A task-general connectivity model reveals variation in convergence of cortical inputs to functional regions of the cerebellum.

While resting-state fMRI studies have provided a broad picture of the connectivity between human neocortex and cerebellum, the degree of convergence of cortical inputs onto cerebellar circuits remains unknown. Does each cerebellar region receive input from a single cortical area or convergent inputs from multiple cortical areas? Here, we use task-based fMRI data to build a range of cortico-cerebellar connectivity models, each allowing for a different degree of convergence. We compared these models by their ability to predict cerebellar activity patterns for novel Task Sets. Models that allow some degree of convergence provided the best predictions, arguing for convergence of multiple cortical inputs onto single cerebellar voxels. Importantly, the degree of convergence varied across the cerebellum with the highest convergence observed in areas linked to language, working memory, and social cognition. These findings suggest important differences in the way that functional subdivisions of the cerebellum support motor and cognitive function.

Predicting brain activation maps for arbitrary tasks with cognitive encoding models.

A deep understanding of the neural architecture of mental function should enable the accurate prediction of a specific pattern of brain activity for any psychological task, based only on the cognitive functions known to be engaged by that task. Encoding models (EMs), which predict neural responses from known features (e.g., stimulus properties), have succeeded in circumscribed domains (e.g., visual neuroscience), but implementing domain-general EMs that predict brain-wide activity for arbitrary tasks has been limited mainly by availability of datasets that 1) sufficiently span a large space of psychological functions, and 2) are sufficiently annotated with such functions to allow robust EM specification. We examine the use of EMs based on a formal specification of psychological function, to predict cortical activation patterns across a broad range of tasks. We utilized the Multi-Domain Task Battery, a dataset in which 24 subjects completed 32 ten-minute fMRI scans, switching tasks every 35 s and engaging in 44 total conditions of diverse psychological manipulations. Conditions were annotated by a group of experts using the Cognitive Atlas ontology to identify putatively engaged functions, and region-wise cognitive EMs (CEMs) were fit, for individual subjects, on neocortical responses. We found that CEMs predicted cortical activation maps of held-out tasks with high accuracy, outperforming a permutation-based null model while approaching the noise ceiling of the data, without being driven solely by either cognitive or perceptual-motor features. Hierarchical clustering on the similarity structure of CEM generalization errors revealed relationships amongst psychological functions. Spatial distributions of feature importances systematically overlapped with large-scale resting-state functional networks (RSNs), supporting the hypothesis of functional specialization within RSNs while grounding their function in an interpretable data-driven manner. Our implementation and validation of CEMs provides a proof of principle for the utility of formal ontologies in cognitive neuroscience and motivates the use of CEMs in the further testing of cognitive theories.

Evaluating brain parcellations using the distance-controlled boundary coefficient.

One important approach to human brain mapping is to define a set of distinct regions that can be linked to unique functions. Numerous brain parcellations have been proposed, using cytoarchitectonic, structural, or functional magnetic resonance imaging (fMRI) data. The intrinsic smoothness of brain data, however, poses a problem for current methods seeking to compare different parcellations. For example, criteria that simply compare within-parcel to between-parcel similarity provide even random parcellations with a high value. Furthermore, the evaluation is biased by the spatial scale of the parcellation. To address this problem, we propose the distance-controlled boundary coefficient (DCBC), an unbiased criterion to evaluate discrete parcellations. We employ this new criterion to evaluate existing parcellations of the human neocortex in their power to predict functional boundaries for an fMRI data set with many different tasks, as well as for resting-state data. We find that common anatomical parcellations do not perform better than chance, suggesting that task-based functional boundaries do not align well with sulcal landmarks. Parcellations based on resting-state fMRI data perform well; in some cases, as well as a parcellation defined on the evaluation data itself. Finally, multi-modal parcellations that combine functional and anatomical criteria perform substantially worse than those based on functional data alone, indicating that functionally homogeneous regions often span major anatomical landmarks. Overall, the DCBC advances the field of functional brain mapping by providing an unbiased metric that compares the predictive ability of different brain parcellations to define brain regions that are functionally maximally distinct.

Continuous manipulation of mental representations is compromised in cerebellar degeneration.

We introduce a novel perspective on how the cerebellum might contribute to cognition, hypothesizing that this structure supports dynamic transformations of mental representations. In support of this hypothesis, we report a series of neuropsychological experiments comparing the performance of individuals with degenerative cerebellar disorders on tasks that either entail continuous, movement-like mental operations or more discrete mental operations. In the domain of visual cognition, the cerebellar disorders group exhibited an impaired rate of mental rotation, an operation hypothesized to require the continuous manipulation of a visual representation. In contrast, the cerebellar disorders group showed a normal processing rate when scanning items in visual working memory, an operation hypothesized to require the maintenance and retrieval of remembered items. In the domain of mathematical cognition, the cerebellar disorders group was impaired at single-digit addition, an operation hypothesized to primarily require iterative manipulations along a mental number-line; this group was not impaired on arithmetic tasks linked to memory retrieval (e.g. single-digit multiplication). These results, obtained in tasks from two disparate domains, point to a potential constraint on the contribution of the cerebellum to cognitive tasks. Paralleling its role in motor control, the cerebellum may be essential for coordinating dynamic, movement-like transformations in a mental workspace.

Functional boundaries in the human cerebellum revealed by a multi-domain task battery.

