Aspects Of Motor Behavior Research Articles

Prolonged STAT1 signaling in neurons causes hyperactive behavior

The interferon (IFN)-induced STAT1 signaling pathway is a canonical immune pathway that has also been implicated in regulating neuronal activity. The pathway is enriched in brains of individuals with autism spectrum disorder (ASD) and schizophrenia (SZ). Over-activation of the STAT1 pathway causes pathological transcriptional responses, however it is unclear how these responses might translate into behavioral phenotypes. We hypothesized that prolonged STAT1 signaling in neurons would be sufficient to cause behavioral deficits associated with neurodevelopmental disorders. In this study, we developed a novel mouse model with the clinical STAT1 gain-of-function mutation, T385M, in neurons. These mice were hyperactive and displayed neural hypoactivity with less neuron counts in the caudate putamen. Driving the STAT1 gain-of-function mutation exclusively in dopaminergic neurons, which project to the caudate putamen of the dorsal striatum, mimicked some hyperactive behaviors without a reduction of neurons. Moreover, we demonstrated that this phenotype is neuron specific, as mice with prolonged STAT1 signaling in all excitatory or inhibitory neurons or in microglia were not hyperactive. Overall, these findings suggest that STAT1 signaling in neurons is a crucial player in regulating striatal neuron activity and aspects of motor behavior.

The shifting role of the cerebellum in executive, emotional and social processing across the lifespan

The cerebellum’s anatomical and functional organization and network interactions between the cerebellum and the cerebral cortex and subcortical structures are dynamic across the lifespan. Executive, emotional and social (EES) functions have likewise evolved during human development from contributing to primitive behaviors during infancy and childhood to being able to modulate complex actions in adults. In this review, we address how the importance of the cerebellum in the processing of EES functions might change across development. This evolution is driven by the macroscopic and microscopic modifications of the cerebellum that are occurring during development including its increasing connectivity with distant supra-tentorial cortical and sub-cortical regions. As a result of anatomical and functional changes, neuroimaging and clinical data indicate that the importance of the role of the cerebellum in human EES-related networks shifts from being crucial in newborns and young children to being only supportive later in life. In early life, given the immaturity of cortically mediated EES functions, EES functions and motor control and perception are more closely interrelated. At that time, the cerebellum due to its important role in motor control and sequencing makes EES functions more reliant on these computational properties that compute spatial distance, motor intent, and assist in the execution of sequences of behavior related to their developing EES expression. As the cortical brain matures, EES functions and decisions become less dependent upon these aspects of motor behavior and more dependent upon high-order cognitive and social conceptual processes. At that time, the cerebellum assumes a supportive role in these EES-related behaviors by computing their motor and sequential features. We suspect that this evolving role of the cerebellum has complicated the interpretation of its contribution to EES computational demands.

Executive Dysfunction and the Prefrontal Cortex.

This article summarizes the cognitive and behavioral functions of the prefrontal cortex with an emphasis on executive cognitive functions and the clinical consequences associated with executive dysfunction. The clinical manifestations of lesions to the lateral prefrontal, orbitofrontal, medial prefrontal, and frontopolar cortex are reviewed. Traditional lesion studies have emphasized the role of a brain region in controlling a cognitive function. With advances in neurology, neuropsychology, and neuroimaging, the participation of the prefrontal cortex in large-scale networks has been established with recognition that cognitive dysfunction can arise not only from a lesion within a network but also from degenerative disease targeting these large-scale, dynamic neural networks. Although executive dysfunction can result from frontal lobe injury, this article highlights the role of distributed processes subserving executive functions. An atypical phenotype of Alzheimer disease has been described that selectively targets parietal-temporal-frontal networks important for core executive functions. Executive function comprises working memory, cognitive flexibility, and inhibition and depends on top-down (ie, goal-driven) control of distributed processes occurring throughout the brain. The exact behavioral output (ie, function) depends on the content of the processes being controlled. Prefrontal cortex regions serve key cognitive functions related to social, emotional, and motivational aspects of behavior. The dorsal lateral prefrontal cortex plays a role in working memory, goal-driven attention, task switching, planning, problem-solving, and novelty-seeking. The ventral lateral prefrontal cortex plays a role in inhibition, response selection, and monitoring; the medial prefrontal cortex in self-knowledge, motivation, emotional regulation, and updating goal-directed behavior; the orbitofrontal cortex in personality, inhibition, and emotional and social reasoning. Although dysexecutive syndromes have been traditionally associated with dorsolateral prefrontal cortex injury, it is now recognized that they can also result from an impaired parietal-temporal-frontal system, which is targeted in a distinct form of atypical Alzheimer disease. This dysexecutive Alzheimer phenotype is characterized by impaired task performance on a wide battery of neuropsychological tests and simple daily tasks that require executive control. In contrast, dysexecutive syndromes more localized to the frontal lobe involve impaired executive control of social, emotional, and motivational aspects of behavior.

