-brain barrier, engineered exosomes carrying RVG (rabies viral glycoprotein) targeting peptide, sgRNA (single guide RNA), and dCas9-DNMT3A (named RVG-CRISPRi-Exo) were efficiently delivered into the brain lesions and induced specific methylation of SNCA. In vivo, FUS combined with RVG-CRISPRi-Exo significantly improved motor performance, balance coordination, and neurosensitivity in PD mice, greatly down-regulated the elevation of α-synuclein (α-syn) caused by modeling, rescued cell apoptosis, and alleviated the progression of PD in mice. [18F]-FP-DTBZ imaging suggested that the synaptic function of the nigrostriatal pathway could be restored, which was conducive to the control of motor behavior in PD mice. Pyrosequencing results showed that RVG-CRISPRi-Exo could methylate CpG at specific sites of SNCA, and this fine-tuned editing achieved good therapeutic effects in PD model mice. In vitro, RVG-CRISPRi-Exo down-regulated SNCA transcripts and α-syn expression and relieved neuronal cell damage. Collectively, our findings provide a proof-of-principle for the development of targeted brain nanodelivery based on engineered exosomes and provide insights into epigenetic regulation of brain diseases.

What we can do with sounds

Auditory perception can be dynamic when sound sources are in motion or changing, when the listener is moving relative to the source of sound, or both. Moreover, our engagement with the acoustic environment is often active rather than passive. That is, sounds can be brought into use to support and guide perceptual-motor behaviour. This presentation will review examples of recent empirical work on the role of auditory perception in the control of motor behaviour: what we can do with sounds. Data from experiments on intercepting moving objects without vision, acoustic navigation and orientation in people with visual impairments, exploration and learning of novel digital musical instruments, and rhythmic sounds in gait rehabilitation, all demonstrate different ways that sounds can convey action-relevant information for skilful listeners. Furthermore, they point to a need to consider the auditory system not merely as a passive antenna for inert distal stimuli, but as integrated within an active meaning-seeking organism interacting with a dynamic environment.

Rate versus synchrony codes for cerebellar control of motor behavior

Information transmission between neural populations could occur through either coordinated changes in firing rates or the precise transmission of spike timing. We investigate the code for information transmission from a part of the cerebellar cortex that is crucial for the accurate execution of a quantifiable motor behavior. Simultaneous recordings from Purkinje cell pairs in the cerebellum of rhesus macaques reveal how these cells coordinate their activity to drive smooth pursuit eye movements. Purkinje cells show millisecond-scale coordination of spikes (synchrony), but the level of synchrony is small and insufficient to impact the firing of downstream vestibular nucleus neurons. Analysis of previous metrics that purported to reveal Purkinje cell synchrony demonstrates that these metrics conflate changes in firing rate and neuron-neuron covariance. We conclude that the output of the cerebellar cortex uses primarily a rate rather than a synchrony code to drive the activity of downstream neurons and thus control motor behavior.

Short-term hindlimb unloading negatively affects dopaminergic transmission in the nigrostriatal system of mice.

The nigrostriatal system composed of the dorsal striatum and the substantia nigra (SN) is highly involved in the control of motor behavior. Various extremal and pathological conditions as well as social isolation (SI) may cause an impairment of locomotor function; however, corresponding alterations in the nigrostriatal dopaminergic pathway are far from full understanding. Here, we analyzed the effect of 3-day hindlimb unloading (HU) and SI on the key players of dopamine transmission in the nigrostriatal system of CD1 mice. Three groups of mice were analyzed: group-housed (GH), SI, and HU animals. Our data showed a significant decrease in the expression and phosphorylation of tyrosine hydroxylase (TH) in the SN and dorsal striatum of HU mice that suggested attenuation of dopamine synthesis in response to HU. In the dorsal striatum of HU mice, the downregulation of TH expression was also observed indicating the effect of unloading; however, TH phosphorylation at Ser40 was mainly affected by SI pointing on an impact of isolation too. Expression of dopamine receptors D1 in the dorsal striatum of HU mice was increased suggesting a compensatory response, but the activity of downstream signaling pathways involving protein kinase A and cAMP response element-binding protein was inhibited. At the same time, SI alone did not affect expression of DA receptors and activity of downstream signaling in the dorsal striatum. Obtained data let us to conclude that HU was the main factor which impaired dopamine transmission in the nigrostriatal system but SI made some contribution to its negative effects.

