Cerebellar Contribution Research Articles

P218 Cerebellar involvement in facial emotion discrimination: A TMS study

The contribution of cerebellum to affective processing has been neglected for a long time. Recently, an increasing number of studies on both healthy participants and patients with cerebellar abnormalities pointed to a possible role of the cerebellum in the emotions regulation and perception. In this study, we aimed to investigate the involvement of the cerebellum in emotion discrimination by means of transcranial magnetic stimulation (TMS). We presented participants with pairs of faces with different emotional expressions (happy or angry) and we asked them to indicate whether the two faces showed the same or a different emotion. Triple-pulse TMS (20 Hz) was delivered between the first and the second face presentation over the left cerebellum, the primary visual cortex and the vertex (control site). Analyses suggest that cerebellar TMS impaired participants’ performance in emotion discrimination, in line with previous evidence on the link between cerebellum and emotional processing.

Cerebellar contributions to biological motion perception in autism and typical development.

Growing evidence suggests that posterior cerebellar lobe contributes to social perception in healthy adults. However, they know little about how this process varies across age and with development. Using cross-sectional fMRI data, they examined cerebellar response to biological (BIO) versus scrambled (SCRAM) motion within typically developing (TD) and autism spectrum disorder (ASD) samples (age 4-30 years old), characterizing cerebellar response and BIO > SCRAM-selective effective connectivity, as well as associations with age and social ability. TD individuals recruited regions throughout cerebellar posterior lobe during BIO > SCRAM, especially bilateral lobule VI, and demonstrated connectivity with right posterior superior temporal sulcus (RpSTS) in left VI, Crus I/II, and VIIIb. ASD individuals showed BIO > SCRAM activity in left VI and left Crus I/II, and bilateral connectivity with RpSTS in Crus I/II and VIIIb/IX. No between-group differences emerged in well-matched subsamples. Among TD individuals, older age predicted greater BIO > SCRAM response in left VIIb and left VIIIa/b, but reduced connectivity between RpSTS and widespread regions of the right cerebellum. In ASD, older age predicted greater response in left Crus I and bilateral Crus II, but decreased effective connectivity with RpSTS in bilateral Crus I/II. In ASD, increased BIO > SCRAM signal in left VI/Crus I and right Crus II, VIIb, and dentate predicted lower social symptomaticity; increased effective connectivity with RpSTS in right Crus I/II and bilateral VI and I-V predicted greater symptomaticity. These data suggest that posterior cerebellum contributes to the neurodevelopment of social perception in both basic and clinical populations. Hum Brain Mapp 38:1914-1932, 2017. © 2017 Wiley Periodicals, Inc.

Cerebellar tDCS Modulates Neural Circuits during Semantic Prediction: A Combined tDCS-fMRI Study.

It has been proposed that the cerebellum acquires internal models of mental processes that enable prediction, allowing for the optimization of behavior. In language, semantic prediction speeds speech production and comprehension. Right cerebellar lobules VI and VII (including Crus I/II) are engaged during a variety of language processes and are functionally connected with cerebral cortical language networks. Further, right posterolateral cerebellar neuromodulation modifies behavior during predictive language processing. These data are consistent with a role for the cerebellum in semantic processing and semantic prediction. We combined transcranial direct current stimulation (tDCS) and fMRI to assess the behavioral and neural consequences of cerebellar tDCS during a sentence completion task. Task-based and resting-state fMRI data were acquired in healthy human adults (n = 32; μ = 23.1 years) both before and after 20 min of 1.5 mA anodal (n = 18) or sham (n = 14) tDCS applied to the right posterolateral cerebellum. In the sentence completion task, the first four words of the sentence modulated the predictability of the final target word. In some sentences, the preceding context strongly predicted the target word, whereas other sentences were nonpredictive. Completion of predictive sentences increased activation in right Crus I/II of the cerebellum. Relative to sham tDCS, anodal tDCS increased activation in right Crus I/II during semantic prediction and enhanced resting-state functional connectivity between hubs of the reading/language networks. These results are consistent with a role for the right posterolateral cerebellum beyond motor aspects of language, and suggest that cerebellar internal models of linguistic stimuli support semantic prediction.SIGNIFICANCE STATEMENT Cerebellar involvement in language tasks and language networks is now well established, yet the specific cerebellar contribution to language processing remains unclear. It is thought that the cerebellum acquires internal models of mental processes that enable prediction, allowing for the optimization of behavior. Here we combined neuroimaging and neuromodulation to provide evidence that the cerebellum is specifically involved in semantic prediction during sentence processing. We found that activation within right Crus I/II was enhanced when semantic predictions were made, and we show that modulation of this region with transcranial direct current stimulation alters both activation patterns and functional connectivity within whole-brain language networks. For the first time, these data show that cerebellar neuromodulation impacts activation patterns specifically during predictive language processing.

