Figure - available from: The Cerebellum
This content is subject to copyright. Terms and conditions apply.
Cerebellar functional connectivity differences between patients and controls: Figure depicts group differences in dentate nucleus functional connectivity (DNFC) between patients and controls. Light blue color indicates areas of reduced DNFC while red indicates areas of increased DNFC, superimposed on a customized T1 template. a) and b) represents decreased DNFC in TSpure and TS + OCD patients with the right precentral gyrus, right prefrontal, left postcentral gyrus, bilateral thalamus, left inferior temporal gyrus, left lobule IX, and left crus II, and an increased DNFC with the bilateral lobule VI and right crus I compared to controls; c) represents decreased DNFC in OCD patients with right pre and left postcentral gyrus, bilateral thalamus, left inferior temporal gyrus, and left crus II and increased DNFC with bilateral prefrontal, left fronto-orbital cortex, and left crus I compared to Ctrls. Results were p < 0.05, FDR corrected. The color bar represents t values
Source publication
Tourette syndrome (TS) and obsessive–compulsive disorder (OCD) are two neurodevelopmental disorders characterized by repetitive behaviors. Our recent study in drug-naive children with TS and OCD provided evidence of cerebellar involvement in both disorders. In addition, cerebellar functional connectivity (FC) was similar in TS patients without como...
Citations
... Prior studies have mainly examined state severity measures of obsessive-compulsive symptoms (e.g., the CY-BOCS) as possible moderators of patients' cognitive performance and may have lacked consideration of the role of other clinical factors of the disorder, such as disease duration, the type of obsessions/compulsions, and comorbid conditions [102][103][104]. Further, regarding the association of TS and OCD specifically, emerging evidence points to different neurobiological underpinnings in OCD with TS and without it [105][106][107]. Hypothetically, different neural correlates of OCD in the context of TS as compared to "pure" OCD might further be associated with differences in neuropsychological profiles. ...
Background: Cognitive functions represent foundational factors for mental health and quality of life (QoL). In Tourette syndrome (TS), psychiatric comorbidities are common and have been inconsistently reported to affect the cognition and QoL of patients, while the role of tic disorder duration has not been yet explored. Methods: To examine how comorbidities and TS duration may influence cognition and QoL, N = 80 children with TS (6–16 years) were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV). Standardized questionnaires were used to assess the presence and severity of TS main comorbidities and QoL. Data were interpreted using linear correlations, regression, and mediation analysis. Results: Depression and attention-deficit/hyperactivity disorder (ADHD) symptoms accounted for poorer cognitive performance. Anxiety oppositely predicted better cognitive performance, while no significant role for obsessive compulsive disorder (OCD) was observed. Disease duration was associated with lower total IQ, verbal reasoning, and working memory abilities. Depression, anxiety, and TS duration also deeply influenced QoL measures. Conclusions: TS common comorbidities have a differential impact on the cognitive abilities of children and adolescents, which translates into a complex influence on their perceived QoL. A longer clinical history of tics was related to worse cognitive outcomes, which prompts further consideration of disease duration in both clinical and research settings involving children and adolescents.
... Tikoo et al.'s [17] study showed that patients with pure TS and patients with composite of TS and OCD exhibited similar FC alteration in contrast with controls, while pure patients with OCD showed distinctive patterns of FC changes prominently involving the cerebellum and the frontoparietal network. These studies have demonstrated that patients with TS who have comorbidities or patients with pure ADHD or OCD have shared and specific FC patterns compared with pure TS [16][17][18]. ...
Tourette syndrome (TS) is a developmental neuropsychiatric disorder characterized by repetitive, stereotyped, involuntary tics, the neurological basis of which remains unclear. Although traditional resting-state MRI (rfMRI) studies have identified abnormal static functional connectivity (FC) in patients with TS, dynamic FC (dFC) remains relatively unexplored. The rfMRI data of 54 children with TS and 46 typically developing children (TDC) were analyzed using group independent component analysis to obtain independent components (ICs), and a sliding-window approach to generate dFC matrices. All dFC matrices were clustered into two reoccurring states, the state transition metrics were obtained. We conducted Granger causality and nodal topological analyses to further investigate the brain regions that may play the most important roles in driving whole-brain switching between different states. We found that children with TS spent more time in state 2 (PFDR < 0.001), a state characterized by strong connectivity between ICs, and switched more quickly between states (PFDR = 0.025) than TDC. The default mode network (DMN) may play an important role in abnormal state transitions because the FC that changed the most between the two states was between the DMN and other networks. Additionally, the DMN had increased degree centrality, efficiency and altered causal influence on other networks. Certain alterations related to executive function (r = –0.309, P < 0.05) and tic symptom ratings (r = 0.282; 0.413, P < 0.05) may represent important aspects of the pathophysiology of TS. These findings facilitate our understanding of the neural basis for the clinical presentation of TS.
