scholarly journals Computational Modeling for Neuropsychological Assessment of Bradyphrenia in Parkinson’s Disease

2020 ◽  
Vol 9 (4) ◽  
pp. 1158 ◽  
Author(s):  
Alexander Steinke ◽  
Florian Lange ◽  
Caroline Seer ◽  
Merle K. Hendel ◽  
Bruno Kopp

The neural mechanisms of cognitive dysfunctions in neurological diseases remain poorly understood. Here, we conjecture that this unsatisfying state-of-the-art is in part due to the non-specificity of the typical behavioral indicators for cognitive dysfunctions. Our study addresses the topic by advancing the assessment of cognitive dysfunctions through computational modeling. We investigate bradyphrenia in Parkinson’s disease (PD) as an exemplary case of cognitive dysfunctions in neurological diseases. Our computational model conceptualizes trial-by-trial behavioral data as resulting from parallel cognitive and sensorimotor reinforcement learning. We assessed PD patients ‘on’ and ‘off’ their dopaminergic medication and matched healthy control (HC) participants on a computerized version of the Wisconsin Card Sorting Test. PD patients showed increased retention of learned cognitive information and decreased retention of learned sensorimotor information from previous trials in comparison to HC participants. Systemic dopamine replacement therapy did not remedy these cognitive dysfunctions in PD patients but incurred non-desirable side effects such as decreasing cognitive learning from positive feedback. Our results reveal novel insights into facets of bradyphrenia that are indiscernible by observable behavioral indicators of cognitive dysfunctions. We discuss how computational modeling may contribute to the advancement of future research on brain–behavior relationships and neuropsychological assessment.

2016 ◽  
Vol 2 (4) ◽  
pp. 252-259
Author(s):  
Na Ye ◽  
Tao Feng

Barker first used transcranial magnetic stimulation in 1985 in human brain function research. Since then, it has gradually been developed into a secure and non-invasive treatment method for neurological diseases. In 1994, Pascual Leone first used it for the treatment of Parkinson's disease (PD) and observed an improvement in the motor symptoms of most of the patients. Recent studies have confirmed that both motor and non-motor symptoms of patients with PD could be improved through biochemical, electrophysiological, and functional magnetic resonance imaging analysis. Different therapeutic applications can be achieved by adjusting the stimulation parameters. Physical factors affecting the therapeutic effect include the shape and size of the coil, array orientation, materials and intensity, frequency of stimulus, etc.; the biological factors include stimulating targets, baseline, circadian rhythms, cerebral cortex thickness, and so on. This paper will review these factors and provide a reference for future research.


2021 ◽  
Vol 13 ◽  
Author(s):  
Claudia Gianelli ◽  
Carlotta Maiocchi ◽  
Nicola Canessa

Increasing evidence shows that the typical motor symptoms of Parkinson’s disease (PD) are often accompanied, if not preceded, by cognitive dysfunctions that are potentially linked to further complications of the disease. Notably, these cognitive dysfunctions appear to have a significant impact in the domain of action processing, as indicated by specific impairments for action-related stimuli in general, and verbs in particular. In this mini-review, we focus on the use of the action fluency test as a tool to investigate action processing, in PD patients. We discuss the current results within the embodied cognition framework and in relation to general action-related impairments in PD, while also providing an outlook on open issues and possible avenues for future research. We argue that jointly addressing action semantic processing and motor dysfunctions in PD patients could pave the way to interventions where the motor deficits are addressed to improve both motor and communicative skills since the early disease stages, with a likely significant impact on quality of life.


2020 ◽  
Vol 10 (12) ◽  
pp. 1000
Author(s):  
Alexander Steinke ◽  
Bruno Kopp

Cognitive inflexibility is a well-documented, yet non-specific corollary of many neurological diseases. Computational modeling of covert cognitive processes supporting cognitive flexibility may provide progress toward nosologically specific aspects of cognitive inflexibility. We review computational models of the Wisconsin Card Sorting Test (WCST), which represents a gold standard for the clinical assessment of cognitive flexibility. A parallel reinforcement-learning (RL) model provides the best conceptualization of individual trial-by-trial WCST responses among all models considered. Clinical applications of the parallel RL model suggest that patients with Parkinson’s disease (PD) and patients with amyotrophic lateral sclerosis (ALS) share a non-specific covert cognitive symptom: bradyphrenia. Impaired stimulus-response learning appears to occur specifically in patients with PD, whereas haphazard responding seems to occur specifically in patients with ALS. Computational modeling hence possesses the potential to reveal nosologically specific profiles of covert cognitive symptoms, which remain undetectable by traditionally applied behavioral methods. The present review exemplifies how computational neuropsychology may advance the assessment of cognitive flexibility. We discuss implications for neuropsychological assessment and directions for future research.