Cerebellar complex spikes multiplex complementary behavioral information.

Purkinje cell (PC) discharge, the only output of cerebellar cortex, involves 2 types of action potentials, high-frequency simple spikes (SSs) and low-frequency complex spikes (CSs). While there is consensus that SSs convey information needed to optimize movement kinematics, the function of CSs, determined by the PC’s climbing fiber input, remains controversial. While initially thought to be specialized in reporting information on motor error for the subsequent amendment of behavior, CSs seem to contribute to other aspects of motor behavior as well. When faced with the bewildering diversity of findings and views unraveled by highly specific tasks, one may wonder if there is just one true function with all the other attributions wrong? Or is the diversity of findings a reflection of distinct pools of PCs, each processing specific streams of information conveyed by climbing fibers? With these questions in mind, we recorded CSs from the monkey oculomotor vermis deploying a repetitive saccade task that entailed sizable motor errors as well as small amplitude saccades, correcting them. We demonstrate that, in addition to carrying error-related information, CSs carry information on the metrics of both primary and small corrective saccades in a time-specific manner, with changes in CS firing probability coupled with changes in CS duration. Furthermore, we also found CS activity that seemed to predict the upcoming events. Hence PCs receive a multiplexed climbing fiber input that merges complementary streams of information on the behavior, separable by the recipient PC because they are staggered in time.

A Revised Computational Neuroanatomy for Motor Control.

We discuss a new framework for understanding the structure of motor control. Our approach integrates existing models of motor control with the reality of hierarchical cortical processing and the parallel segregated loops that characterize cortical-subcortical connections. We also incorporate the recent claim that cortex functions via predictive representation and optimal information utilization. Our framework assumes that each cortical area engaged in motor control generates a predictive model of a different aspect of motor behavior. In maintaining these predictive models, each area interacts with a different part of the cerebellum and BG. These subcortical areas are thus engaged in domain-appropriate system identification and optimization. This refocuses the question of division of function among different cortical areas. What are the different aspects of motor behavior that are predictively modeled? We suggest that one fundamental division is between modeling of task and body whereas another is the model of state and action. Thus, we propose that the posterior parietal cortex, somatosensory cortex, premotor cortex, and motor cortex represent task state, body state, task action, and body action, respectively. In the second part of this review, we demonstrate how this division of labor can better account for many recent findings of movement encoding, especially in the premotor and posterior parietal cortices.

Enhanced Performance Stabilization Increases Performance Variability in a Virtual Interception Task.

