Impact of task-related changes in heart rate on estimation of hemodynamic response and model fit.

The blood oxygen level dependent (BOLD) signal, as measured using functional magnetic resonance imaging (fMRI), is widely used as a proxy for changes in neural activity in the brain. Physiological variables such as heart rate (HR) and respiratory variation (RV) affect the BOLD signal in a way that may interfere with the estimation and detection of true task-related neural activity. This interference is of particular concern when these variables themselves show task-related modulations. We first establish that a simple movement task reliably induces a change in HR but not RV. In group data, the effect of HR on the BOLD response was larger and more widespread throughout the brain than were the effects of RV or phase regressors. The inclusion of HR regressors, but not RV or phase regressors, had a small but reliable effect on the estimated hemodynamic response function (HRF) in M1 and the cerebellum. We next asked whether the inclusion of a nested set of physiological regressors combining phase, RV, and HR significantly improved the model fit in individual participants' data sets. There was a significant improvement from HR correction in M1 for the greatest number of participants, followed by RV and phase correction. These improvements were more modest in the cerebellum. These results indicate that accounting for task-related modulation of physiological variables can improve the detection and estimation of true neural effects of interest.

Laterality Differences in Cerebellar-Motor Cortex Connectivity.

Lateralization of function is an important organizational feature of the motor system. Each effector is predominantly controlled by the contralateral cerebral cortex and the ipsilateral cerebellum. Transcranial magnetic stimulation studies have revealed hemispheric differences in the stimulation strength required to evoke a muscle response from the primary motor cortex (M1), with the dominant hemisphere typically requiring less stimulation than the nondominant. The current study assessed whether the strength of the connection between the cerebellum and M1 (CB-M1), known to change in association with motor learning, have hemispheric differences and whether these differences have any behavioral correlate. We observed, in right-handed individuals, that the connection between the right cerebellum and left M1 is typically stronger than the contralateral network. Behaviorally, we detected no lateralized learning processes, though we did find a significant effect on the amplitude of reaching movements across hands. Furthermore, we observed that the strength of the CB-M1 connection is correlated with the amplitude variability of reaching movements, a measure of movement precision, where stronger connectivity was associated with better precision. These findings indicate that lateralization in the motor system is present beyond the primary motor cortex, and points to an association between cerebellar M1 connectivity and movement execution.

Individuals with cerebellar degeneration show similar adaptation deficits with large and small visuomotor errors.

The cerebellum has long been recognized to play an important role in motor adaptation. Individuals with cerebellar ataxia exhibit impaired learning in visuomotor adaptation tasks such as prism adaptation and force field learning. Both types of tasks involve the adjustment of an internal model to compensate for an external perturbation. This updating process is error driven, with the error signal based on the difference between anticipated and actual sensory information. This process may entail a credit assignment problem, with a distinction made between error arising from faulty representation of the environment and error arising from noise in the controller. We hypothesized that people with ataxia may perform poorly at visuomotor adaptation because they attribute a greater proportion of their error to their motor control difficulties. We tested this hypothesis using a computational model based on a Kalman filter. We imposed a 20-deg visuomotor rotation in either a single large step or in a series of smaller 5-deg steps. The ataxic group exhibited a comparable deficit in both conditions. The computational analyses indicate that the patients' deficit cannot be accounted for simply by their increased motor variability. Rather, the patients' deficit in learning may be related to difficulty in estimating the instability in the environment or variability in their motor system.

Dynamic modulation of cerebellar excitability for abrupt, but not gradual, visuomotor adaptation.

The cerebellum is critically important for error-driven adaptive motor learning, as evidenced by the fact that cerebellar patients do not adapt well to sudden predictable perturbations. However, recent work has shown that cerebellar patients adapt much better if the perturbation is gradually introduced. Here we explore physiological mechanisms that underlie this distinction between abrupt and gradual motor adaptation in humans. We used transcranial magnetic stimulation to evaluate whether neural mechanisms within the cerebellum contribute to either process during a visuomotor reach adaptation. When a visuomotor rotation was introduced abruptly, cerebellar excitability changed early in learning and approached baseline levels near the end of the adaptation block. However, we observed no modulation of cerebellar excitability when we presented the visuomotor rotation gradually during learning. Similarly, we did not observe cerebellar modulation during trial-by-trial adaptation to random visuomotor displacements or during reaches without perturbations. This suggests that the cerebellum is most active during the early phases of adaptation when large perturbations are successfully compensated.

Task goals influence online corrections and adaptation of reaching movements.

Everyday movements often have multiple solutions. Many of these solutions arise from biomechanical redundancies. Often, however, the goal does not require a unique movement. To examine how people exploit task-related redundancy, we observed as participants produced three-dimensional (3-D) reaching movements, moving to one of two rectangular targets that were diagonally oriented in the frontal (x, y) plane. On most trials, the movement was perturbed by a vertical, velocity-dependent force. Since participants were free to move in 3-D space, online corrections could involve movement along the perturbed, vertical dimension, as well as the nonperturbed, horizontal dimension. If the motor system exploits task redundancies, then corrections along the horizontal dimension should depend on the orientation of the target. Consistent with this prediction, participants modified both the horizontal and vertical coordinates of the trajectory over the course of learning, and the horizontal component was sensitive to the orientation of the target. Furthermore, participants produced online corrections with a horizontal component that brought the hand closer to the target. These results suggest that we not only correct for mismatches between expected and experienced forces but also exploit task-specific redundancies to efficiently improve performance.

