Cerebellar neurocognition: Insights into the bottom of the brain

Baillieux, Hanne; Smet, Hyo Jung De; Paquier, Philippe; Deyn, Peter Paul De; Mariën, Peter

doi:10.1016/j.clineuro.2008.05.013

Cited by 293 publications

(209 citation statements)

References 115 publications

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“…These brain regions are involved in the regulation of cognitive and affective processes disturbed in neuropsychiatric diseases. 13,14 Thus far, up to Figure 1 The effect of overexpression of nine miRNAs on endogenous DISC1 mRNA levels. MiR-135b-5p, miR-559, miR-23a-3p, miR-23b-3p, miR-130a-5p, miR-135a-5p, miR-323-3p, miR-409-3p, and miR-548c-3p were overexpressed in HEK293FT cells and relative levels of endogenous DISC1 and the housekeeping gene, GAPDH, measured using qRT-PCR.…”

Section: Discussionmentioning

confidence: 99%

Allele-specific regulation of DISC1 expression by miR-135b-5p

et al. 2013

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Disrupted-in-schizophrenia-1 (DISC1) gene has been established as a risk factor for various neuropsychiatric phenotypes. Both coding and regulatory variants in DISC1 have been identified and associated with these phenotypes in genetic studies. MicroRNAs (miRNAs) are important regulators of protein coding genes. Since the miRNA-mRNA target recognition mechanism is vulnerable to disruption by DNA polymorphisms, we investigated whether polymorphisms in the DISC1 3 0 UTR affect binding of miRNAs and lead to allele-specific regulation of DISC1. We identified four predicted polymorphic miRNA target sites in the DISC1 3 0 UTR, and demonstrated that miR-135b-5p regulates the level of DISC1 mRNA. Moreover, DISC1 regulation by miR135b-5p is allele specific: miR-135b-5p only binds to the major allele (A) of rs11122396, not to the minor allele (G). Thus, the G allele may be functionally related to the DISC1-associated phenotypes by abolishing regulation by miR-135b-5p, leading to elevated DISC1 levels. European Journal of Human Genetics (2014) 22, 840-843; doi:10.1038/ejhg.2013 published online 30 October 2013 Keywords: DISC1; microRNA; miR-135b-5p; neuropsychiatric disorder; allele-specific regulation INTRODUCTIONGenetic variants of the Disrupted-in-schizophrenia-1 (DISC1) gene have been associated with various neuropsychiatric phenotypes. 1 The initially identified translocation 2 reduces DISC1 expression to half normal levels, suggesting haploinsufficiency as the mechanism of disease susceptibility in translocation carriers. 3 In addition, expression quantitative trait loci affecting the expression of DISC1 have been identified 4,5 and shown to associate with age of onset in recurrent major depression. 6 We hypothesized that differential regulation of DISC1 expression may contribute to the wide range of DISC1-associated disorders.MicroRNAs (miRNAs) are small non-coding RNA molecules that repress gene expression by binding to their target mRNAs. There are no previous reports on miRNA regulation of DISC1, although in general miRNAs regulate about half of human genes. We were especially interested in putative polymorphic miRNA target sites in the DISC1 3 0 UTR that could lead to differential regulation of DISC1. MATERIALS AND METHODSSee Supplementary Methods. RESULTSWe identified four SNPs (rs11122396, rs980989, rs9308481, and rs11803088) within putative binding sites of nine human miRNAs (miR-23a-3p, miR-23b-3p, miR-130a-5p, miR-135a-5p, miR-135b-5p, miR-323-3p, miR-409-3p, miR-548c-3p, and miR-559) (Table 1) through bioinformatic target prediction (see SupplementaryMethods). We first tested the effect of each of these miRNAs on endogenous DISC1 expression in vitro. We transfected a commercial miRNA precursor of each miRNA, a negative control miRNA, or a positive control siRNA, into HEK293FT cells and measured DISC1 mRNA levels by qRT-PCR. We found that two of the nine miRNAs, miR-135b-5p and miR-559, significantly reduced DISC1 mRNA expression: miR-559 by 23.7% (P ¼ 0.009) and miR-135b-5p by 16.2% (P ¼ 0.039), comp...

