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Schematic Representation of (A) deep cerebellar nuclei on axial T1w, (B) cerebellar peduncles on sagittal, (C) relevant structures on coronal T1w and (D) cerebellocerebral loop pathways are shown. Abbreviations: CH: Cerebellar Hemisphere, CPC: Cortico-Ponto-Cerebellar Pathways, DN: Dentate Nucleus, DRTC: Dentate-Rubro-Thalamo-Cortical Pathways, ICP: Inferior Cerebellar Peduncle, LV: Lateral Ventricles, MCP: Middle Cerebellar Peduncle, RN: Red Nucleus, SCP: Superior Cerebellar Peducles Tha: Thalamus.
Source publication
Cerebellar white matter (WM) connections to the central nervous system are classified functionally into the Spinocerebellar (SC), vestibulocerebellar (VC), and cerebrocerebellar subdivisions. The SC pathways project from spinal cord to cerebellum, whereas the VC pathways project from vestibular organs of the inner ear. Cerebrocerebellar connections...
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Context 1
... best known functional role of the cerebellum is the integration of sensory and motor functions of the brain during coordination of fine movements along with its roles in cognitive, emotional and language functions. The cerebellar connections are functionally divided into the vestibulocerebellar (VC), SC and cerebrocerebellar connections (see Figure 1; Mendoza and Foundas, 2007).The SC pathways project from spinal cord to cerebellum and play a role in relaying non- conscious proprioceptive/kinesthetic information from the muscle spindles and tendons, and non-conscious cutaneous feedback (e.g., pressure, touch and pain). The VC connections are the fibers originating from the vestibular organs of the inner ear and project to the brainstem and eventually to cerebellum which maintains balance and equilibrium of the body (Snell, 2009). ...
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... main GM constituents of DRTC are the red and dentate nuclei have a clear contrast enhancement in the DWI non-diffusion b0 image because of iron content in adults (Hallgren and Sourander, 1958). Thus to reconstruct DRTC (see Figures 1B-D, 4B, 5B, 6B), the DWI non-diffusion b0 image was used for delineating the structures of dentate and red nuclei. The first ROI is seeded in dentate nucleus (see Figures 2F, 3D) which can be identified at the level of pontomedullary junction and second ROI in ipsilateral red nucleus (see Figures 2G, 3D) axially at the level of the cerebral peduncle in the pons. ...
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... all CPC pathways (see Figure 1D), the first ROI was placed in MCP which can be identified at the coronal section of the dorsal surface of brainstem in Red-Green-Blue color map (see Figures 2A, 3E). For FPC (see Figures 1D, 4C, 5C, 6C) the second ROI was placed in the contralateral frontal lobe which can be defined as anterior to the central sulcus at the axial level right above cingulate gyrus at the color-coded map (see Figure 3F). ...
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... all CPC pathways (see Figure 1D), the first ROI was placed in MCP which can be identified at the coronal section of the dorsal surface of brainstem in Red-Green-Blue color map (see Figures 2A, 3E). For FPC (see Figures 1D, 4C, 5C, 6C) the second ROI was placed in the contralateral frontal lobe which can be defined as anterior to the central sulcus at the axial level right above cingulate gyrus at the color-coded map (see Figure 3F). ...
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... Note that the total cerebellar white matter volume is slightly greater than total cerebellar tract volume (see Table 2). Cerebellar gray matter is identical to cerebellar cortex; cerebral white matter is the lobar white matter beneath the cerebral cortical sheet (see Figure 1). * The ratio of total cerebellar GM-to-WM is ∼3.29 ± 0.24, whereas the ratio of cerebral GM-to WM is approximately 1.10 ± 0.11. ...
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... order to highlight the potential functional roles of the cerebrocerebellar fiber tracts, we provided a summary in Table 1 that also included the corticospinal and sensory fiber tracts as a reference, despite that these tracts evolved developmentally to their final form at different fetal stages (Scott et al., 2012;Takahashi et al., 2014). Our finding that both FPC and DRTC project to similar cerebral domains provides some evidence for the presence of cerebrocerebellar loop as described by other researchers (Catani and Thiebaut de Schotten, 2012;Koziol et al., 2014; see Figure 1). Contrary to Buckner et al. (2011) report based on functional MRI, we did not observe direct connection between the FPC or DRTC pathways with Brodmann areas 9 and 46. ...
