Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing

Stoodley, Catherine J.; Schmahmann, Jeremy D.

doi:10.1016/j.cortex.2009.11.008

Cited by 1,173 publications

(987 citation statements)

References 224 publications

(264 reference statements)

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“…The cerebellar hemispheres have been implicated in higher cognitive processes (Kelly & Strick, 2003; Stoodley & Schmahmann, 2009; Stoodley & Schmahmann, 2010; Stoodley et al, 2012) and thus, the foliation defects identified in the anterior cerebellum tentatively suggest a connection between these cerebellar defects and intellectual disability and autistic phenotypes associated with CHARGE syndrome. Separately, the relationship between cerebellar anomalies and autism is well established and in contrast to other brain regions, gross and microscopic changes in the cerebellum are most frequently associated with autism (Becker & Stoodley, 2013).…”

Section: Discussionmentioning

confidence: 99%

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

Whittaker

Kasah

Donovan

et al. 2017

American J of Med Genetics Pt C

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Mutations in the gene encoding the ATP dependent chromatin‐remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital‐urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio‐temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay.

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Section: Discussionmentioning

confidence: 99%

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

Whittaker

Kasah

Donovan

et al. 2017

American J of Med Genetics Pt C

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“…MCP mot is predominantly associated with motor‐sensory function, originates in the caudal pons and runs superior‐medially toward the anterior cerebellum. Past studies have found evidence of a rostral pons to posterior cerebellum and caudal pons to anterior cerebellum connection (Schmahmann, Rosene, & Pandya, 2004; Spitzer & Karplus, 1907; Sunderland, 1940; Von Bechterew, 1885), which is further supported by evidence that points to a caudal pons anterior lobe of cerebellum sensorimotor representation (Buckner, Krienen, Castellanos, Diaz, & Yeo, 2011; Schmahmann, MacMore, & Vangel, 2009; Schmahmann & Pandya, 1997; Schmahmann & Sherman, 1998; Stoodley & Schmahmann, 2010). The superior cerebellar peduncle pathway (SCP) consists primarily of efferent output neurons traveling from the cerebellum to higher brain centers via the mid‐brain (Hüttlova et al., 2014; Mittal et al., 2014; Ojemann et al., 2013; Schmahmann et al., 2004; Takahashi, Song, Folkerth, Grant, & Schmahmann, 2013; Von Bechterew, 1885; Wang et al., 2003).…”

Section: Introductionmentioning

confidence: 89%

High‐angular resolution diffusion imaging tractography of cerebellar pathways from newborns to young adults

Levman

Lim

et al. 2016

Brain and Behavior

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IntroductionMany neurologic and psychiatric disorders are thought to be due to, or result in, developmental errors in neuronal cerebellar connectivity. In this connectivity analysis, we studied the developmental time‐course of cerebellar peduncle pathways in pediatric and young adult subjects.MethodsA cohort of 80 subjects, newborns to young adults, was studied on a 3T MR system with 30 diffusion‐weighted measurements with high‐angular resolution diffusion imaging (HARDI) tractography.ResultsQualitative and quantitative results were analyzed for age‐based variation. In subjects of all ages, the superior cerebellar peduncle pathway (SCP) and two distinct subpathways of the middle cerebellar peduncle (MCP), as described in previous ex vivo studies, were identified in vivo with this technique: pathways between the rostral pons and inferior‐lateral cerebellum (MCP cog), associated predominantly with higher cognitive function, and pathways between the caudal pons and superior‐medial cerebellum (MCP mot), associated predominantly with motor function.DiscussionOur findings showed that the inferior cerebellar peduncle pathway (ICP), involved primarily in proprioception and balance appears to have a later onset followed by more rapid development than that exhibited in other tracts. We hope that this study may provide an initial point of reference for future studies of normal and pathologic development of cerebellar connectivity.

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“…Although the cerebellum has been traditionally associated with motor control, recently a growing body of clinical and experimental evidences has suggested that it may be also involved in non-motor functions [6][7][8]. In fact, it has been shown that cerebellar abnormalities, e.g.…”

Section: Introductionmentioning

confidence: 99%

Superior Cerebellar Peduncle Atrophy Predicts Cognitive Impairment in Relapsing Remitting Multiple Sclerosis Patients with Cerebellar Symptoms: A DTI Study

Nicoletti¹,

Valentino²,

Chiriaco³

et al. 2017

J Mult Scler

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IntroductionThe presence of cognitive dysfunctions in Multiple Sclerosis (MS) has been well described as one of the most common co-morbidities [1][2][3], with a prevalence ranging from 45% to 65% [4]. The most affected cognitive domains in MS are memory, visuospatial perception, executive functions, attention and information processing speed [5].Although the cerebellum has been traditionally associated with motor control, recently a growing body of clinical and experimental evidences has suggested that it may be also involved in non-motor functions [6][7][8]. In fact, it has been shown that cerebellar abnormalities, e.g. lesions, are associated with cognitive impairment as measured by neuropsysiological tests [9]. Thus, evidences suggest that the cerebellum has an important role in monitoring sensory information and providing adaptation of both motor and non-motor functions to perform contextually relevant behaviours [10,11].The cognitive role of the cerebellum is mainly due to its strong connections with several higher-level cortical regions, such as with the controlateral cerebral hemispheres in both feed forward and feedback directions. The feed forward loop (Figure 1 in blue) connects cortical areas via middle cerebellar peduncle (MCP) with deep cerebellar nuclei, including the dentate nucleus (DN) (afferent pathway). The feedback loop (Figure 1 in orange) connects the deep cerebellar nuclei with motor cortex, via the superior cerebellar peduncle (SCP), the red nucleus and the thalamus (Th) (efferent pathway) [12,13].Disconnections of the fibers to the thalamus, negatively involve the limbic circuitry avoiding the mediation and regulation of many cognitive functions [14,15]. Although many studies have shown a strong association between thalamic atrophy and cognitive function [16][17][18], no one focused on its microstructural changes, as well as on abnormalities of MCP, SCP and DN, and on their relationships to cognitive functions in MS.Diffusion tensor imaging (DTI) is one of the most sensitive methods for detecting subtle alterations of white matter [19] (WM) by evaluating the directional movement of water molecules in the brain. Analysis of DTI images could indeed distinguish between regions where fibers present a strong alignment from those with a lower coherence. Diffusion properties are summarized by several indices, in particular by fractional anisotropy (FA) that refers to the degree to which diffusion is direction-dependent. FA is used to quantify the changes in WM microstructure, which might be related to development or progression of a specific disease [20].The aim of this study was to investigate a group of patients affected by relapsing-remitting multiple sclerosis with (RR-MSc) and without (RR-MSnc) cerebellar signs, in order to determine the alteration of FA in the Th, MCP, SCP and DN and their correlation to cognitive functions, as assessed by neuropsysiological tests. In particular, we examined two hypotheses:

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Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing

Cited by 1,173 publications

References 224 publications

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

High‐angular resolution diffusion imaging tractography of cerebellar pathways from newborns to young adults

Superior Cerebellar Peduncle Atrophy Predicts Cognitive Impairment in Relapsing Remitting Multiple Sclerosis Patients with Cerebellar Symptoms: A DTI Study

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