Cortical-cerebellar Networks Research Articles

Functional connectivity of cortical-cerebellar networks in relation to sensorimotor behavior and clinical features in autism spectrum disorder.

Sensorimotor issues are present in the majority of individuals with autism spectrum disorder (ASD) and are associated with core symptoms. The neural systems associated with these impairments remain unclear. Using a visually guided precision gripping task during functional magnetic resonance imaging, we characterized task-based connectivity and activation of cortical, subcortical, and cerebellar visuomotor networks. Participants with ASD (n = 19; ages 10-33) and age- and sex-matched neurotypical controls (n = 18) completed a visuomotor task at low and high force levels. Relative to controls, individuals with ASD showed reduced functional connectivity of right primary motor-anterior cingulate cortex and left anterior intraparietal lobule (aIPL)-right Crus I at high force only. At low force, increased caudate, and cerebellar activation each were associated with sensorimotor behavior in controls, but not in ASD. Reduced left aIPL-right Crus I connectivity was associated with more severe clinically rated ASD symptoms. These findings suggest that sensorimotor problems in ASD, particularly at high force levels, involve deficits in the integration of multimodal sensory feedback and reduced reliance on error-monitoring processes. Adding to literature positing that cerebellar dysfunction contributes to multiple developmental issues in ASD, our data implicate parietal-cerebellar connectivity as a key neural marker underlying both core and comorbid features of ASD.

Resting-State Brain Network Dysfunctions Associated With Visuomotor Impairments in Autism Spectrum Disorder.

Background: Individuals with autism spectrum disorder (ASD) show elevated levels of motor variability that are associated with clinical outcomes. Cortical–cerebellar networks involved in visuomotor control have been implicated in postmortem and anatomical imaging studies of ASD. However, the extent to which these networks show intrinsic functional alterations in patients, and the relationship between intrinsic functional properties of cortical–cerebellar networks and visuomotor impairments in ASD have not yet been clarified.Methods: We examined the amplitude of low-frequency fluctuation (ALFF) of cortical and cerebellar brain regions during resting-state functional MRI (rs-fMRI) in 23 individuals with ASD and 16 typically developing (TD) controls. Regions of interest (ROIs) with ALFF values significantly associated with motor variability were identified for for patients and controls respectively, and their functional connectivity (FC) to each other and to the rest of the brain was examined.Results: For TD controls, greater ALFF in bilateral cerebellar crus I, left superior temporal gyrus, left inferior frontal gyrus, right supramarginal gyrus, and left angular gyrus each were associated with greater visuomotor variability. Greater ALFF in cerebellar lobule VIII was associated with less visuomotor variability. For individuals with ASD, greater ALFF in right calcarine cortex, right middle temporal gyrus (including MT/V5), left Heschl's gyrus, left post-central gyrus, right pre-central gyrus, and left precuneus was related to greater visuomotor variability. Greater ALFF in cerebellar vermis VI was associated with less visuomotor variability. Individuals with ASD and TD controls did not show differences in ALFF for any of these ROIs. Individuals with ASD showed greater posterior cerebellar connectivity with occipital and parietal cortices relative to TD controls, and reduced FC within cerebellum and between lateral cerebellum and pre-frontal and other regions of association cortex.Conclusion: Together, these findings suggest that increased resting oscillations within visuomotor networks in ASD are associated with more severe deficits in controlling variability during precision visuomotor behavior. Differences between individuals with ASD and TD controls in the topography of networks showing relationships to visuomotor behavior suggest atypical patterns of cerebellar–cortical specialization and connectivity in ASD that underlies previously documented visuomotor deficits.