Performing a motor task depends on the level of performance stabilization and movement control, and both aspects of motor behavior are related to motor learning (retention and transfer) and adaptation (predictable and unpredictable perturbations). Yet few studies have further investigated the underlying dynamics that may elicit these benefits. In this study, we investigated the effects of two levels of performance stabilization on motor performance and control while learning to intercept a virtual moving target. We randomly divided 40 participants of both sexes (Mage = 26.02 years, SD = 2.02) into a Stabilization Group (SG) and a Superstabilization Group (SSG). We considered the performance stabilized when a moving target was intercepted three times in a row and superstabilized when the same criterion was repeated six times. We analyzed outcome variables related to performance accuracy (absolute spatial error) and variability(coefficient of variation) and motor control (relative time to peak velocity-tPV% and its coefficient of variation) on both the first and last blocks of practice trials. Both groups showed comparable increases in performance accuracy from the first to the last block (p = .001, ηp2 = 1.00), but SSG presented higher variability than SG (p = .05, ηp2 = .70). Concerning motor control, both groups started the experiment with low tPV% and finished with comparably high tPV% and variability. Thus, although practicing two levels of performance stabilization led to similar performance accuracy and movement control, superstabilization resulted in higher performance variability with no loss of accuracy. Enhanced stabilization may increase the ability to adapt to environmental changes, but more research is needed to demonstrate this. These findings add to an understanding of the relationship between levels of performance stabilization and performance variability and may have implications for professional interventions (e.g. sports, rehabilitation) in considering the benefits of practice beyond performance stabilization.

Transcranial magnetic stimulation: a non-invasive window into the excitatory circuits involved in human motor behavior.

Transcranial magnetic stimulation (TMS) is one of the most popular non-invasive tools for investigating the cortical circuits involved in human movement. Stimulation of the primary motor cortex elicits motor evoked potentials in peripheral muscles, the amplitude of which reflects the net excitability of circuits in the cortex and spinal cord. A number of methods exist to help broadly distinguish between excitatory and inhibitory influences on corticospinal output, allowing us to probe changes in the respective cortical circuits before and during movement. Something that has rarely been considered in human TMS studies, however, is the idea that specific populations of excitatory neurons might underlie different aspects of motor behavior. The current article provides a brief review of recent TMS studies which suggest that it is possible to selectively probe distinct excitatory inputs to corticospinal neurons during a range of movement-related states, from the preparation and execution of movements, to the suppression of unwanted movements. Together with recent advancements in computational modelling of the mechanisms of TMS and the capacity to record single-cell responses to TMS in behaving non-human primates, this avenue of research has the potential to shed light on the motor circuits underlying the repertoire of human motor behaviors, as well as their pathophysiology in diseases of the motor system.

Engraftable Induced Pluripotent Stem Cell-Derived Neural Precursors for Brain Repair.

Stem cell transplantation has attracted great interest for treatment of neurodegenerative diseases to provide neuroprotection, repair the lesioned neuronal network and restore functionality. Parkinson's disease (PD), in particular, has been a preferred target because motor disability that constitutes a core pathology of the disease is associated with local loss of dopaminergic neurons in a specific brain area, the substantia nigra pars compacta. These cells project to the striatum where they deliver the neurotransmitter dopamine that is involved in control of many aspects of motor behavior. Therefore, cell transplantation approaches in PD aim to replenish dopamine deficiency in the striatum. A major challenge in developing cell therapy approaches is the ability to generate large numbers of transplantable cells in a reliable and reproducible manner. In recent years the technological breakthrough of induced pluripotent stem cells (iPSCs) has demonstrated that this is possible at a preclinical level, accelerating clinical translation. A second important issue is to efficiently differentiate iPSCs into dopaminergic neuronal progenitors with restricted proliferation potential in order to avoid cellular overgrowth in vivo and minimize the risk of tumorigenesis. Here we describe an effective protocol that includes human iPSC differentiation to the dopaminergic lineage and enrichment in neuronal precursor cells expressing the polysialylated form of the neural cell adhesion molecule PSA-NCAM, through magnetically activated cell sorting. The resulting cells are transplanted and shown to survive, differentiate, and integrate within a striatal lesion model generated by unilateral 6-hydroxydopamine administration in mice of the NOD/SCID strain that supports xenografts.

Synergistic Nigral Output Pathways Shape Movement

Locomotion relies on the activity of basal ganglia networks, where, as the output, the substantia nigra pars reticulata (SNr) integrates incoming signals and relays them to downstream areas. The cellular and circuit substrates of such a complex function remain unclear. We hypothesized that the SNr controls different aspects of locomotion through coordinated cell-type-specific sub-circuits. Using anatomical mapping, single-cell qPCR, and electrophysiological techniques, we identified two SNr sub-populations: the centromedial-thalamo projectors (CMps) and the SN compacta projectors (SNcps), which are genetically targeted based on vesicular transporter for gamma-aminobutyric acid (VGAT) or parvalbumin (PV) expression, respectively. Optogenetic manipulation of these two sub-types across a series of motor tests provided evidence that they govern different aspects of motor behavior. While CMp activity supports the continuity of motor patterns, SNcp modulates the immediate motor drive behind them. Collectively, our data suggest that at least two different sub-circuitsarise from the SNr, engage different behavioral motor components, and collaborate to produce correct locomotion.