A sex difference in mouse dopaminergic projections from the midbrain to basolateral amygdala

BackgroundDopaminergic circuits play important roles in the motivational control of behavior and dysfunction in dopaminergic circuits have been implicated in several psychiatric disorders, such as schizophrenia and depression. While these disorders exhibit different incidence rates in men and women, the potential sex differences in the underlying neural circuits are not well-understood. Previous anatomical tracing studies in mammalian species have revealed a prominent circuit projection connecting the dopaminergic midbrain ventral tegmental area (VTA) to the basolateral amygdala (BLA), which is involved in emotional processing and associative learning. However, whether there is any sex difference in this anatomical circuit remains unknown.MethodsTo study the potential sex differences in the VTA-to-BLA dopaminergic circuit, we injected two viral vectors encoding fluorescent reporters of axons and synaptic boutons (AAV–FLEX–tdTomato and AAV–FLEX–SynaptophysinGFP, respectively) into the VTA of a mouse transgenic driver line (tyrosine hydroxylase promoter-driven Cre, or TH-Cre), which restricts the reporter expression to dopaminergic neurons. We then used confocal fluorescent microscopy to image the distribution and density of dopaminergic axons and synaptic boutons in serial sections of both male and female mouse brain.ResultsWe found that the overall labeling intensity of VTA-to-BLA dopaminergic projections is intermediate among forebrain dopaminergic pathways, significantly higher than the projections to the prefrontal cortex, but lower than the projections to the nucleus accumbens. Within the amygdala areas, dopaminergic axons are concentrated in BLA. Although the size of BLA and the density of dopaminergic axons within BLA are similar between male and female mice, the density of dopaminergic synaptic boutons in BLA is significantly higher in male brain than female brain.ConclusionsOur results demonstrate an anatomical sex difference in mouse dopaminergic innervations from the VTA to BLA. This finding may provide a structural foundation to study neural circuit mechanisms underlying sex differences in motivational and emotional behaviors and related psychiatric dysfunctions.

Modulation of Resting-State Brain Complexity After Bilateral Cerebellar Anodal Transcranial Direct Current Stimulation in Children with Autism Spectrum Disorders: a Randomized Controlled Trial Study.

Autism spectrum disorders (ASD) are heterogeneous neurodevelopmental disorders characterized by aberrant neural networks. Cerebellum is best known for its role in controlling motor behaviors; however, recently, there have been significant reports showed that dysfunction in cerebellar-cerebral networks contributes significantly to many of the clinical features of ASD. Hereby, this is a randomized controlled trial (RCT) study examining the potential modulating effects of bilateral anodal tDCS stimulation over cerebellar hemispheres on the resting-state brain complexity in children with ASD. Thirty-six children with ASD (aged 4-14) years old were divided equally and randomly into a tDCS treatment group, which underwent 10 sessions (20-min duration, five sessions/per week) of bilateral anodal tDCS stimulation applied over left and right cerebellar hemispheres, and control group underwent the same procedures, but with sham tDCS stimulation. Resting-state brain complexity was evaluated through recording and calculating the approximate entropy (ApxEnt) values of the resting-state electroencephalograph (EEG) data obtained from a 64-channel EEG system before and after the interventions. Repeated measures of ANOVA showed that tDCS had significant effects on the treatment group (Wilks' Lambda = 0.29, F (15, 16) = 2.67, p = 0.03) compared with the control group. Analyzed data showed a significant increase in the averaged ApxEnt values in the right frontal cortical region (F (1, 16) = 10.46, p = 0.005) after the bilateral cerebellar anodal tDCS stimulation. Besides, the Cohen's d effect size showed a large effect size (0.70-0.92) of bilateral cerebellar anodal tDCS on the ApxEnt values increases in the left and right frontal cortical regions, the right central cortical region, and left parietal cortical region. However, there were no any significant differences or increases in the brain complexity before and after the sham tDCS stimulation of the control group. Bilateral cerebellar anodal tDCS modulated and increased the brain complexity in children with ASD with no any reported adverse effect. Hereby, cerebellum and cerebellar-cerebral circuitry would serve as a promising target for non-invasive brain stimulation and neuro-modulation as a therapeutic intervention.

