scholarly journals Cerebellar GABA Levels and Cognitive Interference in Parkinson’s disease and Healthy Comparators

2020 ◽  
Vol 11 (1) ◽  
pp. 16
Author(s):  
Federica Piras ◽  
Daniela Vecchio ◽  
Francesca Assogna ◽  
Clelia Pellicano ◽  
Valentina Ciullo ◽  
...  

The neuroanatomical and molecular substrates for cognitive impairment in Parkinson Disease (PD) are far from clear. Evidence suggests a non-dopaminergic basis, and a crucial role for cerebellum in cognitive control in PD. We investigated whether a PD cognitive marker (response inhibition) was differently controlled by g-amino butyric acid (GABA) and/or by glutamate-glutamine (Glx) levels in the cerebellum of idiopathic PD patients, and healthy comparators (HC). Magnetic resonance spectroscopy of GABA/Glx (MEGA-PRESS acquisition sequence) was performed at 3 Tesla, and response inhibition assessed by the Stroop Word-Color Test (SWCT) and the Wisconsin Card Sorting Test (WCST). Linear correlations between cerebellar GABA/Glx levels, SWCT time/error interference effects and WCST perseverative errors were performed to test differences between correlation coefficients in PD and HC. Results showed that higher levels of mean cerebellar GABA were associated to SWCT increased time and error interference effects in PD, and the contrary in HC. Such effect dissociated by hemisphere, while correlation coefficients differences were significant in both right and left cerebellum. We conclude that MRS measured levels of cerebellar GABA are related in PD patients with decreased efficiency in filtering task-irrelevant information. This is crucial for developing pharmacological treatments for PD to potentially preserve cognitive functioning.

2019 ◽  
Vol 19 (6) ◽  
pp. 405-418
Author(s):  
Maciej Bieliński ◽  
Natalia Lesiewska ◽  
Roman Junik ◽  
Anna Kamińska ◽  
Andrzej Tretyn ◽  
...  

Background:Obesity is a chronic condition associated with poorer cognitive functioning. Wisconsin Card Sorting Test (WCST) is a useful tool for evaluating executive functions. In this study, we assessed the association between dopaminergic gene polymorphisms: DAT1 (SLC6A3), COMTVal158Met, DRD4 (48-bp variable number of tandem repeats - VNTR) and WCST parameters to investigate the functions of the frontal lobes in obese individuals.Objective:To find the significant correlations between polymorphisms of DAT1, COMTVal158Met, DRD4 and executive functions in obese subjects.Methods:The analysis of the frequency of individual alleles was performed in 248 obese patients (179 women, 69 men). Evaluation of the prefrontal cortex function (operating memory and executive functions) was measured with the Wisconsin Card Sorting Test (WCST). Separate analyzes were performed in age subgroups to determine different activities and regulation of genes in younger and older participants.Results:Scores of WCST parameters were different in the subgroups of women and men and in the age subgroups. Regarding the COMT gene, patients with A/A and G/A polymorphisms showed significantly better WCST results in WCST_P, WCST_CC and WCST_1st. Regarding DAT1 men with L/L and L/S made less non-perseverative errors, which was statistically significant. In DRD4, significantly better WCST_1st results were found only in older women with S allele.Conclusion:Obtained results indicate the involvement of dopaminergic transmission in the regulation of prefrontal cortex function. Data analysis indicates that prefrontal cortex function may ensue, from different elements such as genetic factors, metabolic aspects of obesity, and hormonal activity (estrogen).


2021 ◽  
pp. 003329412198899
Author(s):  
Robert I. Block ◽  
Gerry Jager ◽  
Maartje Luijten ◽  
Nick F. Ramsey

Many American and Dutch adolescents use marijuana regularly. There is concern that such use may impair cognitive function more in adolescents than adults. We examined effects of regular marijuana use on long-term memory and perseveration among American and Dutch adolescents. We administered Buschke's Selective Reminding Test (BSRT) to assess long-term memory and the Wisconsin Card Sorting Test (WCST) to assess perseveration in male teenagers. Usable test data were obtained for 12 American marijuana users, 13 American controls, 9 Dutch marijuana users, and 12 Dutch controls. In BSRT, users showed lower overall long-term storage than controls (adjusted means ± SE's for numbers of words per trial of 9.4 ± 0.2, 13.4 ± 0.3, 11.7 ± 0.2, and 12.4 ± 0.2 for American users, Dutch users, American controls, and Dutch controls, respectively). Marijuana was associated with memory effects only in American, not Dutch, users. Bivariate Pearson correlations for American and Dutch users combined showed associations of lower total recall with more uses in the previous year and lifetime (r = –0.61 and r = –0.53, respectively); and more perseverative errors with more uses in the previous year (r = 0.55). Some findings were consistent with the possibility that regular adolescent marijuana use causes deficits in cognition, especially memory. However, a causal interpretation cannot be inferred from our findings and is challenging to reconcile with the observation of memory deficits only in American users. Our study was novel in examining the influence of nationality on marijuana's cognitive effects. More studies of this topic should compare effects across nationalities or cultures.


