Abnormally Reduced Frontal Cortex Activity During Trail Making Test in Prodromal Parkinson's Disease – A fNIRS Study

AbstractBoth intrinsic and extrinsic motivation are believed to involve brain regions that are innervated by the dopaminergic pathway. Although dopaminergic neurons in the midbrain deteriorate in Parkinson’s disease (PD), it remains unclear whether intrinsic motivation is impaired in PD patients. To address this issue, we investigated intrinsic motivation in PD patients using a task designed to assess the “Pandora effect,” which constitutes a curiosity for resolving uncertainty, even if this curiosity is likely to result in negative consequences. Twenty-seven PD patients and 27 age-matched healthy controls (HCs) completed a curiosity task in which they were required to decide either to view or skip negative pictures (e.g., snakes, spiders) and an examination battery that included the Mini-Mental State Examination, a verbal fluency test, the Trail Making Test, 10-word recall tests, and questionnaires for behavioral inhibition/activation and depression. DaTSCAN images to assess the distribution of dopamine transporters in the striatum were acquired only from PD patients. The results revealed that PD patients, relative to the HCs, viewed the pictures less frequently under both the certain and uncertain conditions. However, both the PD patients and HCs viewed the pictures at a higher frequency under the uncertain condition than under the certain condition. In the PD patients, the proportion of pictures viewed under the certain condition was positively correlated with the distribution of dopamine transporters in the striatum. These results suggest that despite the overall decreasing level of interest in viewing negative pictures, the motivation to resolve uncertainty is relatively intact in PD patients.

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Evaluation of Motor and Cognitive Performance in People with Parkinson’s Disease Using Instrumented Trail-Making Test

Gerontology ◽

10.1159/000515940 ◽

2021 ◽

pp. 1-7

Author(s):

Ram kinker Mishra ◽

Catherine Park ◽

He Zhou ◽

Bijan Najafi ◽

T. Adam Thrasher

Keyword(s):

Older Adults ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Performance ◽

Pairwise Comparison ◽

Walking Test ◽

Cognitively Normal ◽

Early Results ◽

Trail Making ◽

Changes Over Time

Introduction: Parkinson’s disease (PD) progressively impairs motor and cognitive performance. The current tools to detect decline in motor and cognitive functioning are often impractical for busy clinics and home settings. To address the gap, we designed an instrumented trail-making task (iTMT) based on a wearable sensor (worn on the shin) with interactive game-based software installed on a tablet. The iTMT test includes reaching to 5 indexed circles, a combination of numbers (1–3) and letters (A&B) randomly positioned inside target circles, in a sequential order, which virtually appears on a screen kept in front of the participants, by rotating one’s ankle joint while standing and holding a chair for safety. By measuring time to complete iTMT task (iTMT time), iTMT enables quantifying cognitive-motor performance. Purpose: This study’s objective is to examine the feasibility of iTMT to detect early cognitive-motor decline in PDs. Method: Three groups of volunteers, including 14 cognitively normal (CN) older adults, 14 PDs, and 11 mild cognitive impaireds (MCI), were recruited. Participants completed MoCA, 20 m walking test, and 3 trials of iTMT. Results: All participants enabled to complete iTMT with <3 min, indicating high feasibility. The average iTMT time for CN-Older, PD, and MCI participants were 20.9 ± 0.9 s, 32.3 ± 2.4 s, and 40.9 ± 4.5 s, respectively. After adjusting for age and education level, pairwise comparison suggested large effect sizes for iTMT between CN-older versus PD (Cohen’s d = 1.7, p = 0.024) and CN-older versus MCI (d = 1.57, p < 0.01). Significant correlations were observed when comparing iTMT time with the gait speed (r = −0.4, p = 0.011) and MoCA score (r = −0.56, p < 0.01). Conclusion: This study demonstrated the feasibility and early results supporting the potential application of iTMT to determine cognitive-motor and distinguishing individuals with MCI and PD from CN-older adults. Future studies are warranted to test the ability of iTMT to track its subtle changes over time.