Cognitive aspects of human motor activity: Contribution of right hemisphere and cerebellum

Cognitive aspects of human motor activity: Contribution of right hemisphere and cerebellum

The inion response revisited: evidence for a possible cerebellar contribution to vestibular-evoked potentials produced by air-conducted sound stimulation.

This study investigated the effect of eye gaze and head position on vestibular-evoked potentials (VsEPs). Head position would be expected to affect myogenic sources, and eye position is known to affect ocular myogenic responses (ocular vestibular-evoked myogenic potentials), whereas a neurogenic source should behave otherwise. Eleven healthy subjects were recruited, and VsEPs, using 72-channel EEG, were recorded at a fixed intensity above the vestibular threshold. Three eye gaze and three head positions were tested (-20°, 0°, and +20° to the horizontal). Short-latency potentials showed that in addition to the expected effect of gaze on infraocular (IO') leads, where up-gaze gives a maximum response, significant changes in amplitude were also observed in electrodes remote from the eyes and in particular, from contralateral parietal-occipital (PO) and neck (CB') leads. Short-latency potentials of similar latency were observed (p10/n17 and n10/p17, respectively). The pattern of change with gaze in the PO leads was distinct from that observed for the IO' leads. For the PO leads, the maximum response was obtained with neutral gaze, and this was also distinct from that observed for CB' electrodes, where a maximal response was observed with head flexion in the second wave but not the first. Evidence of modulation of N42 and N1 potentials with both eye and head position was also observed. Head- and eye-position manipulation thus suggests that the inion response consists of an early neurogenic component, as well as myogenic responses. The p10/n17 at PO, in particular, may be an indicator of vestibulocerebellar projections.NEW & NOTEWORTHY Loud sounds were used to activate vestibular receptors in human volunteers and the effects of head and eye position studied for short-latency responses. A potential (p10/n17) recorded in the parieto-occipital leads showed behavior not expected for a response with a myogenic origin. Source modeling suggested a possible origin from the cerebellum. It may represent a new indicator of human vestibulocerebellar function.

Cerebellar response to familiar and novel stimuli: An fMRI study.

Historically known for its key contribution to motor behavior, the cerebellum continues to break boundaries. Researchers have demonstrated the cerebellum also plays a role in learning, memory, and more recent evidence for contributions in language, attention, working memory, emotions, and social processes. Here, we present a study that adds to the list of nonmotor processes of the cerebellum. We used images of faces and outdoor scenes to examine the cerebellar response to familiar and novel stimuli. Participants were familiarized with a subset of stimuli, and then underwent functional MRI (fMRI) where they were presented with the previously stimuli and new stimuli while making "old" and "new" judgment. In a familiar versus novel contrast, familiar stimuli (faces and scenes combined) activated bilateral regions of the cerebellum including I-IV, V, VI, Crus I, and Crus II. When separated by type, familiar faces had greater activation of bilateral I-IV than novel faces. These results demonstrate the cerebellar role in determining familiarity and contribute to continuing research supporting cerebellar contributions to nonmotor processes. (PsycINFO Database Record

"Cerebellar contribution to visuo-attentional alpha rhythm: insights from weightlessness".