The Neurobiology of Personal Control During Reward Learning and Its Relationship to Mood

BackgroundThe majority of reward learning neuroimaging studies have not focused on the motivational aspects of behavior, such as the inherent value placed on choice itself. The experience and affective value of personal control may have particular relevance for psychiatric disorders, including depression. MethodsWe adapted a functional magnetic resonance imaging reward task that probed the value placed on exerting control over one’s decisions, termed choice value, in 122 healthy participants. We examined activation associated with choice value; personally chosen versus passively received rewards; and reinforcement learning metrics, such as prediction error. Relationships were tested between measures of motivational orientation (categorized as autonomy, control, and impersonal) and subclinical depressive symptoms. ResultsAnticipating personal choice activated left insula, cingulate, right inferior frontal cortex, and ventral striatum (pfamilywise error–corrected < .05). Ventral striatal activations to choice were diminished in participants with subclinical depressive symptoms. Personally chosen rewards were associated with greater activation of the insula and inferior frontal gyrus, cingulate cortex, hippocampus, thalamus, and substantia nigra compared with rewards that were passively received. In participants who felt they had little control over their own behavior (impersonal orientation), prediction error signals in nucleus accumbens were stronger during passive trials. ConclusionsPrevious findings regarding personal choice have been verified and advanced through the use of both reinforcement learning models and correlations with psychopathology. Personal choice has an impact on the extended reward network, potentially allowing these clinically important areas to be addressed in ways more relevant to personality styles, self-esteem, and symptoms such as motivational anhedonia.

Motor deficits in 16-month-old male and female 3xTg-AD mice

Motor deficits are some of the most prevalent non-cognitive symptoms of Alzheimer’s disease (AD) with patients showing impairments in speech, gait and fine motor skills. We investigated motor behaviour in 16-month-old male and female 3xTg-AD mice and their B6129SF2 wildtype (WT) controls. The 3xTg-AD mice develop extracellular Aβ plaques and tau tangles in the hippocampus and motor cortex between 6 and 9 months of age. Previously we showed that at 6 months of age, 3xTg-AD mice performed better on tests of motor coordination and motor learning than WT mice. The aim of our experiment was to use a battery of motor behaviour tests to determine if this superior motor performance was present in older mice. On the Rotarod, the aged 3xTg-AD mice showed better motor coordination and learning than WT mice. Although females performed better than males, this sex difference was confounded by body weight as females weighed less than males. There were no significant genotype or sex differences on the wire hang or grid suspension tasks, nor in stride length or stride width, but 3xTg-AD mice performed worse than WT mice on the balance beam. In comparison to the 6-month-old mice, an age-related decline in most aspects of motor behaviour was apparent. These results indicate that different sub-domains of motor function are affected differently in the 3xTg-AD mice and that aging does not have the same effect on all motor behaviours.

Differential effects of Foxp2 disruption in distinct motor circuits

Disruptions of the FOXP2 gene cause a speech and language disorder involving difficulties in sequencing orofacial movements. FOXP2 is expressed in cortico-striatal and cortico-cerebellar circuits important for fine motor skills, and affected individuals show abnormalities in these brain regions. We selectively disrupted Foxp2 in the cerebellar Purkinje cells, striatum or cortex of mice and assessed the effects on skilled motor behaviour using an operant lever-pressing task. Foxp2 loss in each region impacted behaviour differently, with striatal and Purkinje cell disruptions affecting the variability and the speed of lever-press sequences, respectively. Mice lacking Foxp2 in Purkinje cells showed a prominent phenotype involving slowed lever pressing as well as deficits in skilled locomotion. In vivo recordings from Purkinje cells uncovered an increased simple spike firing rate and decreased modulation of firing during limb movements. This was caused by increased intrinsic excitability rather than changes in excitatory or inhibitory inputs. Our findings show that Foxp2 can modulate different aspects of motor behaviour in distinct brain regions, and uncover an unknown role for Foxp2 in the modulation of Purkinje cell activity that severely impacts skilled movements.

