Lobule VI Research Articles

Abnormal cerebellar volume in somatic vs. non-somatic delusional disorders

BackgroundThere is abundant evidence for cerebellar involvement in schizophrenia, where the cerebellum has been suggested to contribute to cognitive, affective and motor dysfunction. More recently, specific cerebellar regions have also been associated with psychotic symptoms, particularly with auditory verbal hallucinations. In contrast, little is known about cerebellar contributions to delusions, and even less is known about whether cerebellar involvement differs by delusional content.MethodsUsing structural magnetic resonance imaging at 1.0 T together with cerebellum-optimized segmentation techniques, we investigated gray matter volume (GMV) in 14 patients with somatic-type delusional disorder (S-DD), 18 patients with non-somatic delusional disorder (NS-DD) and 18 patients with schizophrenia (SZ) with persistent non-somatic delusions. A total of 32 healthy controls (HC) were included. Between-group comparisons were adjusted for age, gender, chlorpromazine equivalents and illness duration.ResultsCompared to HC, S-DD patients showed decreased GMV in left lobule VIIIa. In addition, S-DD patients showed decreased GMV in lobule V and increased GMV in bilateral lobule VIIa/crus II compared to NS-DD. Patients with SZ showed increased GMV in right lobule VI and VIIa/crus I compared to HC. Significant differences between HC and NS-DD were not found.ConclusionsThe data support the notion of cerebellar dysfunction in psychotic disorders. Distinct cerebellar deficits, predominantly linked to sensorimotor processing, may be detected in delusional disorders presenting with predominantly somatic content.

Temporal Invariance in SCA6 Is Related to Smaller Cerebellar Lobule VI and Greater Disease Severity.

Regulating muscle force and timing are fundamental for accurate motor performance. In spinocerebellar ataxia type 6 (SCA6), there is evidence that individuals have greater force dysmetria but display better temporal accuracy during fast goal directed contractions. Here, we test whether greater temporal accuracy occurs in all individuals with SCA6, and can be explained by lesser temporal variability. Further we examine whether it is linked to disease severity and specific degenerative changes in the cerebellum. Nineteen human participants with SCA6 (13 woman) and 18 healthy controls performed fast goal-directed ankle dorsiflexion contractions aiming at a spatiotemporal target. We quantified the endpoint control of these contractions, gray matter (GM) integrity of the cerebellum, and disease severity using the International Cooperative Ataxia Rating Scale (ICARS). SCA6 individuals exhibited lower temporal endpoint error and variability than the healthy controls (p = 0.008). Statistically, SCA6 clustered into two distinct groups for temporal variability. A group with low temporal variability ranging from 10 to 19% (SCA6a) and a group with temporal variability similar to healthy controls (SCA6b; 19-40%).SCA6a exhibited greater disease severity than SCA6b, as assessed with ICARS (p < 0.001). Lower temporal variability, which was not associated with disease duration (R2 = 0.1, p > 0.2), did correlate with both greater ICARS (R2 = 0.3) and reduced GM volume in cerebellar lobule VI (R2 = 0.35). Other cerebellar lobules did not relate to temporal variability. We provide new evidence that a subset of SCA6 with greater loss of GM in cerebellum lobule VI exhibit temporal invariance and more severe ataxia than other SCA6 individuals.SIGNIFICANCE STATEMENT Variability is an inherent feature of voluntary movement, and traditionally more variability in the targeted output infers impaired performance. For example, cerebellar patients present exacerbated temporal variability during multijoint movements, which is thought to contribute to their motor deficits. In the current work, we show that in a subgroup of spinocerebellar ataxia type 6 individuals, temporal variability is lower than that of healthy controls when performing single-joint fast-goal directed movements. This invariance related to exacerbated atrophy of lobule VI of the cerebellum and exacerbated disease severity. The relation between invariance and disease severity suggests that pathological motor variability can manifest not only as an exacerbation but also as a reduction relative to healthy controls.

Volumetric reduction of cerebellar lobules associated with memory decline across the adult lifespan.

