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Cerebellar parcellation in schizophrenia and bipolar disorder
Abstract
Objective:
The cerebellum is involved in cognitive processing and emotion control. Cerebellar alterations could explain symptoms of schizophrenia spectrum disorder (SZ) and bipolar disorder (BD). In addition, literature suggests that lithium might influence cerebellar anatomy. Our aim was to study cerebellar anatomy in SZ and BD, and investigate the effect of lithium METHODS: Participants from 7 centers worldwide underwent a 3T MRI. We included 182 patients with SZ, 144 patients with BD and 322 controls. We automatically segmented the cerebellum using the CERES pipeline. All outputs were visually inspected RESULTS: Patients with schizophrenia SZ showed a smaller global cerebellar grey matter volume compared to controls, with most of the changes located to the cognitive part of the cerebellum (Crus II and lobule VIIb). This decrease was present in the subgroup of patients with recent-onset SZ. We did not find any alterations in the cerebellum in patients with BD. However, patients medicated with lithium had a larger size of the anterior cerebellum, compared to patients not treated with lithium.
Conclusion:
Our multicenter study supports a distinct pattern of cerebellar alterations in SZ and BD.
... Furthermore, significant differences in gray matter volume, along with potentially adaptive changes in the cerebellum, have been reported in unaffected relatives of patients with bipolar disorder [28,51]. Only two studies, to our knowledge, investigated cortical thickness in cerebellum [53,59] reporting respectively similar or increased CT in all cerebellar lobules. To our knowledge, no study investigated CT alterations in both the cerebral cortex and cerebellum. ...
... Notably, the cerebellum showed opposing pattern of CT variations aligned with its functional division: the sensorimotor (anterior lobe) and cognitive-affective (posterior lobe) regions displayed opposite structural alterations, suggesting distinct roles in BD pathophysiology [92]. Previous studies investigating cerebellar grey matter alterations in BD reported contrasting results studies [2,7,23,27,53,58,59,62,64,79,84,99]. Potential causes for the discrepancies among the results regarding cerebellar alterations in previous MRI studies on BD likely stem from differences in sample characteristics, including variations in sample size and the inclusion of patients with BD Type II, as well as factors such as differing illness durations, comorbidities, and medication use across studies. ...
... Therefore, it is essential to consider the background and homogeneity in the history of each sample of subjects. To the best of our knowledge, there are only two studies employing the CERES segmentation method on BD subjects (Kim et al., 2020a; [59]). In contrast with our results, Kim et al. identified widespread cortical thickening in the cerebellum of BD subjects (n = 90) compared to healthy controls (n = 166), with a specific reduction of left lobule IX volume. ...
Recent studies suggested that structural changes in the cerebellum are implicated in the pathophysiology of bipolar disorder (BD). Here, we aimed to characterize the structural alterations of cerebellar lobules in BD, evaluating their possible relation with those occurring in the rest of the brain. One-hundred-fifty-five type I BD patients were recruited and compared with one-hundred-nineteen controls subjects. Cerebral cortical thickness (CT) was evaluated vertex-wise, while cerebellar CT at the level of its twelve lobules. A widespread pattern of cortical thinning was found in several clusters of BD patients. In the cerebellum, we found an anterior thinning (lobule I_II, III, X) and a posterior thickening (crus I, crus II, lobule VI and lobule IX) of its lobules in BD. Exploring the relation between cerebral and cerebellar CT changes in BD patients, after correcting for age and disease duration, the CT of a large subset of cerebral regions, found thinned in BD, were also inversely correlated with the thickening of cerebellar lobule IX. We speculate that this lobule may undergo adaptive changes to compensate the widespread cortical thinning which characterizes BD syndrome. Such a compensatory adaptation of the cerebellum would be similar to that found in other neurological and psychiatric disorders.
... Laidi et al. (2019) examined the effect of lithium on cerebellar anatomy in bipolar disorder and schizophrenia using 3 Tesla magnetic resonance imaging (3T MRI) [20]. The study found no alterations in the cerebellum in bipolar disorder patients; however, they did find patients medicated with lithium had a larger size of the anterior cerebellum compared to patients not treated with lithium [20]. ...
... Laidi et al. (2019) examined the effect of lithium on cerebellar anatomy in bipolar disorder and schizophrenia using 3 Tesla magnetic resonance imaging (3T MRI) [20]. The study found no alterations in the cerebellum in bipolar disorder patients; however, they did find patients medicated with lithium had a larger size of the anterior cerebellum compared to patients not treated with lithium [20]. According to the authors, the anterior cerebellum is connected to the sensorimotor cortex, which may explain why patients medicated with lithium display cerebellar motor syndrome [20]. ...
... The study found no alterations in the cerebellum in bipolar disorder patients; however, they did find patients medicated with lithium had a larger size of the anterior cerebellum compared to patients not treated with lithium [20]. According to the authors, the anterior cerebellum is connected to the sensorimotor cortex, which may explain why patients medicated with lithium display cerebellar motor syndrome [20]. However, the study found no effects of lithium in the posterior cerebellum, while abnormalities were seen in schizophrenia patients [20]. ...
The aim of this systematic literature review was to investigate the role of the cerebellum in the affective symptoms observed in patients with bipolar disorder. The present systematic literature review included clinical studies conducted from 2013-2023 among adult populations with bipolar I and II disorders, along with their specifiers. With regard to cerebellar pathology, it was found that those with bipolar disorder performed worse than their healthy counterparts in their ability to comprehend the mental states of others and in identifying negative mental states. Additionally, individuals with bipolar disorder had reduced gray matter loss in regions such as lobules I-IX, crus I, and crus II, different functional activation patterns of the thalamus, striatum, and hippocampus on functional magnetic resonance imaging (fMRI), and increased cortical thickness. Cerebro-cerebellar functional connectivities were altered in patients with bipolar disorder. The effects of lamotrigine and lithium on cerebellar volume and abnormalities are also discussed in this paper. The present systematic literature review illustrates the emerging involvement of the cerebellum in bipolar disorder and its affective symptoms and paves the way for future research and a better understanding of bipolar disorder.
... Moreover, we also found that mean age and illness duration were negatively associated with the GMV in the left Crus II, which might suggest that schizophrenia is a progressive disorder. Consistent with our findings in this meta-analysis, multiple former studies identified decreased GMVs mainly located in the left Crus II, right lobule VI, and right lobule VIII (35, 36,[65][66][67]. In a meta-analysis of 283 volumetric brain studies, decreased cerebellar volume was identified in medicated patients with schizophrenia (68). ...
... Moberget et al. (35) found regional decreased GMVs in the bilateral Crus I, left Crus II, right lobule VIII, and right lobule IX in a large voxel-wise level megaanalysis and clarified that the cerebellum was a critical point of brain connectivity in patients with schizophrenia spectrum disorders. A worldwide multicenter study (66), including 182 patients with schizophrenia and 198 healthy controls, suggested that GMV losses mainly occurred in lobule VIIb and Crus II. The volume changes in the cerebellum may be the most vigorous and stable brain imaging findings in patients with schizophrenia. ...
... First, all the included studies were VBM studies conducted mainly from the perspective of the whole brain, and the details of subregional cerebellar information were hard to obtain, except for the specific peak coordinates. Technically, more precise segmentation approaches have been applied to cerebellar subfields (66). However, diverse novel methods (95) have only been applied in limited studies, which do not have enough quantity to conduct a meta-analysis. ...
Background
In schizophrenia, the structural changes in the cerebellum are associated with patients’ cognition and motor deficits. However, the findings are inconsistent owing to the heterogeneity in sample size, magnetic resonance imaging (MRI) scanners, and other factors among them. In this study, we conducted a meta-analysis to characterize the anatomical changes in cerebellar subfields in patients with schizophrenia.
Methods
Systematic research was conducted to identify studies that compare the gray matter volume (GMV) differences in the cerebellum between patients with schizophrenia and healthy controls with a voxel-based morphometry (VBM) method. A coordinate-based meta-analysis was adopted based on seed-based d mapping (SDM) software. An exploratory meta-regression analysis was conducted to associate clinical and demographic features with cerebellar changes.
Results
Of note, 25 studies comprising 996 patients with schizophrenia and 1,109 healthy controls were included in the present meta-analysis. In patients with schizophrenia, decreased GMVs were demonstrated in the left Crus II, right lobule VI, and right lobule VIII, while no increased GMV was identified. In the meta-regression analysis, the mean age and illness duration were negatively associated with the GMV in the left Crus II in patients with schizophrenia.
Conclusion
The most significant structural changes in the cerebellum are mainly located in the posterior cerebellar hemisphere in patients with schizophrenia. The decreased GMVs of these regions might partly explain the cognitive deficits and motor symptoms in patients with schizophrenia.
... The postero-superior "cognitive" cerebellum has been implicated in several psychiatric disorders. For example, there is now strong evidence [20,41,42] that the volume of the posterior cerebellum is reduced in schizophrenia. In the field of autism, despite initial studies in small samples [11,43] suggesting that there might be atypicalities in this region, recent larger studies [15,16] found no compelling evidence for volumetric alterations of the cerebellum. ...
... We decided to perform the cerebellar parcellation with the CERES pipeline. This automated parcellation method is well validated, has been successfully applied to healthy populations [49] and psychiatric disorders [16,41] and outperforms other cerebellar parcellation methods [28]. To the best of our knowledge, this study is to date the largest to investigate the association between the cerebellar morphology and symptoms related to autism. ...
Background
The cerebellum contains more than 50% of all neurons in the brain and is involved in a broad range of cognitive functions, including social communication and social cognition. Inconsistent atypicalities in the cerebellum have been reported in individuals with autism compared to controls suggesting the limits of categorical case control comparisons. Alternatively, investigating how clinical dimensions are related to neuroanatomical features, in line with the Research Domain Criteria approach, might be more relevant. We hypothesized that the volume of the “cognitive” lobules of the cerebellum would be associated with social difficulties.
Methods
We analyzed structural MRI data from a large pediatric and transdiagnostic sample (Healthy Brain Network). We performed cerebellar parcellation with a well-validated automated segmentation pipeline (CERES). We studied how social communication abilities—assessed with the social component of the Social Responsiveness Scale (SRS)—were associated with the cerebellar structure, using linear mixed models and canonical correlation analysis.
