The Cerebellum and Implicit Sequencing: Evidence from Cerebellar Ataxia

Morgan, Owen P.; Slapik, Mitchell B.; Iannuzzelli, Katherine G.; LaConte, Stephen M.; Lisinski, Jonathan; Nopoulos, Peg; Cochran, Ashley M.; Kronemer, Sharif I.; Rosenthal, Liana S.; Marvel, Cherie L.

doi:10.1007/s12311-020-01206-7

Cited by 14 publications

(6 citation statements)

References 75 publications

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“…A subset of participants received motor, cognitive, and dual task paradigms following Kronemer and colleagues 45 , 46 . (See also Supplementary Information for method details and group sample sizes per task).…”

Section: Methodsmentioning

confidence: 99%

Characterization of basal ganglia volume changes in the context of HIV and polysubstance use

Monick

Joyce

Chugh

et al. 2022

Sci Rep

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HIV and psychoactive substances can impact the integrity of the basal ganglia (BG), a neural substrate of cognition, motor control, and reward-seeking behaviors. This study assessed BG gray matter (GM) volume as a function of polysubstance (stimulant and opioid) use and HIV status. We hypothesized that comorbid polysubstance use and HIV seropositivity would alter BG GM volume differently than would polysubstance use or HIV status alone. We collected structural MRI scans, substance use history, and HIV diagnoses. Participants who had HIV (HIV +), a history of polysubstance dependence (POLY +), both, or neither completed assessments for cognition, motor function, and risk-taking behaviors (N = 93). All three clinical groups showed a left-lateralized pattern of GM reduction in the BG relative to controls. However, in the HIV + /POLY + group, stimulant use was associated with increased GM volume within the globus pallidus and putamen. This surpassed the effects from opioid use, as indicated by decreased GM volume throughout the BG in the HIV-/POLY + group. Motor learning was impaired in all three clinical groups, and in the HIV + /POLY + group, motor learning was associated with increased caudate and putamen GM volume. We also observed associations between BG GM volume and risk-taking behaviors in the HIV + /POLY- and HIV-/POLY + groups. The effects of substance use on the BG differed as a function of substance type used, HIV seropositivity, and BG subregion. Although BG volume decreased in association with HIV and opioid use, stimulants can, inversely, lead to BG volume increases within the context of HIV.

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Section: Methodsmentioning

confidence: 99%

Characterization of basal ganglia volume changes in the context of HIV and polysubstance use

Monick

Joyce

Chugh

et al. 2022

Sci Rep

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“…Participants were administered a locally developed finger tapping task ( Eierud et al, 2011 ; Morgan et al, 2021 ). Participants were asked to tap in synchrony with a cross that flashed at 1, 2, 3, or 4 Hz and to rest otherwise.…”

Section: Methodsmentioning

confidence: 99%

“…Participants were administered a locally developed finger tapping task (Eierud et al, 2011;Morgan et al, 2021).…”

Section: Finger Tapping Taskmentioning

confidence: 99%

“…Spinocerebellar ataxia (SCA) is a genetic and progressive neurodegenerative disease in which cell death occurs in the cerebellum, leading to degradative changes in movement, cognition, and mood ( Kansal et al, 2017 ; Hoche et al, 2018 ; Slapik et al, 2019 ; Kronemer et al, 2021 ; Morgan et al, 2021 ; NINDS, 2021 ; Joyce et al, 2022 ). Research has only begun to examine iron deposition related to SCA and other forms of ataxia.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative susceptibility mapping of basal ganglia iron is associated with cognitive and motor functions that distinguish spinocerebellar ataxia type 6 and type 3