Wireless multi-lateral optofluidic microsystems for real-time programmable optogenetics and photopharmacology

In vivo optogenetics and photopharmacology are two techniques for controlling neuronal activity that have immense potential in neuroscience research. Their applications in tether-free groups of animals have been limited in part due to tools availability. Here, we present a wireless, battery-free, programable multilateral optofluidic platform with user-selected modalities for optogenetics, pharmacology and photopharmacology. This system features mechanically compliant microfluidic and electronic interconnects, capabilities for dynamic control over the rates of drug delivery and real-time programmability, simultaneously for up to 256 separate devices in a single cage environment. Our behavioral experiments demonstrate control of motor behaviors in grouped mice through in vivo optogenetics with co-located gene delivery and controlled photolysis of caged glutamate. These optofluidic systems may expand the scope of wireless techniques to study neural processing in animal models.

The Role of Basal Ganglia and Its Neuronal Connections in the Development of Stuttering: A Review Article.

Dysfluent speech has the potential to lower one's standard of living drastically. Although there is a lot of theoretical support for basal ganglia dysfunction in developmental stuttering, there isn't any imaging data to back it up. According to several studies, there is a difference in gray matter volume between people who stammer and those who don't. According to studies, the right inferior longitudinal fasciculus and the uncinate fasciculus have higher fractional anisotropy (FA) than fluent controls. A high fractional anisotropy means good white matter integrity in these areas. In children who stutter, grey matter volume was higher in the Rolandic operculum, middle frontal gyrus, superior temporal gyrus, and inferior parietal lobule. These regions are found to be more active in adults who stammer as their speech fluency improves. Stuttering is previously linked to structural deficiencies in the corpus callosum. However, there are differences in the directionality of the findings between studies, which are unknown. According to current theories, stuttering is caused by a breakdown in the integration of auditory data in speech motor planning, which affects behavior tasks that rely on basal ganglia structures. According to some studies, connectivity in the left inferior frontal gyrus (IFG) and basal ganglia of persons with stuttering (PWS) was significantly reduced. Still, it was more robust in the left supplementary motor cortex (SMC) and premotor cortex (PMC) (primary motor cortex). In the Broca's region, there was also decreased perfusion and spectroscopic indicators of neuronal density. Spontaneous speech is more affected by stuttering than conversation, reading, sentence repetition, or singing. As per the dual process theory of language formation, the basal ganglia are essential for formulaic phrases, but the left hemisphere is important for innovative, freshly constructed sentences. According to current theories on their functional traits and connections to cortical areas of control, the basal ganglia are the complex networks in charge of organizing, initiating, carrying out, and controlling motor behaviors. Given the distinct neuroanatomical characteristics of people who stutter, more research into this cohort is required to further our understanding of the illness. The primary goal of this review article is to fill in any knowledge voids between the neuroanatomical structure of the basal ganglia and the onset of stuttering.

Regulation of early cerebellar development.