Effects of Naloxone and Caffeine on Responding under a Progressive-Duration Schedule of Food Delivery

In 2 experiments, we investigated the utility of a progressive-duration schedule as an assay for measuring drug effects. In both experiments, rats responded on a schedule of reinforcement in which food delivery was contingent upon response duration. Response requirements increased after each reinforcer delivery in a fashion similar to that of progressive-ratio schedules. Naloxone (1.0, 3.0, and 10.0 mg/kg) produced dose-dependent decreases in breaking points, a finding consistent with those of previous studies demonstrating that opioid antagonists may reduce the reinforcing efficacy of highly palatable foods in sated organisms. In a second experiment, caffeine (3.0, 6.25, and 12.5 mg/kg) sometimes produced increases in breaking points but reduced efficiency by increasing the proportions of lever presses that were too short to satisfy reinforcer requirements. Food deprivation had similar effects. The progressive-duration schedule shows promise as an assay sensitive to motivational aspects of behavior; however, distinguishing the rate-altering effects of drugs from their effects on motivating operations may pose interpretation challenges.

Rostro-caudal Connectional Heterogeneity of the Dorsal Part of the Macaque Prefrontal Area 46.

Based on neural tracer injections we found evidence for 3 connectionally distinct sectors of the dorsal part of the macaque prefrontal area 46 (46d), located at different rostro-caudal levels. Specifically, a rostral sector displayed an almost exclusive and extensive intraprefrontal connectivity and extraprefrontal connections limited to superior temporal areas and the caudal cingulate area 31. Conversely, both a middle and a caudal sector were characterized by robust, topographically organized connections with parietal and frontal sensorimotor areas. Both these sectors shared connections with caudal and medial superior parietal areas (V6A and PGm) where visuospatial information is combined with gaze- and arm-related signals for visuomotor control of arm reaching and/or eye movements. However, the caudal sector was preferentially connected to parietal and frontal oculomotor areas, whereas the middle one was preferentially connected to skeletomotor, mostly arm-related, parietal and premotor areas. The present study provides evidence for a rostro-caudal organization of area 46d similar to that described for the ventrolateral prefrontal cortex, in which more caudal areas are relatively more directly involved in controlling different aspects of motor behavior and more rostral areas are most likely involved in higher order, possibly more abstract, cognitive functions.

P168 Modulating cortical excitability of human motor cortex byβ- andγ-band transcranial alternating current stimulation (tACS)

Introduction Transcranial alternating current stimulation (tACS) is a non-invasive technique capable of interacting with endogenous brain oscillations in a frequency-specific manner (Zaehle et al., 2010; Feurra et al., 2011). Synchronized oscillatory activity at beta (15–30 Hz) and gamma (30–90 Hz) frequency range is of particular importance in the motor system. Importantly, recent work on tACS has provided evidence that beta and gamma oscillations are causally linked to aspects of motor behavior (Pogosyan et al., 2009; Joundi et al., 2012). Despite this, little is known about the mechanisms underlying tACS. The present study investigated the effects of beta- and gamma-frequency tACS on various measures of cortical excitability, as indexed by TMS. Methods Subjects participated in five experimental sessions separated by at least one week. In Session 1, all subjects had a MEG scan in order to determine individual beta and gamma peak frequency for subsequent tACS sessions. In Sessions 2–4, subjects underwent tACS at beta, low gamma, high gamma frequency or a sham stimulation. tACS was applied for 20 min over the left M1 and the contralateral orbit at intensity adjusted below individual phosphene- and discomfort threshold. TMS protocols, including a single-pulse MEP, SICI 2.5 ms and ICF, were performed at rest before, during (at 5 and 15 min) and after tACS. A single MEP and SICI 2.5 ms were also recorded during movement preparation before and after tACS. Results High gamma tACS increased single-pulse MEP and decreased SICI amplitudes during 15 min and 5 min of tACS, respectively, when compared to sham. Conversely, the opposite trend was observed for a single-pulse MEP at 5 min and SICI at 15 min. In both cases, within-session changes from baseline at an early time point were correlated with those at a later time point during stimulation. No inter-protocol correlations were found at 5 min or 15 min during high gamma tACS. No after-effects of tACS were observed in any of the stimulation sessions as compared to sham. Conclusions Single-pulse MEP and SICI amplitudes reflecting general corticospinal excitability and GABA A -mediated inhibition at the level of the primary motor cortex, respectively, were affected online in a duration-dependent manner by high gamma tACS. These changes resemble homeostatic-like plasticity, although no effect lasting beyond the stimulation period was observed. In addition, changes observed early could predict subsequent changes later on during stimulation.