2020 ◽  
Vol 23 (11) ◽  
pp. 731-737
Author(s):  
Yuzuru Kataoka ◽  
Takamitsu Shimada ◽  
Yoko Koide ◽  
Hiroaki Okubo ◽  
Takashi Uehara ◽  
...  

Abstract Background Patients with schizophrenia (SCZ) display impaired executive functions compared with healthy controls (HCs). Furthermore, unaffected first-degree relatives (FRs) of patients with SCZ independently perform worse executive functions than do HCs. However, few studies have investigated the differences in executive functions assessed among patients with SCZ, FRs, and HCs, and the findings are inconsistent. Methods We investigated diagnostic differences in executive functions, namely (1) numbers of categories achieved (CA), (2) total errors (TE), and (3) percentage of perseverative errors of Nelson types (%PEN), using the Wisconsin card sorting test among patients with SCZ (n = 116), unaffected FRs (n = 62), and HCs (n = 146) at a single institute. Correlations between these executive functions and clinical variables were investigated. Results Significant differences existed in all executive functions among diagnostic groups (CA, F2,319 = 15.5, P = 3.71 × 10–7; TE, F2,319 = 16.2, P = 2.06 × 10–7; and %PEN, F2,319 = 21.3, P = 2.15 × 10–9). Patients with SCZ had fewer CA and more TE and %PEN than those of HCs (CA, Cohen’s d = −0.70, P = 5.49 × 10–8; TE, d = 0.70, P = 5.62 × 10–8; and %PEN, d = 0.82, P = 2.85 × 10−10) and FRs (TE, d = 0.46, P = 3.73 × 10–3 and %PEN, d = 0.38, P = .017). Of the 3 executive functions, CA and %PEN of FRs were intermediately impaired between patients with SCZ and HCs (CA, d = −0.41, P = .011 and %PEN, d = 0.41, P = .012). In contrast, no significant difference in TE existed between FRs and HCs (d = 0.22, P = .18). Although CA and TE were affected by the duration of illness (P < .017), %PEN was not affected by any clinical variable in patients with SCZ (P > .017). Conclusions Executive function, particularly %PEN, could be a useful intermediate phenotype for understanding the genetic mechanisms implicated in SCZ pathophysiology.


1998 ◽  
Vol 83 (3) ◽  
pp. 1075-1080 ◽  
Author(s):  
Ryuji Sato ◽  
Toru Hosokawa ◽  
Atsushi Tanaka ◽  
Norio Murai

The present study was designed to investigate characteristics by 38 school-age children in Grades 2, 4, and 6 of perseverative errors using the Wisconsin Card Sorting Test. Children's performance was measured as number of categories completed and perseverative errors, which were classified into perseverative errors of types described by Milner in 1963 and Nelson in 1976. Analysis indicated that the number of completed categories increased and perseverative errors decreased across age groups. Perseverative errors (Milner) were very similar in these grades and perseverative errors (Nelson) were significantly different between children in Grades 2 and 4. The results suggested a pattern of development for shifting inhibiting set.


2011 ◽  
Vol 23 (10) ◽  
pp. 1552-1559 ◽  
Author(s):  
Seishi Terada ◽  
Shuhei Sato ◽  
Hajime Honda ◽  
Yuki Kishimoto ◽  
Naoya Takeda ◽  
...  

ABSTRACTBackground: The Wisconsin Card Sorting Test (WCST) has long been used to investigate deficits in executive function in humans. The majority of studies investigating deficient WCST performance focused on the number of categories achieved (CA) and the number of perseverative errors of the Nelson type (PEN). However, there is insufficient evidence that these two measures reflect the same neural deficits.Methods: Twenty AD patients with high PEN scores, and 20 age- and sex-matched AD patients with low PEN scores were selected. All 40 subjects underwent brain SPECT, and the SPECT images were analyzed by Statistical Parametric Mapping.Results: No significant differences were found between high and low PEN score groups with respect to years of education, Addenbrooke's Cognitive Examination scores, and Mini-Mental State Examination scores. However, higher z scores for hypoperfusion in the bilateral rectal and orbital gyri were observed in the high PEN score group compared with the low PEN score group.Conclusions: Our results suggest that functional activity of the bilateral rectal and orbital gyri is closely related to PEN scores on a modified WCST (mWCST). The PEN score on a mWCST might be a promising index of dysfunction of the orbitofrontal area among patients with mild AD.