Dynamic brain glucose metabolism identifies anti-correlated cortical-cerebellar networks at rest

It remains unclear whether resting state functional magnetic resonance imaging (rfMRI) networks are associated with underlying synchrony in energy demand, as measured by dynamic 2-deoxy-2-[18F]fluoroglucose (FDG) positron emission tomography (PET). We measured absolute glucose metabolism, temporal metabolic connectivity (t-MC) and rfMRI patterns in 53 healthy participants at rest. Twenty-two rfMRI networks emerged from group independent component analysis (gICA). In contrast, only two anti-correlated t-MC emerged from FDG-PET time series using gICA or seed-voxel correlations; one included frontal, parietal and temporal cortices, the other included the cerebellum and medial temporal regions. Whereas cerebellum, thalamus, globus pallidus and calcarine cortex arose as the strongest t-MC hubs, the precuneus and visual cortex arose as the strongest rfMRI hubs. The strength of the t-MC linearly increased with the metabolic rate of glucose suggesting that t-MC measures are strongly associated with the energy demand of the brain tissue, and could reflect regional differences in glucose metabolism, counterbalanced metabolic network demand, and/or differential time-varying delivery of FDG. The mismatch between metabolic and functional connectivity patterns computed as a function of time could reflect differences in the temporal characteristics of glucose metabolism as measured with PET-FDG and brain activation as measured with rfMRI.

Terra incognita-cerebellar contributions to neuropsychiatric and cognitive dysfunction in behavioral variant frontotemporal dementia.

Although converging evidence has positioned the human cerebellum as an important relay for intact cognitive and neuropsychiatric processing, changes in this large structure remain mostly overlooked in behavioral variant frontotemporal dementia (bvFTD), a disease which is characterized by cognitive and neuropsychiatric deficits. The present study assessed whether degeneration in specific cerebellar subregions associate with indices of cognition and neuropsychiatric performance in bvFTD. Our results demonstrate a relationship between cognitive and neuropsychiatric decline across various domains of memory, language, emotion, executive, visuospatial function, and motivation and the degree of gray matter degeneration in cerebellar lobules V–VII. Most notably, bilateral cerebellar lobule VII and the posterior vermis emerged as distinct for memory processes, the right cerebellar hemisphere underpinned emotion, and the posterior vermis was highlighted in language dysfunction in bvFTD. Based on cortico-cerebellar connectivity maps, these findings in the cerebellum are consistent with the neural connections with the cortices involved in these domains in patients with bvFTD. Overall, the present study underscores the significance of cortical-cerebellar networks associated with cognition and neuropsychiatric dysfunction in bvFTD.

Changes in regional brain glucose metabolism measured with F-18-FDG-PET in essential tremor

There is growing evidence that essential tremor (ET) is a multiple-system disorder. Previous PET studies in ET typically have measured brain oxygen consumption and cerebral blood flow. To compare ET patients with control subjects to investigate any regional change in cerebral glucose metabolism through statistical parametric mapping (SPM) analysis of F-18-fluorodeoxyglucose positron emission tomography (F-18-FDG-PET). We studied 17 patients with ET (17 men; mean age, 67.3 ± 4.8 years) and age-sex matched normal subjects. All subjects underwent FDG-PET imaging, and evaluated severity of tremor symptoms was measured as score on the Fahn-Tolosa-Marin rating scale (FTM). We also evaluated detailed the medical history and neurological examinations in all patients. The mean age of tremor onset was 57.6 ± 12.9 years and the mean FTM score was 15.1 ± 4.9. Brain FDG-PET analysis demonstrated hypometabolism in the medial frontal lobe, medial temporal lobe, and the precuneus of parietal lobe. However, there was no significant difference of glucose metabolism in the cerebellum. We propose that motor symptom of ET are caused by electrophysiological disturbances within cortical-cerebellar networks, rather than degenerative process of cerebellum, because the metabolism of the cerebellum was normal at rest. Furthermore, the abnormal glucose metabolism in the cerebral regions that do not mainly participate in motor function suggest that these regions may play a role as early markers of non-motor manifestations.

Differences in Regional Glucose Metabolism of the Brain Measured with F-18-FDG-PET in Patients with Essential Tremor According to Their Response to Beta-Blockers.