Human brain adaptation in weightlessness follows the necessity to reshape the dynamic integration of the neural information acquired in the new environment. This basic aspect was here studied by the electroencephalogram (EEG) dynamics where oscillatory modulations were measured during a visuo-attentional state preceding a visuo-motor docking task. Astronauts in microgravity conducted the experiment in free-floating aboard the International Space Station, before the space flight and afterwards. We observed stronger power decrease (~ERD: event related desynchronization) of the ~10 Hz oscillation from the occipital-parietal (alpha ERD) to the central areas (mu ERD). Inverse source modelling of the stronger alpha ERD revealed a shift from the posterior cingulate cortex (BA31, from the default mode network) on Earth to the precentral cortex (BA4, primary motor cortex) in weightlessness. We also observed significant contribution of the vestibular network (BA40, BA32, and BA39) and cerebellum (lobule V, VI). We suggest that due to the high demands for the continuous readjustment of an appropriate body posture in free-floating, this visuo-attentional state required more contribution from the motor cortex. The cerebellum and the vestibular network involvement in weightlessness might support the correction signals processing necessary for postural stabilization, and the increased demand to integrate incongruent vestibular information.

Distinct Cerebellar Contributions to Cognitive-Perceptual Dynamics During Natural Viewing.

The crucial role of the cerebellum in motor learning and coordination is very well known. Considerable interest has recently shifted toward its contribution to nonmotor tasks, such as working memory, emotion, and language. However, the cognitive role and functional subdivisions of the cerebellum, particularly in dynamic, ecologically realistic contexts, are not yet established. By analyzing functional neuroimaging data acquired while participants viewed a short dramatic movie, we found that posterior and inferior cerebellar regions are reliably engaged in dynamic perceptual and affective processes with no explicit motor component. These cerebellar regions show significant relevance to visual salience and unexpected turning points of the movie. Our results demonstrate that distinct functional subdivisions of the cerebellum are robustly engaged in real-life cognitive processes, playing specific roles through a dynamic interaction with higher order regions in the cerebral cortex.

Cerebellar contribution to motor and cognitive performance in multiple sclerosis: An MRI sub-regional volumetric analysis

Objective: To investigate the role of cerebellar sub-regions on motor and cognitive performance in multiple sclerosis (MS) patients. Methods: Whole and sub-regional cerebellar volumes, brain volumes, T2 hyperintense lesion volumes (LV), and motor performance scores were obtained from 95 relapse-onset MS patients and 32 healthy controls (HC). MS patients also underwent an evaluation of working memory and processing speed functions. Cerebellar anterior and posterior lobes were segmented using the Spatially Unbiased Infratentorial Toolbox (SUIT) from Statistical Parametric Mapping (SPM12). Multivariate linear regression models assessed the relationship between magnetic resonance imaging (MRI) measures and motor/cognitive scores. Results: Compared to HC, only secondary progressive multiple sclerosis (SPMS) patients had lower cerebellar volumes (total and posterior cerebellum). In MS patients, lower anterior cerebellar volume and brain T2 LV predicted worse motor performance, whereas lower posterior cerebellar volume and brain T2 LV predicted poor cognitive performance. Global measures of brain volume and infratentorial T2 LV were not selected by the final multivariate models. Conclusion: Cerebellar volumetric abnormalities are likely to play an important contribution to explain motor and cognitive performance in MS patients. Consistently with functional mapping studies, cerebellar posterior–inferior volume accounted for variance in cognitive measures, whereas anterior cerebellar volume accounted for variance in motor performance, supporting the assessment of cerebellar damage at sub-regional level.

Cerebellar volume change in response to electroconvulsive therapy in patients with major depression

Electroconvulsive therapy (ECT) is remarkably effective in severe major depressive disorder (MDD). Growing evidence has accumulated for brain structural and functional changes in response to ECT, primarily within cortico-limbic regions that have been considered in current neurobiological models of MDD. Despite increasing evidence for important cerebellar contributions to affective, cognitive and attentional processes, investigations on cerebellar effects of ECT in depression are yet lacking. In this study, using cerebellum-optimized voxel-based analysis methods, we investigated cerebellar volume in 12 MDD patients who received right-sided unilateral ECT. 16 healthy controls (HC) were included. Structural MRI data was acquired before and after ECT and controls were scanned once. Baseline structural differences in MDD compared to HC were located within the "cognitive cerebellum" and remained unchanged with intervention. ECT led to gray matter volume increase of left cerebellar area VIIa crus I, a region ascribed to the "affective/limbic cerebellum". The effects of ECT on cerebellar structure correlated with overall symptom relief. These findings provide preliminary evidence that structural change of the cerebellum in response to ECT may be related to the treatment's antidepressant effects.

