Behavioral Measures of Saccade Latency and Inhibition in Manifest and Premanifest Huntington's Disease

Turner, Travis H.; Goldstein, Jody; Hamilton, Joanne M.; Jacobson, Mark W.; Pirogovsky, Eva; Peavy, Guerry M.; Corey–Bloom, Jody

doi:10.1080/00222895.2011.580390

Cited by 18 publications

(16 citation statements)

References 23 publications

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“…In this context then, our results in Q140 mice showing about 30% loss of corticostriatal terminals prior to striatal neuron loss and prominent motor decline suggest that corticostriatal synaptic pruning may occur during premanifest HD, and at least in part account for the observed abnormalities in striatal activity. Given the important role that cortical excitatory drive plays in the motor role of striatum, the early loss of corticostriatal input, together with a deficiency in thalamic input, may help explain the growing motor slowing evident in premanifest HD (Bechtel et al, 2010; Biglan et al, 2009; Blekher et al, 2004; de Boo et al, 1997; Delval et al, 2011; Kirkwood et al, 1999, 2000; Rao et al, 2008, 2011; Siemers et al, 1996; Tabrizi et al, 2011; Turner et al, 2011). Premanifest corticostriatal terminal loss might be expected as an early reflection of a pathogenic process that in symptomatic HD causes significant regional thinning of cerebral cortex (Douaud et al, 2006; Kassubek et al, 2004b; Muhlau et al, 2007; Rosas et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…For example, numerous studies have noted that premanifest HD individuals are slowed in the initiation and/or execution of a variety of motor tasks involving the eyes, hands or lower limbs (Bechtel et al, 2010; Biglan et al, 2009; Blekher et al, 2004; de Boo et al, 1997; Delval et al, 2011; Kirkwood et al, 1999, 2000; Rao et al, 2008, 2011; Siemers et al, 1996; Tabrizi et al, 2011; Turner et al, 2011). This defect is mild in premanifest cases not yet near clinical onset, but more severe in those near onset (Bechtel et al, 2010; Kirkwood et al, 2000; Rao et al, 2008, 2011; Rupp et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Loss of corticostriatal and thalamostriatal synaptic terminals precedes striatal projection neuron pathology in heterozygous Q140 Huntington's disease mice

Deng

Wong

Bricker-Anthony

et al. 2013

Neurobiology of Disease

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Motor slowing, forebrain white matter loss, and striatal shrinkage have been reported in premanifest Huntington’s disease (HD) prior to overt striatal neuron loss. We carried out detailed LM and EM studies in a genetically precise HD mimic, heterozygous Q140 HD knock-in mice, to examine the possibility that loss of corticostriatal and thalamostriatal terminals prior to striatal neuron loss underlies these premanifest HD abnormalities. In our studies, we used VGLUT1 and VGLUT2 immunolabeling to detect corticostriatal and thalamostriatal (respectively) terminals in dorsolateral (motor) striatum over the first year of life, prior to striatal projection neuron pathology. VGLUT1+ axospinous corticostriatal terminals represented about 55% of all excitatory terminals in striatum, and VGLUT2+ axospinous thalamostriatal terminals represented about 35%, with VGLUT1+ and VGLUT2+ axodendritic terminals accounting for the remainder. In Q140 mice, a significant 40% shortfall in VGLUT2+ axodendritic thalamostriatal terminals and a 20% shortfall in axospinous thalamostriatal terminals was already observed at 1 month of age, but VGLUT1+ terminals were normal in abundance. The 20% deficiency in VGLUT2+ thalamostriatal axospinous terminals persisted at 4 and 12 months in Q140 mice, and an additional 30% loss of VGLUT1+ corticostriatal terminals was observed at 12 months. The early and persistent deficiency in thalamostriatal axospinous terminals in Q140 mice may reflect a development defect, and the impoverishment of this excitatory drive to striatum may help explain early motor defects in Q140 mice and in premanifest HD. The loss of corticostriatal terminals at 1 year in Q140 mice is consistent with prior evidence from other mouse models of corticostriatal disconnection early during progression, and can explain both the measurable bradykinesia and striatal white matter loss in late premanifest HD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Loss of corticostriatal and thalamostriatal synaptic terminals precedes striatal projection neuron pathology in heterozygous Q140 Huntington's disease mice

Deng

Wong

Bricker-Anthony

et al. 2013

Neurobiology of Disease

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“…Premanifest HD individuals are slowed in initiation and/or execution of motor tasks (Siemers et al, 1996 ; de Boo et al, 1997 ; Kirkwood et al, 1999 , 2000 ; Blekher et al, 2004 ; Rao et al, 2008 , 2011 ; Biglan et al, 2009 ; Bechtel et al, 2010 ; Delval et al, 2011 ; Tabrizi et al, 2011 ; Turner et al, 2011 ). This defect is mild in individuals not near clinical onset, but more severe in those near onset (Kirkwood et al, 2000 ; Rao et al, 2008 ; Bechtel et al, 2010 ; Rupp et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Differential loss of thalamostriatal and corticostriatal input to striatal projection neuron types prior to overt motor symptoms in the Q140 knock-in mouse model of Huntington's disease

Deng

Wong

Wan

et al. 2014

Front. Syst. Neurosci.

