A cerebellar approach to aggression

Infratentorial gray matter atrophy and excess in primary craniocervical dystonia

BackgroundThe posterior cerebellar lobules seem to be the anatomical substrate of cognitive cerebellar processes, but their microstructural alterations in multiple sclerosis (MS) remain unclear.ObjectivesTo correlate diffusion metrics in lobules VI to VIIIb in persons with clinically isolated syndrome (PwCIS) and in cognitively impaired persons with MS (CIPwMS) with their cognitive performances.MethodsSixty-nine patients (37 PwCIS, 32 CIPwMS) and 36 matched healthy subjects (HS) underwent 3T magnetic resonance imaging, including 3D T1-weighted and diffusion tensor imaging (DTI). Fractional anisotropy (FA) and mean diffusivity (MD) were calculated within each lobule and in the cerebellar peduncles. We investigated the correlations between cognitive outcomes and the diffusion parameters of cerebellar sub-structures and performed multiple linear regression analysis to predict cognitive disability.ResultsFA was generally lower and MD was higher in the cerebellum and specifically in the vermis Crus II, lobules VIIb and VIIIb in CIPwMS compared with PwCIS and HS. In hierarchical regression analyses, 31% of the working memory z score variance was explained by FA in the left lobule VI and in the left superior peduncle. Working memory was also associated with MD in the vermis Crus II. FA in the left lobule VI and right VIIIa predicted part of the information processing speed (IPS) z scores.ConclusionDTI indicators of cerebellar microstructural damage were associated with cognitive deficits in MS. Our results suggested that cerebellar lobular alterations have an impact on attention, working memory and IPS.

Cerebellar transcranial direct current stimulation (tDCS) combined with language therapy can aid in chronic aphasia recovery, but the neural mechanisms and biomarkers of treatment efficacy remain uncertain. In this secondary analysis of data from a previously conducted clinical trial, we used a randomized, double-blind, sham-controlled, within-subject crossover design with a study sample of 19 participants with post-stroke aphasia. We assessed the degree to which baseline properties of cerebro-cerebellar white matter tracts can predict or moderate longitudinal treatment effects at three time points: post-treatment, 2 weeks post-treatment, and 2 months post-treatment. Tract properties were measured by fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI). We also tested whether there are differential effects between trained and untrained language tasks and between cerebellar tDCS polarity (anodal and cathodal). Baseline measures of tracts connecting the left lesioned cortex to the right posterolateral cerebellum (stimulation target) influenced treatment gains for untrained tasks, relative to sham control. In contrast, for the trained task, treatment gains were influenced by baseline measures of tracts connecting the non-stimulated left cerebellum with the contralateral right cerebral cortex. Although there were no consistent effects from cerebellar tDCS polarity, a highly consistent pattern emerged across all tasks and tracts. Specifically, language improvements were predicted by a baseline tract profile (i.e., higher FA and lower MD) typically associated with higher white matter integrity, especially within the context of stroke-induced white matter decline. These findings corroborate the potential for baseline tract properties as a biomarker of treatment efficacy and support the notion that adjuvant (cerebellar tDCS + language) therapy preferentially benefits individuals with relatively preserved structural connections within functionally relevant networks. ClinicalTrials.gov, identifier (NCT02901574).

Growing evidence suggests that posterior cerebellar lobe contributes to social perception in healthy adults. However, we know little about how this process varies across age and with development. Using cross-sectional fMRI data, we examined cerebellar response to biological (BIO) versus scrambled (SCRAM) motion within typically developing (TD) and autism spectrum disorder (ASD) samples (age 4–30 y), 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.