et al. 2022

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BackgroundIn spinocerebellar ataxia type 3 (SCA3), volume loss has been reported in the basal ganglia, an iron-rich brain region, but iron content has not been examined. Recent studies have reported that patients with SCA6 have markedly decreased iron content in the cerebellar dentate, coupled with severe volume loss. Changing brain iron levels can disrupt cognitive and motor functions, yet this has not been examined in the SCAs, a disease in which iron-rich regions are affected.MethodsIn the present study, we used quantitative susceptibility mapping (QSM) to measure tissue magnetic susceptibility (indicating iron concentration), structural volume, and normalized susceptibility mass (indicating iron content) in the cerebellar dentate and basal ganglia in people with SCA3 (n = 10) and SCA6 (n = 6) and healthy controls (n = 9). Data were acquired using a 7T Philips MRI scanner. Supplemental measures assessed motor, cognitive, and mood domains.ResultsPutamen volume was lower in both SCA groups relative to controls, replicating prior findings. Dentate susceptibility mass and volume in SCA6 was lower than in SCA3 or controls, also replicating prior findings. The novel finding was that higher basal ganglia susceptibility mass in SCA6 correlated with lower cognitive performance and greater motor impairment, an association that was not observed in SCA3. Cerebellar dentate susceptibility mass, however, had the opposite relationship with cognition and motor function in SCA6, suggesting that, as dentate iron is depleted, it relocated to the basal ganglia, which contributed to cognitive and motor decline. By contrast, basal ganglia volume loss, rather than iron content, appeared to drive changes in motor function in SCA3.ConclusionThe associations of higher basal ganglia iron with lower motor and cognitive function in SCA6 but not in SCA3 suggest the potential for using brain iron deposition profiles beyond the cerebellar dentate to assess disease states within the cerebellar ataxias. Moreover, the role of the basal ganglia deserves greater attention as a contributor to pathologic and phenotypic changes associated with SCA.

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“…For the upper limb, the concept of sequential, intermittent predictive control has substantial support ( Fishbach et al, 2007 ; Houk et al, 2007 ; van de Kamp et al, 2013 ; Loram et al, 2014 ; Zenzeri et al, 2014 ; Morgan et al, 2021 ). Previous studies have decomposed upper limb reaching movements and sustained manual control into sub-movements ( Milner, 1992 ; Rohrer and Hogan, 2003 ; Fishbach et al, 2007 ; Goble and Brown, 2007 ; van de Kamp et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

What is the contribution of voluntary and reflex processes to sensorimotor control of balance?

Cherif

Zenzeri

Loram

2022

Front. Bioeng. Biotechnol.

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The contribution to balance of spinal and transcortical processes including the long-latency reflex is well known. The control of balance has been modelled previously as a continuous, state feedback controller representing, long-latency reflexes. However, the contribution of slower, variable delay processes has not been quantified. Compared with fixed delay processes (spinal, transcortical), we hypothesize that variable delay processes provide the largest contribution to balance and are sensitive to historical context as well as current states. Twenty-two healthy participants used a myoelectric control signal from their leg muscles to maintain balance of their own body while strapped to an actuated, inverted pendulum. We study the myoelectric control signal (u) in relation to the independent disturbance (d) comprising paired, discrete perturbations of varying inter-stimulus-interval (ISI). We fit the closed loop response, u from d, using one linear and two non-linear non-parametric (many parameter) models. Model M1 (ARX) is a generalized, high-order linear-time-invariant (LTI) process with fixed delay. Model M1 is equivalent to any parametric, closed-loop, continuous, linear-time-invariant (LTI), state feedback model. Model M2, a single non-linear process (fixed delay, time-varying amplitude), adds an optimized response amplitude to each stimulus. Model M3, two non-linear processes (one fixed delay, one variable delay, each of time-varying amplitude), add a second process of optimized delay and optimized response amplitude to each stimulus. At short ISI, the myoelectric control signals deviated systematically both from the fixed delay LTI process (M1), and also from the fixed delay, time-varying amplitude process (M2) and not from the two-process model (M3). Analysis of M3 (all fixed delay and variable delay response amplitudes) showed the variable (compared with fixed) delay process 1) made the largest contribution to the response, 2) exhibited refractoriness (increased delay related to short ISI) and 3) was sensitive to stimulus history (stimulus direction 2 relative to stimulus 1). For this whole-body balance task and for these impulsive stimuli, non-linear processes at variable delay are central to control of balance. Compared with fixed delay processes (spinal, transcortical), variable delay processes provided the largest contribution to balance and were sensitive to historical context as well as current states.

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The Cerebellum and Implicit Sequencing: Evidence from Cerebellar Ataxia

Cited by 14 publications

References 75 publications

Characterization of basal ganglia volume changes in the context of HIV and polysubstance use

Characterization of basal ganglia volume changes in the context of HIV and polysubstance use

Quantitative susceptibility mapping of basal ganglia iron is associated with cognitive and motor functions that distinguish spinocerebellar ataxia type 6 and type 3

What is the contribution of voluntary and reflex processes to sensorimotor control of balance?

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