2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Manan Binth Taj Noor ◽  
Nusrat Zerin Zenia ◽  
M Shamim Kaiser ◽  
Shamim Al Mamun ◽  
Mufti Mahmud

Abstract Neuroimaging, in particular magnetic resonance imaging (MRI), has been playing an important role in understanding brain functionalities and its disorders during the last couple of decades. These cutting-edge MRI scans, supported by high-performance computational tools and novel ML techniques, have opened up possibilities to unprecedentedly identify neurological disorders. However, similarities in disease phenotypes make it very difficult to detect such disorders accurately from the acquired neuroimaging data. This article critically examines and compares performances of the existing deep learning (DL)-based methods to detect neurological disorders—focusing on Alzheimer’s disease, Parkinson’s disease and schizophrenia—from MRI data acquired using different modalities including functional and structural MRI. The comparative performance analysis of various DL architectures across different disorders and imaging modalities suggests that the Convolutional Neural Network outperforms other methods in detecting neurological disorders. Towards the end, a number of current research challenges are indicated and some possible future research directions are provided.


Author(s):  
Robbin Romijnders ◽  
Elke Warmerdam ◽  
Clint Hansen ◽  
Julius Welzel ◽  
Gerhard Schmidt ◽  
...  

Abstract Background Identification of individual gait events is essential for clinical gait analysis, because it can be used for diagnostic purposes or tracking disease progression in neurological diseases such as Parkinson’s disease. Previous research has shown that gait events can be detected from a shank-mounted inertial measurement unit (IMU), however detection performance was often evaluated only from straight-line walking. For use in daily life, the detection performance needs to be evaluated in curved walking and turning as well as in single-task and dual-task conditions. Methods Participants (older adults, people with Parkinson’s disease, or people who had suffered from a stroke) performed three different walking trials: (1) straight-line walking, (2) slalom walking, (3) Stroop-and-walk trial. An optical motion capture system was used a reference system. Markers were attached to the heel and toe regions of the shoe, and participants wore IMUs on the lateral sides of both shanks. The angular velocity of the shank IMUs was used to detect instances of initial foot contact (IC) and final foot contact (FC), which were compared to reference values obtained from the marker trajectories. Results The detection method showed high recall, precision and F1 scores in different populations for both initial contacts and final contacts during straight-line walking (IC: recall $$=$$ = 100%, precision $$=$$ = 100%, F1 score $$=$$ = 100%; FC: recall $$=$$ = 100%, precision $$=$$ = 100%, F1 score $$=$$ = 100%), slalom walking (IC: recall $$=$$ = 100%, precision $$\ge$$ ≥ 99%, F1 score $$=$$ = 100%; FC: recall $$=$$ = 100%, precision $$\ge$$ ≥ 99%, F1 score $$=$$ = 100%), and turning (IC: recall $$\ge$$ ≥ 85%, precision $$\ge$$ ≥ 95%, F1 score $$\ge$$ ≥ 91%; FC: recall $$\ge$$ ≥ 84%, precision $$\ge$$ ≥ 95%, F1 score $$\ge$$ ≥ 89%). Conclusions Shank-mounted IMUs can be used to detect gait events during straight-line walking, slalom walking and turning. However, more false events were observed during turning and more events were missed during turning. For use in daily life we recommend identifying turning before extracting temporal gait parameters from identified gait events.


2021 ◽  
Vol 22 (9) ◽  
pp. 4676
Author(s):  
Katja Badanjak ◽  
Sonja Fixemer ◽  
Semra Smajić ◽  
Alexander Skupin ◽  
Anne Grünewald

With the world’s population ageing, the incidence of Parkinson’s disease (PD) is on the rise. In recent years, inflammatory processes have emerged as prominent contributors to the pathology of PD. There is great evidence that microglia have a significant neuroprotective role, and that impaired and over activated microglial phenotypes are present in brains of PD patients. Thereby, PD progression is potentially driven by a vicious cycle between dying neurons and microglia through the instigation of oxidative stress, mitophagy and autophagy dysfunctions, a-synuclein accumulation, and pro-inflammatory cytokine release. Hence, investigating the involvement of microglia is of great importance for future research and treatment of PD. The purpose of this review is to highlight recent findings concerning the microglia-neuronal interplay in PD with a focus on human postmortem immunohistochemistry and single-cell studies, their relation to animal and iPSC-derived models, newly emerging technologies, and the resulting potential of new anti-inflammatory therapies for PD.