The human cerebellum plays an essential role in motor control, is involved in cognitive function and helps to regulate emotional responses. However, little is known about the relationship between cerebellar lobules and age-related memory decline. We aimed to investigate volume alterations in cerebellar lobules at different ages and assess their correlations with reduced memory recall abilities. A sample of 275 individuals were divided into the following four groups: 20-35 years (young), 36-50 years (early-middle age), 51-65 years (late-middle age), and 66-89 years (old). Volumes of the cerebellar lobules were obtained using volBrain software. Analysis of covariance and post hoc analysis were used to analyze group differences in cerebellar lobular volumes, and multiple comparisons were performed using the Bonferroni method. Spearman correlation was used to investigate the relationship between lobular volumes and memory recall scores. In this study, we found that older adults had smaller cerebellar volumes than the other subjects. Volumetric decreases in size were noted in bilateral lobule VI and lobule crus I. Moreover, the volumes of bilateral lobule crus I, lobule VI, and right lobule IV were significantly associated with memory recall scores. In the present study, we found that some lobules of the cerebellum appear more predisposed to age-related changes than other lobules. These findings provide further evidence that specific regions of the cerebellum could be used to assess the risk of memory decline across the adult lifespan.

Distinct cerebellar regions for body motion discrimination.

Visual processing of human movements is critical for adaptive social behavior. Cerebellar activations have been observed during biological motion discrimination in prior neuroimaging studies, and cerebellar lesions may be detrimental for this task. However, whether the cerebellum plays a causal role in biological motion discrimination has never been tested. Here, we addressed this issue in three different experiments by interfering with the posterior cerebellar lobe using transcranial magnetic stimulation (TMS) during a biological discrimination task. In Experiments 1 and 2, we found that TMS delivered at onset of the visual stimuli over the vermis (vermal lobule VI), but not over the left cerebellar hemisphere (left lobule VI/Crus I), interfered with participants’ ability to distinguish biological from scrambled motion compared to stimulation of a control site (vertex). Interestingly, when stimulation was delivered at a later time point (300 ms after stimulus onset), participants performed worse when TMS was delivered over the left cerebellar hemisphere compared to the vermis and the vertex (Experiment 3). Our data show that the posterior cerebellum is causally involved in biological motion discrimination and suggest that different sectors of the posterior cerebellar lobe may contribute to the task at different time points.

Action perception recruits the cerebellum and is impaired in patients with spinocerebellar ataxia.

Our cerebellum has been proposed to generate prediction signals that may help us plan and execute our motor programmes. However, to what extent our cerebellum is also actively involved in perceiving the action of others remains to be elucidated. Using functional MRI, we show here that observing goal-directed hand actions of others bilaterally recruits lobules VI, VIIb and VIIIa in the cerebellar hemispheres. Moreover, whereas healthy subjects (n = 31) were found to be able to discriminate subtle differences in the kinematics of observed limb movements of others, patients suffering from spinocerebellar ataxia type 6 (SCA6; n = 21) were severely impaired in performing such tasks. Our data suggest that the human cerebellum is actively involved in perceiving the kinematics of the hand actions of others and that SCA6 patients' deficits include a difficulty in perceiving the actions of other individuals. This finding alerts us to the fact that cerebellar disorders can alter social cognition.

Altered putamen and cerebellum connectivity among different subtypes of Parkinson's disease.

ObjectiveImpairment of basal ganglia (BG)‐thalamo‐cortical circuit causes various symptoms of Parkinson's disease (PD). We investigated the functional connectivity (FC) patterns of putamen among PD subtypes and healthy control (HC) and explored their clinical significance.MethodsA total of 16 patients with tremor‐dominant (TD) PD, 23 patients with postural instability and gait difficulty‐dominant (PIGD) PD, and 31 HC that underwent functional magnetic resonance imaging were observed. Voxel‐wise FC analysis was performed by computing correlation between bilateral putamen and other voxels within the brain. Correlation analysis was performed between FC strength and clinical symptoms.ResultsCompared with PIGD group, TD group showed increased FC between left putamen and right cerebellum lobule VI and cerebellum crus I, then we compared the cerebellum FC difference among the three groups. The cerebellum lobule VI FC difference was mainly involved in motor related cortex, and the cerebellum crus I FC difference was related to cognition areas. While compared with HC, TD and PIGD groups both had significant FC difference brain areas correlated with motor and cognition symptoms. The connectively of putamen and right cerebellum lobules VI and I showed positive correlation with tremor and Montreal Cognitive Assessment degree of scores, respectively. The connectivity of putamen and sensorimotor cortex had negative correlation with PIGD scores.ConclusionsThe altered connectivity of BG‐cortical circuit in patients with PD was related to PIGD symptoms. Motor and cognitive impairments declined slower in patients with TD PD, which may be related to increased functional connectivity between putamen and cerebellum.