Automatically Characterizing Sensory-Motor Patterns Underlying Reach-to-Grasp Movements on a Physical Depth Inversion Illusion

Recently, movement variability has been of great interest to motor control physiologists as it constitutes a physical, quantifiable form of sensory feedback to aid in planning, updating, and executing complex actions. In marked contrast, the psychological and psychiatric arenas mainly rely on verbal descriptions and interpretations of behavior via observation. Consequently, a large gap exists between the body's manifestations of mental states and their descriptions, creating a disembodied approach in the psychological and neural sciences: contributions of the peripheral nervous system to central control, executive functions, and decision-making processes are poorly understood. How do we shift from a psychological, theorizing approach to characterize complex behaviors more objectively? We introduce a novel, objective, statistical framework, and visuomotor control paradigm to help characterize the stochastic signatures of minute fluctuations in overt movements during a visuomotor task. We also quantify a new class of covert movements that spontaneously occur without instruction. These are largely beneath awareness, but inevitably present in all behaviors. The inclusion of these motions in our analyses introduces a new paradigm in sensory-motor integration. As it turns out, these movements, often overlooked as motor noise, contain valuable information that contributes to the emergence of different kinesthetic percepts. We apply these new methods to help better understand perception-action loops. To investigate how perceptual inputs affect reach behavior, we use a depth inversion illusion (DII): the same physical stimulus produces two distinct depth percepts that are nearly orthogonal, enabling a robust comparison of competing percepts. We find that the moment-by-moment empirically estimated motor output variability can inform us of the participants' perceptual states, detecting physiologically relevant signals from the peripheral nervous system that reveal internal mental states evoked by the bi-stable illusion. Our work proposes a new statistical platform to objectively separate changes in visual perception by quantifying the unfolding of movement, emphasizing the importance of including in the motion analyses all overt and covert aspects of motor behavior.

Ultrasonic Vocalizations in Mice During Exploratory Behavior are Context-Dependent

While rat ultrasonic vocalizations (USVs) are known to vary with anticipation of an aversive vs. positive stimulus, little is known about USVs in adult mice in relation to behaviors. We recorded the calls of adult C57BL/6J male mice under different environmental conditions by exposing mice to both novel and familiar environments that varied in stress intensity through the addition of bright light or shallow water. In general, mouse USVs were significantly more frequent and of longer duration in novel environments. Particularly, mice in dimly-lit novel environments performed more USVs while exhibiting unsupported rearing and walking behavior, and these calls were mostly at high frequency. In contrast, mice exhibited more low frequency USVs when engaging in supported rearing behavior in novel environments. These findings are consistent with data from rats suggesting that low-frequency calls are made under aversive conditions and high-frequency calls occur in non-stressful conditions. Our findings increase understanding of acoustic signals associated with exploratory behaviors relevant to cognitive and motivational aspects of behavior.

Influence of motivation on control hierarchy in the human frontal cortex.