... Olivito et al. (2017) reported hypoconnectivity between the left dentate nucleus and DMN and regions involved in the theory of mind, as well as hyperconnectivity in dentatocerebellar networks, in individuals with autism spectrum disorder (ASD). Tikoo et al. (2022) investigated dentatocerebellar and dentato-cortical RSFC as well as cerebellar peduncle white matter integrity in drug-naïve children with either Tourette syndrome (TS) or obsessive-compulsive disorder (OCD), as well as children diagnosed with both TS and OCD. The broad pattern of results suggested many similarities in dentate RSFC abnormalities between the TS and TS + OCD groups compared to HC, with the OCD group demonstrating a more distinct pattern of abnormalities. ...
For years, the cerebellum was left out of functional magnetic resonance imaging (fMRI) studies due to technological limitations. The advent of novel data acquisition and reconstruction strategies (e.g., whole-brain simultaneous multi-slice imaging) employing multi-channel array coils has overcome such limitations, ushering unprecedented improvements in temporal signal-to-noise ratio and spatiotemporal resolution. Here, we aim to provide a brief report on the deep cerebellar nuclei, specifically focusing on the dentate nuclei, the primary output nuclei, situated within both cognitive and motor cerebello-cerebral circuits. We highlight the importance of functional parcellation in refining our understanding of broad resting-state functional connectivity (RSFC) in both health and disease. First, we review work relevant to the functional topography of the dentate nuclei, including recent advances in functional parcellation. Next, we review RSFC studies using the dentate nuclei as seed regions of interest in neurological and psychiatric populations and discuss the potential benefits of applying functionally defined subdivisions. Finally, we discuss recent technological advances and underscore ultrahigh-field neuroimaging as a tool to potentiate functionally parcellated RSFC analyses in clinical populations.
... To date, the majority of previous diffusion tensor imaging (DTI) studies in OCD used hypothesis-free whole-brain comparison analysis (i.e., tract-based spatial statistics [TBSS]) to identify specific regions of WM alterations across the whole brain and reported compromised integrity in several WM regions in OCD patients including the superior cerebellar peduncle (SCP). 11,20 The SCP is known as the cerebello-thalamic tract, the tract connecting the dentate nucleus, one of the deep cerebellar nuclei, and the thalamus. [21][22][23][24] However, those findings may not be sufficient to determine whether the WM integrity of the cerebello-thalamic tract is actually altered in OCD, as those findings are derived from hypothesis-free whole-brain comparison analysis, making it difficult to distinguish between the cerebello-thalamic tract and adjacent WM fibers, such as the central tegmental tract or medial longitudinal fasciculus. ...
... This study aimed to elucidate whether aberrant WM integrity of the cerebello-thalamic tract is observed in medicationfree OCD patients using probabilistic tractography compared to that of healthy controls (HCs). 31 Taking into consideration previous functional 16,[32][33][34][35] and structural studies in OCD, 11,20 we hypothesized that the WM integrity of the cerebello-thalamic tract is compromised in medication-free OCD patients compared to HCs. Specifically, we expected that decreased fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) would be observed in the cerebello-thalamic tract of OCD patients. ...
... To date, two DTI studies using whole-brain TBSS have reported cerebello-thalamic WM abnormalities in OCD patients. 11,20 In line with the current study results, Jayarajan et al. 20 reported that OCD patients showed increased RD in the WM region overlapping with the right cerebello-thalamic tract compared to HCs, but no significant group differences were found in FA values. 20 On the other hand, Tikoo et al. 11 reported significantly lower FA and higher MD in WM regions overlapping with the left cerebello-thalamic tract in OCD patients than in HCs. ...
Objective:
The cerebello-thalamic tract is the only efferent white matter (WM) bundle of the cerebellum that connects the cerebellum to the thalamus and has recently attracted much attention in obsessive-compulsive disorder (OCD) with its integral role in higher order cognitive functions commonly impaired in OCD patients. Previous neuroimaging studies have shown that the cerebello-thalamic circuit is functionally impaired in OCD patients. However, the WM integrity of the cerebello-thalamic tract in OCD, which may underly functional abnormalities of the cerebello-thalamic circuit, is not yet sufficiently understood. Therefore, the current study aimed to elucidate whether compromised cerebello-thalamic WM integrity is observed in medication-free OCD patients.