The study of cerebellar development has been at the forefront of neuroscience since the pioneering work of Wilhelm His Sr., Santiago Ramón y Cajal and many others since the 19th century. They laid the foundation to identify the circuitry of the cerebellum, already revealing its stereotypic three-layered cortex and discerning several of its neuronal components. Their work was fundamental in the acceptance of the neuron doctrine, which acknowledges the key role of individual neurons in forming the basic units of the nervous system. Increasing evidence shows that the cerebellum performs a variety of homeostatic and higher order neuronal functions beyond the mere control of motor behaviour. Over the last three decades, many studies have revealed the molecular machinery that regulates distinct aspects of cerebellar development, from the establishment of a cerebellar anlage in the posterior brain to the identification of cerebellar neuron diversity at the single cell level. In this review, we focus on summarizing our current knowledge on early cerebellar development with a particular emphasis on the molecular determinants that secure neuron specification and contribute to the diversity of cerebellar neurons.

Animal robots: Research foundation, key technologies and development forecasts

<p indent="0mm">Animal robots are a class of bio-syncretic robots with the visual, auditory and tactile perception capabilities of animals. They make use of the animal’s inherent motor system and act directly on specific brain regions (nucleus) or nervous systems of animal carriers through simulated neural signals to induce neuronal activity in the relevant functional brain regions in order to achieve motor behavior control of the carriers. This type of special robots has natural and significant advantages in many aspects such as locomotor stability, flexibility, environmental adaptability and energy supply for its locomotion, overcoming the difficulties of traditional bionic robots in terms of distribution drive, environmental perception and energy supply. It has significant theoretical and application values and is one of the important research directions in the development of robotics. The research was highly integrated with animal intelligence and machine intelligence, involving animal behavior, neuroscience, microelectromechanical technology, mechanics and communication technology, and is a frontier area of multidisciplinary integration. These robots are expected to perform tasks that are not possible for humans or traditional bionic robots. It can be used in the field of public security to perform tasks such as counter-terrorism, search and rescue, and temporal awareness. In the civilian field, it can be widely used in environmental surveys and detection of confined spaces. In scientific research, it can be used as a research tool to explore the structure of motor neural networks and unknown areas such as neural information interaction patterns, neuroplasticity and functional repair. In this paper, we review the development of animal locomotor behavior regulation in the past <sc>20 years,</sc> systematically sort out the relationship between the animal locomotor nervous system and the locomotor behavior regulation, and briefly summarize the neural mechanisms of animal locomotor regulation, the generation and transmission of animal locomotor regulation signals, the composition and characteristics of signals regulating animal locomotor behaviors, and microelectrode fabrication and implantation techniques. According to the motion scenarios of different animal robots (in water, on land and in the air), the stimulation modulation methods, the brain areas (nucleus) that are stimulated and the corresponding movement modulation behaviors of the animal robots studied are summarized. The important research results of several typical animal robots are categorized and reviewed in terms of methods for locomotor modulation behaviors, optimization of remote control stimulation systems, and research on automatic navigation systems, and the research problems and key technical challenges that need to be broken through for future animal robots are summarized and discussed. Based on this, to effectively play the role of animal robots and meet the needs of practical applications, the paper outlines a framework for future research on animal robots based on the bottlenecks in animal behavioral control technology and summarizes and analyzes four aspects of animal robots, including research on motor neural control mechanisms, miniaturization of stimulation and control systems, application of communication and navigation technologies, and design strategies for self-powered systems. The future development trends and application prospects of animal robots are predicted.

A genetically defined insula-brainstem circuit selectively controls motivational vigor

The anterior insular cortex (aIC) plays a critical role in cognitive and motivational control of behavior, but the underlying neural mechanism remains elusive. Here, we show that aIC neurons expressing Fezf2 (aICFezf2), which are the pyramidal tract neurons, signal motivational vigor and invigorate need-seeking behavior through projections to the brainstem nucleus tractus solitarii (NTS). aICFezf2 neurons and their postsynaptic NTS neurons acquire anticipatory activity through learning, which encodes the perceived value and the vigor of actions to pursue homeostatic needs. Correspondingly, aIC → NTS circuit activity controls vigor, effort, and striatal dopamine release but only if the action is learned and the outcome is needed. Notably, aICFezf2 neurons do not represent taste or valence. Moreover, aIC → NTS activity neither drives reinforcement nor influences total consumption. These results pinpoint specific functions of aIC → NTS circuit for selectively controlling motivational vigor and suggest that motivation is subserved, in part, by aIC's top-down regulation of dopamine signaling.