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Background:
Diffusion Tensor Imaging (DTI) studies of traumatic brain injury (TBI) have focused on alterations in microstructural features of deep white matter fibers (DWM), though post-mortem studies have demonstrated that injured axons are often observed at the gray-white matter interface where superficial white matter fibers (SWM) mediate local...
Citations
... A major shift has begun towards re-conceptualizing the cerebellum as a regulator of both motor and non-motor systems [36-38, 110, 116-124]. The cerebellum and numerous non-motor brain regions are densely connected [110,112,116,125,126], the cerebellum is specifically activated during cognitive tasks [114,127,128], and cerebellar damage produces impairments in linguistic, visuospatial and executive functions [129][130][131][132]. A "universal cerebellar transform" theory posits that the cerebellum modulates thought and motor control using the same algorithmic scheme [117]. ...
High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.
... Structural [4,5] and functional imaging [6,7] in humans, as well as tract-tracing studies in preclinical models [8], have contributed to this evidence. ...
The cerebellum, through its connectivity with the cerebral cortex, plays an integral role in regulating cognitive and affective processes, and its dysregulation can result in neurodevelopmental disorder (NDD)-related behavioural deficits. Identifying cerebellar-cerebral functional connectivity (FC) profiles in children with NDDs can provide insight into common connectivity profiles and their correlation to NDD-related behaviours. 479 participants from the Province of Ontario Neurodevelopmental Disorders (POND) network (typically developing = 93, Autism Spectrum Disorder = 172, Attention Deficit/Hyperactivity Disorder = 161, Obsessive-Compulsive Disorder = 53, mean age = 12.2) underwent resting-state functional magnetic resonance imaging and behaviour testing (Social Communication Questionnaire, Toronto Obsessive-Compulsive Scale, and Child Behaviour Checklist – Attentional Problems Subscale). FC components maximally correlated to behaviour were identified using canonical correlation analysis. Results were then validated by repeating the investigation in 556 participants from an independent NDD cohort provided from a separate consortium (Healthy Brain Network (HBN)). Replication of canonical components was quantified by correlating the feature vectors between the two cohorts. The two cerebellar-cerebral FC components that replicated to the greatest extent were correlated to, respectively, obsessive-compulsive behaviour (behaviour feature vectors, rPOND-HBN = −0.97; FC feature vectors, rPOND-HBN = −0.68) and social communication deficit contrasted against attention deficit behaviour (behaviour feature vectors, rPOND-HBN = −0.99; FC feature vectors, rPOND-HBN = −0.78). The statistically stable (|z| > 1.96) features of the FC feature vectors, measured via bootstrap re-sampling, predominantly comprised of correlations between cerebellar attentional and control network regions and cerebral attentional, default mode, and control network regions. In both cohorts, spectral clustering on FC loading values resulted in subject clusters mixed across diagnostic categories, but no cluster was significantly enriched for any given diagnosis as measured via chi-squared test (p > 0.05). Overall, two behaviour-correlated components of cerebellar-cerebral functional connectivity were observed in two independent cohorts. This suggests the existence of generalizable cerebellar network differences that span across NDD diagnostic boundaries.
... KOZIOL showed that the cerebellar connection is composed of feedforward and feedback connections between the brain and cerebellum [2]. Zaf, et al. used diffusion tensor tractography to demonstrate the existence of the cerebral-cerebellar circuit, indicating that the cortical-pontine-cerebellar pathway plays a role in regulating voluntary movement and exercise plan execution, as well as advanced cognitive, visual, and auditory functions [3]. Christophe Habas believes that "resting-state" static and dynamic functional connectivity networks are fundamental to the neocerebellum's cognitive functions in motor and nonmotor tasks [4]. ...
The error-related potential (ErrP) is a weak explicit representation of the human brain for individual wrong behaviors. Previously, ErrP-related research usually focused on the design of automatic correction and the error correction mechanisms of high-risk pipeline-type judgment systems. Mounting evidence suggests that the cerebellum plays an important role in various cognitive processes. Thus, this study introduced cerebellar information to enhance the online classification effect of error-related potentials. We introduced cerebellar regional characteristics and improved discriminative canonical pattern matching (DCPM) in terms of data training and model building. In addition, this study focused on the application value and significance of cerebellar error-related potential characterization in the selection of excellent ErrP-BCI subjects (brain–computer interface). Here, we studied a specific ErrP, the so-called feedback ErrP. Thirty participants participated in this study. The comparative experiments showed that the improved DCPM classification algorithm proposed in this paper improved the balance accuracy by approximately 5–10% compared with the original algorithm. In addition, a correlation analysis was conducted between the error-related potential indicators of each brain region and the classification effect of feedback ErrP-BCI data, and the Fisher coefficient of the cerebellar region was determined as the quantitative screening index of the subjects. The screened subjects were superior to other subjects in the performance of the classification algorithm, and the performance of the classification algorithm was improved by up to 10%.