Methods:
In this study, diffusion tensor imaging was acquired from 106 medication-free OCD patients and 105 matched healthy controls (HCs). Probabilistic tractography was then used to reconstruct the cerebello-thalamic tract with accurate anatomical features. Three diffusion indices (fractional anisotropy, FA; mean diffusivity, MD; radial diffusivity, RD) were measured from the reconstructed bilateral cerebello-thalamic tract and then compared between groups.
Results:
We found that patients with OCD showed significantly increased MD and RD in the right cerebello-thalamic tract compared to HCs, and there was no difference in FA between groups.
Conclusion:
Our findings may indicate the underlying structural abnormalities of the dysfunctional cerebello-thalamic circuit in OCD patients. Therefore, our findings are expected to provide novel insights into the pathophysiology of OCD on the cerebello-thalamic WM architecture, extending our knowledge from the existing functional neurobiological model of OCD.
... Our search returned a total of 470 journal articles, of which sixteen studies fulfilled the eligibility criteria and entered full-text data extraction [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]. One more study was included, comprising an OCD subtype known as pediatric autoimmune neuropsychiatric disorder associated with Streptococci (PANDAS) [43]. ...
... One more study was included, comprising an OCD subtype known as pediatric autoimmune neuropsychiatric disorder associated with Streptococci (PANDAS) [43]. Fifteen studies used the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for the diagnosis of OCD [27,[29][30][31][32][33][34][35][36][37][39][40][41][42][43]. The OCD diagnosis was established in index patients using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) [44] in twelve studies [27-29, 31, 32, 34, 36, 38, 39, 41-43]. ...
... The OCD diagnosis was established in index patients using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) [44] in twelve studies [27-29, 31, 32, 34, 36, 38, 39, 41-43]. Children's Y-BOCS (CY-BOCS) [45] was used in publications that investigated OCD in children and adolescents, defined as individuals younger than 18 years old [30,33,35,37,40]. ...
Previous neuroimaging studies have suggested that obsessive–compulsive disorder (OCD) is associated with altered resting-state functional connectivity of the cerebellum. In this study, we aimed to describe the most significant and reproducible microstructural abnormalities and cerebellar changes associated with obsessive–compulsive disorder (OCD) using diffusion tensor imaging (DTI) investigations. PubMed and EMBASE were searched for relevant studies using the PRISMA 2020 protocol. A total of 17 publications were chosen for data synthesis after screening titles and abstracts, full-text examination, and executing the inclusion criteria. The patterns of cerebellar white matter (WM) integrity loss, determined by fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) metrics, varied across studies and symptoms. Changes in fractional anisotropy (FA) values were described in six publications, which were decreased in four and increased in two studies. An increase in diffusivity parameters of the cerebellum (i.e., MD, RD, and AD) in OCD patients was reported in four studies. Alterations of the cerebellar connectivity with other brain areas were also detected in three studies. Heterogenous results were found in studies that investigated cerebellar microstructural abnormalities in correlation with symptom dimension or severity. OCD’s complex phenomenology may be characterized by changes in cerebellar WM connectivity across wide networks, as shown by DTI studies on OCD patients in both children and adults. Classification features in machine learning and clinical tools for diagnosing OCD and determining the prognosis of the disorder might both benefit from using cerebellar DTI data.
... Because of its involvement in a wide range of functions, the impaired cerebellum is associated with several psychiatric and neurological disorders. [5][6][7][8] Earlier studies have already found structural and functional anomalies in patients with ASD, which involved the cerebellum areas. [9][10][11] Even though the cerebellar structure is small, it is still rich in neurons, and so it has been shown to have functional topography across its subregions. ...
... 17,35,36 Cortical thickness is a morphological indicators that is related to neurobiological processes. 8,37,38 The normalized cortical thickness is the result of its normalization with the cube root of the intracranial volume. 14 The present study found a significant difference between the ASD and TD groups in the overall mean values of normalized cortical thickness of the 24 cerebellar lobules, suggesting the presence of altered cerebellar structure in patients with ASD compared to typically developing individuals. ...
Objective:
This study uses structural magnetic resonance imaging to explore changes in the cerebellar lobules in patients with autism spectrum disorder (ASD) and further analyze the correlation between cerebellar structural changes and clinical symptoms of ASD.
Methods:
A total of 75 patients with ASD and 97 typically developing (TD) subjects from Autism Brain Imaging Data Exchange dataset were recruited. We adopted an advanced automatic cerebellar lobule segmentation technique called CEREbellum Segmentation to segment each cerebellar hemisphere into 12 lobules. Normalized cortical thickness of each lobule was recorded, and group differences in the cortical measures were evaluated. Correlation analysis was also performed between the normalized cortical thickness and the score of Autism Diagnostic Interview-Revised.