We assign the anatomical names of functional activation regions in the brain, based on the probabilistic cyto-architectonic atlas by Anatomy 1.7 from an analysis of correlations between regional cerebral blood flow (rCBF) and clinical parameters of the non-demented Parkinson's disease (PD) patients by SPM8. We evaluated Anatomy 1.7 of SPM toolbox compared to 'Talairach Daemon' (TD) Client 2.4.2 software. One hundred and thirty-six patients (mean age 60.0 ± 9.09 years; 73 women and 63 men) with non-demented PD were selected. Tc-99m-HMPAO brain single-photon emission computed tomography (SPECT) scans were performed on the patients using a two-head gamma-camera. We analyzed the brain image of PD patients by SPM8 and found the anatomical names of correlated regions of rCBF perfusion with the clinical parameters using TD Client 2.4.2 and Anatomy 1.7. The SPM8 provided a correlation coefficient between clinical parameters and cerebral hypoperfusion by a simple regression method. To the clinical parameters were added age, duration of disease, education period, Hoehn and Yahr (H&Y) stage and Korean mini-mental state examination (K-MMSE) score. Age was correlated with cerebral perfusion in the Brodmann area (BA) 6 and BA 3b assigned by Anatomy 1.7 and BA 6 and pyramis in gray matter by TD Client 2.4.2 with p < 0.001 uncorrected. Also, assigned significant correlated regions were found in the left and right lobules VI (Hem) with duration of disease, in left and right lobules VIIa crus I (Hem) with education, in left insula (Ig2), left and right lobules VI (Hem) with H&Y, and in BA 4a and 6 with K-MMSE score with p < 0.05 uncorrected by Anatomy 1.7, respectively. Most areas of correlation were overlapped by two different anatomical labeling methods, but some correlation areas were found with different names. Age was the most significantly correlated clinical parameter with rCBF. TD Client found the exact anatomical name by the peak intensity position of the cluster while Anatomy 1.7 of SPM8 toolbox, using the cyto-architectonic probability maps, assigned the anatomical name by percentage value of the probability.

Treatment of Psychiatric Symptoms Associated With a Frontal Lobe Tumor Through Surgical Resection

This work aims to exploit a novel graph neural network to predict the sex of the brain topological network, and to find the sex differences in the cerebrum and cerebellum. A two-branch multi-scale graph convolutional network (TMGCN) is designed to analyze the sex differences of the brain. Two complementary templates are used to construct cerebrum and cerebellum networks, respectively, followed by a two-branch sub-network with multi-scale filters and a trainable weighted fusion strategy for the final prediction. Finally, a trainable graph topk-pooling layer is utilized in our model to visualize key brain regions relevant to the prediction. The proposed TMGCN achieves a prediction accuracy of 84.48%. In the cerebellum, the bilateral Crus I-II, lobule VI and VIIb, and the posterior vermis (VI-X) are discriminative for this task. As for the cerebrum, the discriminative brain regions consist of the bilateral inferior temporal gyrus, the bilateral fusiform gyrus, the bilateral parahippocampal gyrus, the bilateral cingulate gyrus, the bilateral medial ventral occipital cortex, the bilateral lateral occipital cortex, the bilateral amygdala, and the bilateral hippocampus. This study tackles the sex prediction problem from a more comprehensive view, and may provide the resting-state fMRI evidence for further study of sex differences in the cerebellum and cerebrum.

The cerebellum is involved in sensorimotor operations, cognitive tasks and affective processes. Here, we revisit the concept of the cerebellar syndrome in the light of recent advances in our understanding of cerebellar operations. The key symptoms and signs of cerebellar dysfunction, often grouped under the generic term of ataxia, are discussed. Vertigo, dizziness, and imbalance are associated with lesions of the vestibulo-cerebellar, vestibulo-spinal, or cerebellar ocular motor systems. The cerebellum plays a major role in the online to long-term control of eye movements (control of calibration, reduction of eye instability, maintenance of ocular alignment). Ocular instability, nystagmus, saccadic intrusions, impaired smooth pursuit, impaired vestibulo-ocular reflex (VOR), and ocular misalignment are at the core of oculomotor cerebellar deficits. As a motor speech disorder, ataxic dysarthria is highly suggestive of cerebellar pathology. Regarding motor control of limbs, hypotonia, a- or dysdiadochokinesia, dysmetria, grasping deficits and various tremor phenomenologies are observed in cerebellar disorders to varying degrees. There is clear evidence that the cerebellum participates in force perception and proprioceptive sense during active movements. Gait is staggering with a wide base, and tandem gait is very often impaired in cerebellar disorders. In terms of cognitive and affective operations, impairments are found in executive functions, visual-spatial processing, linguistic function, and affective regulation (Schmahmann's syndrome). Nonmotor linguistic deficits including disruption of articulatory and graphomotor planning, language dynamics, verbal fluency, phonological, and semantic word retrieval, expressive and receptive syntax, and various aspects of reading and writing may be impaired after cerebellar damage. The cerebellum is organized into (a) a primary sensorimotor region in the anterior lobe and adjacent part of lobule VI, (b) a second sensorimotor region in lobule VIII, and (c) cognitive and limbic regions located in the posterior lobe (lobule VI, lobule VIIA which includes crus I and crus II, and lobule VIIB). The limbic cerebellum is mainly represented in the posterior vermis. The cortico-ponto-cerebellar and cerebello-thalamo-cortical loops establish close functional connections between the cerebellum and the supratentorial motor, paralimbic and association cortices, and cerebellar symptoms are associated with a disruption of these loops.