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Cognitive and Physiological Substrates of Impaired Sentence Processing in Parkinson's Disease

Journal of Cognitive Neuroscience ◽

10.1162/jocn.1993.5.4.480 ◽

1993 ◽

Vol 5 (4) ◽

pp. 480-498 ◽

Cited By ~ 38

Author(s):

Murray Grossman ◽

Susan Carvell ◽

Stephen Gollomp ◽

Matthew B. Stern ◽

Martin Reivich ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Frontal Cortex ◽

Sentence Processing ◽

Sentence Comprehension ◽

Short Term Memory ◽

Brain Regions ◽

Positron Emission ◽

Left Caudate ◽

Regional Cerebral Glucose Metabolism

Sentence comprehension is a complex process involving at least a grammatical processor and a procedural component that supports language computations. One type of cerebral architecture that may underlie sentence processing is a network of distributed brain regions. We report two experiments designed to evaluate the cognitive and physiological substrate of sentence processing diaculties in nondemented patients with Parkinson's disease (PD). In the first experiment, patients answered simple questions about sentences that varied in their computational demands. Group and individual patient analyses indicated that PD patients are significantly compromised on this task, and that their difficulties become more prominent as the computational demands of the sentences increase. We manipulated the set of sentences to stress performance aspects of sentence processing. PD patients were compromised in their ability to detect errors in the presence and nature of a sentence's grammatical morphemes, suggesting a deficit in selective attention, but their ability to answer questions about a sentence was not afFected by short-term memory factors. In the second experiment, positron emission tomography was used to correlate this pattern of sentence comprehension impairment with regional cerebral glucose metabolism (rCMRgl) obtained at rest in a representative subset of these PD patients. Grammatical comprehension and attention in sentence processing correlated significantly with mesial frontal rCMRgl. Regression analyses confirmed the central role of left mesial frontal cortex, and identified a subsidiary role for left caudate in overall sentence comprehension, for left dorsolateral frontal cortex in grammatical processing, and for bilateral dorsolateral frontal cortex in attending to the presence of grammatical features. We conclude that compromised mesial frontal functioning underlies in part the sentence processing deficit of these patients, and these data illustrate one method for mapping portions of a sentence processing mechanism onto a distributed cerebral architecture.

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Gene expression of the nicotinic acetylcholine receptor α4 subunit in the frontal cortex in Parkinson's disease patients

Neuroscience Letters ◽

10.1016/0304-3940(95)11367-6 ◽

1995 ◽

Vol 187 (3) ◽

pp. 173-176 ◽

Cited By ~ 14

Author(s):

Hannsjörg Schröder ◽

Robert A.I. de Vos ◽

Ernst N.H. Jansen ◽

Christina Birtsch ◽

Andrea Wevers ◽

...

Keyword(s):

Gene Expression ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Frontal Cortex ◽

Acetylcholine Receptor ◽

Nicotinic Acetylcholine Receptor ◽

Nicotinic Acetylcholine

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Parkinson’s Disease Master Regulators on Substantia Nigra and Frontal Cortex and Their Use for Drug Repositioning

Molecular Neurobiology ◽

10.1007/s12035-020-02203-x ◽

2020 ◽

Author(s):

D. M. Vargas ◽

M. A. De Bastiani ◽

R. B. Parsons ◽

F. Klamt

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Frontal Cortex ◽

Drug Repositioning ◽

Master Regulators

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Environmental Enrichment Attenuates Oxidative Stress and Alters Detoxifying Enzymes in an A53T α-Synuclein Transgenic Mouse Model of Parkinson’s Disease

Antioxidants ◽

10.3390/antiox9100928 ◽

2020 ◽

Vol 9 (10) ◽

pp. 928

Author(s):

Jung Hwa Seo ◽

Seong-Woong Kang ◽

Kyungri Kim ◽

Soohyun Wi ◽

Jang Woo Lee ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Olfactory Bulb ◽

Frontal Cortex ◽

Brain Stem ◽

Environmental Enrichment ◽

Brain Regions ◽

Wild Type ◽

Detoxifying Enzymes

Although environmental enrichment (EE) is known to reduce oxidative stress in Parkinson’s disease (PD), the metabolic alternations for detoxifying endogenous and xenobiotic compounds according to various brain regions are not fully elucidated yet. This study aimed to further understand the role of EE on detoxifying enzymes, especially those participating in phase I of metabolism, by investigating the levels of enzymes in various brain regions such as the olfactory bulb, brain stem, frontal cortex, and striatum. Eight-month-old transgenic PD mice with the overexpression of human A53T α-synuclein and wild-type mice were randomly allocated to either standard cage condition or EE for 2 months. At 10 months of age, the expression of detoxifying enzymes was evaluated and compared with wild-type of the same age raised in standard cages. EE improved neurobehavioral outcomes such as olfactory and motor function in PD mice. EE-treated mice showed that oxidative stress was attenuated in the olfactory bulb, brain stem, and frontal cortex. EE also reduced apoptosis and induced cell proliferation in the subventricular zone of PD mice. The overexpression of detoxifying enzymes was observed in the olfactory bulb and brain stem of PD mice, which was ameliorated by EE. These findings were not apparent in the other experimental regions. These results suggest the stage of PD pathogenesis may differ according to brain region, and that EE has a protective effect on the PD pathogenesis by decreasing oxidative stress.

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