Circuit Mechanisms of Parkinson’s Disease

High-Throughput Microelectrode Arrays for Precise Functional Localization of the Globus Pallidus Internus

“…Second, when comparing the heatmaps on both sides, it is observed that the field potential power in the S1Tr, Hip, and deep brain nuclei on PD-induced side significantly increases, while the upper and middle part of the thalamus shows a significant decrease. This is consistent with the neural circuit model of PD [ 19 ], where the lack of dopamine in the SNc of the PD-induced side leads to excessive GPi output, resulting in excessive inhibition in the thalamus and motor cortex.…”

High-Throughput Microelectrode Arrays for Precise Functional Localization of the Globus Pallidus Internus

“…Second, when comparing the heatmaps on both sides, it is observed that the field potential power in the S1Tr, Hip, and deep brain nuclei on PD-induced side significantly increases, while the upper and middle part of the thalamus shows a significant decrease. This is consistent with the neural circuit model of PD [ 19 ], where the lack of dopamine in the SNc of the PD-induced side leads to excessive GPi output, resulting in excessive inhibition in the thalamus and motor cortex.…”

Motor sequence analysis as a sensitive biomarker of dopaminergic degeneration in a non-human primate model of parkinsonism

“…Despite the maintenance of task execution in paradigms such as the Staircase test, detailed analysis of the Brinkman task revealed consistent reorganization of motor sequences, suggesting that compensatory mechanisms sustain performance at the expense of movement efficiency and structural organization. This pattern is consistent with the literature on dopaminergic compensation, in which pre- and postsynaptic adaptations, as well as reorganization of basal ganglia circuits, allow preservation of motor function despite significant neuronal loss (Berardelli et al, 2001; Brotchie & Fitzer-Attas, 2009; McGregor & Nelson, 2019; Perez et al, 2008). Thus, preserved global performance does not imply absence of motor deficit, but rather reflects behavioral adaptations that mask underlying alterations in movement organization.…”

Fiber‐Specific White Matter Alterations in Parkinson's Disease Patients with GBA Gene Mutations

“…The observed changes in patients with GBA-PD indicate a reduction in density and bundle cross-sectional size 20,35 within WM fiberspecific pathways crucial for motor and cognitive functions (ie, CST, fornix, MCP, SLF-III, and parts of cortico-striatal-thalamic networks). These WM tracts are commonly implicated in PD pathology, 10,11,26 further supporting our results. Our findings also demonstrated lower GCase enzymatic activity in patients with GBA-PD than in those with iPD and healthy control subjects, which agrees with previous studies showing lower levels of GCase activity in induced pluripotent stem cell-derived dopaminergic neurons 36 and brain samples of GBA-PD patients, notably in the substantia nigra and the putamen.…”

“…The observed changes in patients with GBA‐PD indicate a reduction in density and bundle cross‐sectional size 20,35 within WM fiber‐specific pathways crucial for motor and cognitive functions (ie, CST, fornix, MCP, SLF‐III, and parts of cortico‐striatal‐thalamic networks). These WM tracts are commonly implicated in PD pathology, 10,11,26 further supporting our results.…”

High-Throughput Microelectrode Arrays for Precise Functional Localization of the Globus Pallidus Internus

“…Second, when comparing the heatmaps on both sides, it is observed that the field potential power in the S1Tr, Hip, and deep brain nuclei on PD-induced side significantly increases, while the upper and middle part of the thalamus shows a significant decrease. This is consistent with the neural circuit model of PD [ 19 ], where the lack of dopamine in the SNc of the PD-induced side leads to excessive GPi output, resulting in excessive inhibition in the thalamus and motor cortex.…”

Motor sequence analysis as a sensitive biomarker of dopaminergic degeneration in a non-human primate model of parkinsonism