Results:
Results from analysis of variance showed that the normalized cortical thickness of the ASD group differed significantly from that of the TD group; specifically, the ASD group had lower normalized cortical thickness than the TD group. Post-hoc analysis revealed that the differences were more predominant in the left lobule VI, left lobule Crus I and left lobule X, and in the right lobule VI and right lobule Crus I. Lowered normalized cortical thickness in the left lobule Crus I in the ASD patients correlated positively with the abnormality of development evident at or before 36 months subscore.
Conclusion:
These results suggest abnormal development of cerebellar lobule structures in ASD patients, and such abnormality might significantly influence the pathogenesis of ASD. These findings provide new insights into the neural mechanisms of ASD, which may be clinically relevant to ASD diagnosis.
... Two studies focused on obsessive-compulsive symptoms and only included healthy participants with no control group thus their NOS score was low (Gasso et al., 2015;Grazioplene et al., 2022). Three studies lacked one score due to poor control selection (Pagliaccio et al., 2021;Tikoo et al., 2021;Zarei et al., 2011) and the other studies reached the complete NOS score. ...
... The rest of the studies used the TBSS method. One study purely focused on cerebellar involvement (Tikoo et al., 2021). ...
... Gasso and colleagues found higher MD in the anterior and posterior lobe of the right cerebellum and culmen and lingual lobes of the left cerebellum (Gasso et al., 2015). Tikoo and colleagues, (Tikoo et al., 2021) showed that paediatric patients with Tourette's syndrome and OCD had higher FA in all three cerebellar peduncles but patients with mere OCD diagnosis, had lower FA in all three cerebellar peduncles compared to healthy controls. The importance of cerebellum in OCD has also been highlighted by functional MRI study that showed decreased functional connectivity of dentate nucleus with the left crus II of the cerebellum. ...
Microstructural alterations in white matter are evident in obsessive-compulsive disorder (OCD) both in adult and paediatric populations. Paediatric patients go through the process of maturation and thus may undergo different pathophysiology than adult OCD. Findings from studies in paediatric obsessive-compulsive disorder have been inconsistent, possibly due to their small sample size or heterogeneous populations. The aim of this review is to provide a comprehensive overview of white matter structures in paediatric obsessive-compulsive disorder and their correlation with clinical features. Based on PRISMA guidelines, we performed a systematic search on diffusion tensor imaging studies that reported fractional anisotropy, mean diffusivity, radial diffusivity, or axial diffusivity alterations between paediatric patients with obsessive-compulsive disorder and healthy controls using voxel-based analysis, or tract-based spatial statistics. We identified fifteen relevant studies. Most studies reported changes predominantly in the corpus callosum, cingulum, arcuate fasciculus, uncinate fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, forceps minor and major, and the cerebellum in paediatric obsessive-compulsive disorder. These alterations included increased and decreased fractional anisotropy and radial diffusivity, and increased mean and axial diffusivity in different white matter tracts. These changes were associated with obsessive-compulsive disorder symptoms. Moreover, specific genetic polymorphisms were linked with cerebellar white matter changes in paediatric obsessive-compulsive disorder. White matter changes are widespread in paediatric OCD patients. These changes are often associated with symptoms however there are controversies in the direction of changes in some tracts.
... The ITG is known to be involved in high-order cognitive functions, including visual and language comprehension and emotion regulation (Lin et al. 2020). A previous study found that altered DN-ITG FC might reflect poor insight levels (Tikoo et al. 2021). Hence, we speculated that the altered FC between the DN and ITG in our study might reflect the pathophysiology and perhaps serve a key role in underlying cognitive impairment in patients with PIGD-PD. ...
Cerebellar dysfunction may substantially contribute to the clinical symptoms of Parkinson’s disease (PD). The role of cerebellar subregions in tremors and gait disturbances in PD remains unknown. To investigate alterations in cerebellar subregion volumes and functional connectivity (FC), as well as FC between the dentate nucleus (DN) and ventral lateral posterior nucleus (VLp) of the thalamus, which are potentially involved in different PD motor subtypes. We conducted morphometric and resting-state functional connectivity analyses in various cerebellar subregions in 22 tremor-dominant (TD)-PD and 35 postural instability gait difficulty dominant (PIGD)-PD patients and 38 sex- and age-matched healthy controls (HCs). The volume and FC alterations in various cerebellar subregions and the neural correlates of these changes with the clinical severity scores were investigated. The PIGD-PD group showed greater FC between the right motor cerebellum (CBMm) and left postcentral gyrus than the HC group, and a higher FC was associated with less severe PIGD symptoms. In contrast, the TD-PD group had decreased FC between the right DN and left VLp compared with the PIGD-PD and HC groups, and lower FC was associated with worse TD symptoms. Furthermore, the PIGD-PD group had higher FC between the left DN and left inferior temporal gyrus than the TD-PD group. Morphometric analysis revealed that the TD-PD group showed a significantly higher volume of left CBMm than the HC group. Our findings point to differential alteration patterns in cerebellar subregions and offer a new perspective on the pathophysiology of motor subtypes of PD.