Dedicated and intrinsic models of time perception.

Two general frameworks have been articulated to describe how the passage of time is perceived. One emphasizes that the judgment of the duration of a stimulus depends on the operation of dedicated neural mechanisms specialized for representing the temporal relationships between events. Alternatively, the representation of duration could be ubiquitous, arising from the intrinsic dynamics of nondedicated neural mechanisms. In such models, duration might be encoded directly through the amount of activation of sensory processes or as spatial patterns of activity in a network of neurons. Although intrinsic models are neurally plausible, we highlight several issues that must be addressed before we dispense with models of duration perception that are based on dedicated processes.

Evidence for reduced cerebellar volumes in trichotillomania.

BACKGROUND: Limited knowledge exists regarding the neurobiology of trichotillomania (TTM). Cerebellum (CBM) volumes were explored, given its role in complex, coordinated motor sequences. METHODS: Morphometric magnetic resonance imaging (MRI) scans were obtained for 14 female subjects with DSM-IV diagnoses of TTM and 12 age-, education-, and gender-matched normal control (NC) participants. Parcellation was performed utilizing a recently developed methodology to measure subterritory volumes of the CBM. Regions were defined based on knowledge of the structural and functional subunits of the CBM. RESULTS: As predicted, significant group differences were reported for CBM raw cortical volumes (p = .008) that survived correction for total brain volume (TBV; p = .037) and head circumference (HC; p = .011). A priori and post hoc group raw volume comparisons for CBM subterritories and functional clusters revealed many significant differences. However, most differences failed to withstand correction for total CBM volumes (TCV). Smaller volumes were consistently reported for the TTM versus NC cohorts. Total Massachusetts General Hospital Hair Pulling Scale (MGHHPS) scores were significantly inversely correlated with left primary sensorimotor cluster volumes (p = .008), with smaller volumes associated with more severe TTM symptoms. CONCLUSIONS: These findings implicate the CBM in the neurobiology of TTM, with reduced subterritory volumes reported for the TTM versus NC groups.

Cerebellar damage produces selective deficits in verbal working memory.

The cerebellum is often active in imaging studies of verbal working memory, consistent with a putative role in articulatory rehearsal. While patients with cerebellar damage occasionally exhibit a mild impairment on standard neuropsychological tests of working memory, these tests are not diagnostic for exploring these processes in detail. The current study was designed to determine whether damage to the cerebellum is associated with impairments on a range of verbal working memory tasks, and if so, under what circumstances. Moreover, we assessed the hypothesis that these impairments are related to impaired rehearsal mechanisms. Patients with damage to the cerebellum (n = 15) exhibited a selective deficit in verbal working memory: spatial forward and backward spans were normal, but forward and backward verbal spans were lower than controls. While the differences were significant, digit spans were relatively preserved, especially in comparison to the dramatic reductions typically observed in classic 'short-term memory' patients with perisylvian brain damage. The patients tended to be more impaired on a verbal version compared to a spatial version of a working memory task with a long delay and this impairment was correlated with overall symptom and dysarthria severity. These results are consistent with a contribution of the cerebellum to rehearsal and suggest that inclusion of a delay before recall is especially detrimental in individuals with cerebellar damage. However, when we examined markers of rehearsal (i.e. word-length and articulatory suppression effects) in an immediate serial recall task, we found that qualitative aspects of the patients' rehearsal strategies were unaffected. We propose that the cerebellum may contribute to verbal working memory during the initial phonological encoding and/or by strengthening memory traces rather than by fundamentally subserving covert articulatory rehearsal.

MRI-based surface-assisted parcellation of human cerebellar cortex: an anatomically specified method with estimate of reliability.

We revisit here a surface assisted parcellation (SAP) system of the human cerebellar cortex originally described in Makris, N., Hodge, S.M., Haselgrove, C., Kennedy, D.N., Dale, A., Fischl, B., Rosen, B.R., Harris, G., Caviness, V.S., Jr., Schmahmann, J.D., 2003. Human cerebellum: surface-assisted cortical parcellation and volumetry with magnetic resonance imaging. J Cogn Neurosci 15, 584-599. This system preserves the topographic and morphologic uniqueness of the individual cerebellum and allows for volumetric analysis and representation of multimodal structural and functional data on the cerebellar cortex. This methodology integrates features of automated routines of the program FreeSurfer as well as semi-automated and manual procedures of the program Cardviews to create 64 cerebellar parcellation units based on fissure information and anatomical landmarks of the cerebellar surface. Using this technique, we undertook the parcellation of ten cerebella by two independent raters. The reliability of the resulting parcellation units (64 total) was high, with an average Intraclass Correlation Coefficient (ICC) of 0.724 in the vermis and 0.853 in the hemispheres. Clusters of parcellation units were then created, based on lobar and connectivity data and functional hypotheses. These 36 clusters, when treated as anatomical units, had an average ICC of 0.933. Whereas the individual units provide a high level of detail and anatomical specificity, the clusters add flexibility to the analysis by providing higher reliability.