2019 ◽  
Vol 9 (6) ◽  
pp. 141 ◽  
Author(s):  
Kopp ◽  
Steinke ◽  
Bertram ◽  
Skripuletz ◽  
Lange

We explored short-term behavioral plasticity on the Modified Wisconsin Card Sorting Test (M-WCST) by deriving novel error metrics by stratifying traditional set loss and perseverative errors. Separating the rule set and the response set allowed for the measurement of performance across four trial types, crossing rule set (i.e., maintain vs. switch) and response demand (i.e., repeat vs. alternate). Critically, these four trial types can be grouped based on trial-wise feedback on t − 1 trials. Rewarded (correct) maintain t − 1 trials should lead to error enhancement when the response demands shift from repeat to alternate. In contrast, punished (incorrect) t − 1 trials should lead to error suppression when the response demands shift from repeat to alternate. The results supported the error suppression prediction: An error suppression effect (ESE) was observed across numerous patient samples. Exploratory analyses show that the ESE did not share substantial portions of variance with traditional neuropsychological measures of executive functioning. They further point into the direction that striatal or limbic circuit neuropathology may be associated with enhanced ESE. These data suggest that punishment of the recently executed response induces behavioral avoidance, which is detectable as the ESE on the WCST. The assessment of the ESE might provide an index of response-related avoidance learning on the WCST.


2015 ◽  
Vol 22 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Monika Mak ◽  
Ernest Tyburski ◽  
Łukasz Madany ◽  
Andrzej Sokołowski ◽  
Agnieszka Samochowiec

AbstractThe cerebellum has long been perceived as a structure responsible for the human motor function. According to the contemporary approach, however, it plays a significant role in complex behavior regulatory processes. The aim of this study was to describe executive functions in patients after cerebellar surgery. The study involved 30 patients with cerebellar pathology. The control group comprised 30 neurologically and mentally healthy individuals, matched for sex, age, and number of years of education. Executive functions were measured by the Wisconsin Card Sorting Test (WCST), Stroop Color Word Test (SCWT), Trail Making Test (TMT), and working memory by the Digit Span. Compared to healthy controls, patients made more Errors and Perseverative errors in the WCST, gave more Perseverative responses, and had a lower Number of categories completed. The patients exhibited higher response times in all three parts of the SCWT and TMT A and B. No significant differences between the two groups were reported in their performance of the SCWT and TMT with regard to the measures of absolute or relative interference. The patients had lower score on the backward Digit Span. Patients with cerebellar pathology may exhibit some impairment within problem solving and working memory. Their worse performance on the SCWT and TMT could, in turn, stem from their poor motor–somatosensory control, and not necessarily executive deficits. Our results thus support the hypothesis of the cerebellum’s mediating role in the regulation of the activity of the superordinate cognitive control network in the brain. (JINS, 2016, 22, 47–57)


2009 ◽  
Vol 40 (10) ◽  
pp. 1635-1646 ◽  
Author(s):  
K. E. Scholes ◽  
M. T. Martin-Iverson

BackgroundThe effects of cannabis use on neuropsychological indices that show characteristic disturbances in schizophrenia are unclear. The effect of cannabis use on these cognitive functions is of particular interest given the hypothesized association between cannabis use and schizophrenia. Therefore, this study aimed to examine the effects of cannabis use on attentional control, working memory and executive functioning, in both healthy individuals and patients with schizophrenia.MethodNeuropsychological performance was assessed in 36 cannabis users who were otherwise healthy, 35 healthy non-users, 22 cannabis-using patients with schizophrenia, and 49 non-using patients with schizophrenia. Participants were administered the Stroop task, the letter–number sequencing and spatial span subtests of the Wechsler Memory Scale, and the Wisconsin Card Sorting Test (WCST).ResultsPatients with schizophrenia (both cannabis users and non-users) showed significantly poorer performance across all neuropsychological tasks, relative to controls; however, there were no significant differences between schizophrenic cannabis users and schizophrenic non-users on any measures, with the exception of increased non-perseverative errors on the WCST in cannabis-using patients. Similarly, healthy cannabis users showed no significant differences from healthy non-users in any of the cognitive domains, with the exception of a schizophrenic-like increase in perseveration on the WCST.ConclusionsAmongst both healthy individuals and patients with schizophrenia there appears to be little difference in cognitive performance between cannabis users and non-users, suggesting that cannabis use has only subtle effects on the neurocognitive performance indices assessed here, which have been well established to be disturbed in schizophrenia.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1934 ◽  
Author(s):  
Philip Lindner ◽  
Per Carlbring ◽  
Erik Flodman ◽  
Amanda Hebert ◽  
Stephanie Poysti ◽  
...  

Little is known about the individual factors that predict outcomes in Internet-administered psychological treatments. We hypothesized that greater cognitive flexibility (i.e. the ability to simultaneously consider several concepts and tasks and switch effortlessly between them in response to changes in environmental contingencies) would provide a better foundation for learning and employing the cognitive restructuring techniques taught and exercised in therapy, leading to greater treatment gains. Participants in three trials featuring Internet-administered psychological treatments for depression (n = 36), social anxiety disorder (n = 115) and tinnitus (n = 53) completed the 64-card Wisconsin Card Sorting Test (WCST) prior to treatment. We found no significant associations between perseverative errors on the WCST and treatment gains in any group. We also found low accuracy in the classification of treatment responders. We conclude that lower cognitive flexibility, as captured by perseverative errors on the WCST, should not impede successful outcomes in Internet-delivered psychological treatments.


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