Selective Manipulation of G-Protein γ7 Subunit in Mice Provides New Insights into Striatal Control of Motor Behavior.

Stimulatory coupling of dopamine D1 (D1R) and adenosine A2A receptors (A2AR) to adenylyl cyclase within the striatum is mediated through a specific Gαolfβ2γ7 heterotrimer to ultimately modulate motor behaviors. To dissect the individual roles of the Gαolfβ2γ7 heterotrimer in different populations of medium spiny neurons (MSNs), we produced and characterized conditional mouse models, in which the Gng7 gene was deleted in either the D1R- or A2AR/D2R-expressing MSNs. We show that conditional loss of γ7 disrupts the cell type-specific assembly of the Gαolfβ2γ7 heterotrimer, thereby identifying its circumscribed roles acting downstream of either the D1Rs or A2ARs in coordinating motor behaviors, including in vivo responses to psychostimulants. We reveal that Gαolfβ2γ7/cAMP signal in D1R-MSNs does not impact spontaneous and amphetamine-induced locomotor behaviors in male and female mice, while its loss in A2AR/D2R-MSNs results in a hyperlocomotor phenotype and enhanced locomotor response to amphetamine. Additionally, Gαolfβ2γ7/cAMP signal in either D1R- or A2AR/D2R-expressing MSNs is not required for the activation of PKA signaling by amphetamine. Finally, we show that Gαolfβ2γ7 signaling acting downstream of D1Rs is selectively implicated in the acute locomotor-enhancing effects of morphine. Collectively, these results support the general notion that receptors use specific Gαβγ proteins to direct the fidelity of downstream signaling pathways and to elicit a diverse repertoire of cellular functions. Specifically, these findings highlight the critical role for the γ7 protein in determining the cellular level, and hence, the function of the Gαolfβ2γ7 heterotrimer in several disease states associated with dysfunctional striatal signaling.SIGNIFICANCE STATEMENT Dysfunction or imbalance of cAMP signaling in the striatum has been linked to several neurologic and neuropsychiatric disorders, including Parkinson's disease, dystonia, schizophrenia, and drug addiction. By genetically targeting the γ7 subunit in distinct striatal neuronal subpopulations in mice, we demonstrate that the formation and function of the Gαolfβ2γ7 heterotrimer, which represents the rate-limiting step for cAMP production in the striatum, is selectively disrupted. Furthermore, we reveal cell type-specific roles for Gαolfβ2γ7-mediated cAMP production in the control of spontaneous locomotion as well as behavioral and molecular responses to psychostimulants. Our findings identify the γ7 protein as a novel therapeutic target for disease states associated with dysfunctional striatal cAMP signaling.

Visual and somatosensory feedback mechanisms of precision manual motor control in autism spectrum disorder

BackgroundIndividuals with autism spectrum disorder (ASD) show deficits processing sensory feedback to reactively adjust ongoing motor behaviors. Atypical reliance on visual and somatosensory feedback each have been reported during motor behaviors in ASD suggesting that impairments are not specific to one sensory domain but may instead reflect a deficit in multisensory processing, resulting in reliance on unimodal feedback. The present study tested this hypothesis by examining motor behavior across different visual and somatosensory feedback conditions during a visually guided precision grip force test.MethodsParticipants with ASD (N = 43) and age-matched typically developing (TD) controls (N = 23), ages 10–20 years, completed a test of precision gripping. They pressed on force transducers with their index finger and thumb while receiving visual feedback on a computer screen in the form of a horizontal bar that moved upwards with increased force. They were instructed to press so that the bar reached the level of a static target bar and then to hold their grip force as steadily as possible. Visual feedback was manipulated by changing the gain of the force bar. Somatosensory feedback was manipulated by applying 80 Hz tendon vibration at the wrist to disrupt the somatosensory percept. Force variability (standard deviation) and irregularity (sample entropy) were examined using multilevel linear models.ResultsWhile TD controls showed increased force variability with the tendon vibration on compared to off, individuals with ASD showed similar levels of force variability across tendon vibration conditions. Individuals with ASD showed stronger age-associated reductions in force variability relative to controls across conditions. The ASD group also showed greater age-associated increases in force irregularity relative to controls, especially at higher gain levels and when the tendon vibrator was turned on.ConclusionsOur findings that disrupting somatosensory feedback did not contribute to changes in force variability or regularity among individuals with ASD suggests a reduced ability to integrate somatosensory feedback information to guide ongoing precision manual motor behavior. We also document stronger age-associated gains in force control in ASD relative to TD suggesting delayed development of multisensory feedback control of motor behavior.