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Section: Discussionmentioning

confidence: 99%

Allele-specific regulation of DISC1 expression by miR-135b-5p

et al. 2013

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“…In the past years, claims for an additional cognitive function of the cerebellum have been raised [for review, see Haarmeier and Thier (2007), Thach (2007), Timmann and Daum (2007), Baillieux et al (2008), and Glickstein and Doron (2008)], and the traditional belief of the motor dominant role is challenged by studies demonstrating that the cerebellum is involved in a variety of nonmotor functions (Akshoomoff and Courchesne, 1992;Courchesne et al, 1994;Fiez, 1996;Townsend et al, 1999;Cabeza and Nyberg, 2000;Allen and Courchesne, 2003;Schweizer et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Anatomical Correlate of Impaired Covert Visual Attentional Processes in Patients with Cerebellar Lesions

Baier¹,

Dieterich²,

Stoeter³

et al. 2010

J. Neurosci.

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In the past years, claims of cognitive and attentional function of the cerebellum have first been raised but were later refuted. One reason for this controversy might be that attentional deficits only occur when specific cerebellar structures are affected. To further elucidate this matter and to determine which cerebellar regions might be involved in deficits of covert visual attention, we used new brain imaging tools of lesion mapping that allow a direct comparison with control patients. A total of 26 patients with unilateral right-sided cerebellar infarcts were tested on a covert visual attention task. Eight (31%) patients showed markedly slowed responses, especially in trials in which an invalid cue necessitated reorienting of the focus of attention for target detection. Compared with the 18 patients who performed within the range of healthy control subjects, only the impaired patients had lesions of cerebellar vermal structures such as the pyramid. We suggest that these midcerebellar regions are indirectly involved in covert visual attention via oculomotor control mechanisms. Thus, specific cerebellar structures do influence attentional orienting, whereas others do not.

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“…Furthermore, given that cognitive testing is widely used in concussion management, we aimed to determine the extent to which the WBB measures provide additional information about concussion recovery that is not captured by cognitive testing. Whereas a biological connection between cognition and postural stability may exist, perhaps via the cerebellum, 18 this aim was motivated more by the practical need to determine whether both tests are necessary to track concussion recovery. Therefore, the purpose of our study was to evaluate WBB performance for assessing temporal changes in postural stability among concussed student-athletes by comparing balance metrics at 3 time points: preinjury, 3 days postconcussion, and 7 days postconcussion.…”

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confidence: 99%

Evaluation of Nintendo Wii Balance Board as a Tool for Measuring Postural Stability After Sport-Related Concussion

Merchant‐Borna¹,

Jones

Janigro³

et al. 2017

Journal of Athletic Training

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Context: Recent changes to postconcussion guidelines indicate that postural-stability assessment may augment traditional neurocognitive testing when making return-to-participation decisions. The Balance Error Scoring System (BESS) has been proposed as 1 measure of balance assessment. A new, freely available software program to accompany the Nintendo Wii Balance Board (WBB) system has recently been developed but has not been tested in concussed patients.Objective: To evaluate the feasibility of using the WBB to assess postural stability across 3 time points (baseline and postconcussion days 3 and 7) and to assess concurrent and convergent validity of the WBB with other traditional measures (BESS and Immediate Post-Concussion Assessment and Cognitive Test [ImPACT] battery) of assessing concussion recovery.Design: Cohort study. Setting: Athletic training room and collegiate sports arena. Patients or Other Participants: We collected preseason baseline data from 403 National Collegiate Athletic Association Division I and III student-athletes participating in contact sports and studied 19 participants (age ¼ 19.2 6 1.2 years, height ¼ 177.7 6 8.0 cm, mass ¼ 75.3 6 16.6 kg, time from baseline to day 3 postconcussion ¼ 27.1 6 36.6 weeks) who sustained concussions. Main Outcome Measure(s):We assessed balance using single-legged and double-legged stances for both the BESS and WBB, focusing on the double-legged, eyes-closed stance for the WBB, and used ImPACT to assess neurocognition at 3 time points. Descriptive statistics were used to characterize the sample. Mean differences and Spearman rank correlation coefficients were used to determine differences within and between metrics over the 3 time points. Individual-level changes over time were also assessed graphically.Results: The WBB demonstrated mean changes between baseline and day 3 postconcussion and between days 3 and 7 postconcussion. It was correlated with the BESS and ImPACT for several measures and identified 2 cases of abnormal balance postconcussion that would not have been identified via the BESS.Conclusions: When accompanied by the appropriate analytic software, the WBB may be an alternative for assessing postural stability in concussed student-athletes and may provide additional information to that obtained via the BESS and ImPACT. However, verification among independent samples is required.

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Cerebellar neurocognition: Insights into the bottom of the brain

Cited by 293 publications

References 115 publications

Allele-specific regulation of DISC1 expression by miR-135b-5p

Allele-specific regulation of DISC1 expression by miR-135b-5p

Anatomical Correlate of Impaired Covert Visual Attentional Processes in Patients with Cerebellar Lesions

Evaluation of Nintendo Wii Balance Board as a Tool for Measuring Postural Stability After Sport-Related Concussion

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