Reticular formation responses to magnetic brain stimulation of primary motor cortex

Transcranial magnetic stimulation (TMS) of cerebral cortex is a popular technique for the non-invasive investigation of motor function. TMS is often assumed to influence spinal circuits solely via the corticospinal tract. We were interested in possible trans-synaptic effects of cortical TMS on the ponto-medullary reticular formation in the brainstem, which is the source of the reticulospinal tract and could also generate spinal motor output. We recorded from 210 single units in the reticular formation of three anaesthetized macaque monkeys whilst TMS was performed over primary motor cortex. Short latency responses were observed consistent with activation of a cortico-reticular pathway. However, we also demonstrated surprisingly powerful responses at longer latency, which often appeared at lower threshold than the earlier effects. These late responses seemed to be generated partly as a consequence of the sound click made by coil discharge, and changed little with coil location. This novel finding has implications for the design of future studies using TMS, as well as suggesting a means of non-invasively probing an otherwise inaccessible important motor centre

Direction of Movement Is Encoded in the Human Primary Motor Cortex

The present study investigated how direction of hand movement, which is a well-described parameter in cerebral organization of motor control, is incorporated in the somatotopic representation of the manual effector system in the human primary motor cortex (M1). Using functional magnetic resonance imaging (fMRI) and a manual step-tracking task we found that activation patterns related to movement in different directions were spatially disjoint within the representation area of the hand on M1. Foci of activation related to specific movement directions were segregated within the M1 hand area; activation related to direction 0° (right) was located most laterally/superficially, whereas directions 180° (left) and 270° (down) elicited activation more medially within the hand area. Activation related to direction 90° was located between the other directions. Moreover, by investigating differences between activations related to movement along the horizontal (0°+180°) and vertical (90°+270°) axis, we found that activation related to the horizontal axis was located more anterolaterally/dorsally in M1 than for the vertical axis, supporting that activations related to individual movement directions are direction- and not muscle related. Our results of spatially segregated direction-related activations in M1 are in accordance with findings of recent fMRI studies on neural encoding of direction in human M1. Our results thus provide further evidence for a direct link between direction as an organizational principle in sensorimotor transformation and movement execution coded by effector representations in M1

Multidimensional Recording (MDR) and Data Sharing: An Ecological Open Research and Educational Platform for Neuroscience

Primate neurophysiology has revealed various neural mechanisms at the single-cell level and population level. However, because recording techniques have not been updated for several decades, the types of experimental design that can be applied in the emerging field of social neuroscience are limited, in particular those involving interactions within a realistic social environment. To address these limitations and allow more freedom in experimental design to understand dynamic adaptive neural functions, multidimensional recording (MDR) was developed. MDR obtains behavioral, neural, eye position, and other biological data simultaneously by using integrated multiple recording systems. MDR gives a wide degree of freedom in experimental design because the level of behavioral restraint is adjustable depending on the experimental requirements while still maintaining the signal quality. The biggest advantage of MDR is that it can provide a stable neural signal at higher temporal resolution at the network level from multiple subjects for months, which no other method can provide. Conventional event-related analysis of MDR data shows results consistent with previous findings, whereas new methods of analysis can reveal network mechanisms that could not have been investigated previously. MDR data are now shared in the public server Neurotycho.org. These recording and sharing methods support an ecological system that is open to everyone and will be a valuable and powerful research/educational platform for understanding the dynamic mechanisms of neural networks

Contribution of primary motor cortex to compensatory balance reactions

<p>Abstract</p> <p>Background</p> <p>Rapid compensatory arm reactions represent important response strategies following an unexpected loss of balance. While it has been assumed that early corrective actions arise largely from sub-cortical networks, recent findings have prompted speculation about the potential role of cortical involvement. To test the idea that cortical motor regions are involved in early compensatory arm reactions, we used continuous theta burst stimulation (cTBS) to temporarily suppress the hand area of primary motor cortex (M1) in participants prior to evoking upper limb balance reactions in response to whole body perturbation. We hypothesized that following cTBS to the M1 hand area evoked EMG responses in the stimulated hand would be diminished. To isolate balance reactions to the upper limb participants were seated in an elevated tilt-chair while holding a stable handle with both hands. The chair was held vertical by a magnet and was triggered to fall backward unpredictably. To regain balance, participants used the handle to restore upright stability as quickly as possible with both hands. Muscle activity was recorded from proximal and distal muscles of both upper limbs.</p> <p>Results</p> <p>Our results revealed an impact of cTBS on the amplitude of the EMG responses in the stimulated hand muscles often manifest as inhibition in the stimulated hand. The change in EMG amplitude was specific to the target hand muscles and occasionally their homologous pairs on the non-stimulated hand with no consistent effects on the remaining more proximal arm muscles.</p> <p>Conclusions</p> <p>Present findings offer support for cortical contributions to the control of early compensatory arm reactions following whole-body perturbation.</p

Detecting and correcting partial errors: Evidence for efficient control without conscious access

Appropriate reactions to erroneous actions are essential to keeping behavior adaptive. Erring, however, is not an all-or-none process: electromyographic (EMG) recordings of the responding muscles have revealed that covert incorrect response activations (termed "partial errors") occur on a proportion of overtly correct trials. The occurrence of such "partial errors" shows that incorrect response activations could be corrected online, before turning into overt errors. In the present study, we showed that, unlike overt errors, such "partial errors" are poorly consciously detected by participants, who could report only one third of their partial errors. Two parameters of the partial errors were found to predict detection: the surface of the incorrect EMG burst (larger for detected) and the correction time (between the incorrect and correct EMG onsets; longer for detected). These two parameters provided independent information. The correct(ive) responses associated with detected partial errors were larger than the "pure-correct" ones, and this increase was likely a consequence, rather than a cause, of the detection. The respective impacts of the two parameters predicting detection (incorrect surface and correction time), along with the underlying physiological processes subtending partial-error detection, are discussed

Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive

Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson’s disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model

Structural cerebellar correlates of cognitive functions in spinocerebellar ataxia type 2

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease involving the cerebellum and characterized by a typical motor syndrome. In addition, the presence of cognitive impairment is now widely acknowledged as a feature of SCA2. Given the extensive connections between the cerebellum and associative cerebral areas, it is reasonable to hypothesize that cerebellar neurodegeneration associated with SCA2 may impact on the cerebellar modulation of the cerebral cortex, thus resulting in functional impairment. The aim of the present study was to investigate and quantitatively map the pattern of cerebellar gray matter (GM) atrophy due to SCA2 neurodegeneration and to correlate that with patients' cognitive performances. Cerebellar GM maps were extracted and compared between SCA2 patients (n = 9) and controls (n = 33) by using voxel-based morphometry. Furthermore, the relationship between cerebellar GM atrophy and neuropsychological scores of the patients was assessed. Specific cerebellar GM regions were found to be affected in patients. Additionally, GM loss in cognitive posterior lobules (VI, Crus I, Crus II, VIIB, IX) correlated with visuospatial, verbal memory and executive tasks, while additional correlations with motor anterior (V) and posterior (VIIIA, VIIIB) lobules were found for the tasks engaging motor and planning components. Our results provide evidence that the SCA2 neurodegenerative process affects the cerebellar cortex and that MRI indices of atrophy in different cerebellar subregions may account for the specificity of cognitive symptomatology observed in patients, as result of a cerebello-cerebral dysregulation

When Two Become One: The Limits of Causality Analysis of Brain Dynamics

Biological systems often consist of multiple interacting subsystems, the brain being a prominent example. To understand the functions of such systems it is important to analyze if and how the subsystems interact and to describe the effect of these interactions. In this work we investigate the extent to which the cause-and-effect framework is applicable to such interacting subsystems. We base our work on a standard notion of causal effects and define a new concept called natural causal effect. This new concept takes into account that when studying interactions in biological systems, one is often not interested in the effect of perturbations that alter the dynamics. The interest is instead in how the causal connections participate in the generation of the observed natural dynamics. We identify the constraints on the structure of the causal connections that determine the existence of natural causal effects. In particular, we show that the influence of the causal connections on the natural dynamics of the system often cannot be analyzed in terms of the causal effect of one subsystem on another. Only when the causing subsystem is autonomous with respect to the rest can this interpretation be made. We note that subsystems in the brain are often bidirectionally connected, which means that interactions rarely should be quantified in terms of cause-and-effect. We furthermore introduce a framework for how natural causal effects can be characterized when they exist. Our work also has important consequences for the interpretation of other approaches commonly applied to study causality in the brain. Specifically, we discuss how the notion of natural causal effects can be combined with Granger causality and Dynamic Causal Modeling (DCM). Our results are generic and the concept of natural causal effects is relevant in all areas where the effects of interactions between subsystems are of interest

Nobody Is Perfect: ERP Effects Prior to Performance Errors in Musicians Indicate Fast Monitoring Processes

Background: One central question in the context of motor control and action monitoring is at what point in time errors can be detected. Previous electrophysiological studies investigating this issue focused on brain potentials elicited after erroneous responses, mainly in simple speeded response tasks. In the present study, we investigated brain potentials before the commission of errors in a natural and complex situation. Methodology/Principal Findings: Expert pianists bimanually played scales and patterns while the electroencephalogram (EEG) was recorded. Event-related potentials (ERPs) were computed for correct and incorrect performances. Results revealed differences already 100 ms prior to the onset of a note (i.e., prior to auditory feedback). We further observed that erroneous keystrokes were delayed in time and pressed more slowly. Conclusions: Our data reveal neural mechanisms in musicians that are able to detect errors prior to the execution of erroneous movements. The underlying mechanism probably relies on predictive control processes that compare the predicted outcome of an action with the action goal

Synaptic Transmission and Plasticity in an Active Cortical Network

BACKGROUND: The cerebral cortex is permanently active during both awake and sleep states. This ongoing cortical activity has an impact on synaptic transmission and short-term plasticity. An activity pattern generated by the cortical network is a slow rhythmic activity that alternates up (active) and down (silent) states, a pattern occurring during slow wave sleep, anesthesia and even in vitro. Here we have studied 1) how network activity affects short term synaptic plasticity and, 2) how synaptic transmission varies in up versus down states. METHODOLOGY/PRINCIPAL FINDINGS: Intracellular recordings obtained from cortex in vitro and in vivo were used to record synaptic potentials, while presynaptic activation was achieved either with electrical or natural stimulation. Repetitive activation of layer 4 to layer 2/3 synaptic connections from ferret visual cortex slices displayed synaptic augmentation that was larger and longer lasting in active than in silent slices. Paired-pulse facilitation was also significantly larger in an active network and it persisted for longer intervals (up to 200 ms) than in silent slices. Intracortical synaptic potentials occurring during up states in vitro increased their amplitude while paired-pulse facilitation disappeared. Both intracortical and thalamocortical synaptic potentials were also significantly larger in up than in down states in the cat visual cortex in vivo. These enhanced synaptic potentials did not further facilitate when pairs of stimuli were given, thus paired-pulse facilitation during up states in vivo was virtually absent. Visually induced synaptic responses displayed larger amplitudes when occurring during up versus down states. This was further tested in rat barrel cortex, where a sensory activated synaptic potential was also larger in up states. CONCLUSIONS/SIGNIFICANCE: These results imply that synaptic transmission in an active cortical network is more secure and efficient due to larger amplitude of synaptic potentials and lesser short term plasticity