Impaired Adaptive Motor Learning Is Correlated With Cerebellar Hemispheric Gray Matter Atrophy in Spinocerebellar Ataxia Patients: A Voxel-Based Morphometry Study.

Objective: To evaluate the degree to which recently proposed parameters measured via a prism adaptation task are correlated with changes in cerebellar structure, specifically gray matter volume (GMV), in patients with spinocerebellar degeneration (SCD).Methods: We performed whole-brain voxel-based morphometry (VBM) analysis on 3-dimensional T1-weighted images obtained from 23 patients with SCD [Spinocerebellar ataxia type 6 (SCA6), 31 (SCA31), 3/Machado-Joseph disease (SCA3/MJD), and sporadic cortical cerebellar atrophy (CCA)] and 21 sex- and age-matched healthy controls (HC group). We quantified a composite index representing adaptive motor learning abilities in a hand-reaching task with prism adaptation. After controlling for age, sex, and total intracranial volume, we analyzed group-wise differences in GMV and regional GMV correlations with the adaptive learning index.Results: Compared with the HC group, the SCD group showed reduced adaptive learning abilities and smaller GMV widely in the lobules IV-VIII in the bilateral cerebellar hemispheres. In the SCD group, the adaptive learning index was correlated with cerebellar hemispheric atrophy in the right lobule VI, the left Crus I. Additionally, GMV of the left supramarginal gyrus showed a correlation with the adaptive learning index in the SCD group, while the supramarginal region did not accompany reduction of GMV.Conclusions: This study indicated that a composite index derived from a prism adaptation task was correlated with GMV of the lateral cerebellum and the supramarginal gyrus in patients with SCD. This study should contribute to the development of objective biomarkers for disease severity and progression in SCD.

Diffusion tensor imaging in orthostatic tremor: a tract-based spatial statistics study.

ObjectiveThe pathogenesis of orthostatic tremor (OT) is unknown. We investigated OT‐related white matter changes and their correlations with scores from a neuropsychological testing battery.MethodsDiffusion tensor imaging measures were compared between 14 OT patients and 14 age‐ and education‐matched healthy controls, using whole‐brain tract‐based spatial statistics analysis. Correlations between altered diffusion metrics and cognitive performance in OT group were assessed.ResultsIn all cognitive domains (attention, executive function, visuospatial ability, verbal memory, visual memory, and language), OT patients’ cognitive performance was significantly worse than that of healthy controls. OT patients demonstrated altered diffusivity metrics not only in the posterior lobe of the cerebellum (left cerebellar lobule VI) and in its efferent cerebellar fibers (left superior cerebellar peduncle), but also in medial lemniscus bilaterally (pontine tegmentum), anterior limb of the internal capsule bilaterally, right posterior limb of the internal capsule, left anterior corona radiata, right insula, and the splenium of corpus callosum. No relationship was found between diffusion measures and disease duration in OT patients. Diffusion white matter changes, mainly those located in right anterior limb of the internal capsule, were correlated with poor performance on tests of executive function, visuospatial ability, verbal memory, and visual memory in OT patients.InterpretationWhite matter changes were preferentially located in the cerebellum, its efferent pathways, as well as in the pontine tegmentum and key components of the frontal–thalamic–cerebellar circuit. Further work needs to be done to understand the evolution of these white matter changes and their functional consequences.

FMRI of shared-stream priming of lexical identification by object semantics along the ventral visual processing stream

Distributed sub-systems of the brain's semantic network have been shown to process semantics associated with visual features of objects (e.g., shape, colour) in the ventral visual processing stream, whereas semantics associated with actions are processed in the dorsal stream. Orthographic lexical processing has also been shown to occur in the ventral stream. Past research from our lab (Neudorf et al., 2019) has demonstrated a temporal (i.e., reaction time) priming advantage for object primes over action primes in the lexical decision task consistent with ventral shared-stream processing of visual feature object semantics and orthographic lexical identification, whereby object primes produced larger priming effects than action primes. The current experiment explored this paradigm using functional magnetic resonance imaging (fMRI) and identified the potential loci of shared-stream processing to regions in the ventral stream just anterior to colour sensitive visual area V4 cortex in the left fusiform gyrus and anterior to lexical and shape sensitive regions in the left fusiform gyrus, as well as in cerebellar lobule VI. Action priming showed more activation than object priming in dorsal stream motion related regions of the right parietal occipital junction, right superior occipital gyrus, and bilateral visual area V3. The fMRI activation observed in this experiment supports the theory that spatially shared-stream activation occurs in the ventral stream during object (but not action) priming of lexical identification, which is consistent with our earlier behavioural research showing that these processes are also temporally shared.