The frontal cortex mediates cognitive control and motivation to shape human behavior. It is generally observed that medial frontal areas are involved in motivational aspects of behavior, whereas lateral frontal regions are involved in cognitive control. Recent models of cognitive control suggest a rostro-caudal gradient in lateral frontal regions, such that progressively more rostral (anterior) regions process more complex aspects of cognitive control. How motivation influences such a control hierarchy is still under debate. Although some researchers argue that both systems work in parallel, others argue in favor of an interaction between motivation and cognitive control. In the latter case it is yet unclear how motivation would affect the different levels of the control hierarchy. This was investigated in the present functional MRI study applying different levels of cognitive control under different motivational states (low vs high reward anticipation). Three levels of cognitive control were tested by varying rule complexity: stimulus-response mapping (low-level), flexible task updating (mid-level), and sustained cue-task associations (high-level). We found an interaction between levels of cognitive control and motivation in medial and lateral frontal subregions. Specifically, flexible updating (mid-level of control) showed the strongest beneficial effect of reward and only this level exhibited functional coupling between dopamine-rich midbrain regions and the lateral frontal cortex. These findings suggest that motivation differentially affects the levels of a control hierarchy, influencing recruitment of frontal cortical control regions depending on specific task demands.

The Organization of Prefrontal-Subthalamic Inputs in Primates Provides an Anatomical Substrate for Both Functional Specificity and Integration: Implications for Basal Ganglia Models and Deep Brain Stimulation

The identification of a hyperdirect cortico-subthalamic nucleus connection highlighted the important role of the subthalamic nucleus (STN) in regulating behavior. However, this pathway was shown primarily from motor areas. Hyperdirect pathways associated with cognitive and motivational cortical regions are particularly relevant given recent data from deep brain stimulation, both for neurologic and psychiatric disorders. Our experiments were designed to demonstrate the existence and organization of prefrontal-STN projections, help delineate the "limbic" STN, and determine whether convergence between cortico-STN fibers from functionally diverse cortical areas exists in the STN. We injected anterograde tracers in the ventromedial prefrontal, orbitofrontal, anterior cingulate, and dorsal prefrontal cortices of Macaca nemestrina and Macaca fascicularis to analyze the organization of terminals and passing fibers in the STN. Results show a topographically organized prefrontal hyperdirect pathway in primates. Limbic areas project to the medial tip of the nucleus, straddling its border and extending into the lateral hypothalamus. Associative areas project to the medial half, motor areas to the lateral half. Limbic projections terminated primarily rostrally and motor projections more caudally. The extension of limbic projections into the lateral hypothalamus, suggests that this region be included in the STN. A high degree of convergence exists between projections from functionally diverse cortical areas, creating potentially important interfaces between terminal fields. Taken together, the results provide an anatomical substrate to extend the role of the hyperdirect pathway in models of basal ganglia function, and new keys for understanding deep brain stimulation effects on cognitive and motivational aspects of behavior.

Stochastic aspects of motor behavior and their dependence on auditory feedback in experienced cellists

This study aimed to investigate movement accuracy of experienced cellists, the statistical properties of their note sequences during a reciprocal task, and the degree to which these movement characteristics depend on auditory feedback. Nine experienced cellists were asked to shift alternately between two notes using only their index finger to make contact with the string and fingerboard. Shifting sequences continued for two minutes at a rate of one note per second. The task was performed under two conditions: with auditory feedback (provided by the bow) or without auditory feedback (i.e., without the use of bow). When the bow was used, subjects had no difficulty in shifting between target notes with precision and stability. Some variability was present, but notes in these sequences were generally uncorrelated. The contact data and correlations in most bowed trials resembled those expected of a renewal process, a process in which successive values are statistically independent and identically distributed. Without the bow, subjects lost their ability to reach the same target positions accurately; contact locations tended to drift and had a random quality, indicating that without the bow subjects were uncertain of the target location in relation to the spatial location of their fingertips. Within these unbowed sequences, finger positions were highly correlated—within and between note sequences. In some trials without the bow, the statistical correlation patterns of the sequence were consistent with the expectations of a discrete Wiener process. Throughout our study, computer simulations of renewal and Wiener processes enabled us to determine the types of correlations to be expected from these theoretical models. The implications of the statistical results in terms of subject behavior are discussed.