Results
In 850 children and teenagers (mean age 10.8 ± 3 years; range 5–18 years), we found a significant association between the cerebellum, IQ and social communication performance in our canonical correlation model.
Limitations
Cerebellar parcellation relies on anatomical boundaries, which does not overlap with functional anatomy. The SRS was originally designed to identify social impairments associated with autism spectrum disorders.
Conclusion
Our results unravel a complex relationship between cerebellar structure, social performance and IQ and provide support for the involvement of the cerebellum in social and cognitive processes.
... In the literature, there are previous studies conducted on cerebellar segmental volumetric with magnetic resonance imaging (MRI) in schizophrenia, bipolar disorder, and cerebellum maturation and aging throughout life [8,17]. However, we could not find a cerebellar segmental volumetric study in VAH in the literature review. ...
... Laidi et al. studied the volumes of cerebellar structures with volBrain CERES in patients with schizophrenia spectrum disorder and bipolar disorder. In this study, the total gray matter volume of the cerebellum is low in patients with schizophrenia spectrum disorder, and most of the changes exist in Crus II and lobule VIIB, which are the cognitive part of the cerebellum [8]. In our study, there was no change in lobule Crus II and lobule VIIB in the cerebellar VAH group, but cerebellar lobule I-II, III, IV, VIIIA and X gray matter volumes were low. ...
Purpose
Vertebral arteries (VAs) provide blood circulation to the posterior fossa in general and are the main blood supply of the posterior fossa structures of the brain. Our aim in this study is to analyze the segmental volumetric values of cerebellar structures with the voxel-based volumetric analysis system in individuals with unilateral vertebral artery hypoplasia.
Methods
In this retrospective study, segmental volumetric values/percentile ratios of cerebellar lobules were calculated using 3D fast spoiled gradient recall acquisition in steady-state (3D T1 FSPGR) MRI sequence images of the brain in individuals with unilateral vertebral artery hypoplasia (VAH) and in those without bilateral VAH and any symptoms of vertebrobasilar insufficiency as the control group was evaluated in volBrain (http://volbrain.upv.es/).
Results
The VAH group consisted of 50 (19 males/31 females) and the control group had 50 (21 males/29 females) individuals. The cerebellar lobule III, IV, VIIIA and X total volumes and the cerebellar lobule I–II, III, IV, VIIIA and X gray matter volumes were lower in the hypoplastic side than the non-hypoplastic cases and also than the contralateral side of the hypoplastic cases in the VAH group. In addition, it was found that that lobules IV and V had lower cortical thickness and lobules I–II had a higher coverage rate in the intracranial cavity in the hypoplastic side than the non-hypoplastic cases and also than the contralateral side of the hypoplastic cases (p < 0.05).
Conclusion
In this study, it was found that cerebellar lobule III, IV, VIIIA, X total volumes and cerebellar lobule I–II, III, IV, VIIIA, X gray matter volumes in addition to lobule IV, V cortical thicknesses were low in individuals with unilateral VAH. Being aware of these variations and taking them into account during future volumetric studies on the cerebellum are very important.
... For example, right crura Ia and Ib showed reduced functional connectivity with different areas in the CEN and DMN in unmedicated bipolar disorder [190]. Several other studies have shown that these regions of the CCS, that are expanded over primate evolution [118,119,163], are susceptible to alterations related to bipolar disorder [191][192][193]. Transdiagnostic accounts of mental disorder, investigating common alterations (e.g., genetic or neural), or the p-factor [194,195], have underscored a general role of the cerebellum in mental health [196], although this could not be replicated in a later study [197]. ...
... fMRI activations of crura I-II in cognitive tasks including language and social cognition [15,198,199], and resting-state connectivity analyses in complementary winner-takes-all network [90,175,177] and gradient-based [89] approaches imply involvement of the ansiform area in transmodal networks and cognition. Moreover, these areas also show alterations in mental disorders [190][191][192][193]. That primate cerebellar volumes in general relate to cognition is further supported by the relationship between cerebellar folding and tool use [160] and by the correlation between residual cerebellar volume and primate general intelligence [157,158]. ...
The longstanding idea that the cerebral cortex is the main neural correlate of human cognition can be elaborated by comparative analyses along the vertebrate phylogenetic tree that support the view that the cerebello-cerebral system is suited to support non-motor functions more generally. In humans, diverse accounts have illustrated cerebellar involvement in cognitive functions. Although the neocortex, and its transmodal association cortices such as the prefrontal cortex, have become disproportionately large over primate evolution specifically, human neocortical volume does not appear to be exceptional relative to the variability within primates. Rather, several lines of evidence indicate that the exceptional volumetric increase of the lateral cerebellum in conjunction with its connectivity with the cerebral cortical system may be linked to non-motor functions and mental operation in primates. This idea is supported by diverging cerebello-cerebral adaptations that potentially coevolve with cognitive abilities across other vertebrates such as dolphins, parrots, and elephants. Modular adaptations upon the vertebrate cerebello-cerebral system may thus help better understand the neuroevolutionary trajectory of the primate brain and its relation to cognition in humans. Lateral cerebellar lobules crura I-II and their reciprocal connections to the cerebral cortical association areas appear to have substantially expanded in great apes, and humans. This, along with the notable increase in the ventral portions of the dentate nucleus and a shift to increased relative prefrontal-cerebellar connectivity, suggests that modular cerebellar adaptations support cognitive functions in humans. In sum, we show how comparative neuroscience provides new avenues to broaden our understanding of cerebellar and cerebello-cerebral functions in the context of cognition.
... The cerebellum is connected to almost every region of the brain except the visual cortex and represents a potential therapeutic target. 17,18 Understanding the exact location of cerebellar changes in bipolar disorders and schizophrenia is essential. Because it affects the cerebellar stimulation site and brain stimulation in the cerebellum and distant cortical regions. ...
... 20 In recent studies, it is seen that MR images give more reliable results in various brain segmentations with volBrain (Ceres) software. 12,17,21 Acer and Sahin used two different methods for cerebellum volume estimation. The cerebellum volume was found to be 116.34 ...
Aim: Vestibular neuritis is one of the most common causes of acute spontaneous vertigo. In our study, we aimed to analyze the cerebellum volume and cerebellum connections in patients diagnosed with vestibular neuritis using the VolBrain program. Materials and Methods: 10 patients and 9 healthy (control) persons were included in the study. Automatic segmentation and volumetric analysis of cerebellum and cerebellum lobules were investigated using magnetic resonance images (MRI) of 19 people. Results: The volumes of 10 cerebellar regions were measured and compared between the patient and control groups. The total volume of the cerebellum was calculated as 123.82 ± 2.57 cm3 in the control group and 119.97 ± 4.15 cm3 in the patient group. In addition, the average amount of gray matter in the cerebellum was 90.63 ± 6.59 cm3 in the control group and 87.87 ± 16.12 cm3 in the patient group. We found volumetric changes to be statistically significant. Conclusion: By performing cerebellum segmentation with 3D T1 sequence of MRI images taken from patients diagnosed with vestibular neuritis, volume measurement and more detailed examinations can be performed easily with the help of the volBrain program. Moreover, its low cost and its usefulness in diagnosis suggest that this method will be beneficial.
... A recent study using a large multisite sample of individuals with SZ (n = 983) and healthy control subjects (n = 1349) demonstrated that total cerebellar GM volumetric reductions are one of the strongest and most consistent morphological alterations (22). Similar results have been found in other studies that identified GM volume reductions specific to the posterior cerebellar regions (23)(24)(25)(26). However, previous studies have focused on either ASD or SZ exclusively, and as a result, the extent to which there are morphological differences between these two conditions has not been definitively quantified. ...
... This discrepancy can be partly explained by the difference of the sample size between previous studies and the present study. Namely, although previous studies included a large number of participants from multisites (22,24), participants in the present study were recruited from a single site, and their number was modest. Consequently, our sample size was possibly insufficient to detect the same effect as observed in the previous studies. ...
Background
Although cerebellar morphological involvement has been increasingly recognized in autism spectrum disorders (ASD) and schizophrenia (SZ), the extent to which there are morphological differences between them has not been definitively quantified. Furthermore, although previous studies have demonstrated increased anatomical cerebellar-cerebral correlations in both conditions, differences between their associations have not been well characterized.
Methods
We compared cerebellar volume between males with ASD (n = 31), those with SZ (n = 28) and typically developing (TD) males (n = 49). A total of 31 cerebellar sub-regions were investigated with the cerebellum segmented into their constituent lobules, in gray matter (GM) and white matter (WM) separately. Additionally, structural correlations with the contralateral cerebrum were analyzed for each cerebellar lobule.
Results
We found significantly larger WM volume in the bilateral lobules VI and Crus I in the ASD group than in other groups. While WM or GM volumes of these right lobules had positive associations with ASD symptoms, there was a negative association between GM volume of the right Crus I and SZ symptoms. We further observed, in the ASD group specifically, significant correlations between WM of the right lobule VI and WM of the left frontal pole (r = .67), and between GM of the right lobule VI and the left caudate (r = .60).
Conclusions
Our findings support evidence that cerebellar morphology is involved in ASD and SZ with different mechanisms. Furthermore, this study showed that these biological differences require consideration when determining diagnostic criteria and treatment for these disorders.
... Regarding the cerebellar volume, there was no statistically significant difference between patients with BD and HCs, which is in contrast with the findings of previous studies that reported cerebellar atrophy in patients with BD (Baldacara et al., 2011;Kim et al., 2013). Indeed, a recent study on 144 patients with BD and 322 HCs did not find any significant difference in cerebellar lobules volumes between the two groups (Laidi et al., 2019). In our study, only the left lobule IX showed a statistically significant decrease in the volume after Bonferroni correction. ...
... Although we did not find a significant association between lithium treatment and cerebellar subregional volume/thickness in patients with BD, Hibar et al. (2018) found that cerebral cortical thickness was significantly greater in lithium-treated patients with BD than in lithiumnaïve patients. Laidi et al. (2019) also found a greater volume of the left anterior cerebellum gray matter in lithium-treated patients with BD than in lithium-naïve patients. We also could not find a significant association between mean illness duration and depressive symptom severity and cerebellar cortical thickness and volume. ...