Emerging research in non-human animals implicates cerebellar projections to the ventral tegmental area (VTA) in appetitive behaviors, but these circuits have not been characterized in humans. Here, we mapped cerebello-VTA white-matter connectivity in humans using probabilistic tractography on diffusion imaging data from the Human Connectome Project. We uncovered the topographical organization of these connections by separately tracking from parcels of cerebellar lobule VI, crus I/II, vermis, paravermis, and cerebrocerebellum. Results revealed that connections from the cerebellum to the VTA predominantly originate in the right hemisphere, interposed nucleus, and paravermal cortex, and terminate mostly ipsilaterally. Paravermal crus I sends the most connections to the VTA compared to other lobules. We discovered a medial-to-lateral gradient of connectivity, such that the medial cerebellum has the highest connectivity with the VTA. Individual differences in microstructure were associated with measures of negative affect and social functioning. By splitting the tracts into quarters, we found that the socio-affective effects were driven by the third quarter of the tract, corresponding to the point at which the fibers leave the deep nuclei. Taken together, we produced detailed maps of cerebello-VTA structural connectivity for the first time in humans and established their relevance for trait differences in socio-affective regulation.

The inability to wait for a target before initiating an action (i.e., waiting impulsivity) is one of the main features of addictive behaviors. Current interventions for addiction, such as transcranial Direct Current Stimulation (tDCS), have been suggested to improve this inability. Nonetheless, the effects of tDCS on waiting impulsivity and underlying electrophysiological (EEG) markers are still not clear. Therefore, this study aimed to evaluate the effects of neuromodulation over the right inferior frontal gyrus (rIFG) on the behavior and EEG markers of reward anticipation (i.e., cue and target-P3 and underlying delta/theta power) during a premature responding task. For that, forty healthy subjects participated in two experimental sessions, where they received active and sham tDCS over the rIFG combined with EEG recording during the task. To evaluate transfer effects, participants also performed two control tasks to assess delay discounting and motor inhibition. The active tDCS decreased the cue-P3 and target-P3 amplitudes, as well as delta power during target-P3. While no tDCS effects were found for motor inhibition, active tDCS increased the discounting of future rewards when compared to sham. These findings suggest a tDCS-induced modulation of the P3 component and underlying oscillatory activity during waiting impulsivity and the discounting of future rewards.

BackgroundImpulsivity is a core feature of borderline personality disorder (BPD) and is closely related to suicide risk and destructive and aggressive behaviors. Although transcranial direct current stimulation (tDCS) has shown its promising effects as an intervention to modulate impulsivity, no study has explored its potential regarding BPD.Methods/designThis is a multicenter, crossover, double-blind study comparing active versus sham tDCS (2 mA, 30 min), applied over the dorsolateral prefrontal cortex for five consecutive days in 50 BPD patients. Participants will be assessed for impulsivity, depressive symptoms, and suicide risk. The main efficacy criteria on reduction of impulsivity will be the amplitude variation of one specific evoked potential detected by electroencephalography (EEG) during the balloon analogue risk task. Baseline measures will be compared to scores obtained immediately after sessions, then 12 and 30 days later.DiscussionThis study investigates the safety and effects of tDCS, which may have a significant impact on impulsivity in patients with BPD and may be useful to reduce risky behaviors.Trial registrationClinicalTrials.gov, NCT03498937. Registered on 17 April 2018.