Serotonergic control of the glutamatergic neurons of the subthalamic nucleus.

The subthalamic nucleus (STN) houses a dense cluster of glutamatergic neurons that play a central role in the functional dynamics of the basal ganglia, a group of subcortical structures involved in the control of motor behaviors. Numerous anatomical, electrophysiological, neurochemical and behavioral studies have reported that serotonergic neurons from the midbrain raphe nuclei modulate the activity of STN neurons. Here, we describe this serotonergic innervation and the nature of the regulation exerted by serotonin (5-hydroxytryptamine, 5-HT) on STN neuron activity. This regulation can occur either directly within the STN or at distal sites, including other structures of the basal ganglia or cortex. The effect of 5-HT on STN neuronal activity involves several 5-HT receptor subtypes, including 5-HT1A, 5-HT1B, 5-HT2C and 5-HT4 receptors, which have garnered the highest attention on this topic. The multiple regulatory effects exerted by 5-HT are thought to be modified under pathological conditions, altering the activity of the STN, or due to the benefits and side effects of treatments used for Parkinson's disease, notably the dopamine precursor l-DOPA and high-frequency STN stimulation. Originally understood as a motor center, the STN is also associated with decision making and participates in mood regulation and cognitive performance, two domains of personality that are also regulated by 5-HT. The literature concerning the link between 5-HT and STN is already important, and the functional overlap is evident, but this link is still not entirely understood. The understanding of this link between 5-HT and STN should be increased due to the possible importance of this regulation in the control of fronto-STN loops and inherent motor and non-motor behaviors.

Impaired Motor Timing in Tourette Syndrome: Results From a Case-Control Study in Children.

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics. Co-occurrence of attention-deficit/hyperactivity disorder (ADHD) or obsessive–compulsive disorder (OCD) is very frequent in the pediatric population as well as the presence of an impairment of the executive functions. The aim of our study was to investigate motor timing, that is, the temporal organization of motor behavior, in a pediatric population of Tourette patients. Thirty-seven Tourette patients (divided in 22 “pure” Tourette patients and 15 with ADHD) were compared with 22 healthy age- and gender-matched subjects. All subjects underwent a neuropsychiatric screening and were tested for their planning and decision-making abilities by using a standardized test, such as Tower of London (ToL). Two experimental paradigms were adopted: finger-tapping test (FTT), a free motor tapping task, and synchronization–continuation task. An accuracy index was calculated as measure of ability of synchronization. We found that “pure” TS as well as TS+ADHD showed lower scores in the FTT for the dominant and non-dominant hands than controls. Moreover, in the synchronization and continuation test, we observed an overall lack of accuracy in both TS groups in the continuation phase for 2,000 ms (supra-second interval), interestingly, with opposite direction of accuracy index. Thus, “pure” TS patients were classified as “behind the beat,” whereas, TS+ADHD as “ahead of the beat.” The performance in the finger tapping was inversely correlated to ToL total scores and execution time, whereas we did not find any correlation with the accuracy index of the synchronization and continuation test. In conclusion, here, we explored motor timing ability in a childhood cohort of Tourette patients, confirming that patients exhibit an impaired temporal control of motor behavior and these findings may be explained by the common underlying neurobiology of TS and motor timing.