2021 ◽  
Vol 22 (12) ◽  
pp. 6277
Author(s):  
Joanna A. Motyl ◽  
Joanna B. Strosznajder ◽  
Agnieszka Wencel ◽  
Robert P. Strosznajder

Molecular studies have provided increasing evidence that Parkinson’s disease (PD) is a protein conformational disease, where the spread of alpha-synuclein (ASN) pathology along the neuraxis correlates with clinical disease outcome. Pathogenic forms of ASN evoke oxidative stress (OS), neuroinflammation, and protein alterations in neighboring cells, thereby intensifying ASN toxicity, neurodegeneration, and neuronal death. A number of evidence suggest that homeostasis between bioactive sphingolipids with opposing function—e.g., sphingosine-1-phosphate (S1P) and ceramide—is essential in pro-survival signaling and cell defense against OS. In contrast, imbalance of the “sphingolipid biostat” favoring pro-oxidative/pro-apoptotic ceramide-mediated changes have been indicated in PD and other neurodegenerative disorders. Therefore, we focused on the role of sphingolipid alterations in ASN burden, as well as in a vast range of its neurotoxic effects. Sphingolipid homeostasis is principally directed by sphingosine kinases (SphKs), which synthesize S1P—a potent lipid mediator regulating cell fate and inflammatory response—making SphK/S1P signaling an essential pharmacological target. A growing number of studies have shown that S1P receptor modulators, and agonists are promising protectants in several neurological diseases. This review demonstrates the relationship between ASN toxicity and alteration of SphK-dependent S1P signaling in OS, neuroinflammation, and neuronal death. Moreover, we discuss the S1P receptor-mediated pathways as a novel promising therapeutic approach in PD.


Author(s):  
Mohammad Zamanian ◽  
Małgorzata Kujawska ◽  
Marjan Nikbakht Zadeh ◽  
Amin Hassanshahi ◽  
Soudeh Ramezanpour ◽  
...  

Background & objective: Neurological diseases are becoming a significant problem worldwide, with the elderly at a higher risk of being affected. Several researchers have investigated the neuroprotective effects of Carvacrol (CAR) (5-isopropyl-2-methyl phenol). This review systematically surveys the existing literature on the impact of CAR when used as a neuroprotective agent in neurological diseases. Methods: The systematic review involved English articles published in the last ten years obtained from PubMed, Google Scholar, and Scopus databases. The following descriptors were used to search the literature: “Carvacrol” [Title] AND “neuroprotective (neuroprotection)” [Title] OR “stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, seizure, epilepsy [Title]. Results: : A total of 208 articles were retrieved during the search process, but only 20 studies met the eligibility criteria and were included for review. A total of 20 articles were identified, in which the efficacy of CAR was described in experimental models of stroke, traumatic brain injury, Parkinson’s disease, Alzheimer’s disease, , epilepsy, and seizure, through motor deficits improvements in neurochemical activity, especially antioxidant systems, reducing inflammation, oxidative stress and apoptosis as well as inhibition of TRPC1 and TRPM7. Conclusion : The data presented in this study support the beneficial impact of CAR on behavioural and neurochemical deficits. CAR benefits accrue because of its anti-apoptotic, antioxidant, and anti-inflammatory properties. Therefore, CAR has emerged as an alternative treatment for neurological disorders based on its properties.


2021 ◽  
Vol 27 ◽  
Author(s):  
Niklas Frahm ◽  
Michael Hecker ◽  
Uwe Zettl

: Polypharmacy is an important aspect of medication management and particularly affects elderly and chronically ill people. Patients with dementia, Parkinson’s disease (PD) or multiple sclerosis (MS) are at high risk for multimedication due to their complex symptomatology. Our aim was to provide an overview of different definitions of polypharmacy and to present the current state of research on polypharmacy in patients with dementia, PD or MS. The most common definition of polypharmacy in the literature is the concomitant use of ≥5 medications (quantitative definition approach). Polypharmacy rates of up to >50% have been reported for patients with dementia, PD or MS, although MS patients are on average significantly younger than those with dementia or PD. The main predictor of polypharmacy is the complex symptom profile of these neurological disorders. Potentially inappropriate medication (PIM), drug-drug interactions, poor treatment adherence, severe disease course, cognitive impairment, hospitalisation, poor quality of life, frailty and mortality have been associated with polypharmacy in patients with dementia, PD or MS. For patients with polypharmacy, either the avoidance of PIM (selective deprescribing) or the substitution of PIM with more suitable drugs (appropriate polypharmacy) is recommended to achieve a more effective therapeutic management.


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