ObjectiveIn this study, there was an investigation as to whether there is a functional difference in essential tremor (ET), according to responses to beta-blockers, by evaluating regional changes in cerebral glucose metabolism.Materials and MethodsSeventeen male patients with ET were recruited and categorized into two groups: 8 that responded to medical therapy (group A); and 9 that did not respond to medical therapy (group B). Eleven age-sex matched healthy control male subjects were also included in this study. All subjects underwent F-18 fluorodeoxyglucose (FDG)-PET, and evaluated for their severity of tremor symptoms, which were measured as a score on the Fahn-Tolosa-Marin tremor rating scale (FTM). The FDG-PET images were analyzed using a statistical parametric mapping program.ResultsThe mean FTM score 6 months after the initiation of propranolol therapy was significantly lower in group A (18.13 > 8.13), compared with group B (14.67 = 14.67). The glucose metabolism in group A in the left basal ganglia was seen to be decreased, compared with group B. The ET showed a more significantly decreased glucose metabolism in both the fronto-temporo-occipital lobes, precuneus of right parietal lobe, and both cerebellums compared with the healthy controls.ConclusionEssential tremor is caused by electrophysiological disturbances within the cortical-cerebellar networks and degenerative process of the cerebellum. Furthermore, ET may have different pathophysiologies in terms of the origin of disease according to the response to first-line therapy.

Ensemble neuronal responses in a large-scale realistic model of the cerebellar cortex

Realistic simulation of central networks remains a challenge due to the complexity of internal connectivity and cellular mechanisms involved. We have recently built a realistic model of the cerebellar granular layer [1], which has now been extended to include the molecular layer and Purkinje cells (PC). The model is built in NEURON-PYTHON and is fully scalable, thus allowing to simulate large-scale networks of arbitrary size. The model is made of conductance-based multicompartmental neurons and incorporates dynamic synaptic mechanisms. The model accounts for the principal neuronal types (granule and Golgi cells in the granular layer; Purkinje cells and stellate cells in the molecular layer) and for their density and connectivity (including gap-junctions between Golgi cell dendrites). As in the real network, mossy fiber (mf) branching gives origin to clusters of glomeruli aligned along the parasaggittal plane. The functionality of this cortical cerebellar network model was validated using input patterns, whose impact has been demonstrated previously. (1) Low frequency random mf inputs, simulating background resting activity, induced low frequency oscillations in the granular layer. (2) High frequency bursts delivered to specific mf bundles activated multiple activity spots within the granular layer, with a center-surround configuration. (3) Collision of inputs from multiple active mf bundles generated either coincident excitation or inhibition [2]. (4) Low-frequency MF bursts were reliably transmitted through the granular layer toward PCs aligned along the vertical axis as well as to PCs laying along the parallel fiber axis. Conversely, high-frequency bursts were strongly amplified and transmitted toward PC aligned along the vertical axis but not along the parallel fiber axis[3]. These results, by closely matching experimental recordings, suggest that the model network can be further used to investigate the mechanisms of cerebellar functioning.

BOLD Coherence Reveals Segregated Functional Neural Interactions When Adapting to Distinct Torque Perturbations

In the natural world, we experience and adapt to multiple extrinsic perturbations. This poses a challenge to neural circuits in discriminating between different context-appropriate responses. Using event-related fMRI, we characterized the neural dynamics involved in this process by randomly delivering a position- or velocity-dependent torque perturbation to subjects' arms during a target-capture task. Each perturbation was color-cued during movement preparation to provide contextual information. Although trajectories differed between perturbations, subjects significantly reduced error under both conditions. This was paralleled by reduced BOLD signal in the right dentate nucleus, the left sensorimotor cortex, and the left intraparietal sulcus. Trials included "NoGo" conditions to dissociate activity related to preparation from execution and adaptation. Subsequent analysis identified perturbation-specific neural processes underlying preparation ("NoGo") and adaptation ("Go") early and late into learning. Between-perturbation comparisons of BOLD magnitude revealed negligible differences for both preparation and adaptation trials. However, a network-level analysis of BOLD coherence revealed that by late learning, response preparation ("NoGo") was attributed to a relative focusing of coherence within cortical and basal ganglia networks in both perturbation conditions, demonstrating a common network interaction for establishing arbitrary visuomotor associations. Conversely, late-learning adaptation ("Go") was attributed to a focusing of BOLD coherence between a cortical-basal ganglia network in the viscous condition and between a cortical-cerebellar network in the positional condition. Our findings demonstrate that trial-to-trial acquisition of two distinct adaptive responses is attributed not to anatomically segregated regions, but to differential functional interactions within common sensorimotor circuits.