Human Cerebellar Sub-millimeter Diffusion Imaging Reveals the Motor and Non-motor Topography of the Dentate Nucleus.

The reciprocal cortico-cerebellar loops that underlie cerebellar contributions to motor and cognitive behavior form one of the largest systems in the primate brain. Work with non-human primates has shown that the dentate nucleus, the major output nucleus of the cerebellum, contains topographically distinct connections to both motor and non-motor regions, yet there is no evidence for how the cerebellar cortex connects to the dentate nuclei in humans. Here we used in-vivo sub-millimeter diffusion imaging to characterize this fundamental component of the cortico-cerebellar loop, and identified a pattern of superior motor and infero-lateral non-motor connectivity strikingly similar to that proposed by animal work. Crucially, we also present first evidence that the dominance for motor connectivity observed in non-human primates may be significantly reduced in man - a finding that is in accordance with the proposed increase in cerebellar contributions to higher cognitive behavior over the course of primate evolution.

Treatment of autistic spectrum disorder with insulin-like growth factors.

There are no treatments for the core symptoms of autistic spectrum disorder (ASD), but there is now more knowledge on emerging mechanisms and on mechanism-based therapies. In autism there are altered synapses: genes affected are commonly related to synaptic and immune function. Dysregulation of activity-dependent signaling networks may have a key role the etiology of autism. There is an over-activation of IGF-AKT-mTor in autism spectrum disorders. Morphological and electro-physiological defects of the cerebellum are linked to system-wide ASD-like behavior defects. The molecular basis for a cerebellar contribution has been demonstrated in a mouse model. These have led to a potential mechanism-based use of drug targets and mouse models. Neurotrophic factors are potential candidates for the treatment. Insulin-like growth factor-1 (IGF-1) is altered in autism. It reduces neuro-inflammation: by causing changes of cytokines such as IL-6 and microglial function. IGF-1 reduces the defects in the synapse. It alleviates NMDA-induced neurotoxicity via the IGF-AKT-mTor pathway in microglia. IGF-1 may rescue function in Rett syndrome and ASD caused by changes of the SCHANK3 gene. There are recently pilot studies of the treatment of Rett syndrome and of SCHANK3 gene deficiency syndromes. The FDA has granted Orphan drug designations for Fragile X syndrome, SCHANK3 gene deficiency syndrome and Rett syndrome.

Cerebellar output encodes a corrective saccadic command (Commentary on Sun et al.).

Cerebellar output encodes a corrective saccadic command (Commentary on Sun et al.).

Frontoparietal cortex and cerebellum contribution to the update of actual and mental motor performance during the day.

Actual and imagined movement speed increases from early morning until mid-afternoon. Here, we investigated the neural correlates of these daily changes. Fifteen subjects performed actual and imagined right finger opposition movement sequences at 8 am and 2 pm. Both actual and imagined movements were significantly faster at 2 pm than 8 am. In the morning, actual movements significantly activated the left primary somatosensory and motor areas, and bilaterally the cerebellum; in the afternoon activations were similar but reduced. Contrast analysis revealed greater activity in the cerebellum, the left primary sensorimotor cortex and parietal lobe in the morning than in the afternoon. Imagined movements in the morning significantly activated the parietal association cortices bilaterally, the left supplementary and premotor areas, and the right orbitofrontal cortex and cerebellum. In the afternoon, the frontal lobe was significantly activated with the right cerebellum. Contrast analysis revealed increased activity in the left parietal lobe in the morning than in the afternoon. For both tasks, speed in the morning was significantly related to the BOLD signal in the brain areas resulted more active. These findings suggest that motor performance is continuously updated on a daily basis with a predominant role of the frontoparietal cortex and cerebellum.