BackgroundAlthough symptoms of depressive episodes in patients with bipolar depressive episodes (BDE) and major depressive disorder (MDD) are similar, the treatment strategies for these disorders are completely different, suggesting that BDE and MDD have different neurobiological backgrounds. In this study, we examined the relationship between brain function and clinical symptoms, particularly cognitive function, in female individuals with bipolar disorder and MDD experiencing depressive episodes.MethodsRegional homogeneity (ReHo) was analyzed in 51 medication-free female patients with BDE, 63 medication-free female patients with MDD, and 45 female healthy controls (HCs). Depressive symptom severity was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24), and multidimensional cognitive function was evaluated using the MATRICS Consensus Cognition Battery. Partial correlation analysis was used to explore the links between the brain regions and clinical characteristics. A support vector machine (SVM) was used to assess the classification accuracy.ResultsCompared with HCs, patients with BDE and MDD had decreased ReHo in the left lobule VI of the cerebellum and increased ReHo in the left precuneus. Patients with BDE also had reduced ReHo in the left lobules IV–V of the cerebellum and increased ReHo in the right putamen, unlike patients with MDD who had no significant differences in these regions. Patients with BDE exhibited more severe cognitive deficits in processing speed, attention, word learning, and overall cognitive function than those with MDD. In patients with BDE, a significant negative correlation was found between the right putamen and HAMD-24 scores. However, no significant association was observed between abnormal ReHo levels and cognitive function. The SVM effectively differentiated between patients with BDE, MDD, and HCs.ConclusionCognitive impairment was more severe in female patients with BDE than in those with MDD. Changes in the ReHo values of the right putamen and left lobules IV–V may serve as unique neuroimaging markers for BDE. Alterations in the ReHo values of the left precuneus and left lobule VI could serve as common pathophysiological mechanisms for BDE and MDD in women and indicate depressive states.

Cerebellar representation during phonetic processing in tonal and non-tonal language speakers: An ALE meta-analysis

Evidence suggests that the cerebellum contributes to cognition as well as motor function. We investigated cerebellar grey matter (GM) and white matter (WM) changes from magnetic resonance images in dementia with Lewy bodies (DLB), Alzheimer׳s disease (AD) and healthy older subjects using voxel-based morphometry (VBM). Subjects (39 controls, 41 DLB, and 48 AD) underwent magnetic resonance imaging as well as clinical and cognitive assessments. VBM used SPM8 with a cerebellar brain mask to define the subspace for voxel analysis. Statistical analyses were conducted using the general linear model. Relative to findings in controls, VBM analysis revealed cerebellar GM loss in lobule VI bilaterally in AD and in left Crus I and right Crus II regions in DLB. WM deficits were confined to AD in the bilateral middle cerebellar peduncles. DLB demonstrates a different pattern of cerebellar GM loss which, although not significantly different from that in AD, could be an important feature in understanding the neurobiology of DLB and warrants further investigation.

Serotonin modulates diverse phenotypes and functions including depressive, aggressive, impulsive, and feeding behaviors, all of which have reward-related components. To date, research has focused on understanding these effects by measuring and manipulating dorsal raphe serotonin neurons and using single-receptor approaches. These studies have led to a better understanding of the heterogeneity of serotonin actions on behavior; however, they leave open many questions about the timing and location of serotonin's actions modulating the neural circuits that drive these behaviors. Recent advances in genetically encoded fluorescent biosensors, including the GPCR activation-based sensor for serotonin (GRAB-5-HT), enable the measurement of serotonin release in mice on a timescale compatible with a single rewarding event without corelease confounds. Given substantial evidence from slice electrophysiology experiments showing that serotonin influences neural activity of the striatal circuitry, and the known role of the dorsal medial striatal (DMS) in reward-directed behavior, we focused on understanding the parameters and timing that govern serotonin release in the DMS in the context of reward consumption, external reward value, internal state, and cued reward. Overall, we found that serotonin release is associated with each of these and encodes reward anticipation, value, approach, and consumption in the DMS.