The Cerebellum in Frontotemporal Dementia: a Meta-Analysis of Neuroimaging Studies.

Frontotemporal dementia (FTD) is a neurodegenerative brain disorder primarily affecting the frontal and/or temporal lobes. Three main subtypes have been recognized: behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA), each of which has a distinct clinical and cognitive profile. Although the role of the cerebellum in cognition is increasingly accepted, knowledge of cerebellar changes across neuroimaging modalities and their contribution to behavioural and cognitive changes in FTD syndromes is currently scant. We conducted an anatomical/activation likelihood estimation (ALE) meta-analysis in 53 neuroimaging studies (structural MRI: 42; positron emission tomography: 6; functional MRI: 4; single-photon emission computed tomography: 1) to identify the patterns of cerebellar changes and their relations to profiles of behavioural and cognitive deficits in FTD syndromes. Overall, widespread bilateral cerebellar changes were found in FTD and notably the patterns were subtype specific. In bvFTD, ALE peaks were identified in the bilateral Crus, left lobule VI, right lobules VIIb and VIIIb. In SD, focal cerebellar changes were located in the left Crus I and lobule VI. A separate ALE meta-analysis on PNFA studies was not performed due to the limited number of studies available. In addition, the ALE analysis indicated that bilateral Crus I and Crus II were associated with behavioural disruption and cognitive dysfunction. This ALE meta-analysis provides the quantification of the location and extent of cerebellar changes across the main FTD syndromes, which in turn provides evidence of cerebellar contributions to behavioural and cognitive changes in FTD. These results bring new insights into the mechanisms mediating FTD symptomatology.

Extensive cerebellar and thalamic degeneration in spinocerebellar ataxia type 10

IntroductionSpinocerebellar ataxia type 10 (SCA10) is a hereditary neurodegenerative disorder caused by repeat expansions in the ATXN10 gene. Patients present with cerebellar ataxia frequently accompanied by seizures. Even though loss of cerebellar Purkinje neurons has been described, its brain degeneration pattern is unknown. Our aim was to characterize the gray and white matter degeneration patterns in SCA10 patients and the association with clinical features. MethodsWe enrolled 18 patients with molecular diagnosis of SCA10 and 18 healthy individuals matched for age and sex. All participants underwent brain MRI including high-resolution anatomical and diffusion images. Whole-brain Tract-Based Spatial Statistics (TBSS) and Voxel-Based Morphometry (VBM) were performed to identify white and grey matter degeneration respectively. A second analysis in the cerebellum identified the unbiased pattern of degeneration. Motor impairment was assessed using the SARA Scale. ResultsTBSS analysis in the patient group revealed white matter atrophy exclusively in the cerebellum. VBM analysis showed extensive grey matter degeneration in the cerebellum, brainstem, thalamus, and putamen. Significant associations between cerebellar degeneration and SARA scores were found. Additionally, degeneration in thalamic GM and WM in the cerebellar lobule VI were significantly associated with the presence of seizures. ConclusionThe results show that besides cerebellum and brainstem, brain degeneration in SCA10 includes predominantly the putamen and thalamus; involvement of the latter is strongly associated with seizures. Analysis of the unbiased degeneration pattern in the cerebellum suggests lobules VIIIb, IX, and X as the primary cerebellar targets of the disease, which expands to the anterior lobe in later stages.

Sensorimotor, language, and working memory representation within the human cerebellum.