Spontaneous, synchronized, and corrective timing behavior in cerebellar lesion patients

To successfully navigate through and interact with a dynamic environment it is necessary to acquire and use adequate temporal information to guide behavior. Apart from several areas in the cerebral cortex and cortico-striatal networks, the cerebellum has been proposed to engage in the processing of temporal information. Damage to the cerebellum can impair precise event-based temporal processing in motor and non-motor behavior. To further substantiate cerebellar contributions to temporal processing and to explore its specific role in adapting to a dynamic environment, we investigated sensorimotor temporal processing in ten patients with cerebellar lesions and a corresponding number of healthy matched controls. Experimental tasks included simple self-paced repetitive finger-tapping (spontaneous motor tempo), temporally non-adaptive (isochronous pacing) and adaptive (tempo-changing pacing) sensorimotor synchronization with auditory sequences (synchronization-continuation tapping), and a perceptual tempo judgment. The results indicate that patients' performance diverges systematically from controls on several measures. Cerebellar patients demonstrate more variable self-paced tapping, larger negative asynchronies when synchronizing with isochronous pacing sequences, altered automatic error correction responses to tempo changes (phase correction), and decreased perceptual sensitivity to these perturbations, especially for small accelerations. These findings confirm imprecise temporal processing in cerebellar patients, and hint at a specific impairment in the tens-of-milliseconds range preceding critical events, in line with a temporally predictive account of cerebellar function. Moreover, this cerebellar profile complements previous findings concerning dysfunctional temporal processing in basal ganglia patients assessed with the same experimental setup, suggesting structural and functional differentiation within an integrative temporal processing network.

Functional Evidence for a Cerebellar Node of the Dorsal Attention Network.

The "dorsal attention network" or "frontoparietal network" refers to a network of cortical regions that support sustained attention and working memory. Recent work has demonstrated that cortical nodes of the dorsal attention network possess intrinsic functional connections with a region in ventral cerebellum, in the vicinity of lobules VII/VIII. Here, we performed a series of task-based and resting-state fMRI experiments to investigate cerebellar participation in the dorsal attention network in humans. We observed that visual working memory and visual attention tasks robustly recruit cerebellar lobules VIIb and VIIIa, in addition to canonical cortical dorsal attention network regions. Across the cerebellum, resting-state functional connectivity with the cortical dorsal attention network strongly predicted the level of activation produced by attention and working memory tasks. Critically, cerebellar voxels that were most strongly connected with the dorsal attention network selectively exhibited load-dependent activity, a hallmark of the neural structures that support visual working memory. Finally, we examined intrinsic functional connectivity between task-responsive portions of cerebellar lobules VIIb/VIIIa and cortex. Cerebellum-to-cortex functional connectivity strongly predicted the pattern of cortical activation during task performance. Moreover, resting-state connectivity patterns revealed that cerebellar lobules VIIb/VIIIa group with cortical nodes of the dorsal attention network. This evidence leads us to conclude that the conceptualization of the dorsal attention network should be expanded to include cerebellar lobules VIIb/VIIIa. The functional participation of cerebellar structures in nonmotor cortical networks remains poorly understood and is highly understudied, despite the fact that the cerebellum possesses many more neurons than the cerebral cortex. Although visual attention paradigms have been reported to activate cerebellum, many researchers have largely dismissed the possibility of a cerebellar contribution to attention in favor of a motor explanation, namely, eye movements. The present study demonstrates that a cerebellar subdivision (mainly lobules VIIb/VIIIa), which exhibits strong intrinsic functional connectivity with the cortical dorsal attention network, also closely mirrors a myriad of cortical dorsal attention network responses to visual attention and working memory tasks. This evidence strongly supports a reconceptualization of the dorsal attention network to include cerebellar lobules VIIb/VIIIa.

MRI Evidence of Cerebellar and Extraocular Muscle Atrophy Differently Contributing to Eye Movement Abnormalities in SCA2 and SCA28 Diseases.