The cerebellum plays a role in conscious episodic memory retrieval

The cerebellum has traditionally been considered to be primarily dedicated to motor functions. Its phylogenetic development and connectivity suggest, however, that it also may play a role in cognitive processes in the human brain. In order to examine a potential cognitive role for the cerebellum in human beings, a positron emission tomography (PET) study was conducted during a "pure thought experiment": subjects intentionally recalled a specific past personal experience (consciously retrieved episodic memory). Since there was no motor or sensory input or output, the design eliminated the possibility that cerebellar changes in blood flow were due to motor activity. During silent recall of a consciously retrieved episodic memory, activations were observed in the right lateral cerebellum, left medial dorsal thalamus, medial and left orbital frontal cortex, anterior cingulate, and a left parietal region. These activations confirm a cognitive role for the cerebellum, which may participate in an interactive cortical-cerebellar network that initiates and monitors the conscious retrieval of episodic memory.

The cerebellum plays a role in conscious episodic memory retrieval

The cerebellum has traditionally been considered to be primarily dedicated to motor functions. Its phylogenetic development and connectivity suggest, however, that it also may play a role in cognitive processes in the human brain. In order to examine a potential cognitive role for the cerebellum in human beings, a positron emission tomography (PET) study was conducted during a “pure thought experiment”: subjects intentionally recalled a specific past personal experience (consciously retrieved episodic memory). Since there was no motor or sensory input or output, the design eliminated the possibility that cerebellar changes in blood flow were due to motor activity. During silent recall of a consciously retrieved episodic memory, activations were observed in the right lateral cerebellum, left medial dorsal thalamus, medial and left orbital frontal cortex, anterior cingulate, and a left parietal region. These activations confirm a cognitive role for the cerebellum, which may participate in an interactive cortical-cerebellar network that initiates and monitors the conscious retrieval of episodic memory. Hum. Brain Mapping 8:226–234, 1999. © 1999 Wiley-Liss, Inc.

Cerebellar guidance of premotor network development and sensorimotor learning.

Single unit and imaging studies have shown that the cerebellum is especially active during the acquisition phase of certain motor and cognitive tasks. These data are consistent with the hypothesis that particular sensorimotor procedures are acquired and stored in the cerebellar cortex and that this knowledge can then be exported to the cerebral cortex and premotor networks for more efficient execution. In this article we present a model to illustrate how the cerebellar cortex might guide the development of cortical-cerebellar network connections and how a similar mechanism operating in the adult could mediate the exportation of sensorimotor knowledge from the cerebellum to the motor cortex. The model consists of a three-layered recurrent network representing the cerebello-thalamocortical-ponto-cerebellar limb premotor network. The cerebellar cortex is not explicitly modeled. Our simulations show that Hebbian learning combined with weight normalization allows the emergence of reciprocal and modular structure in the limb premotor network. Reciprocal connections allow activity to reverberate around specific loops. Modularity organizes the connections into specific channels. Furthermore, we show that cerebellar learning can be exported to motor cortex through these modular and reciprocal premotor circuits. In particular, we simulate developmental alignment of visuomotor relations and their realignment as a consequence of prism exposure. The exportation of sensorimotor knowledge from the cerebellum to the motor cortex may allow faster and more efficient execution of learned motor responses.