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The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders.

Mosconi MW, Wang Z, Schmitt LM, Tsai P, Sweeney JA - Front Neurosci (2015)

Bottom Line: Each of these behaviors has been found to be impaired in ASD, suggesting that multiple distinct circuits of the cerebellum may be involved in the pathogenesis of patients' sensorimotor impairments.Preclinical studies of monogenetic conditions associated with ASD also have identified selective defects of the cerebellum and documented behavioral rescues when the cerebellum is targeted.Based on these findings, we propose that cerebellar circuits may prove to be promising targets for therapeutic development aimed at rescuing sensorimotor and other clinical symptoms of different forms of ASD.

View Article: PubMed Central - PubMed

Affiliation: Clinical Child Psychology Program and Schiefelbusch Institute for Life Span Studies, University of Kansas Lawrence, KS, USA ; Center for Autism and Developmental Disabilities, University of Texas Southwestern Dallas, TX, USA ; Department of Psychiatry, University of Texas Southwestern Dallas, TX, USA ; Department of Pediatrics, University of Texas Southwestern Dallas, TX, USA.

ABSTRACT
The cerebellum has been repeatedly implicated in gene expression, rodent model and post-mortem studies of autism spectrum disorder (ASD). How cellular and molecular anomalies of the cerebellum relate to clinical manifestations of ASD remains unclear. Separate circuits of the cerebellum control different sensorimotor behaviors, such as maintaining balance, walking, making eye movements, reaching, and grasping. Each of these behaviors has been found to be impaired in ASD, suggesting that multiple distinct circuits of the cerebellum may be involved in the pathogenesis of patients' sensorimotor impairments. We will review evidence that the development of these circuits is disrupted in individuals with ASD and that their study may help elucidate the pathophysiology of sensorimotor deficits and core symptoms of the disorder. Preclinical studies of monogenetic conditions associated with ASD also have identified selective defects of the cerebellum and documented behavioral rescues when the cerebellum is targeted. Based on these findings, we propose that cerebellar circuits may prove to be promising targets for therapeutic development aimed at rescuing sensorimotor and other clinical symptoms of different forms of ASD.

No MeSH data available.


Related in: MedlinePlus

To assess precision gripping control during rise, sustained, and relaxation phases, individuals pressed against two opposing load cells while receiving visual feedback from the monitor in front of them. Individuals viewed two horizontal bars: a red/green target bar and a white force bar. The white force bar moved upward with increased force, and individuals were instructed to press on the load cells as quickly as possible when the target bar turned green so that the force bar reached the height of the target bar. They also were instructed to keep the force bar as close as possible to the target bar until the target bar turned red again, and then to release the load cells as fast as possible. Adapted with permission from Wang et al. (2015).
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Figure 3: To assess precision gripping control during rise, sustained, and relaxation phases, individuals pressed against two opposing load cells while receiving visual feedback from the monitor in front of them. Individuals viewed two horizontal bars: a red/green target bar and a white force bar. The white force bar moved upward with increased force, and individuals were instructed to press on the load cells as quickly as possible when the target bar turned green so that the force bar reached the height of the target bar. They also were instructed to keep the force bar as close as possible to the target bar until the target bar turned red again, and then to release the load cells as fast as possible. Adapted with permission from Wang et al. (2015).

Mentions: Feedback control of sustained precision grip also appears to be disrupted in ASD. During sustained control of grip, visual feedback information from visual cortex is projected to posterior parietal cortex, and then anterior to premotor and primary cortices (Glickstein and Stein, 1991). A more efficient subcortical route through posterior cerebellum also is used to translate visual-spatial feedback information into a more precise motor command executed by motor cortex (Glickstein and Stein, 1991; Stein and Glickstein, 1992). Mosconi et al. (2015) and Wang et al. (2015) each found that individuals with ASD show increased sustained force variability during a precision gripping test in which they receive online visual feedback about their performance (Figure 3). In these studies, participants pressed on two opposing load cells with their thumb and index finger while a horizontal force bar moved upwards with increased force. They were instructed to press on the load cells so that the force bar reached the same level as a static target bar, and then to keep it there as steadily as possible. Individuals with ASD showed increased variability of their force output over time that became more severe at higher force levels and in relation to the gain of visual feedback (Mosconi et al., 2015). Elevations in force variability were evident both at the lowest and highest visual gains, suggesting that individuals with ASD have a reduced ability to process highly degraded and highly magnified visual feedback information.