Background:
Numerous studies have suggested that structural changes in the cerebellum are implicated in the pathophysiology of bipolar disorder (BD). We aimed to investigate differences in the volume and cortical thickness of the cerebellar subregions between patients with BD and healthy controls (HCs).
Methods:
Ninety patients with BD and one hundred sixty-six HCs participated in this study and underwent T1-weighted structural magnetic resonance imaging. We analyzed the volume and cortical thickness of each cerebellar hemisphere divided into 12 subregions using T1-weighted images of participants. One-way analysis of covariance was used to evaluate differences between the groups, with age, sex, medication, and total intracranial cavity volume used as covariates.
Results:
The BD group had significantly increased cortical thickness of the cerebellum in all cerebellar subregions compared to the HC group. The cortical thicknesses of the whole cerebellum and each hemisphere were also significantly thicker in the BD group than in the HC group. The volume of the left lobule IX was significantly lower in patients with BD than in HCs, whereas no significant differences in the volumes were observed in the other subregions.
Limitations:
Our cross-sectional design cannot provide a causal relationship between the increased cortical thickness of the cerebellum and the risk of BD.
Conclusions:
We observed widespread and significant cortical thickening in all the cerebellar subregions. Our results provide evidence for the involvement of the cerebellum in BD. Further studies are required to integrate neurobiological evidence and structural brain imaging to elucidate the pathophysiology of BD.
... Various studies have reported that epilepsy and multiple sclerosis in childhood and adolescence cause volume loss in the cerebellum (Lawson et al. 2000(Lawson et al. , 2008Weier et al. 2016). Various authors examining the cerebellum in neuropsychiatric disorders have found evidence of volume loss (Baldaçara et al. 2008;Laidi et al. 2019). Therefore, it is important to examine whether cerebellar development is normal or not radiologically in the pediatric period. ...
Developmental studies of cerebellar lobules were limited. To our knowledge, structural asymmetry has not been studied in immature cerebellar lobules in the 1–18 age group. This study investigated the effect of age and gender on the volumetric development and asymmetry of the global cerebellum and cerebellar lobules in children and adolescents. In this retrospective study, we included 670 individuals [376 (56.1%) males] aged 1–18 years with normal brain MRIs between 2012 and 2021. volBrain CERES automatically segmented the right and left sides of the cerebellar lobules on three-dimensional T1-weighted MRIs. Volume and asymmetry data from individuals in 16 different age ranges were compared with SPSS (ver.28). The absolute volumetric development of the total cerebellum was consistent with the “S” development model in both sexes. The developmental trajectories of the cerebellar lobules were different from each other and showed sexual dimorphism. In the 1–18 age group, the absolute volumes of the total cerebellum and cerebellar lobules were significantly greater in males (p < 0.05). Absolute volumes of lobules IV, VIIB, VIIIA and VIIIB in the age groups had more gender differences. However, sexual dimorphism was insignificant in the cerebellum’s total and lobular relative volume. Lobules IV, V, VI, VIIIA and VIIIB had left > right asymmetry and other lobules and total cerebellum had right > left asymmetry. This study confirmed the developmental heterogeneity and sexual dimorphism in the cerebellar lobules. It also provided volumetric data of the immature cerebellum to enable comparison in various neurological and neuropsychiatric diseases.
... We decided to perform the cerebellar parcellation with the CERES pipeline. This automated parcellation method is well validated, has been successfully applied to healthy populations , psychiatric disorders (Laidi et al., 2022(Laidi et al., , 2019) and outperforms other cerebellar parcellation methods (Carass et al., 2018). To the best of our knowledge, this study is to date the largest to investigate the association between the cerebellar morphology and symptoms related to autism. ...
Background. The cerebellum contains more than 50% of all neurons in the brain and is involved in a broad range of cognitive functions, including social communication and social cognition. Inconsistent atypicalities in the cerebellum have been reported in individuals with autism compared to controls suggesting the limits of categorical case control comparisons. Alternatively, investigating how clinical dimensions are related to neuroanatomical features, in line with the Research Domain Criteria approach, might be more relevant. We hypothesized that the volume of the “cognitive” lobules of the cerebellum would be associated with social difficulties.
Methods.We analyzed structural MRI data from a large pediatric and transdiagnostic sample (Healthy Brain Network). We performed cerebellar parcellation with a well-validated automated segmentation pipeline (CERES). We studied how social communication abilities – assessed with the social component of the social responsiveness scale (SRS) – were associated with the cerebellar structure, using linear mixed models and canonical correlation analysis.
Results.In 850 children and teenagers (mean age 10.8 ± 3 years; range 5-18 years) we found no associations between social communication abilities and cerebellar structure in linear mixed models. However, we found a significant association between the cerebellum, IQ and social communication performance in our canonical correlation model.
Conclusion. Our results unravel a complex relationship between cerebellar structure, social performance and IQ and provide support for the involvement of the cerebellum in social and cognitive processes.
... al gyrus, right inferior temporal gyrus, respectively. SVM, support vector machine. I)(Premkumar et al., 2009), further supporting our results that cerebellum Crus I/Crus II might participate in the pathological mechanism of schizophrenia. The differences among studies might be associated with the heterogeneity of patients and the analysis methods.Laidi et al. (2019) demonstrated that patients with schizophrenia showed a decrease in the cerebellum (Crus II), whereas there was no corresponding alternation in patients with bipolar disorder, indicating that the abnormalities in cerebellum Crus I and/or Crus II might be specific to schizophrenia. According to these reports and our results of SVM, combin ...
Schizophrenia is a severe mental disorder affecting around 0.5–1% of the global population. A few studies have shown the functional disconnection in the default-mode network (DMN) of schizophrenia patients. However, the findings remain discrepant. In the current study, we compared the intrinsic network organization of DMN of 57 first-diagnosis drug-naïve schizophrenia patients with 50 healthy controls (HCs) using a homogeneity network (NH) and explored the relationships of DMN with clinical characteristics of schizophrenia patients. Receiver operating characteristic (ROC) curves analysis and support vector machine (SVM) analysis were applied to calculate the accuracy of distinguishing schizophrenia patients from HCs. Our results showed that the NH values of patients were significantly higher in the left superior medial frontal gyrus (SMFG) and right cerebellum Crus I/Crus II and significantly lower in the right inferior temporal gyrus (ITG) and bilateral posterior cingulate cortex (PCC) compared to those of HCs. Additionally, negative correlations were shown between aberrant NH values in the right cerebellum Crus I/Crus II and general psychopathology scores, between NH values in the left SMFG and negative symptom scores, and between the NH values in the right ITG and speed of processing. Also, patients’ age and the NH values in the right cerebellum Crus I/Crus II and the right ITG were the predictors of performance in the social cognition test. ROC curves analysis and SVM analysis showed that a combination of NH values in the left SMFG, right ITG, and right cerebellum Crus I/Crus II could distinguish schizophrenia patients from HCs with high accuracy. The results emphasized the vital role of DMN in the neuropathological mechanisms underlying schizophrenia.
... Interestingly, these abnormalities have not been detected in bipolar disorder, and may therefore constitute a distinct type of abnormality specific to schizophrenia (Laidi et al. 2019). ...
Brain anomalies are frequently found in early psychoses. Although they may remain undetected for many years, their interpretation is critical for differential diagnosis. In secondary psychoses, their identification may allow specific management. They may also shed light on various pathophysiological aspects of primary psychoses. Here we reviewed cases of secondary psychoses associated with brain anomalies, reported over a 20-year period in adolescents and young adults aged 13 to 30 years old. We considered age at first psychotic symptoms, relevant medical history, the nature of psychiatric symptoms, clinical red flags, the nature of the brain anomaly reported, and the underlying disease. We discuss the relevance of each brain area in light of normal brain function, recent case-control studies, and postulated pathophysiology. We show that anomalies in all regions, whether diffuse, multifocal, or highly localized, may lead to psychosis, without necessarily being associated with non-psychiatric symptoms. This underlines the interest of neuroimaging in the initial workup, and supports the hypothesis of psychosis as a global network dysfunction that involves many different regions.
... However, all previous results on cerebellar anatomy included smaller samples (10), see also meta-analysis (9) suggesting that, if present, atypicalities could have been detected. In addition, cerebellar atypicalities have been repeatedly reported in other brain disorders such as schizophrenia in samples of the same size as this study (41,42). ...
Background
The cerebellum contains more than 50% of the brain neurons and is involved in social cognition. Cerebellar anatomical atypicalities have repeatedly been reported in individuals with autism. However, studies have yielded inconsistent findings, likely because of a lack of statistical power, and did not capture the clinical and neuroanatomical diversity of autism. Our aim was to better understand cerebellar anatomy and its diversity in autism.
Methods
We studied the cerebellar grey matter morphology in 274 individuals with autism and 219 controls of a multicenter European cohort (EU-AIMS LEAP). To ensure the robustness of our results, we conducted lobular parcellation of the cerebellum with two different pipelines in addition to voxel-based morphometry. We performed statistical analyses with linear, multivariate - including normative modeling - and a meta-analytic approach to capture the diversity of cerebellar anatomy in individuals with autism and controls. Last, we performed a dimensional analysis of cerebellar anatomy in an independent cohort of 352 individuals with autism-related symptoms.
Results
We did not find any significant difference in the cerebellum when comparing individuals with autism and controls using linear models. In addition, there were no significant deviations in our normative models in the cerebellum in individuals with autism. Finally, we found no evidence of cerebellar atypicalities related either to age, IQ, sex or social functioning in individuals with autism.
Conclusions
Despite positive results published in the last decade from relatively small samples, our results suggest that there is no striking difference in cerebellar anatomy of individuals with autism.
... [13][14][15][16] In addition, brains of obese/overweight individuals appear older than their chronological age. 17,18 Similar neurostructural alterations are frequently reported already early in the course of psychotic disorders, [19][20][21] but their origins remain unknown. Considering the multiple mutual links between obesity, FEP, and brain structure, it is possible that obesity contributes to brain alterations in psychosis. ...
Background
Obesity is highly prevalent in schizophrenia, with implications for psychiatric prognosis, possibly through links between obesity and brain structure. In this longitudinal study in first episode of psychosis (FEP), we used machine learning and structural magnetic resonance imaging (MRI) to study the impact of psychotic illness and obesity on brain ageing/neuroprogression shortly after illness onset.