... Ipsilateral pathways are evident also in studies of the human cerebellum. In the feedforward system, DTI studies suggest that there are ipsilateral CPC tracts, traveling from the temporal lobe, occipital lobe (Karavasilis et al., 2019;Keser et al., 2015;Palesi et al., 2017;Sokolov et al., 2014) and parietal lobe (Karavasilis et al., 2019;Keser et al., 2015) to the cerebellum. Microsurgical human post-mortem brain microdissections of the feedback projection reveal an nd-DRTT pathway ( (Meola et al., 2016;Tacyildiz et al., 2021), and DTI fiber tract reconstructions in the living brain identified an nd-DRTT pathway accounting for one-fifth of the overall DRTT (Karavasilis et al., 2019;Keser et al., 2015;Meola et al., 2016;Petersen et al., 2018). ...
... Ipsilateral pathways are evident also in studies of the human cerebellum. In the feedforward system, DTI studies suggest that there are ipsilateral CPC tracts, traveling from the temporal lobe, occipital lobe (Karavasilis et al., 2019;Keser et al., 2015;Palesi et al., 2017;Sokolov et al., 2014) and parietal lobe (Karavasilis et al., 2019;Keser et al., 2015) to the cerebellum. Microsurgical human post-mortem brain microdissections of the feedback projection reveal an nd-DRTT pathway ( (Meola et al., 2016;Tacyildiz et al., 2021), and DTI fiber tract reconstructions in the living brain identified an nd-DRTT pathway accounting for one-fifth of the overall DRTT (Karavasilis et al., 2019;Keser et al., 2015;Meola et al., 2016;Petersen et al., 2018). ...
... In the feedforward system, DTI studies suggest that there are ipsilateral CPC tracts, traveling from the temporal lobe, occipital lobe (Karavasilis et al., 2019;Keser et al., 2015;Palesi et al., 2017;Sokolov et al., 2014) and parietal lobe (Karavasilis et al., 2019;Keser et al., 2015) to the cerebellum. Microsurgical human post-mortem brain microdissections of the feedback projection reveal an nd-DRTT pathway ( (Meola et al., 2016;Tacyildiz et al., 2021), and DTI fiber tract reconstructions in the living brain identified an nd-DRTT pathway accounting for one-fifth of the overall DRTT (Karavasilis et al., 2019;Keser et al., 2015;Meola et al., 2016;Petersen et al., 2018). Our own data would be in line with these ipsilateral cerebellum-cortex correspondences (Fig. 3). ...
The human cerebellum is increasingly recognized to be involved in non-motor and higher-order cognitive functions. Yet, its ties with the entire cerebral cortex have not been holistically studied in a whole-brain exploration with a unified analytical framework. Here, we characterized disso-ciable cortical-cerebellar structural covariation patterns across the brain in n=38,527 UK Bio-bank participants. Our results invigorate previous observations in that important shares of corti-cal-cerebellar structural covariation are described as i) a dissociation between the higher-level cognitive system and lower-level sensorimotor system, as well as ii) an anticorrelation between the visual-attention system and advanced associative networks within the cerebellum. We also discovered a novel pattern of ipsilateral, rather than contralateral, cerebral-cerebellar associations. Furthermore, phenome-wide association assays revealed key phenotypes, including cognitive phenotypes, lifestyle, physical properties, and blood assays, associated with each decomposed covariation pattern, helping to understand their real-world implications. This systems neurosci-ence view paves the way for future studies to explore the implications of these structural covaria-tions, potentially illuminating new pathways in our understanding of neurological and cognitive disorders.
... The cerebellum and cerebrum are connected by networks with feed-forward and feed-backward connections, and these networks play an essential role in the execution of voluntary movements, motor planning, and neurocognitive functions such as abstract thinking and working memory [9,22,34]. The dentato-rubro-thalamo-cortical (DRTC) pathway [3,9,11,15,21] and the cortico-ponto-cerebellar pathway [5] are the major efferent pathway from the cerebellum to the cerebrum and the afferent pathway from the cerebrum to the cerebellum, respectively. The DRTC pathway originates from the DN and the emboliform, globose, and fastigial nuclei; courses through the superior cerebellar peduncle (SCP), contralateral red nucleus (RN), and ventrolateral or ventroanterior nucleus of the thalamus; and projects to the frontal lobe [9,11,24]. ...