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Motor slowing and forebrain white matter loss have been reported in premanifest Huntington's disease (HD) prior to substantial striatal neuron loss. These findings raise the possibility that early motor defects in HD may be related to loss of excitatory input to striatum. In a prior study, we showed that in the heterozygous Q140 knock-in mouse model of HD that loss of thalamostriatal axospinous terminals is evident by 4 months, and loss of corticostriatal axospinous terminals is evident at 12 months, before striatal projection neuron pathology. In the present study, we specifically characterized the loss of thalamostriatal and corticostriatal terminals on direct (dSPN) and indirect (iSPN) pathway striatal projection neurons, using immunolabeling to identify thalamostriatal (VGLUT2+) and corticostriatal (VGLUT1+) axospinous terminals, and D1 receptor immunolabeling to distinguish dSPN (D1+) and iSPN (D1−) synaptic targets. We found that the loss of corticostriatal terminals at 12 months of age was preferential for D1+ spines, and especially involved smaller terminals, presumptively of the intratelencephalically projecting (IT) type. By contrast, indirect pathway D1− spines showed little loss of axospinous terminals at the same age. Thalamostriatal terminal loss was comparable for D1+ and D1− spines at both 4 and 12 months. Regression analysis showed that the loss of VGLUT1+ terminals on D1+ spines was correlated with a slight decline in open field motor parameters at 12 months. Our overall results raise the possibility that differential thalamic and cortical input loss to SPNs is an early event in human HD, with cortical loss to dSPNs in particular contributing to premanifest motor slowing.

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“…In medicine, eye-tracking systems are mainly applied in neuropsychology and ophthalmology research (24). In the fields of psychology and psychiatry, eye-tracking technology has recently been confirmed to be useful in diagnosing various diseases, including Parkinson's disease (25), Huntington's (26), abnormal gaze (27), nervous system degenerative diseases (28) and early Alzheimer's disease (29). Home eye-tracking systems can be used to follow up patients with vertigo (30).…”

Section: Discussionmentioning

confidence: 99%

Preliminary study of abnormalities in saccade dynamics in patients with hyperthyroidism with no pre‑existing eye damage

Sun

Xie

et al. 2020

Exp Ther Med

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The present study investigated the relationship between hyper thyroidism a nd thyroid-associated ophthalmopathy by examining saccade dynamics to identify defects in eye tracking in patients with hyperthyroidism with no pre-existing eye damage and sensitive indicators that discriminated eye tracking ability in hyperthyroidism. A total of 33 outpatients with hyperthyroidism and 26 healthy controls participated in visually guided saccade (VGS) analysis. Patients with hyperthyroidism were divided into groups based on their medication status (medicated vs. unmedicated). Main sequence analysis was performed to identify differences in peak velocity and duration, and a general linear model (GLM) was used to identify differences in latency, peak acceleration and peak deceleration among the groups. The present study compared differences in the Spearman's correlation coefficient of the duration of saccades and the acceleration asymmetric index (R AD) among the groups. V max values (V max was the asymptotic value of the PV of saccades of large amplitude) were significantly different between the healthy control and unmedicated-hyperthyroidism groups. The results of the GLM-based analysis indicated no significant differences in saccade latency among the three groups. Peak acceleration was significantly different between the healthy control and unmedicated-hyperthyroidism groups (P<0.01). Peak deceleration was significantly different between the healthy control, unmedicated-and medicated-hyperthyroidism groups (P<0.01). R AD was significantly different between the healthy control and medicated-hyperthyroidism groups (P=0.004). The results of the present study suggested that patients with hyperthyroidism with no pre-existing eye damage exhibited significantly altered saccade dynamics during VGS. Therefore, R AD may be used as an indicator to monitor the level of eye movement coordination.

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Behavioral Measures of Saccade Latency and Inhibition in Manifest and Premanifest Huntington's Disease

Cited by 18 publications

References 23 publications

Loss of corticostriatal and thalamostriatal synaptic terminals precedes striatal projection neuron pathology in heterozygous Q140 Huntington's disease mice

Loss of corticostriatal and thalamostriatal synaptic terminals precedes striatal projection neuron pathology in heterozygous Q140 Huntington's disease mice

Differential loss of thalamostriatal and corticostriatal input to striatal projection neuron types prior to overt motor symptoms in the Q140 knock-in mouse model of Huntington's disease

Preliminary study of abnormalities in saccade dynamics in patients with hyperthyroidism with no pre‑existing eye damage

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