Methods
We acquired 2 prospective MRI scans on average 1.61 years apart in 183 FEP and 155 control individuals. We used a machine learning model trained on an independent sample of 504 controls to estimate the individual brain ages of study participants and calculated BrainAGE by subtracting chronological from the estimated brain age.
Results
Individuals with FEP had a higher initial BrainAGE than controls (3.39 ± 6.36 vs 1.72 ± 5.56 years; β = 1.68, t(336) = 2.59, P = .01), but similar annual rates of brain ageing over time (1.28 ± 2.40 vs 1.07±1.74 estimated years/actual year; t(333) = 0.93, P = .18). Across both cohorts, greater baseline body mass index (BMI) predicted faster brain ageing (β = 0.08, t(333) = 2.59, P = .01). For each additional BMI point, the brain aged by an additional month per year. Worsening of functioning over time (Global Assessment of Functioning; β = −0.04, t(164) = −2.48, P = .01) and increases especially in negative symptoms on the Positive and Negative Syndrome Scale (β = 0.11, t(175) = 3.11, P = .002) were associated with faster brain ageing in FEP.
Conclusions
Brain alterations in psychosis are manifest already during the first episode and over time get worse in those with worsening clinical outcomes or higher baseline BMI. As baseline BMI predicted faster brain ageing, obesity may represent a modifiable risk factor in FEP that is linked with psychiatric outcomes via effects on brain structure.
... In contrast to these earlier studies, recent research that applied more optimized methods for cerebellar segmentation have successfully identified structural abnormalities in cerebellar hemisphere regions, especially in the posterior cerebellar regions, which are associated with higher cognitive modulation. 27 Namely, reduced GM volume in this region has been found in FES and ChSZ populations, [28][29][30][31][32] whereas increased WM volumes were identified in individuals from UHR groups who both did and did not develop psychosis. 13 Additionally, some of these studies have shown associations between not only such alterations of cerebellar volumes and cognitive deficits but also symptom severity. ...
Aim
Schizophrenia is considered to be a disorder of progressive structural brain abnormalities. Previous studies have indicated that the cerebellar Crus I/II plays a critical role in schizophrenia. We aimed to investigate how specific morphological features in the Crus I/II at different critical stages of the schizophrenia spectrum contribute to the disease.
Methods
The study involved 73 participants on the schizophrenia spectrum (28 with ultra-high risk for psychosis [UHR], 17 with first-episode schizophrenia [FES], and 28 with chronic schizophrenia), and 79 healthy controls. We undertook a detailed investigation into differences in Crus I/II volume using a semi-automated segmentation method optimized for the cerebellum. We analyzed the effects of group and sex, as well as their interaction, on Crus I/II volume in gray matter (GM) and white matter (WM).
Results
Significant group × sex interactions were found in WM volumes of the bilateral Crus I/II; the UHR males demonstrated significantly larger WM volumes compared to the other male groups, whereas no significant group differences were found in the female groups. Additionally, WM and GM volumes of the Crus I/II had positive associations with symptom severity in the UHR group, whereas, in contrast, GM volumes in the FES group were negatively associated with symptom severity.
Conclusions
The present findings provide evidence that the morphology of Crus I/II is involved in schizophrenia in a sex- and disease stage-dependent manner. Additionally, alterations of WM volumes of Crus I/II may have potential as a biological marker of early detection and treatment for UHR individuals.
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... In fact, patients with cerebellar lesions limited to lobule VI experienced minimal motor impairment (Stoodley & Schmahmann, 2010). Specific cerebellum dysfunction have also been associated to cognitive impairment in various pathological conditions such as schizophrenia (Okugawa et al., 2002;James, James, Smith, & Javaloyes, 2004, Laidi et al., 2019, Nenadic et al., 2010, Alzheimer's disease (Thomann et al., 2008), Multiple Sclerosis (Moroso et al., 2017) and neurodevelopmental disorders Attention Deficit/Hyperactivity Disorder and Autism (Bishop, 2002;Courchesne et al., 1994;Ramnani, 2006;Seidman, Valera, & Makris, 2005). ...
Previous literature about the structural characterization of the human cerebellum is related to the context of a specific pathology or focused in a restricted age range. In fact, studies about the cerebellum maturation across the lifespan are scarce and most of them considered the cerebellum as a whole without investigating each lobule. This lack of study can be explained by the lack of both accurate segmentation methods and data availability. Fortunately, during the last years, several cerebellum segmentation methods have been developed and many databases comprising subjects of different ages have been made publically available. This fact opens an opportunity window to obtain a more extensive analysis of the cerebellum maturation and aging. In this study, we have used a recent state‐of‐the‐art cerebellum segmentation method called CERES and a large data set (N = 2,831 images) from healthy controls covering the entire lifespan to provide a model for 12 cerebellum structures (i.e., lobules I‐II, III, IV, VI, Crus I, Crus II, VIIB, VIIIA, VIIIB, IX, and X). We found that lobules have generally an evolution that follows a trajectory composed by a fast growth and a slow degeneration having sometimes a plateau for absolute volumes, and a decreasing tendency (faster in early ages) for normalized volumes. Special consideration is dedicated to Crus II, where slow degeneration appears to stabilize in elder ages for absolute volumes, and to lobule X, which does not present any fast growth during childhood in absolute volumes and shows a slow growth for normalized volumes.
... Previous neurostructural findings regarding cerebellum in FEP are less consistent. In keeping with our results, a number of individual studies reported lower GM volumes of cerebellum in all stages of SZ (35)(36)(37)(38)(39)(40)(41), including those at ultra-high risk (UHR) for psychosis (39,42), FEP (40), or in the largest such study, a multisite mega-analyses of 983 participants and 1,349 healthy controls (19). However, cerebellar findings from metaanalyses exploring GM volume abnormalities in FEP are inconsistent, with some reports finding cerebellar alterations only in certain subgroups or not at all (3)(4)(5). ...
Background
Neurostructural alterations are often reported in first episode of psychosis (FEP), but there is heterogeneity in the direction and location of findings between individual studies. The reasons for this heterogeneity remain unknown. Obesity is disproportionately frequent already early in the course of psychosis and is associated with smaller brain volumes. Thus, we hypothesized that obesity may contribute to brain changes in FEP.
Method
We analyzed MRI scans from 120 participants with FEP and 114 healthy participants. In primary analyses, we performed voxel-based morphometry (VBM) with small volume corrections to regions associated with FEP or obesity in previous meta-analyses. In secondary analyses, we performed whole-brain VBM analyses.
Results
In primary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in a) left fronto-temporal region (pTFCE = 0.008) and b) left postcentral gyrus (pTFCE = 0.043). When controlling for FEP, BMI was associated with lower GM volume in left cerebellum (pTFCE < 0.001). In secondary analyses, we found that when controlling for BMI, FEP had lower GM volume than healthy participants in the a) cerebellum (pTFCE = 0.004), b) left frontal (pTFCE = 0.024), and c) right temporal cortex (pTFCE = 0.031). When controlling for FEP, BMI was associated with lower GM volume in cerebellum (pTFCE = 0.004). Levels of C-reactive protein, HDL and LDL-cholesterol correlated with obesity related neurostructural alterations.
Conclusions
This study suggests that higher BMI, which is frequent in FEP, may contribute to cerebellar alterations in schizophrenia. As previous studies showed that obesity-related brain alterations may be reversible, our findings raise the possibility that improving the screening for and treatment of obesity and associated metabolic changes could preserve brain structure in FEP.
Background
Schizophrenia, a multifaceted psychiatric disorder characterized by functional dysconnectivity, poses significant challenges in clinical practice. This study explores the potential of functional connectivity (FC)-based searchlight multivariate pattern analysis (CBS-MVPA) to discriminate between schizophrenia patients and healthy controls while also predicting clinical variables.
Study Design
We enrolled 112 schizophrenia patients and 119 demographically matched healthy controls. Resting-state functional magnetic resonance imaging data were collected, and whole-brain FC subnetworks were constructed. Additionally, clinical assessments and cognitive evaluations yielded a dataset comprising 36 clinical variables. Finally, CBS-MVPA was utilized to identify subnetworks capable of effectively distinguishing between the patient and control groups and predicting clinical scores.
Study Results
The CBS-MVPA approach identified 63 brain subnetworks exhibiting significantly high classification accuracies, ranging from 62.2% to 75.6%, in distinguishing individuals with schizophrenia from healthy controls. Among them, 5 specific subnetworks centered on the dorsolateral superior frontal gyrus, orbital part of inferior frontal gyrus, superior occipital gyrus, hippocampus, and parahippocampal gyrus showed predictive capabilities for clinical variables within the schizophrenia cohort.
Conclusion
This study highlights the potential of CBS-MVPA as a valuable tool for localizing the information related to schizophrenia in terms of brain network abnormalities and capturing the relationship between these abnormalities and clinical variables, and thus, deepens our understanding of the neurological mechanisms of schizophrenia.
Introduction
Cerebellar alterations, including both volumetric changes in the cerebellar vermis and dysfunctions of the corticocerebellar connections, have been documented in psychotic disorders. Starting from the clinical observation of a bipolar patient with cerebellar hypoplasia, the purpose of this review is to summarize the data in the literature about the association between hypoplasia of the cerebellar vermis and psychotic disorders [schizophrenia (SCZ) and bipolar disorder (BD)].
Methods
A bibliographic search on PubMed has been conducted, and 18 articles were finally included in the review: five used patients with BD, 12 patients with SCZ and one subject at psychotic risk.
Results
For SCZ patients and subjects at psychotic risk, the results of most of the reviewed studies seem to suggest a gray matter volume reduction coupled with an increase in white matter volumes in the cerebellar vermis, compared to healthy controls. Instead, the results of the studies on BD patients are more heterogeneous with evidence showing a reduction, no difference or even an increase in cerebellar vermis volume compared to healthy controls.
Conclusions
From the results of the reviewed studies, a possible correlation emerged between cerebellar vermis hypoplasia and psychotic disorders, especially SCZ, ultimately supporting the hypothesis of psychotic disorders as neurodevelopmental disorders.