The cerebellum is involved in a wide range of behaviours. A key organisational principle from animal studies is that somatotopically corresponding sensory input and motor output reside in the same cerebellar cortical areas. However, compelling evidence for a similar arrangement in humans and whether it extends to cognitive functions is lacking. To address this, we applied cerebellar optimised whole‐brain functional MRI in 20 healthy subjects. To assess spatial overlap within the sensorimotor and cognitive domains, we recorded activity to a sensory stimulus (vibrotactile) and a motor task; the Sternberg verbal working memory (VWM) task; and a verb generation paradigm. Consistent with animal data, sensory and motor activity overlapped with a somatotopic arrangement in ipsilateral areas of the anterior and posterior cerebellum. During the maintenance phase of the Sternberg task, a positive linear relationship between VWM load and activity was observed in right Lobule VI, extending into Crus I bilaterally. Articulatory movement gave rise to bilateral activity in medial Lobule VI. A conjunction of two independent language tasks localised activity during verb generation in right Lobule VI‐Crus I, which overlapped with activity during VWM. These results demonstrate spatial compartmentalisation of sensorimotor and cognitive function in the human cerebellum, with each area involved in more than one aspect of a given behaviour, consistent with an integrative function. Sensorimotor localisation was uniform across individuals, but the representation of cognitive tasks was more variable, highlighting the importance of individual scans for mapping higher order functions within the cerebellum.

Cerebellar Gray Matter and Olfactory Performance.

The role of the cerebellum in the chemical senses is still poorly understood. This voxel-based morphometry (VBM) study investigated associations between gray matter volume (GMV) in subregions of the cerebellum and olfactory performance. VBM data from 48 men were analyzed. The participants were tested with a standardized olfactory test that measured olfactory threshold, discrimination, and identification ability. The investigated sample covered a wide range of olfactory performance, including individuals with a reduced sense of smell (anosmia and hyposmia) and normosmia. The computed regression analyses revealed a positive association between olfactory identification performance and GMV in lobule VI. This cerebellar subregion is involved in higher-order cognitive functions (language and memory), which are necessary prerequisites for correct odor labeling. Odor detection and discrimination were unrelated to cerebellar GMV.

Normal-Appearing Cerebellar Damage in Neuromyelitis Optica Spectrum Disorder.

The cerebellum plays an important role in motor and cognitive functions. However, whether and how the normal-appearing cerebellum is impaired in patients with neuromyelitis optica spectrum disorders remain unknown. We aimed to identify the occult structural damage of the cerebellum in neuromyelitis optica spectrum disorder and its possible causes at the level of substructures. Normal-appearing gray matter volume of the cerebellar lobules and nuclei and normal-appearing white matter volume of the cerebellar peduncles were compared between patients with neuromyelitis optica spectrum disorder and healthy controls. The cerebellar damage of patients with neuromyelitis optica spectrum disorder in the hemispheric lobule VI, vermis lobule VI, and all cerebellar nuclei and peduncles was related only to spinal lesions; and cerebellar damage in the hemispheric lobules VIII and X was related only to the aquaporin-4 antibody. The mixed cerebellar damage in the hemispheric lobules V and IX and vermis lobule Crus I was related mainly to spinal lesions; and mixed cerebellar damage in the hemispheric lobule VIIb was related mainly to the aquaporin-4 antibody. Other cerebellar substructures showed no significant cerebellar damage. We have shown that the damage in cerebellar normal-appearing white matter and normal-appearing gray matter is associated with aquaporin-4-mediated primary damage or axonal degeneration secondary to spinal lesions or both. The etiologic classifications of substructure-specific occult cerebellar damage may facilitate developing neuroimaging markers for assessing the severity and the results of therapy of neuromyelitis optica spectrum disorder occult cerebellar damage.

Language Cerebro-cerebellar Reorganization in Children After Surgery of Right Cerebellar Astrocytoma: a fMRI Study.

Language processing depends on an integrated circuit involving the left supratentorial language areas and the right posterior lateral cerebellar hemisphere (lobule VI, lobule VII, Crus I, and Crus II). Reorganization of the language system after lesions of the cerebral language areas includes also cerebellar relocation. This is the first study assessing functional language reorganization after lesions concerning primarily the cerebellum, using a fMRI paradigm of phonological covert word production task in six children operated for right cerebellar astrocytoma and in 15 typicallydeveloping children. We found right cerebellar and left frontal activations in healthycontrolsand high variability of reorganizational patterns in patients with early right cerebellar lesion. Also lesions not located in the areas typically involved in language tasks (Crus I and Crus II) can cause reorganization between the two hemispheres or hemispheric language reinforcement of the original lateralization. We discuss the role of several variables in determining the reorganizational pattern such as the site, extension, and timing of surgery. No variables revealed as predictors, suggesting that co-occurring influence of other biological and/or pathological factors are not yet demonstrated. Lesions in the postero-lateral cerebellum seem related to less efficient language performances, as an indicator of the system's functioning.