The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders.

Mosconi MW, Wang Z, Schmitt LM, Tsai P, Sweeney JA - Front Neurosci (2015)

To assess precision gripping control during rise, sustained, and relaxation phases, individuals pressed against two opposing load cells while receiving visual feedback from the monitor in front of them. Individuals viewed two horizontal bars: a red/green target bar and a white force bar. The white force bar moved upward with increased force, and individuals were instructed to press on the load cells as quickly as possible when the target bar turned green so that the force bar reached the height of the target bar. They also were instructed to keep the force bar as close as possible to the target bar until the target bar turned red again, and then to release the load cells as fast as possible. Adapted with permission from Wang et al. (2015).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4555040&req=5

Figure 3: To assess precision gripping control during rise, sustained, and relaxation phases, individuals pressed against two opposing load cells while receiving visual feedback from the monitor in front of them. Individuals viewed two horizontal bars: a red/green target bar and a white force bar. The white force bar moved upward with increased force, and individuals were instructed to press on the load cells as quickly as possible when the target bar turned green so that the force bar reached the height of the target bar. They also were instructed to keep the force bar as close as possible to the target bar until the target bar turned red again, and then to release the load cells as fast as possible. Adapted with permission from Wang et al. (2015).
Mentions: Feedback control of sustained precision grip also appears to be disrupted in ASD. During sustained control of grip, visual feedback information from visual cortex is projected to posterior parietal cortex, and then anterior to premotor and primary cortices (Glickstein and Stein, 1991). A more efficient subcortical route through posterior cerebellum also is used to translate visual-spatial feedback information into a more precise motor command executed by motor cortex (Glickstein and Stein, 1991; Stein and Glickstein, 1992). Mosconi et al. (2015) and Wang et al. (2015) each found that individuals with ASD show increased sustained force variability during a precision gripping test in which they receive online visual feedback about their performance (Figure 3). In these studies, participants pressed on two opposing load cells with their thumb and index finger while a horizontal force bar moved upwards with increased force. They were instructed to press on the load cells so that the force bar reached the same level as a static target bar, and then to keep it there as steadily as possible. Individuals with ASD showed increased variability of their force output over time that became more severe at higher force levels and in relation to the gain of visual feedback (Mosconi et al., 2015). Elevations in force variability were evident both at the lowest and highest visual gains, suggesting that individuals with ASD have a reduced ability to process highly degraded and highly magnified visual feedback information.

Bottom Line: Each of these behaviors has been found to be impaired in ASD, suggesting that multiple distinct circuits of the cerebellum may be involved in the pathogenesis of patients' sensorimotor impairments.Preclinical studies of monogenetic conditions associated with ASD also have identified selective defects of the cerebellum and documented behavioral rescues when the cerebellum is targeted.Based on these findings, we propose that cerebellar circuits may prove to be promising targets for therapeutic development aimed at rescuing sensorimotor and other clinical symptoms of different forms of ASD.

View Article: PubMed Central - PubMed

Affiliation: Clinical Child Psychology Program and Schiefelbusch Institute for Life Span Studies, University of Kansas Lawrence, KS, USA ; Center for Autism and Developmental Disabilities, University of Texas Southwestern Dallas, TX, USA ; Department of Psychiatry, University of Texas Southwestern Dallas, TX, USA ; Department of Pediatrics, University of Texas Southwestern Dallas, TX, USA.

ABSTRACT
The cerebellum has been repeatedly implicated in gene expression, rodent model and post-mortem studies of autism spectrum disorder (ASD). How cellular and molecular anomalies of the cerebellum relate to clinical manifestations of ASD remains unclear. Separate circuits of the cerebellum control different sensorimotor behaviors, such as maintaining balance, walking, making eye movements, reaching, and grasping. Each of these behaviors has been found to be impaired in ASD, suggesting that multiple distinct circuits of the cerebellum may be involved in the pathogenesis of patients' sensorimotor impairments. We will review evidence that the development of these circuits is disrupted in individuals with ASD and that their study may help elucidate the pathophysiology of sensorimotor deficits and core symptoms of the disorder. Preclinical studies of monogenetic conditions associated with ASD also have identified selective defects of the cerebellum and documented behavioral rescues when the cerebellum is targeted. Based on these findings, we propose that cerebellar circuits may prove to be promising targets for therapeutic development aimed at rescuing sensorimotor and other clinical symptoms of different forms of ASD.

No MeSH data available.


Related in: MedlinePlus