Schizophrenia and mood disorders are severe psychiatric disorders with significant morbidity and mortality. Both disorders share high genetic and environmental etiologies. In this chapter, we summarize the structural, morphologic, and proteomic aspects of cerebellar pathology in schizophrenia, bipolar disorder, and major depression.KeywordsCerebellumSchizophreniaBipolar disorderMajor depressionGABA receptorsPhosphodiesterasesReelinFMRPmGluR5Glutamic acid decarboxylasesGFAPPurkinje cells
More and more research has focused on the role of the cerebellum in emotions and social cognition. Structural cerebellar and cerebello-cerebral connectivity abnormalities have been identified in several prevalent neuropsychiatric conditions, which have in some cases even been linked to the severity of the emotional disorder.Non-invasive brain stimulation (NIBS) techniques are currently used to modulate neuronal excitability and tune the connectivity within and between neuronal networks. Targeting the cerebellum with NIBS in order to improve emotions and social behavior in neuropsychiatric conditions seems to be a very interesting and innovative approach. Several studies have already explored the effect of cerebellar vermis stimulation in patients with schizophrenia with promising results. Other neuropsychiatric disorders such as bipolar disorder (BD), obsessive-compulsive disorder (OCD), major depressive disorder, or generalized anxiety disorder (GAD) have received less attention with respect to cerebellar stimulation, although the cerebellum has been implicated in these disorders. We will address NIBS and neuropsychiatric disorders in this chapter. Future research should focus on combining cerebellar NIBS with neuroimaging to unravel the specific role of the cerebellum in emotional disorders. Such studies will be very valuable in establishing causal relationships between the structural and functional abnormalities that can be observed in these disorders, and in the search for neurophysiological biomarkers for emotions. However, it is still unclear which stimulation parameters are optimal. Moreover, an important factor to consider when applying cerebellar NIBS in order to improve emotional or other functioning is cerebellar reserve. Although the cerebellum has a wide variety of plasticity mechanisms and its structural organization intrinsically incorporates a lot of redundancy, this redundancy can be depleted. A certain amount of cerebellar reserve should be preserved to successfully apply NIBS.Systematic studies are therefore needed to clarify the optimal stimulation parameters, and methods should be developed to quantify cerebellar reserve in order to estimate the possible added value of NIBS in the rehabilitation of emotions.
Background
: Bipolar disorder (BP) is a common psychiatric disorder characterized by extreme fluctuations in mood. Recent studies have indicated the involvement of cerebellum in the pathogenesis of BP. However, no study has focused on the precise role of cerebellum exclusively in patients with bipolar I disorder (BP-I).
Methods
: Forty-five patients with BP-I and 40 healthy controls were recruited. All subjects underwent clinical evaluation and Magnetic Resonance diffusion Tension Imaging scans. For structural images, we used a spatially unbiased infratentorial template toolbox to isolate the cerebellum and then preformed voxel-based morphometry (VBM) analyses to assess the difference in cerebellar gray matter volume (GMV) between the two groups. For the functional images, we chose the clusters that survived from VBM analysis as seeds and performed functional connectivity (FC) analysis. Between-group differences were assessed using the independent Students t test or the nonparametric Mann‐Whitney U Test. For multiple comparisons, the results were further corrected with Gaussian random field (GRF) approach (voxel-level P<0.001, cluster-level P<0.05).
Results
: Compared with healthy controls, BP-I patients showed significantly decreased GMV in left lobule V and left lobule VI (P<0.05, GRF corrected). The FC of cerebellum with bilateral superior temporal gyrus, bilateral insula, bilateral rolandic operculum, right putamen, and left precentral gyrus was disrupted in BP-I patients (P<0.05, GRF corrected).
Conclusions
: BP-I patients showed decreased cerebellar GMV and disrupted cerebellar-cortex resting-state FC. This suggests that cerebellar abnormalities may play an important role in the pathogenesis of BP-I.
Background
The cerebellum has a crucial role in mood regulation. While cerebellar grey matter (GM) alterations have been previously reported in bipolar disorder (BD), cerebro-cerebellar white matter (WM) connectivity alterations and cerebellar GM profiles have not been characterised in the context of predominant polarity (PP) and onset polarity (OP) subphenotypes of BD patients which is the aim of the present study.
Methods
Forty-two euthymic BD patients stratified for PP and OP and 42 healthy controls (HC) were included in this quantitative neuroimaging study to evaluate cerebellar GM patterns and cerebro-cerebellar WM connections. Diffusion tensor tractography was used to characterise afferent and efferent cerebro-cerebellar tract integrity. False discovery rate corrections were applied in post-hoc comparisons.
Results
BD patients exhibited higher fractional anisotropy (FA) in fronto-ponto-cerebellar tracts bilaterally compared to HC. Subphenotype-specific FA profiles were identified within the BD cohort. Regarding PP subgroups, we found FA changes in a) left contralateral fronto-ponto-cerebellar tract (depressive-PP > HC) and b) contralateral/ipsilateral fronto-ponto-cerebellar tracts bilaterally (manic-PP > HC). Regarding OP subgroups, we observed FA changes in a) left/right contralateral fronto-ponto-cerebellar tracts (depressive-OP>HC) and b) all fronto-ponto-cerebellar, most parieto-ponto-cerebellar and right contralateral occipito-ponto-cerebellar tracts (manic-OP>HC). In general, greater and more widespread cerebro-cerebellar changes were observed in manic-OP patients than in depressive-OP patients compared to HC. Manic-OP showed higher FA compared to depressive-OP patients in several afferent WM tracts. No GM differences were identified between BD and HC and across BD subgroups.
Conclusions
Our findings highlight fronto-ponto-cerebellar connectivity alterations in euthymic BD. Polarity-related subphenotypes have distinctive cerebro-cerebellar WM signatures with potential clinical and pathobiological implications.
Pollen micro‐morphological features have proven to be helpful for the plant taxonomists in the identification and classification of plants. The utilization of this plant may helpful in the areas of lignocellulosic conversion to biofuels and diversify application toward biomass. The current study was planned with the aim to evaluate the pollen features of complex Ranunculaceous flora of District Chitral, Northern Pakistan using both scanning electron microscopy (SEM) and Light Microscope (LM) for their taxonomic importance. Pollens of 18 Ranunculaceous species belonging to 6 genera were collected from different localities of the research area. SEM and LM were used to examine both qualitative and quantitative micro‐morphological features. Sculptring of the sexine include; Scabrate, psilate, echinate, verrucate, perforate gemmate, and reticulate and so forth. Shape of the pollens was sub‐spheroidal, spheroidal, prolate, subprolate and oblate and so forth. Type of pollen was ranged from mono to tricolpate and tricolporate. Quantitative characters include length/width of the pollen, colpus, exine thickness, and P/E ratio. Based on these micro‐morphological features a taxonomic key was prepared for the fast and correct identification.
Research highlight
• Study of the pollen micro‐morphological features of Ranunculaceous species by SEM and LM.
• Analysing both qualitative and quantitative characters of the pollens.
• Preparation of taxonomic key based on micro‐morphological features for the correct and fast identification.
Background
The neuroanatomical bases of Autism Spectrum Disorders remain largely unknown. Among the most widely discussed candidate endophenotypes, differences in cerebellar volume have been often reported as statistically significant.
Methods
We aimed at objectifying this possible alteration by performing a systematic meta-analysis of the literature, and an analysis of the Autism Brain Imaging Data Exchange (ABIDE 1) cohort. Our meta analysis sought to determine a combined effect size of autism spectrum disorder diagnosis on different measures of the cerebellar anatomy, as well as the effect of possible factors of variability across studies.
We then analyzed the cerebellar volume of 328 patients and 353 controls from the Autism Brain Imaging Data Exchange project.
Results
The meta-analysis of the literature suggested a weak but significant association between autism spectrum disorder diagnosis and increased cerebellar volume (p=0.049, uncorrected), but the analysis of ABIDE did not show any relationship. The studies meta-analyzed were generally underpowered, however, the number of statistically significant findings was larger than expected.
Conclusions
Although we could not provide a conclusive explanation for this excess of significant findings, our analyses would suggest publication bias as a possible reason. Finally, age, sex and intelligence quotient were important sources of cerebellar volume variability, however, independent of autism diagnosis.
Background:
The neuroanatomical bases of autism spectrum disorder remain largely unknown. Among the most widely discussed candidate endophenotypes, differences in cerebellar volume have been often reported as statistically significant.
Methods:
We aimed at objectifying this possible alteration by performing a systematic meta-analysis of the literature and an analysis of the ABIDE (Autism Brain Imaging Data Exchange) cohort. Our meta-analysis sought to determine a combined effect size of autism spectrum disorder diagnosis on different measures of the cerebellar anatomy as well as the effect of possible factors of variability across studies. We then analyzed the cerebellar volume of 328 patients and 353 control subjects from the ABIDE project.
Results:
The meta-analysis of the literature suggested a weak but significant association between autism spectrum disorder diagnosis and increased cerebellar volume (p = .049, uncorrected), but the analysis of ABIDE did not show any relationship. The studies meta-analyzed were generally underpowered; however, the number of statistically significant findings was larger than expected.
Conclusions:
Although we could not provide a conclusive explanation for this excess of significant findings, our analyses would suggest publication bias as a possible reason. Finally, age, sex, and IQ were important sources of cerebellar volume variability, although independent of autism diagnosis.
Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen’s d=−0.293; P=1.71 × 10⁻²¹), left fusiform gyrus (d=−0.288; P=8.25 × 10⁻²¹) and left rostral middle frontal cortex (d=−0.276; P=2.99 × 10⁻¹⁹). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.
Abstract The human cerebellum is involved in language, motor tasks and cognitive processes such as attention or emotional processing. Therefore, an automatic and accurate segmentation method is highly desirable to measure and understand the cerebellum role in normal and pathological brain development. In this work, we propose a patch-based multi-atlas segmentation tool called CERES (CEREbellum Segmentation) that is able to automatically parcellate the cerebellum lobules. The proposed method works with standard resolution magnetic resonance T1-weighted images and uses the Optimized PatchMatch algorithm to speed up the patch matching process. The proposed method was compared with related recent state-of-the-art methods showing competitive results in both accuracy (average DICE of 0.7729) and execution time (around 5 minutes).