... Based on these findings, distant recurrence in the DN is a specific failure pattern in cases with diffuse gliomas in the frontal lobe and thalamus. The mechanism by which recurrence in the DN predominantly occurs in patients with frontal lobe lesions can be explained by the fact that the frontal lobe is the main projection site in the DRTC pathway [15]. In a previous study, an analysis using DTI in 39 healthy subjects revealed that the DRTC pathway projects widely to the frontal lobe, with 30-80% of fibers projecting to Brodmann's area 6 [11]. ...
... DN dentate nucleus, SCP superior cerebellar peduncle, RN red nucleus, IC internal capsule, CV cerebellar vermis, CH cerebellar hemisphere, DP dorsal pons, DRTC dentato-rubro-thalamo-cortical pathway connections were also demonstrated in tractography [11]. Tractography in humans and analysis of retrograde tracer transport in monkeys also revealed that fibers from DN also connect to the ipsilateral thalamus and frontal lobe [3,15,18,21,23]. Based on previous reports [4,7,12,14] and our results, DN lesions developed on the contralateral side in nine, the ipsilateral side in two, and both sides in eight. ...
Background
Distant recurrence can occur by infiltration along white matter tracts or dissemination through the cerebrospinal fluid (CSF). This study aimed to clarify the clinical features and mechanisms of recurrence in the dentate nucleus (DN) in patients with supratentorial gliomas. Based on the review of our patients, we verified the hypothesis that distant DN recurrence from a supratentorial lesion occurs through the dentato-rubro-thalamo-cortical (DRTC) pathway.
Methods
A total of 380 patients with supratentorial astrocytoma, isocitrate dehydrogenase (IDH)-mutant (astrocytoma), oligodendroglioma, IDH mutant and 1p/19q-codeleted (oligodendroglioma), glioblastoma, IDH-wild type (GB), and thalamic diffuse midline glioma, H3 K27-altered (DMG), who underwent tumor resection at our department from 2009 to 2022 were included in this study. Recurrence patterns were reviewed. Additionally, clinical features and magnetic resonance imaging findings before treatment, at the appearance of an abnormal signal, and at further progression due to delayed diagnosis or after salvage treatment of cases with recurrence in the DN were reviewed.
Results
Of the 380 patients, 8 (2.1%) had first recurrence in the DN, 3 were asymptomatic when abnormal signals appeared, and 5 were diagnosed within one month after the onset of symptoms. Recurrence in the DN developed in 8 (7.4%) of 108 cases of astrocytoma, GB, or DMG at the frontal lobe or thalamus, whereas no other histological types or sites showed recurrence in the DN. At the time of the appearance of abnormal signals, a diffuse lesion developed at the hilus of the DN. The patterns of further progression showed that the lesions extended to the superior cerebellar peduncle, tectum, tegmentum, red nucleus, thalamus, and internal capsule along the DRTC pathway.
Conclusion
Distant recurrence along the DRTC pathway is not rare in astrocytomas, GB, or DMG at the frontal lobe or thalamus. Recurrence in the DN developed as a result of the infiltration of tumor cells through the DRTC pathway, not dissemination through the CSF.
... Several preclinical studies showed that DBS of the cerebellar dentate nuclei can promote motor recovery by increasing synaptogenesis and reorganizing perilesional motor areas [69]. There are prominent feed-forward and feedback connections between the motor cortex and cerebellar nuclei [70]. Therefore, DBS of the cerebellum to enhance motor recovery represents an anatomically guided translation from animal studies into clinical trials. ...
Purpose of Review
Stroke remains a leading disabling condition, and many survivors have permanent disability despite acute stroke treatment and subsequent standard-of-care rehabilitation therapies. Adjunctive neuromodulation is an emerging frontier in the field of stroke recovery. In this narrative review, we aim to highlight and summarize various neuromodulation techniques currently being investigated to enhance recovery and reduce impairment in patients with stroke.
