Cognitive and Behavioral Inhibition Deficits in Parkinson’s Disease: The Hayling Test as a Reliable Marker

Siquier, Antònia; Andrés, Pilar

doi:10.3389/fnagi.2020.621603

Cited by 12 publications

(8 citation statements)

References 79 publications

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“…Of note, our analysis of reversal learning using touchscreens was much more sensitive than motor function assessments in M83+/+ mice. Executive dysfunction and deficits in reversal learning and behavioral flexibility are cognitive alterations found in human synucleinopathies [ 41 , 111 , 118 ]; therefore, the touchscreen experiments and MR imaging shown here provide a much more translatable readout from mice to humans [ 94 ]. α-Synuclein toxicity seems to selectively interfere with reversal learning, as we were unable to detect attentional deficits in these mice in early ages, despite pattern of atrophy in the brain that may suggest other cognitive deficits.…”

Section: Discussionmentioning

confidence: 99%

Stress-inducible phosphoprotein 1 (HOP/STI1/STIP1) regulates the accumulation and toxicity of α-synuclein in vivo

et al. 2022

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The predominantly pre-synaptic intrinsically disordered protein α-synuclein is prone to misfolding and aggregation in synucleinopathies, such as Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB). Molecular chaperones play important roles in protein misfolding diseases and members of the chaperone machinery are often deposited in Lewy bodies. Here, we show that the Hsp90 co-chaperone STI1 co-immunoprecipitated α-synuclein, and co-deposited with Hsp90 and Hsp70 in insoluble protein fractions in two mouse models of α-synuclein misfolding. STI1 and Hsp90 also co-localized extensively with filamentous S129 phosphorylated α-synuclein in ubiquitin-positive inclusions. In PD human brains, STI1 transcripts were increased, and in neurologically healthy brains, STI1 and α-synuclein transcripts correlated. Nuclear Magnetic Resonance (NMR) analyses revealed direct interaction of α-synuclein with STI1 and indicated that the STI1 TPR2A, but not TPR1 or TPR2B domains, interacted with the C-terminal domain of α-synuclein. In vitro, the STI1 TPR2A domain facilitated S129 phosphorylation by Polo-like kinase 3. Moreover, mice over-expressing STI1 and Hsp90ß presented elevated α-synuclein S129 phosphorylation accompanied by inclusions when injected with α-synuclein pre-formed fibrils. In contrast, reduced STI1 function decreased protein inclusion formation, S129 α-synuclein phosphorylation, while mitigating motor and cognitive deficits as well as mesoscopic brain atrophy in α-synuclein-over-expressing mice. Our findings reveal a vicious cycle in which STI1 facilitates the generation and accumulation of toxic α-synuclein conformers, while α-synuclein-induced proteostatic stress increased insoluble STI1 and Hsp90.

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Section: Discussionmentioning

confidence: 99%

Stress-inducible phosphoprotein 1 (HOP/STI1/STIP1) regulates the accumulation and toxicity of α-synuclein in vivo

et al. 2022

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“…It also opens new perspectives in understanding the physiopathology of language alterations in various brain disorders. For instance, sentence completion tests have been administered to evaluate cognition in neurodegenerative diseases, such as Alzheimer's disease (Kim & Thompson, 2004;Martyr et al, 2019) Parkinson's disease (Martyr et al, 2019;Siquier & Andrés, 2021) and amyotrophic lateral sclerosis (Abrahams et al, 2005). MEG should bring novel insights in the spectro-temporal correlates of previously reported abnormalities.…”