Neurological disturbances caused by lithium range from simple side effects such as benign tremor to acute reversible neurotoxicity. Rarely, lithium is reported to cause irreversible, permanent neurological sequelae most commonly manifested as cerebellar dysfunction, although other presentations have also been described. We report two cases of persistent cerebellar syndrome following acute lithium toxicity and discuss them in the light of existing literature on the subject. © 2016 Indian Journal of Pharmacology Published by Wolters Kluwer - Medknow.
Growing evidence suggests that sensory, motor, cognitive and affective processes map onto specific, distributed neural networks. Cerebellar subregions are part of these networks, but how the cerebellum is involved in this wide range of brain functions remains poorly understood. It is postulated that the cerebellum contributes a basic role in brain functions, helping to shape the complexity of brain temporal dynamics. We therefore hypothesized that stimulating cerebellar nodes integrated in different networks should have the same impact on the temporal complexity of cortical signals. In healthy humans, we applied intermittent theta burst stimulation (iTBS) to the vermis lobule VII or right lateral cerebellar Crus I/II, subregions that prominently couple to the dorsal-attention/fronto-parietal and default-mode networks, respectively. Cerebellar iTBS increased the complexity of brain signals across multiple time scales in a network-specific manner identified through electroencephalography (EEG). We also demonstrated a region-specific shift in power of cortical oscillations towards higher frequencies consistent with the natural frequencies of targeted cortical areas. Our findings provide a novel mechanism and evidence by which the cerebellum contributes to multiple brain functions: specific cerebellar subregions control the temporal dynamics of the networks they are engaged in.
The anterior cingulate cortex (ACC) is frequently reported to have functionally distinct sub-regions that play key roles in different intrinsic networks. However, the contribution of the ACC, which is connected to several cortical areas and the limbic system, to autism is not clearly understood, although it may be involved in dysfunctions across several distinct but related functional domains. By comparing resting-state fMRI data from persons with autism and healthy controls, we sought to identify the abnormalities in the functional connectivity (FC) of ACC sub-regions in autism. The analyses found autism-related reductions in FC between the left caudal ACC and the right rolandic operculum, insula, postcentral gyrus, superior temporal gyrus, and the middle temporal gyrus. The FC (z-scores) between the left caudal ACC and the right insula was negatively correlated with the Stereotyped Behaviors and Restricted Interests scores of the autism group. These findings suggest that the caudal ACC is recruited selectively in the pathomechanism of autism.
Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10(-7)) and thalamus (d=-0.148; P=4.27 × 10(-3)) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10(-5)) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.Molecular Psychiatry advance online publication, 9 February 2016; doi:10.1038/mp.2015.227.
Alcohol abuse causes cerebellar dysfunction and cerebellar ataxia is a common feature in alcoholics. Alcohol exposure during development also impacts the cerebellum. Children with fetal alcohol spectrum disorder (FASD) show many symptoms associated specifically with cerebellar deficits. However, the cellular and molecular mechanisms are unclear. This special issue discusses the most recent advances in the study of mechanisms underlying alcoholinduced cerebellar deficits. The alteration in GABAA receptor-dependent neurotransmission is a potential mechanism for ethanol-induced cerebellar dysfunction. Recent advances indicate ethanol-induced increases in GABA release are not only in Purkinje cells (PCs), but also in molecular layer interneurons and granule cells. Ethanol is shown to disrupt the molecular events at the mossy fiber – granule cell – Golgi cell (MGG) synaptic site and granule cell parallel fibers – PCs (GPP) synaptic site, which may be responsible for ethanol-induced cerebellar ataxia. Aging and ethanol may affect the smooth endoplasmic reticulum (SER) of PC dendrites and cause dendritic regression. Ethanol withdrawal causes mitochondrial damage and aberrant gene modifications in the cerebellum. The interaction between these events may result in neuronal degeneration, thereby contributing to motoric deficit. Ethanol activates doublestranded RNA (dsRNA)-activated protein kinase (PKR) and PKR activation is involved ethanolinduced neuroinflammation and neurotoxicity in the developing cerebellum. Ethanol alters the development of cerebellar circuitry following the loss of PCs, which could result in modifications of the structure and function of other brain regions that receive cerebellar inputs. Lastly, choline, an essential nutrient is evaluated for its potential protection against ethanol-induced cerebellar damages. Choline is shown to ameliorate ethanol-induced cerebellar dysfunction when given before ethanol exposure.
Abnormal metabolism has been reported in bipolar disorder, however, these studies have been limited to specific regions of the brain. To investigate whole-brain changes potentially associated with these processes, we applied a magnetic resonance imaging technique novel to psychiatric research, quantitative mapping of T1 relaxation in the rotating frame (T1ρ). This method is sensitive to proton chemical exchange, which is affected by pH, metabolite concentrations and cellular density with high spatial resolution relative to alternative techniques such as magnetic resonance spectroscopy and positron emission tomography. Study participants included 15 patients with bipolar I disorder in the euthymic state and 25 normal controls balanced for age and gender. T1ρ maps were generated and compared between the bipolar and control groups using voxel-wise and regional analyses. T1ρ values were found to be elevated in the cerebral white matter and cerebellum in the bipolar group. However, volumes of these areas were normal as measured by high-resolution T1- and T2-weighted magnetic resonance imaging. Interestingly, the cerebellar T1ρ abnormalities were normalized in participants receiving lithium treatment. These findings are consistent with metabolic or microstructural abnormalities in bipolar disorder and draw attention to roles of the cerebral white matter and cerebellum. This study highlights the potential utility of high-resolution T1ρ mapping in psychiatric research.Molecular Psychiatry advance online publication, 6 January 2015; doi:10.1038/mp.2014.157.
The dose-dependent toxicity of the main psychoactive component of cannabis in brain regions rich with cannabinoid CB1 receptors is well known in animal studies. However, research in humans does not show common findings across studies regarding the brain regions that are affected after long-term exposure to cannabis. In the present study we investigate (using Voxel-based Morphometry) grey matter changes in a group of regular cannabis smokers in comparison to a group of occasional smokers matched by the years of cannabis use. We provide evidence that regular cannabis use is associated with grey matter volume reduction in the medial temporal cortex, temporal pole, parahippocampal gyrus, insula, and orbitofrontal cortex; these regions are rich with cannabinoid CB1 receptors and functionally associated with motivational, emotional, and affective processing. Furthermore, these changes correlate with the frequency of cannabis use in the three months prior to inclusion in the study. The age of onset of drug use also influences the magnitude of these changes. Significant grey matter volume reduction could result either from heavy consumption unrelated to the age of onset or instead from recreational cannabis use initiated at an adolescent age. In contrast, the larger grey matter volume detected in the cerebellum of regular smokers without any correlation with the monthly consumption of cannabis may be related to developmental (ontogenic) processes that occur in adolescence.Neuropsychopharmacology accepted article preview online, 17 March 2014; doi:10.1038/npp.2014.67.
Successful accumulation of knowledge is critically dependent on the ability to verify and replicate every part of scientific conduct. However, such principles are difficult to enact when researchers continue to resort on ad-hoc workflows and with poorly maintained code base. In this paper I examine the needs of neuroscience and psychology community, and introduce psychopy_ext, a unifying framework that seamlessly integrates popular experiment building, analysis and manuscript preparation tools by choosing reasonable defaults and implementing relatively rigid patterns of workflow. This structure allows for automation of multiple tasks, such as generated user interfaces, unit testing, control analyses of stimuli, single-command access to descriptive statistics, and publication quality plotting. Taken together, psychopy_ext opens an exciting possibility for a faster, more robust code development and collaboration for researchers.
A growing literature points to a specific role of the cerebellum in affect processing. However, understanding of affect processing disturbances following discrete cerebellar lesions is limited. We administered the Tübingen Affect Battery to assess recognition of emotional facial expression and emotional prosody in 15 patients with a cerebellar infarction and 10 age-matched controls. On emotional facial expression tasks, patients compared to controls showed impaired selection and matching of facial affect. On prosody tasks, patients showed marked impairments in naming affect and discriminating incongruencies. These deficits were more pronounced for negative affects. Our results confirm a significant role of the cerebellum in processing emotional recognition, a component of social cognition.
The cerebellum processes information from functionally diverse regions of the cerebral cortex. Cerebellar input and output nuclei have connections with prefrontal, parietal, and sensory cortex as well as motor and premotor cortex. However, the topography of the connections between the cerebellar and cerebral cortices remains largely unmapped, as it is relatively unamenable to anatomical methods. We used resting-state functional magnetic resonance imaging to define subregions within the cerebellar cortex based on their functional connectivity with the cerebral cortex. We mapped resting-state functional connectivity voxel-wise across the cerebellar cortex, for cerebral-cortical masks covering prefrontal, motor, somatosensory, posterior parietal, visual, and auditory cortices. We found that the cerebellum can be divided into at least 2 zones: 1) a primary sensorimotor zone (Lobules V, VI, and VIII), which contains overlapping functional connectivity maps for domain-specific motor, somatosensory, visual, and auditory cortices; and 2) a supramodal zone (Lobules VIIa, Crus I, and II), which contains overlapping functional connectivity maps for prefrontal and posterior-parietal cortex. The cortical connectivity of the supramodal zone was driven by regions of frontal and parietal cortex which are not directly involved in sensory or motor processing, including dorsolateral prefrontal cortex and the frontal pole, and the inferior parietal lobule.
Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very few descriptions of clinically relevant cases that address this possibility. We performed neurological examinations, bedside mental state tests, neuropsychological studies and anatomical neuroimaging on 20 patients with diseases confined to the cerebellum, and evaluated the nature and severity of the changes in neurological and mental function. Behavioural changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis, and in some cases they were the most noticeable aspects of the presentation. These changes were characterized by: impairment of executive functions such as planning, set-shifting, verbal fluency, abstract reasoning and working memory; difficulties with spatial cognition including visual-spatial organization and memory; personality change with blunting of affect or disinhibited and inappropriate behaviour; and language deficits including agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. We have called this newly defined clinical entity the 'cerebellar cognitive affective syndrome'. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits that link prefrontal, posterior parietal, superior temporal and limbic cortices with the cerebellum.