“…Despite the maintenance of task execution in paradigms such as the Staircase test, detailed analysis of the Brinkman task revealed consistent reorganization of motor sequences, suggesting that compensatory mechanisms sustain performance at the expense of movement efficiency and structural organization. This pattern is consistent with the literature on dopaminergic compensation, in which pre- and postsynaptic adaptations, as well as reorganization of basal ganglia circuits, allow preservation of motor function despite significant neuronal loss (Berardelli et al, 2001; Brotchie & Fitzer-Attas, 2009; McGregor & Nelson, 2019; Perez et al, 2008). Thus, preserved global performance does not imply absence of motor deficit, but rather reflects behavioral adaptations that mask underlying alterations in movement organization.…”

Fiber‐Specific White Matter Alterations in Parkinson's Disease Patients with GBA Gene Mutations

“…The observed changes in patients with GBA-PD indicate a reduction in density and bundle cross-sectional size 20,35 within WM fiberspecific pathways crucial for motor and cognitive functions (ie, CST, fornix, MCP, SLF-III, and parts of cortico-striatal-thalamic networks). These WM tracts are commonly implicated in PD pathology, 10,11,26 further supporting our results. Our findings also demonstrated lower GCase enzymatic activity in patients with GBA-PD than in those with iPD and healthy control subjects, which agrees with previous studies showing lower levels of GCase activity in induced pluripotent stem cell-derived dopaminergic neurons 36 and brain samples of GBA-PD patients, notably in the substantia nigra and the putamen.…”

“…The observed changes in patients with GBA‐PD indicate a reduction in density and bundle cross‐sectional size 20,35 within WM fiber‐specific pathways crucial for motor and cognitive functions (ie, CST, fornix, MCP, SLF‐III, and parts of cortico‐striatal‐thalamic networks). These WM tracts are commonly implicated in PD pathology, 10,11,26 further supporting our results.…”

High-Throughput Microelectrode Arrays for Precise Functional Localization of the Globus Pallidus Internus

“…Second, when comparing the heatmaps on both sides, it is observed that the field potential power in the S1Tr, Hip, and deep brain nuclei on PD-induced side significantly increases, while the upper and middle part of the thalamus shows a significant decrease. This is consistent with the neural circuit model of PD [ 19 ], where the lack of dopamine in the SNc of the PD-induced side leads to excessive GPi output, resulting in excessive inhibition in the thalamus and motor cortex.…”

Motor sequence analysis as a sensitive biomarker of dopaminergic degeneration in a non-human primate model of parkinsonism

“…Despite the maintenance of task execution in paradigms such as the Staircase test, detailed analysis of the Brinkman task revealed consistent reorganization of motor sequences, suggesting that compensatory mechanisms sustain performance at the expense of movement efficiency and structural organization. This pattern is consistent with the literature on dopaminergic compensation, in which pre- and postsynaptic adaptations, as well as reorganization of basal ganglia circuits, allow preservation of motor function despite significant neuronal loss (Berardelli et al, 2001; Brotchie & Fitzer-Attas, 2009; McGregor & Nelson, 2019; Perez et al, 2008). Thus, preserved global performance does not imply absence of motor deficit, but rather reflects behavioral adaptations that mask underlying alterations in movement organization.…”

Fiber‐Specific White Matter Alterations in Parkinson's Disease Patients with GBA Gene Mutations

“…The observed changes in patients with GBA-PD indicate a reduction in density and bundle cross-sectional size 20,35 within WM fiberspecific pathways crucial for motor and cognitive functions (ie, CST, fornix, MCP, SLF-III, and parts of cortico-striatal-thalamic networks). These WM tracts are commonly implicated in PD pathology, 10,11,26 further supporting our results. Our findings also demonstrated lower GCase enzymatic activity in patients with GBA-PD than in those with iPD and healthy control subjects, which agrees with previous studies showing lower levels of GCase activity in induced pluripotent stem cell-derived dopaminergic neurons 36 and brain samples of GBA-PD patients, notably in the substantia nigra and the putamen.…”

“…The observed changes in patients with GBA‐PD indicate a reduction in density and bundle cross‐sectional size 20,35 within WM fiber‐specific pathways crucial for motor and cognitive functions (ie, CST, fornix, MCP, SLF‐III, and parts of cortico‐striatal‐thalamic networks). These WM tracts are commonly implicated in PD pathology, 10,11,26 further supporting our results.…”