Recent Findings
For motor recovery, repetitive transcranial magnetic simulation (rTMS) and direct current stimulation (tDCS) have shown promising results in many smaller-scale trials. Still, their efficacy has yet to be proven in large-scale pivotal trials. A promising large-scale study investigating higher dose tDCS combined with constraint movement therapy to enhance motor recovery is currently underway. MRI-guided tDCS studies in subacute and chronic post-stroke aphasia showed promising benefits for picture-naming recovery. rTMS, particularly inhibitory stimulation over the contralesional homolog, could represent a pathway forward in post-stroke motor recovery in the setting of a well-designed and adequately powered clinical trial. Recently evidenced-based guideline actually supported Level A (definite efficacy) for the use of low-frequency rTMS of the primary motor cortex for hand motor recovery in the post-acute stage of stroke based on the meta-analysis result. Adjunctive vagal nerve stimulation has recently received FDA approval to enhance upper limb motor recovery in chronic ischemic stroke with moderate impairment, and progress has been made to implement it in real-world practice. Despite a few small and large-scale studies in epidural stimulation (EDS), further research on the utilization of EDS in post-stroke recovery is needed. Deep brain stimulation or stent-based neuromodulation has yet to be further tested regarding safety and efficacy.
Summary
Adjunctive neuromodulation to rehabilitation therapy is a promising avenue for promoting post-stroke recovery and decreasing the overall burden of disability. The pipeline for neuromodulation technology remains strong as they span from the preclinical stage to the post-market stage. We are optimistic to see that more neuromodulation tools will be available to stroke survivors in the not-to-distant future.
... neuroimaging technique used to map white matter pathways in vivo, diffusion tensor imaging (DTI) has been widely used in the dissections of white matter fiber bundles via the measurement of anisotropic diffusion (23,24). Unlike the arcuate tract and superior longitudinal tract, which have been frequently noted to play an important role in brain language function, the quantitative analysis of the language-related cerebro-cerebellar pathway (LRCCP) has only sparsely been reported on (25)(26)(27)(28). One possible reason is the LRCCP template or atlas is unavailable for group analysis, as brainstem-related tractography is more challenging than is cerebrum-related tractography. ...
Background:
The cerebellum and cerebral cortex form the most important cortico-cerebellar system in the brain. However, diffusion magnetic resonance imaging (MRI)-based tractography of the connecting white matter between the cerebellum and cerebral cortex, which support language function, has not been extensively reported on. This work aims to serve as a guideline for facilitating the analysis of white matter tracts along the language-related cerebro-cerebellar pathway (LRCCP), which includes the corticopontine, pontocerebellar, corticorubral, rubroolivary, olivocerebellar, and dentatorubrothalamic tracts.
Methods:
The LRCCP templates were developed via processing the high-resolution, population-averaged atlas available in the Human Connectome Project (HCP)-1065 dataset (2017 Q4, 1,200-subject release) in DSI Studio. The deterministic tracking was performed with the manually selected regions of interest (ROIs) on this atlas according to prior anatomic knowledge. Templates were then applied to the MRI datasets of 30 health participants acquired from a single hospital to verify the practicability of the tracking. The diffusion tensor and shape analysis metrics were calculated for all LRCCP tracts. Differences in the tracking metrics between the left and right hemispheres were compared, and the related white matter asymmetry was discussed.
Results:
The LRCCP templates were successfully created and applied to healthy participants for quantitative analysis. Significantly higher mean fractional anisotropy (FA) values were discovered on the left (L) corticorubral tract [L, 0.43±0.02 vs. right (R), 0.41±0.02; P<0.01] and left dentatorubrothalamic tract (L, 0.47±0.02 vs. R, 0.46±0.02; P<0.01). Significant differences in tract volume and streamline number were observed between the corticopontine, corticorubral, and dentatorubrothalamic tracts. The size of the right corticopontine and corticorubral tracts were smaller, and both had smaller streamline numbers and innervation areas when compared with the contralateral sides. The R dentatorubrothalamic tract showed a larger volume (R, 23,582.47±4,160.71 mm3 vs. L, 19,821.27±2,983.91 mm3; P<0.01) and innervation area (R, 2,117.37±433.98 mm2 vs. L, 1,610.00±356.19 mm2; P<0.01) than did the L side. No significant differences were observed in the rubroolivary tracts.
Conclusions:
This work suggests the feasibility of applying tractography templates of the LRCCP to quantitatively evaluate white matter properties associated with language function. Lateralized diffusion metrics were observed in preliminary experiments. LRCCP tractography-based research may provide a potential quantitative method to better understanding neuroplasticity.