Brain atrophy associated with chronic alcohol consumption is partially reversible after cessation of drinking. Recovering alcoholics (RA, 45+/-8 years) were studied with MRI within 1 week of entering treatment, with follow-up at 8 months. Light drinkers (LD) were studied with MRI twice 1 year apart. For each participant, deformation maps of baseline structure and longitudinal size changes between baseline and follow-up scans were created using nonlinear registration techniques. ANCOVA assessed group differences and regression methods examined relationships between deformation maps and measures of drinking severity or baseline atrophy. At baseline, RA showed significant atrophy in the frontal and temporal lobes. Longitudinally, abstainers recovered tissue volumes significantly faster than LD in parietal and frontal lobes. When comparing abstainers to relapsers, additional regions with significantly greater recovery in abstainers were temporal lobes, thalamus, brainstem, cerebellum, corpus callosum, anterior cingulate, insula, and subcortical white matter. Gray matter volume at baseline predicted volume recovery during abstinence better than white matter. Drinking severity was not significantly related to brain structural changes assessed with this method. Longitudinally, deformation-based morphometry confirmed tissue recovery in RAs who maintain long-term sobriety. Abstinence-associated tissue volume gains are significant in focal parts of the fronto-ponto-cerebellar circuit that is adversely affected by heavy drinking.
For many years the cerebellum has been considered to serve as a coordinator of motor function. Likewise, for many years schizophrenia has been considered to be a disease that primarily affects the cerebrum. This review summarizes recent evidence that both these views must be revised in the light of emerging evidence about cerebellar function and the mechanisms of schizophrenia. Evidence indicating that the cerebellum plays a role in higher cortical functions is summarized. Evidence indicating that cerebellar abnormalities occur in schizophrenia is also reviewed. These suggest interesting directions for future research.
The human cerebellum plays an essential role in motor control, is involved in cognitive function (i.e., attention, working memory, and language), and helps to regulate emotional responses. Quantitative in-vivo assessment of the cerebellum is important in the study of several neurological diseases including cerebellar ataxia, autism, and schizophrenia. Different structural subdivisions of the cerebellum have been shown to correlate with differing pathologies. To further understand these pathologies, it is helpful to automatically parcellate the cerebellum at the highest fidelity possible. In this paper, we coordinated with colleagues around the world to evaluate automated cerebellum parcellation algorithms on two clinical cohorts showing that the cerebellum can be parcellated to a high accuracy by newer methods. We characterize these various methods at four hierarchical levels: coarse (i.e., whole cerebellum and gross structures), lobe, subdivisions of the vermis, and the lobules. Due to the number of labels, the hierarchy of labels, the number of algorithms, and the two cohorts, we have restricted our analyses to the Dice measure of overlap. Under these conditions, machine learning based methods provide a collection of strategies that are efficient and deliver parcellations of a high standard across both cohorts, surpassing previous work in the area. In conjunction with the rank-sum computation, we identified an overall winning method.
Objectives:
Quantitative mapping of T1 relaxation in the rotating frame (T1ρ) is a magnetic resonance imaging technique sensitive to pH and other cellular and microstructural factors, and is a potentially valuable tool for identifying brain alterations in bipolar disorder. Recently, this technique identified differences in the cerebellum and cerebral white matter of euthymic patients vs healthy controls that were consistent with reduced pH in these regions, suggesting an underlying metabolic abnormality. The current study built upon this prior work to investigate brain T1ρ differences across euthymic, depressed, and manic mood states of bipolar disorder.
Methods:
Forty participants with bipolar I disorder and 29 healthy control participants matched for age and gender were enrolled. Participants with bipolar disorder were imaged in one or more mood states, yielding 27, 12, and 13 imaging sessions in euthymic, depressed, and manic mood states, respectively. Three-dimensional, whole-brain anatomical images and T1ρ maps were acquired for all participants, enabling voxel-wise evaluation of T1ρ differences between bipolar mood state and healthy control groups.
Results:
All three mood state groups had increased T1ρ relaxation times in the cerebellum compared to the healthy control group. Additionally, the depressed and manic groups had reduced T1ρ relaxation times in and around the basal ganglia compared to the control and euthymic groups.
Conclusions:
The study implicated the cerebellum and basal ganglia in the pathophysiology of bipolar disorder and its mood states, the roles of which are relatively unexplored. These findings motivate further investigation of the underlying cause of the abnormalities, and the potential role of altered metabolic activity in these regions.
The present double-blind crossover study examines the effects of cerebellar transcranial direct current stimulation (tDCS) in controls and in an analogue population to psychosis: individuals reporting elevated symptoms of nonclinical psychosis (NCP). A total of 18 controls and 24 NCP individuals were randomized into conditions consisting of 25 minutes of anodal (active) or sham cerebellar tDCS. Following this, both groups completed a pursuit rotor task designed to measure procedural learning performance. Participants then returned 1-week later and received the corresponding condition (either active or sham) and repeated the pursuit rotor task. Results indicate that in the sham condition, control participants showed significantly greater rates of motor learning when compared with the NCP group. In the active condition, the NCP group exhibited significant improvements in the rate of motor learning and performed at a level that was comparable to controls; these data support the link between cerebellar dysfunction and motor learning. Taken together, tDCS may be a promising treatment mechanism for patient populations and a useful experimental approach in elucidating our understanding of psychosis.
Although cerebellar involvement across a wide range of cognitive and neuropsychiatric phenotypes is increasingly being recognized, previous large-scale studies in schizophrenia (SZ) have primarily focused on supratentorial structures. Hence, the across-sample reproducibility, regional distribution, associations with cerebrocortical morphology and effect sizes of cerebellar relative to cerebral morphological differences in SZ are unknown. We addressed these questions in 983 patients with SZ spectrum disorders and 1349 healthy controls (HCs) from 14 international samples, using state-of-the-art image analysis pipelines optimized for both the cerebellum and the cerebrum. Results showed that total cerebellar grey matter volume was robustly reduced in SZ relative to HCs (Cohens's d=-0.35), with the strongest effects in cerebellar regions showing functional connectivity with frontoparietal cortices (d=-0.40). Effect sizes for cerebellar volumes were similar to the most consistently reported cerebral structural changes in SZ (e.g., hippocampus volume and frontotemporal cortical thickness), and were highly consistent across samples. Within groups, we further observed positive correlations between cerebellar volume and cerebral cortical thickness in frontotemporal regions (i.e., overlapping with areas that also showed reductions in SZ). This cerebellocerebral structural covariance was strongest in SZ, suggesting common underlying disease processes jointly affecting the cerebellum and the cerebrum. Finally, cerebellar volume reduction in SZ was highly consistent across the included age span (16-66 years) and present already in the youngest patients, a finding that is more consistent with neurodevelopmental than neurodegenerative etiology. Taken together, these novel findings establish the cerebellum as a key node in the distributed brain networks underlying SZ.Molecular Psychiatry advance online publication, 16 May 2017; doi:10.1038/mp.2017.106.
Background:
There is a growing body of pre-clinical evidence suggesting that Li may protect neurons from a range of neurotoxic insults, hence the term neuroprotective effects. Does Li have similar effects also in human subjects?
Methods:
We reviewed the neuroimaging literature investigating the association between Li treatment and brain structure.
Results:
There is level I evidence for positive association between Li treatment and brain gray matter volume, which is one of the most replicated neuroimaging findings. It has been reported in 18 cross sectional studies, all 7 prospective studies, including a randomized controlled trial as well as in 2 meta-analyses and one mega-analysis. The association between Li treatment and gray matter volume occurs regardless of mood state, diagnostic subtype, presence or absence of concomitant medications. It was documented in multiple brain regions, including hippocampus, amygdala, anterior cingulate, subgenual cingulate, inferior frontal gyrus, postcentral gyrus, habenula.
Conclusions:
Although some methodological and clinical issues complicate the interpretation of findings, there is robust and highly replicated level 1 evidence for positive association between Li treatment and gray matter volumes. These "neuroprotective" effects of Li have been shown even in healthy subjects and appear independent of prophylactic treatment response. Consequently, Li might help maintain brain health even in patients without bipolar disorders and could possibly demonstrate disease modifying properties in neurodegenerative disorders.
Previous studies have reported MRI abnormalities of the corpus callosum (CC) in patients with bipolar disorder (BD), although only a few studies have directly compared callosal areas in psychotic versus nonpsychotic patients with this disorder. We sought to compare regional callosal areas in a large international multicentre sample of patients with BD and healthy controls.
We analyzed anatomic T1 MRI data of patients with BD-I and healthy controls recruited from 4 sites (France, Germany, Ireland and the United States). We obtained the mid-sagittal areas of 7 CC subregions using an automatic CC delineation. Differences in regional callosal areas between patients and controls were compared using linear mixed models (adjusting for age, sex, handedness, brain volume, history of alcohol abuse/dependence, lithium or antipsychotic medication status, symptomatic status and site) and multiple comparisons correction. We also compared regional areas of the CC between patients with BD with and without a history of psychotic features.
We included 172 patients and 146 controls in our study. Patients with BD had smaller adjusted mid-sagittal CC areas than controls along the posterior body, the isthmus and the splenium of the CC. Patients with a positive history of psychotic features had greater adjusted area of the rostral CC region than those without a history of psychotic features.
We found small to medium effect sizes, and there was no calibration technique among the sites.
Our results suggest that BD with psychosis is associated with a different pattern of interhemispheric connectivity than BD without psychosis and could be considered a relevant neuroimaging subtype of BD.
There is growing evidence that cerebellum plays a crucial role in cognition and emotional regulation. Cerebellum is likely to be involved in the physiopathology of both bipolar disorder and schizophrenia. The objective of our study was to compare cerebellar size between patients with bipolar disorder, patients with schizophrenia, and healthy controls in a multicenter sample. In addition, we studied the influence of psychotic features on cerebellar size in patients with bipolar disorder.
One hundred and fifteen patients with bipolar I disorder, 32 patients with schizophrenia, and 52 healthy controls underwent 3 Tesla MRI. Automated segmentation of cerebellum was performed using FreeSurfer software. Volumes of cerebellar cortex and white matter were extracted. Analyses of covariance were conducted, and age, sex, and intracranial volume were considered as covariates.
Bilateral cerebellar cortical volumes were smaller in patients with schizophrenia compared with patients with bipolar I disorder and healthy controls. We found no significant difference of cerebellar volume between bipolar patients with and without psychotic features. No change was evidenced in white matter.