There is compelling evidence that the human cerebellum is engaged in a wide array of motor and cognitive tasks. A fundamental question centers on whether the cerebellum is organized into distinct functional subregions. To address this question, we employed a rich task battery designed to tap into a broad range of cognitive processes. During four functional MRI sessions, participants performed a battery of 26 diverse tasks comprising 47 unique conditions. Using the data from this multi-domain task battery, we derived a comprehensive functional parcellation of the cerebellar cortex and evaluated it by predicting functional boundaries in a novel set of tasks. The new parcellation successfully identified distinct functional subregions, providing significant improvements over existing parcellations derived from task-free data. Lobular boundaries, commonly used to summarize functional data, did not coincide with functional subdivisions. The new parcellation provides a functional atlas to guide future neuroimaging studies.

Universal Transform or Multiple Functionality? Understanding the Contribution of the Human Cerebellum across Task Domains.

An impressive body of research over the past 30 years has implicated the human cerebellum in a broad range of functions, including motor control, perception, language, working memory, cognitive control, and social cognition. The relatively uniform anatomy and physiology of the cerebellar cortex has given rise to the idea that this structure performs the same computational function across diverse domains. Here we highlight evidence from the human neuroimaging literature that documents the striking functional heterogeneity of the cerebellum, both in terms of task-evoked activity patterns and, as measured under task-free conditions, functional connectivity with the neocortex. Building on these observations, we discuss the theoretical challenges these results present to the idea of a universal cerebellar computation and consider the alternative concept of multiple functionality, the idea that the same underlying circuit implements functionally distinct computations.

Unique degeneration signatures in the cerebellar cortex for spinocerebellar ataxias 2, 3, and 7.

Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative diseases that selectively affect vulnerable neuronal populations in the cerebellum and other subcortical regions. While previous studies have reported subtype differences in the absolute amount of degeneration in specific regions of interest, they failed to account for two important factors. First, they did not control for overall differences in the severity of the degeneration pattern, and second, they did not fully characterize the spatial pattern of degeneration for each SCA subtype. Here, we provide a systematic characterization of the spatial degeneration patterns for three polyQ SCAs (55 patients, either SCA2, SCA3, or SCA7) while controlling for the severity of the degeneration pattern. After this correction, the cerebellar degeneration pattern can successfully classify between the three different SCA subtypes with high cross-validated accuracy. Specifically, degeneration in SCA3 disproportionally affects motor regions of the cerebellar cortex, which explains the relatively severe motor symptoms observed in this subtype. Our results demonstrate that each of the three studied SCA subtypes has a unique cerebellar degeneration signature, hinting at differences in the disease process. Clinically, these differentiable patterns of cerebellar degeneration can be used to reliably discern subtypes, even at relatively early stages of the disease.

Individual Differences in Resting Corticospinal Excitability Are Correlated with Reaction Time and GABA Content in Motor Cortex.

Individuals differ in the intrinsic excitability of their corticospinal pathways and, perhaps more generally, their entire nervous system. At present, we have little understanding of the mechanisms underlying these differences and how variation in intrinsic excitability relates to behavior. Here, we examined the relationship between individual differences in intrinsic corticospinal excitability, local cortical GABA levels, and reaction time (RT) in a group of 20 healthy human adults. We measured corticospinal excitability at rest with transcranial magnetic stimulation, local concentrations of basal GABA with magnetic resonance spectroscopy, and RT with a behavioral task. All measurements were repeated in two separate sessions, and tests of reliability confirmed the presence of stable individual differences. There was a negative correlation between corticospinal excitability and RT, such that larger motor-evoked potentials (MEPs) measured at rest were associated with faster RTs. Interestingly, larger MEPs were associated with higher levels of GABA in M1, but not in three other cortical regions. Together, these results suggest that individuals with more excitable corticospinal pathways are faster to initiate planned responses and have higher levels of GABA within M1, possibly to compensate for a more excitable motor system.SIGNIFICANCE STATEMENT This study brings together physiological, behavioral, and neurochemical evidence to examine variability in the excitability of the human motor system. Previous work has focused on state-based factors (e.g., preparedness, uncertainty), with little attention given to the influence of inherent stable characteristics. Here, we examined how the excitability of the motor system relates to reaction time and the regional content of the inhibitory neurotransmitter GABA. Importantly, motor pathway excitability and GABA concentrations were measured at rest, outside a task context, providing assays of intrinsic properties of the individuals. Individuals with more excitable motor pathways had faster reaction times and, paradoxically, higher concentrations of GABA. We propose that greater GABA capacity in the motor cortex counteracts an intrinsically more excitable motor system.

Neural Adaptations Associated with Interlimb Transfer in a Ballistic Wrist Flexion Task.

Cross education is the process whereby training of one limb gives rise to increases in the subsequent performance of its opposite counterpart. The execution of many unilateral tasks is associated with increased excitability of corticospinal projections from primary motor cortex (M1) to the opposite limb. It has been proposed that these effects are causally related. Our aim was to establish whether changes in corticospinal excitability (CSE) arising from prior training of the opposite limb determine levels of interlimb transfer. We used three vision conditions shown previously to modulate the excitability of corticospinal projections to the inactive (right) limb during wrist flexion movements performed by the training (left) limb. These were: (1) mirrored visual feedback of the training limb; (2) no visual feedback of either limb; and (3) visual feedback of the inactive limb. Training comprised 300 discrete, ballistic wrist flexion movements executed as rapidly as possible. Performance of the right limb on the same task was assessed prior to, at the mid point of, and following left limb training. There was no evidence that variations in the excitability of corticospinal projections (assessed by transcranial magnetic stimulation (TMS)) to the inactive limb were associated with, or predictive of, the extent of interlimb transfer that was expressed. There were however associations between alterations in muscle activation dynamics observed for the untrained limb, and the degree of positive transfer that arose from training of the opposite limb. The results suggest that the acute adaptations that mediate the bilateral performance gains realized through unilateral practice of this ballistic wrist flexion task are mediated by neural elements other than those within M1 that are recruited at rest by single-pulse TMS.