Inhibition of striatonigral autophagy as a link between cannabinoid intoxication and impairment of motor coordination.

The use of cannabis is rapidly expanding worldwide. Thus, innovative studies aimed to identify, understand and potentially reduce cannabis-evoked harms are warranted. Here, we found that Δ9-tetrahydrocannabinol, the psychoactive ingredient of cannabis, disrupts autophagy selectively in the striatum, a brain area that controls motor behavior, both in vitro and in vivo. Boosting autophagy, either pharmacologically (with temsirolimus) or by dietary intervention (with trehalose), rescued the Δ9-tetrahydrocannabinol-induced impairment of motor coordination in mice. The combination of conditional knockout mouse models and viral vector-mediated autophagy-modulating strategies in vivo showed that cannabinoid CB1 receptors located on neurons belonging to the direct (striatonigral) pathway are required for the motor-impairing activity of Δ9-tetrahydrocannabinol by inhibiting local autophagy. Taken together, these findings identify inhibition of autophagy as an unprecedented mechanistic link between cannabinoids and motor performance, and suggest that activators of autophagy might be considered as potential therapeutic tools to treat specific cannabinoid-evoked behavioral alterations.

Motor cortex can directly drive the globus pallidus neurons in a projection neuron type-dependent manner in the rat.

The basal ganglia are critical for the control of motor behaviors and for reinforcement learning. Here, we demonstrate in rats that primary and secondary motor areas (M1 and M2) make functional synaptic connections in the globus pallidus (GP), not usually thought of as an input site of the basal ganglia. Morphological observation revealed that the density of axonal boutons from motor cortices in the GP was 47% and 78% of that in the subthalamic nucleus (STN) from M1 and M2, respectively. Cortical excitation of GP neurons was comparable to that of STN neurons in slice preparations. FoxP2-expressing arkypallidal neurons were preferentially innervated by the motor cortex. The connection probability of cortico-pallidal innervation was higher for M2 than M1. These results suggest that cortico-pallidal innervation is an additional excitatory input to the basal ganglia, and that it can affect behaviors via the cortex-basal ganglia-thalamus motor loop.

Parkinson’s patients delay fixations when circumventing an obstacle and performing a dual cognitive task

BackgroundPeople with Parkinson’s disease (PD) do not differ from neurologically healthy individuals in obstacle circumvention during walking, therefore they are able to use visual feedback adequately to control motor behavior in this task. However, individuals are often distracted by the secondary task when circumventing an obstacle. An increased cognitive load can require prolonged gaze fixation time on a location of interest to compensate for longer information processing duration. Research questionTo investigate the effects of cognitive dual tasking (DT) on gaze behavior during waking with obstacle circumvention in people with PD and control group, and to determine the impact of gaze behavior on motor strategy. MethodsFifteen individuals with PD (PD-group) and 15 neurologically healthy individuals walked at a self-selected speed over a walkway and circumvented an obstacle centered in the walkway. The experimental conditions (5 trials each one) included obstacle circumvention without DT (OC) and obstacle circumvention with DT (OCDT). In the cognitive task, the participant mentally counted the number of times a target number appeared in an audio recording. We analyzed gaze behavior (i.e. number of gaze fixations and duration on the ground and obstacle), standard gait measures and DT cost. Two-way ANOVAs were completed for gait parameters and moment of fixation. ResultsThere was no significant difference in DT cost between groups and no obstacle contacts. The participants performed a longer mean duration of fixations on the ground during OCDT compared to OC. Group x condition interactions indicated that the PD-group delayed the obstacle fixation relative to the NHI for OCDT (p < 0.001) and presented greater medial-lateral body clearance (p < 0.001) and longer double support time (p < 0.001) during OCDT compared to OC. SignificanceThe results of this study suggest that deficits in locomotion during DT in PD-group may be caused, at least in part, by a reduced ability to fixate gaze at appropriate times during walking.