Our results suggest that reduction in cerebellar cortical volume is specific to schizophrenia. Cerebellar dysfunction in bipolar disorder, if present, appears to be more subtle than a reduction in cerebellar volume.
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Humans’ unique cognitive abilities are usually attributed to a greatly expanded neocortex, which has been described as “the crowning achievement of evolution and the biological substrate of human mental prowess” [1
• Rakic P.
Evolution of the neocortex: a perspective from developmental biology.Nat. Rev. Neurosci. 2009; 10: 724-735
• Crossref
• PubMed
• Scopus (726)
• Google Scholar
]. The human cerebellum, however, contains four times more neurons than the neocortex [2
• Azevedo F.A.
• Carvalho L.R.
• Grinberg L.T.
• Farfel J.M.
• Ferretti R.E.
• Leite R.E.
• Jacob Filho W.
• Lent R.
• Herculano-Houzel S.
Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain.J. Comp. Neurol. 2009; 513: 532-541
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• PubMed
• Scopus (872)
• Google Scholar
] and is attracting increasing attention for its wide range of cognitive functions. Using a method for detecting evolutionary rate changes along the branches of phylogenetic trees, we show that the cerebellum underwent rapid size increase throughout the evolution of apes, including humans, expanding significantly faster than predicted by the change in neocortex size. As a result, humans and other apes deviated significantly from the general evolutionary trend for neocortex and cerebellum to change in tandem, having significantly larger cerebella relative to neocortex size than other anthropoid primates. These results suggest that cerebellar specialization was a far more important component of human brain evolution than hitherto recognized and that technical intelligence was likely to have been at least as important as social intelligence in human cognitive evolution. Given the role of the cerebellum in sensory-motor control and in learning complex action sequences, cerebellar specialization is likely to have underpinned the evolution of humans’ advanced technological capacities, which in turn may have been a preadaptation for language.
The cerebellum has classically been linked to motor learning and coordination. However, there is renewed interest in the role of the cerebellum in non-motor functions such as cognition and in the context of different neuropsychiatric disorders. The contribution of neuroimaging studies to advancing understanding of cerebellar structure and function has been limited, partly due to the cerebellum being understudied as a result of contrast and resolution limitations of standard structural magnetic resonance images (MRI). These limitations inhibit proper visualization of the highly compact and detailed cerebellar foliations. In addition, there is a lack of robust algorithms that automatically and reliably identify the cerebellum and its subregions, further complicating the design of large-scale studies of the cerebellum. As such, automated segmentation of the cerebellar lobules would allow detailed population studies of the cerebellum and its subregions. In this manuscript, we describe a novel set of high-resolution in vivo atlases of the cerebellum developed by pairing MR imaging with a carefully validated manual segmentation protocol. Using these cerebellar atlases as inputs, we validate a novel automated segmentation algorithm that takes advantage of the neuroanatomical variability that exists in a given population under study in order to automatically identify the cerebellum, and its lobules. Our automatic segmentation results demonstrate good accuracy in the identification of all lobules (mean Kappa [κ]=0.731; range 0.40-0.89), and the entire cerebellum (mean κ=0.925; range 0.90-0.94) when compared to "gold-standard" manual segmentations. These results compare favorably in comparison to other publically available methods for automatic segmentation of the cerebellum. The completed cerebellar atlases are available freely online (http://imaging-genetics.camh.ca/cerebellum) and can be customized to the unique neuroanatomy of different subjects using the proposed segmentation pipeline (https://github.com/pipitone/MAGeTbrain).
Twenty-five years ago the first human functional neuroimaging studies of cognition discovered a surprising response in the cerebellum that could not be attributed to motor demands. This controversial observation challenged the well-entrenched view that the cerebellum solely contributes to the planning and execution of movement. Recurring neuroimaging findings combined with key insights from anatomy and case studies of neurological patients motivated a reconsideration of the traditional model of cerebellar organization and function. The majority of the human cerebellum maps to cerebral association networks in an orderly manner that includes a mirroring of the prominent cerebral asymmetries for language and attention. These findings inspire exploration of the cerebellum's contributions to a diverse array of functional domains and neuropsychiatric disorders.
Several factors combine to make it feasible to build computer simulations of the cerebellum and to test them in biologically realistic ways. These simulations can be used to help understand the computational contributions of various cerebellar components, including the relevance of the enormous number of neurons in the granule cell layer. In previous work we have used a simulation containing 12000 granule cells to develop new predictions and to account for various aspects of eyelid conditioning, a form of motor learning mediated by the cerebellum. Here we demonstrate the feasibility of scaling up this simulation to over one million granule cells using parallel graphics processing unit (GPU) technology. We observe that this increase in number of granule cells requires only twice the execution time of the smaller simulation on the GPU. We demonstrate that this simulation, like its smaller predecessor, can emulate certain basic features of conditioned eyelid responses, with a slight improvement in performance in one measure. We also use this simulation to examine the generality of the computation properties that we have derived from studying eyelid conditioning. We demonstrate that this scaled up simulation can learn a high level of performance in a classic machine learning task, the cart-pole balancing task. These results suggest that this parallel GPU technology can be used to build very large-scale simulations whose connectivity ratios match those of the real cerebellum and that these simulations can be used guide future studies on cerebellar mediated tasks and on machine learning problems.
The cerebral cortex communicates with the cerebellum via polysynaptic circuits. Separate regions of the cerebellum are connected to distinct cerebral areas, forming a complex topography. In this study we explored the organization of cerebrocerebellar circuits in the human using resting-state functional connectivity MRI (fcMRI). Data from 1,000 subjects were registered using nonlinear deformation of the cerebellum in combination with surface-based alignment of the cerebral cortex. The foot, hand, and tongue representations were localized in subjects performing movements. fcMRI maps derived from seed regions placed in different parts of the motor body representation yielded the expected inverted map of somatomotor topography in the anterior lobe and the upright map in the posterior lobe. Next, we mapped the complete topography of the cerebellum by estimating the principal cerebral target for each point in the cerebellum in a discovery sample of 500 subjects and replicated the topography in 500 independent subjects. The majority of the human cerebellum maps to association areas. Quantitative analysis of 17 distinct cerebral networks revealed that the extent of the cerebellum dedicated to each network is proportional to the network's extent in the cerebrum with a few exceptions, including primary visual cortex, which is not represented in the cerebellum. Like somatomotor representations, cerebellar regions linked to association cortex have separate anterior and posterior representations that are oriented as mirror images of one another. The orderly topography of the representations suggests that the cerebellum possesses at least two large, homotopic maps of the full cerebrum and possibly a smaller third map.
Many studies report volume abnormalities in diverse brain structures in patients with various mental health conditions.
To evaluate whether there is evidence for an excess number of statistically significant results in studies of brain volume abnormalities that suggest the presence of bias in the literature.
PubMed (articles published from January 2006 to December 2009).
Recent meta-analyses of brain volume abnormalities in participants with various mental health conditions vs control participants with 6 or more data sets included, excluding voxel-based morphometry.
Standardized effect sizes were extracted in each data set, and it was noted whether the results were "positive" (P < .05) or not. For each data set in each meta-analysis, I estimated the power to detect at α = .05 an effect equal to the summary effect of the respective meta-analysis. The sum of the power estimates gives the number of expected positive data sets. The expected number of positive data sets can then be compared against the observed number.
From 8 articles, 41 meta-analyses with 461 data sets were evaluated (median, 10 data sets per meta-analysis) pertaining to 7 conditions. Twenty-one of the 41 meta-analyses had found statistically significant associations, and 142 of 461 (31%) data sets had positive results. Even if the summary effect sizes of the meta-analyses were unbiased, the expected number of positive results would have been only 78.5 compared with the observed number of 142 (P < .001).
There are too many studies with statistically significant results in the literature on brain volume abnormalities. This pattern suggests strong biases in the literature, with selective outcome reporting and selective analyses reporting being possible explanations.
Although it has been known for half a century that unique structures evolved in the cerebellum of anthropoid apes and became greatly enlarged in the human brain, the function of these structures still remains unknown. In an attempt to explain their function, a new concept of cerebellar capabilities is proposed, which is based both on neural evidence and on information-processing theory. The phylogenetically newest structures of the cerebellum may contribute to mental skills in much the same way that the phylogenetically older structures contribute to motor skills. In both cases, the cerebellum can send signals from the dentate nucleus to the cerebral frontal cortex via the thalamus. Signals from the older part of the dentate nucleus certainly help the frontal motor cortex to effect the skilled manipulation of muscles, and signals from the newest part of the dentate nucleus may help the frontal association cortex to effect the skilled manipulation of information or ideas. How such mental skills could have evolved in higher primates in the course of phylogenetic and ontogenetic development is shown. The validity of this new concept of cerebellar function can be tested on humans by means of tomographic brain scans.
Mammillary body and cerebellar atrophy have been described as postmorten neuropathologic markers of Korsakoff's syndrome. This study examined whether shrinkage in the mammillary bodies and cerebellum is present consistently in amnesic chronic alcoholics during life and whether the degree of abnormality in these patients differs from that in nonamnesic alcoholic and healthy controls. The severity of shrinkage in the mammillary bodies, cerebellar hemispheres, and cerebellar vermis visualizable on MRI scans was rated on a three-point scale in 33 chronic nonamnesic alcoholics, 9 amnesic alcoholics, and 20 healthy controls. Although both alcoholic groups showed significant mammillary body and cerebellar shrinkage relative to controls, the two patient groups did not differ from each other. Furthermore, four of eight amnesic patients in our sample did not demonstrate clinically significant mammillary body atrophy. These results suggest that alcoholism is associated with mammillary body and cerebellar tissue volume loss but do not provide evidence that these markers distinguish accurately between amnesic and nonamnesic patients. In addition, they suggest that visualizable mammillary body atrophy is not necessary for the development of amnesia in alcoholic patients.
Lithium can have toxic effects on the central nervous system that are both acute and chronic. Uncommonly, a long-lasting cerebellar syndrome follows acute toxicity. The mechanism of cerebellar injury is not well understood. We present 3 cases of this syndrome, with video demonstrating the typical features of this syndrome.
Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome
- J D Schmahmann
Schmahmann JD. Disorders of the cerebellum: ataxia, dysmetria of thought, and the
cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci.
2004;16(3):367-378. doi:10.1176/jnp.16.3.367