Section: Discussionmentioning

confidence: 99%

Spectro-temporal neural dynamics during sentence completion

Coolen

Wens

et al. 2021

Preprint

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This magnetoencephalography (MEG) study aimed at characterizing the spectro-temporal dynamics of brain oscillatory activity elicited by sentence completion (SC). For that purpose, we adapted a version of the SC experimental paradigm typically used in functional magnetic resonance imaging to MEG investigation constraints. Twenty right-handed healthy young adults underwent MEG recordings while they were sequentially presented with short sentences divided in three parts: the first two giving context and the last requiring completion. MEG data were then analysed using a prior-free, non-parametric statistical approach with stringent control of the family-wise error rate. We identified three successive significant neural response patterns associated with distinct spatial and spectro-temporal characteristics: (i) an early (<300 ms) bioccipital 4-10-Hz event-related synchronization (ERS); (ii) an intermediate (at about 400 ms) 8-30-Hz event-related desynchronization (ERD) in an extended semantic network involving the ventral language stream as well as bilateral posterior nodes of the default mode network (DMN) in both hemispheres; (iii) a late (>800 ms) 8-30 Hz ERD involving the left dorsal language stream. Furthermore, the left component of the ventral language stream displayed prolonged ERD after 800 ms compared to the right which showed signs of inhibition in the form of ERS. Overall, this study elucidates the dynamics of the recruitment of the language network that accompany SC and the spectro-temporal signature of an extended semantic network. This MEG adaptation of an SC paradigm also paves the way for novel approaches in presurgical language mapping and may help to understand the neural underpinnings of the alterations of sentence completion in various neurologic disorders affecting language.

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“…The Hayling test is one of the neuropsychological tests that has proven to be especially sensitive to detect inhibitory dysfunctions in PD (Foley et al, 2019; Martyr et al, 2019; Obeso et al, 2011; Siquier & Andrés, 2021b). In this test, two sections (A and B) where 15 incomplete sentences are read aloud are included.…”

Section: Methodsmentioning

confidence: 99%

Facial emotion recognition in Parkinson’s disease: The role of executive and affective domains.

Siquier¹,

Andrés²

2022

Neuropsychology

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Objective: The ability to recognize emotions from facial expression (FER) may be impaired in Parkinson's disease (PD). We aimed to explore FER in PD patients by using a dynamic presentation of emotions across different intensities and to examine the extent to which executive and affective alterations contributed to FER deficits. Method: Fifteen PD patients and 15 healthy controls were assessed on the emotion recognition task (ERT). We also explored how clinical and executive factors could have contributed to ERT accuracy. Results: PD patients showed poorer performance on the ERT, specifically on angry expressions, but they benefited from increased intensity as much as controls did. Differences were also found for apathy, depression, and executive tests, especially in the inhibition domain. Importantly, differences between groups on the ERT disappeared when controlling for inhibition and the affective symptoms. A significant effect of inhibition dysfunction was also observed on the ERT performance. Conclusions: Our findings demonstrate the presence of emotion recognition deficits of morphed facial expressions in patients with PD. Moreover, they suggest that inhibition dysfunctions may act as an important factor negatively influencing FER. The present study highlights the complex nature of emotion processing and its relation with emotionalaffective and cognitive aspects to provide a better understanding of FER deficits in PD. Key PointsQuestion: How do executive and affective dysfunctions contribute to facial emotion recognition (FER) deficits in Parkinson's disease (PD)? Findings: Inhibition dysfunction acts as a relevant contributor to FER deficits in PD. Importance: Our results show a close link between emotional-affective and cognitive levels. Next Steps: Future research examining the complex nature of emotion processing would help to provide a richer understanding of FER in PD.

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Cognitive and Behavioral Inhibition Deficits in Parkinson’s Disease: The Hayling Test as a Reliable Marker

Cited by 12 publications

References 79 publications

Stress-inducible phosphoprotein 1 (HOP/STI1/STIP1) regulates the accumulation and toxicity of α-synuclein in vivo

Stress-inducible phosphoprotein 1 (HOP/STI1/STIP1) regulates the accumulation and toxicity of α-synuclein in vivo

Spectro-temporal neural dynamics during sentence completion

Facial emotion recognition in Parkinson’s disease: The role of executive and affective domains.

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