... This pathway is part of the functional "cerebrocerebellum," and acts to coordinate the initiation, planning and timing of movement [11]. Cerebrocerebellar connections are composed of feed forward and feedback connections between cerebrum and cerebellum including the cortico-ponto-cerebellar (CPC) pathway, which starts from the frontal lobe, creates synapses on the pontine nuclei, and finally arrives at the cerebellar cortex via the middle cerebellar peduncle and the dentate-rubro-thalamocortical tract (DRTT) beingof cerebellar origin [7,[12][13][14]. Typically, the DRTT is described as a decussating pathway, ascending to the contralateral thalamus; however, the existence of a nondecussating (i.e. ...
... To date, only a small number of studies have examined the cerebello-thalamo-cortical and cortico-ponto-cerebellar pathways in vivo (Karavasilis et al., 2019;Keser et al., 2015;Jissendi et al., 2008;Sokolov et al., 2014). This is likely due to the technical challenges present in doing tractography along a long, polysynaptic pathway that has crossovers and sharp turns. ...
Neurobiological models of receptive language have focused on the left-hemisphere perisylvian cortex with the assumption that the cerebellum supports peri-linguistic cognitive processes such as verbal working memory. The goal of this study was to identify language-sensitive regions of the cerebellum then map the structural conectivity profile of these regions. Functional imaging data and diffusion-weighted imaging data from the Human Connectome Project (HCP) were analyzed. We found that (a) working memory, motor activity, and language comprehension activated partially overlapping but mostly unique regions of the cerebellum; (b) the linguistic portion of the cerebello-thalamo-cortical circuit was more extensive than the linguistic portion of the cortico-ponto-cerebellar tract; (c) there was a frontal-lobe bias in the connectivity from the cerebellum to the cerebrum; (d) there was some degree of specificity; and (e) for some of the cerebellar tracts, individual differences in picture identification ability correlated with fractional anisotropy metrics. These findings yield insights into the structural connectivity of the cerebellum as relates to uniquely human process of language comprehension.
... The superior cerebellar peduncle (SCP) is the mainly cerebellar efferent pathway that connects the cerebellum to cerebral regions through the thalamus. In addition, the inferior cerebellar peduncles (ICP) contain efferent connections from the cerebellum to the vestibular nuclei (15,16). All input fibers of the cerebellum need to pass through the middle cerebellar peduncles (MCP) (15). ...
... In addition, the inferior cerebellar peduncles (ICP) contain efferent connections from the cerebellum to the vestibular nuclei (15,16). All input fibers of the cerebellum need to pass through the middle cerebellar peduncles (MCP) (15). After the cerebellar structural and functional lesion, patients with neurological disorders were found to exhibit a range of cognitive deficits, including impaired executive function, spatial cognition, language processing, and emotional regulation (17). ...
“Cognitive dysmetria” theory of schizophrenia (SZ) has highlighted that the cerebellum plays a critical role in understanding the pathogenesis and cognitive impairment in SZ. Despite some studies have reported the structural disruption of the cerebellum in SZ using whole brain approach, specific focus on the voxel-wise changes of cerebellar WM microstructure and its associations with cognition impairments in SZ were less investigated. To further explore the voxel-wise structural disruption of the cerebellum in SZ, the present study comprehensively examined volume and diffusion features of cerebellar white matter in SZ at the voxel level (42 SZ vs. 52 controls) and correlated the observed alterations with the cognitive impairments measured by MATRICS Consensus Cognitive Battery. Combing voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) methods, we found, compared to healthy controls (HCs), SZ patients did not show significant alteration in voxel-level cerebellar white matter (WM) volume and tract-wise and skeletonized DTI features. In voxel-wise DTI features of cerebellar peduncles, compared to HCs, SZ patients showed decreased fractional anisotropy and increased radial diffusivity mainly located in left middle cerebellar peduncles (MCP) and inferior cerebellar peduncles (ICP). Interestingly, these alterations were correlated with overall composite and different cognitive domain (including processing speed, working memory, and attention vigilance) in HCs but not in SZ patients. The present findings suggested that the voxel-wise WM integrity analysis might be a more sensitive way to investigate the cerebellar structural abnormalities in SZ patients. Correlation results suggested that inferior and MCP may be a crucial neurobiological substrate of cognition impairments in SZ, thus adding the evidence for taking the cerebellum as a novel therapeutic target for cognitive impairments in SZ patients.