Spinocerebellar ataxias type 2 and 28 (SCA2, SCA28) are autosomal dominant disorders characterized by progressive cerebellar and oculomotor abnormalities. We aimed to investigate cerebellar, brainstem, and extraocular muscle involvement in the mitochondrial SCA28 disease compared with SCA2. We obtained orbital and brain 1.5 T-magnetic resonance images (MRI) in eight SCA28 subjects, nine SCA2, and nine age-matched healthy subjects. Automated segmentation of cerebellum and frontal lobe was performed using Freesurfer software. Manual segmentations for midbrain, pons, and extraocular muscles were performed using OsiriX. Eye movement abnormalities in SCA2 subjects were characterized by slow horizontal saccades. Subjects with SCA28 variably presented hypometric saccades, saccadic horizontal pursuit, impaired horizontal gaze holding, and superior eyelid ptosis. Quantitative brain MRI demonstrated that cerebellar and pons volumes were significantly reduced in both SCA2 and SCA28 subjects compared with controls (P < 0.03), and in SCA2 subjects compared with SCA28 (P < 0.01). Midbrain and frontal lobe volumes were also significantly reduced in SCA2 compared to controls (P < 0.03), whereas these volumes did not differ between SCA2 and SCA28 and between SCA28 and control subjects. The extraocular muscle areas were 37% to 48% smaller in SCA28 subjects compared with controls (P < 0.002), and 14% to 36% smaller compared with SCA2 subjects (P < 0.03). Extraocular muscle areas did not differ between SCA2 and controls. Our MRI findings support the hypothesis of different cerebellar and extraocular myopathic contributions in the eye movement abnormalities in SCA2 and SCA28 diseases. In SCA28, a myopathic defect selectively involving the extraocular muscles supports a specific impairment of mitochondrial energy metabolism.

Basal ganglia and cerebellar interconnectivity within the human thalamus

Basal ganglia and the cerebellum are part of a densely interconnected network. While both subcortical structures process information in basically segregated loops that primarily interact in the neocortex, direct subcortical interaction has been recently confirmed by neuroanatomical studies using viral transneuronal tracers in non-human primate brains. The thalamus is thought to be the main relay station of both projection systems. Yet, our understanding of subcortical basal ganglia and cerebellar interconnectivity within the human thalamus is rather sparse, primarily due to limitation in the acquisition of in vivo tracing. Consequently, we strive to characterize projections of both systems and their potential overlap within the human thalamus by diffusion MRI and tractography. Our analysis revealed a decreasing anterior-to-posterior gradient for pallido-thalamic connections in: (1) the ventral-anterior thalamus, (2) the intralaminar nuclei, and (3) midline regions. Conversely, we found a decreasing posterior-to-anterior gradient for dentato-thalamic projections predominantly in: (1) the ventral-lateral and posterior nucleus; (2) dorsal parts of the intralaminar nuclei and the subparafascicular nucleus, and (3) the medioventral and lateral mediodorsal nucleus. A considerable overlap of connectivity pattern was apparent in intralaminar nuclei and midline regions. Notably, pallidal and cerebellar projections were both hemispherically lateralized to the left thalamus. While strikingly consistent with findings from transneuronal studies in non-human primates as well as with pre-existing anatomical studies on developmentally expressed markers or pathological human brains, our assessment provides distinctive connectional fingerprints that illustrate the anatomical substrate of integrated functional networks between basal ganglia and the cerebellum. Thereby, our findings furnish useful implications for cerebellar contributions to the clinical symptomatology of movement disorders.

Cerebellar Contribution to Motor and Cognitive Impairment in Multiple Sclerosis Patients: A Sub-Regional Structural MRI Analysis (P4.128)

Cerebellar Contribution to Motor and Cognitive Impairment in Multiple Sclerosis Patients: A Sub-Regional Structural MRI Analysis (P4.128)

Cerebellar contributions to motor control and language comprehension: searching for common computational principles.

The past 25 years have seen the functional domain of the cerebellum extend beyond the realm of motor control, with considerable discussion of how this subcortical structure contributes to cognitive domains including attention, memory, and language. Drawing on evidence from neuroanatomy, physiology, neuropsychology, and computational work, sophisticated models have been developed to describe cerebellar function in sensorimotor control and learning. In contrast, mechanistic accounts of how the cerebellum contributes to cognition have remained elusive. Inspired by the homogeneous cerebellar microanatomy and a desire for parsimony, many researchers have sought to extend mechanistic ideas from motor control to cognition. One influential hypothesis centers on the idea that the cerebellum implements internal models, representations of the context-specific dynamics of an agent's interactions with the environment, enabling predictive control. We briefly review cerebellar anatomy and physiology, to review the internal model hypothesis as applied in the motor domain, before turning to extensions of these ideas in the linguistic domain, focusing on speech perception and semantic processing. While recent findings are consistent with this computational generalization, they also raise challenging questions regarding the nature of cerebellar learning, and may thus inspire revisions of our views on the role of the cerebellum in sensorimotor control.