... To fill this knowledge gap, we have recently used diffusion tensor imaging (DTI) and resting-state functional MRI (rsfMRI) to investigate structural as well as functional brain changes in drug-naïve children with TS, TS+OCD, and OCD (11,12). Those studies demonstrated that TS+OCD shares common neural correlates with TS, but not with OCD, in terms of structural WM changes and functional connectivity abnormalities in fronto-cerebellar and fronto-parietal networks (11,12). ...
... To fill this knowledge gap, we have recently used diffusion tensor imaging (DTI) and resting-state functional MRI (rsfMRI) to investigate structural as well as functional brain changes in drug-naïve children with TS, TS+OCD, and OCD (11,12). Those studies demonstrated that TS+OCD shares common neural correlates with TS, but not with OCD, in terms of structural WM changes and functional connectivity abnormalities in fronto-cerebellar and fronto-parietal networks (11,12). However, our previous DTI analysis (12) focused on cerebellar connections by studying WM microstructural integrity of the three cerebellar peduncles, thus not clarifying the possible pathophysiological contribution of early changes in supratentorial WM bundles in TS and OCD. ...
... Those studies demonstrated that TS+OCD shares common neural correlates with TS, but not with OCD, in terms of structural WM changes and functional connectivity abnormalities in fronto-cerebellar and fronto-parietal networks (11,12). However, our previous DTI analysis (12) focused on cerebellar connections by studying WM microstructural integrity of the three cerebellar peduncles, thus not clarifying the possible pathophysiological contribution of early changes in supratentorial WM bundles in TS and OCD. ...
Tourette syndrome (TS) and early-onset obsessive-compulsive disorder (OCD) are frequently associated and conceptualized as distinct phenotypes of a common disease spectrum. However, the nature of their relationship is still largely unknown on a pathophysiological level. In this study, early structural white matter (WM) changes investigated through diffusion tensor imaging (DTI) were compared across four groups of drug-naïve children: TS-pure (n = 16), TS+OCD (n = 14), OCD (n = 10), and 11 age-matched controls. We analyzed five WM tracts of interest, i.e., cortico-spinal tract (CST), anterior thalamic radiations (ATR), inferior longitudinal fasciculus (ILF), corpus callosum (CC), and cingulum and evaluated correlations of DTI changes to symptom severity. Compared to controls, TS-pure and TS+OCD showed a comparable pattern of increased fractional anisotropy (FA) in CST, ATR, ILF and CC, with FA changes displaying negative correlation to tic severity. Conversely, in OCD, FA decreased in all WM tracts (except for the cingulum) compared to controls and negatively correlated to symptoms. We demonstrate different early WM microstructural alterations in children with TS-pure/TS+OCD as opposed to OCD. Our findings support the conceptualization of TS+OCD as a subtype of TS while suggesting that OCD is characterized by independent pathophysiological mechanisms affecting WM development.
... The cerebellum is also involved in motor control (as well as cognitive processes) and has known anatomical connections to and from the cortex and thalamus. A few studies have found altered cortico-cerebellar connectivity in TS patients, specifically decreased functional connectivity between the cerebellum and frontal regions, as well as between the cerebellum and the thalamus and sensorimotor cortex (Ramkiran et al., 2019;Tikoo et al., 2021). Consistently, decreased regional homogeneity (ReHo), a measure of neural synchronization that looks at a region's connectivity with its nearest neighbors, has been reported in the cerebellum of TS patients (Liu et al., 2017). ...
... The significant negative associations between YGTSS scores and functional connectivity have been found in the cerebellum and in regions belonging to the default mode network and several control networks. Specifically, functional connections within the frontoparietal network and the cerebellum, and between the cerebellum and prefrontal cortex were weaker in patients with more severe symptoms (Tikoo et al., , 2021. In addition, interhemispheric functional connectivity in the anterior cingulate cortex, which is part of the cingulo-opercular network, was weaker with increasing symptom severity (Liao et al., 2017). ...