Characteristics of Tremor Induced by Lesions of the Cerebellum.

It is a clinical experience that acute lesions of the cerebellum induce pathological tremor, which tends to improve. However, quantitative characteristics, imaging correlates, and recovery of cerebellar tremor have not been systematically investigated. We studied the prevalence, quantitative parameters measured with biaxial accelerometry, and recovery of pathological tremor in 68 patients with lesions affecting the cerebellum. We also investigated the correlation between the occurrence and characteristics of tremor and lesion localization using 3D T1-weighted MRI images which were normalized and segmented according to a spatially unbiased atlas template for the cerebellum. Visual assessment detected pathological tremor in 19% while accelerometry in 47% of the patients. Tremor was present both in postural and intentional positions, but never at rest. Two types of pathological tremor were distinguished: (1) low-frequency tremor in 36.76% of patients (center frequency 2.66 ± 1.17Hz) and (2) normal frequency-high-intensity tremor in 10.29% (center frequency 8.79 ± 1.43Hz). The size of the lesion did not correlate with the presence or severity of tremor. Involvement of the anterior lobe and lobule VI was related to high tremor intensity. In all followed up patients with acute cerebellar ischemia, the tremor completely recovered within 8weeks. Our results indicate that cerebellar lesions might induce pathological postural and intentional tremor of 2-3Hz frequency. Due to its low frequency and low amplitude, quantitative tremorometry is neccessary to properly identify it. There is no tight correlation between lesion localization and quantitative characteristics of cerebellar tremor.

Accelerated aging and motor control deficits are related to regional deformation of central cerebellar white matter in alcohol use disorder.

The World Health Organization estimates a 12-month prevalence rate of 8+% for an alcohol use disorder (AUD) diagnosis in people age 15years and older in the United States and Europe, presenting significant health risks that have the potential of accelerating age-related functional decline. According to neuropathological studies, white matter systems of the cerebellum are vulnerable to chronic alcohol dependence. To pursue the effect of AUD on white matter structure and functions in vivo, this study used T1-weighted, magnetic resonance imaging (MRI) to quantify the total corpus medullare of the cerebellum and a finely grained analysis of its surface in 135 men and women with AUD (mean duration of abstinence, 248d) and 128 age- and sex-matched control participants; subsets of these participants completed motor testing. We identified an AUD-related volume deficit and accelerated aging in the total corpus medullare. Novel deformation-based surface morphometry revealed regional shrinkage of surfaces adjacent to lobules I-V, lobule IX, and vermian lobule X. In addition, accelerated aging was detected in the regional surface areas adjacent to lobules I-V, lobule VI, lobule VIIB, and lobules VIII, IX, and X. Sex differences were not identified for any measure. For both volume-based and surface-based analyses, poorer performance in gait and balance, manual dexterity, and grip strength were linked to greater regional white matter structural deficits. Our results suggest that local deformation of the corpus medullare has the potential of identifying structurally and functionally segregated networks affected in AUD.

Cerebellar functional abnormalities in early stage drug-naïve and medicated Parkinson's disease.

Parkinson's disease (PD) is a progressive neurological degenerative disorder characterized by impaired motor function and non-motor dysfunctions. While recent studies have highlighted the role of the cerebellum in PD, our understanding of its role in PD remains limited. In the present study, we used resting-state fMRI to evaluate dysfunctions within the cerebellum in PD patients treated with medication and drug-naïve PD patients. We applied amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) analysis methods. Thirty-one patients with early stage PD (22 drug-naïve and 9 medicated patients) and 31 gender- and age-matched healthy controls were recruited in this study. ALFFs increased in the left cerebellar areas (lobules VI/VIIb/CruI/CruII and the dentate gyrus) and right cerebellar areas (lobules VI/VIIb/VIIIa/CruI/CruII and the dentate gyrus) of all PD patients and in the left and right cerebellar areas (lobules VI/VIIb/CruI and the dentate gyrus) of drug-naive PD patients but were not significantly changed in medicated PD patients. DC increased in the right cerebellar areas of all PD patients and medicated PD patients. All PD patients and all drug-naive PD patients showed significantly weaker functional connectivity (FC) between the left cerebellum and the left medial frontal gyrus. However, FC was significantly stronger between the right cerebellum and the left precentral and right middle occipital gyri in the medicated PD patients than in controls. Furthermore, a correlation analyses revealed that ALFF z scores in the left cerebellum (lobule VI) and right cerebellum (lobule VI/CruI and dentate gyrus) were negatively correlated with Mini-Mental State Examination (MMSE) scores in all PD patients and drug-naive patients. These results indicate that the cerebellum plays an important role in PD, mainly by exerting a compensatory effect in early stage PD. Additionally, antiparkinsonian medicationwould modified PD-induced changes in local neural activity and FC in PD patients. The results of this study offer novel insights into the roles of the cerebellum in early stage drug-naïve PD.

Dissociation between Cerebellar and Cerebral Neural Activities in Humans with Long-Term Bilateral Sensorineural Hearing Loss.

Abnormal neural activity in the cerebellum has been implicated in hearing impairments, but the effects of long-term hearing loss on cerebellar function are poorly understood. To further explore the role of long-term bilateral sensorineural hearing loss on cerebellar function, we investigated hearing loss-induced changes among neural networks within cerebellar subregions and the changes in cerebellar-cerebral connectivity patterns using resting-state functional MRI. Twenty-one subjects with long-term bilateral moderate-to-severe sensorineural hearing loss and 21 matched controls with clinically normal hearing underwent MRI scanning and a series of neuropsychological tests targeting cognition and emotion. Voxel-wise functional connectivity (FC) analysis demonstrated decreased couplings between the cerebellum and other cerebral areas, including the temporal pole (TP), insula, supramarginal gyrus, inferior frontal gyrus (IFG), medial frontal gyrus, and thalamus, in long-term bilateral sensorineural hearing loss patients. An ROI-wise FC analysis found weakened interregional connections within cerebellar subdivisions. Moreover, there was a negative correlation between anxiety and FC between the left cerebellar lobe VI and left insula. Hearing ability and anxiety scores were also correlated with FC between the left cerebellar lobe VI and left TP, as well as the right cerebellar lobule VI and left IFG. Our results suggest that sensorineural hearing loss disrupts cerebellar-cerebral circuits, some potentially linked to anxiety, and interregional cerebellar connectivity. The findings contribute to a growing body showing that auditory deprivation caused by cochlear hearing loss disrupts not only activity with the classical auditory pathway but also portions of the cerebellum that communicates with other cortical networks.

Altered Spatial and Temporal Brain Connectivity in the Salience Network of Sensorineural Hearing Loss and Tinnitus.

Sensorineural hearing loss (SNHL), sometimes accompanied with tinnitus, is associated with dysfunctions within and outside the classical auditory pathway. The salience network, which is anchored in bilateral anterior insula and dorsal anterior cingulate cortex, has been implicated in sensory integration. Partial auditory deprivation could alter the characteristics of the salience network and other related brain areas, thereby contributing to hearing impairments-induced neuropsychiatric symptoms. To test this hypothesis, we performed fMRI scanning and neuropsychological tests on 32 subjects with long-term bilateral hearing impairment and 30 well-matched Controls. Non-directional functional connectivity and directional Granger causality analysis were used to identify aberrant spatial and temporal patterns of connections targeting bilateral anterior insula and dorsal anterior cingulate cortex. We found that the left anterior insula showed decreased connectivity with right precentral gyrus and superior frontal gyrus. The connections between the dorsal anterior cingulate cortex and middle frontal gyrus, superior parietal gyrus and supplementary motor area (SMA) were also reduced. Relative to Controls, SNHL patients showed abnormal effective connectivity of the salience network, including inferior temporal gyrus, cerebellum lobule VI, lobule VIII, precentral gyrus, middle frontal gyrus and SMA. Furthermore, correlation analysis demonstrated that some of these atypical connectivity measures were correlated with performance of neuropsychiatric tests. These findings suggest that the inefficient modulation of the salience network might contribute to the neural basis of SNHL and tinnitus, as well as associated cognition and emotion deficits.