Intra-Extra Dimensional Shift Research Articles

Obesity and cognitive impairment in the adult population: A case-control study

In Western populations, obesity has been shown to have deleterious effects on many functions of the human body, including cognitive functions. To investigate the relationship between obesity and cognitive function impairment in the Saudi adult population. This cross-sectional study was conducted at King Saud University Hospital, Riyadh. All adult visitors to clinics and wards from February 2014 to March 2016 who met the selection criteria were included in the sample. The participants were divided into three comparable groups according to BMI: normal weight (BMI <25; Group I), overweight (BMI 25–29.9; Group II), and obese (BMI ≥30; Group III). The Cambridge Neurophysiological Test Automated Battery (CANTAB) was used to record the following cognitive function parameters: stop signal tasks (SST) and intra-extra dimensional shift (IED). A total of 138 participants were included in the study. The mean age of participants was 22.2 ± 2.7 years. SST mean correct reaction time on GO trials for Group I was 601.6 ± 290.2; for Group II it was 797.8 ± 303.2 (p = 0.011 compared to Group I), and for Group III it was 893.5 ± 378.7 (p < 0.001 compared to Group I). SST median correct reaction time on GO trials for Group I was 551.57 ± 234.49; for Group 2 it was 693.2 ± 275.7 (p = 0.025), and for Group III it was 742.7 ± 287.1 (p = 0.002). The stop signal task stop signal delay (SST SSD) 50% last half was 327.51 ± 178.63 for Group I; for Group II it was 449.5 ± 207.7 (p = 0.020), and for Group III it was 447.4 ± 263.7 (p = 0.028). Group I completed an average of 8.3 ± 1.3 IED stages; Group II completed 7.5 ± 2.6 (p = 0.090), and Group III completed 8.5 ± 0.8 (p = 1.000). PRM values did not differ significantly across groups. However, cognitive function was significantly delayed for the higher BMI groups when a post-hoc Bonferroni correction was applied. Age and gender correlated significantly, as did gender and BMI. Our findings suggest that Saudi subjects with higher BMI values exhibit poorer performance in many domains of cognitive function than Saudi individuals with a BMI in the normal range. • Obesity significantly affects brain structure and cognitive function. • The relationship between obesity and cognitive function impairment. • An increase in BMI is related to a decrease in cognitive performance.

Associations between time-weighted postnatal methylmercury exposure from fish consumption and neurodevelopmental outcomes through 24 years of age in the Seychelles Child Development Study Main Cohort

PurposeMethylmercury (MeHg) is a known neurodevelopmental toxicant in sufficient dosage and is universally found in fish. Current fish advisories for children are based on epidemiology studies examining prenatal exposure with a premise that MeHg exposure resulting from children eating fish could also be neurotoxic and have long-term consequences. However, the evidence that this assumption is true is limited. We investigated postnatal MeHg exposure from regular fish consumption using time weighted Hg measurements to determine if there are neurotoxic consequences. MethodsWe examined 85 neurodevelopmental outcomes measured from ages 9–24 years in the Seychelles Child Development Study Main Cohort (n = 312–550) and examined their association with time-weighted measures of postnatal MeHg exposure in childhood and early adulthood. Postnatal MeHg exposure measured in the first cm of participants’ hair samples collected at seven evaluations were used to create two time-weighted (TW) average MeHg exposure metrics, one for childhood (TW-C) and the other for early adulthood (TW-A). TW-C was based on Hg measures at three ages between 6 months and 5.5 years, and TW-A was based on Hg measured at up to four ages between 17 and 24 years. We examined the association between each of these exposure metrics and the neurodevelopmental outcomes using linear regression with adjustment for covariates known to influence neurodevelopmental outcomes. ResultsThere were 14 statistically significant associations between a postnatal metric and an endpoint. Six were associated with the TW-C and eight with the TW-A. Thirteen were adverse. Only the TW-C association at 9 years with the Bender Gestalt error score showed improvement. TW-C was adversely associated at 9 years with the Continuous Performance Task risk score, at 22 years with the Boston Naming Test (BNT) total and no cues scores, and at 24 years with the Test of Variables of Attention (TOVA) auditory response time variability and visual response time mean on the logarithmic scale. TW-A was adversely associated at 17 years with the Wisconsin Card Sorting Test % total errors, the Woodcock-Johnson passage comprehension, and the CANTAB rapid visual information processing false alarms, and at 22 years with the BNT total and no cue scores, the CANTAB rapid visual information processing false alarms and the intra-extra dimensional shift total errors and trials. ConclusionThese findings suggest that postnatal MeHg exposure may be adversely associated with neurodevelopmental outcomes in early adulthood. However, the associations are statistical and of unknown, if any, clinical significance. The results need confirmation in other cohorts.

Compulsivity and impulsivity in opioid dependence

ObjectiveChronic exposure to illicit opioid drugs can cause serious health and social problems. However, less is known about the differential effect of various opioid treatments, such as methadone and buprenorphine, on neurocognitive domains such as compulsivity and impulsivity, despite their relevance to the treatment of opioid dependence. MethodsA total of 186 participants were recruited with a cross-sectional design: i) illicit heroin users (n = 27), ii) former heroin users stabilized on methadone MMT (n = 48), iii) a buprenorphine maintenance treatment (BMT) group (n = 18), iv) an abstinent (ABS) group with a history of opioid dependence who were previously stabilized on MMT or BMT (n = 29) and v) healthy controls (HC) (n = 64). We used the Intra-Extra Dimensional Shift (IED) and Cambridge Gambling Task (CGT) paradigms for measuring compulsivity and impulsivity constructs respectively. ResultsHeightened compulsivity persisted in the heroin, buprenorphine and abstinent groups. Heroin, methadone and buprenorphine groups exhibited impaired behavioral responses to feedback, consisting of increased deliberation time and poorer risk adjustment. Higher compulsivity measures were negatively associated with opioid dose which may reflect sedation effects. ConclusionsOur results suggest that compulsivity and impulsivity are core neurocognitive dimensions for opioid dependence which differ in their presentation according to the stage of treatment. Participants taking higher morphine equivalent doses performed better in compulsivity measures. These findings have implications for the treatment of opioid dependence and longitudinal studies are warranted.

Latent subgroups of cognitive performance in lead- and manganese-exposed Uruguayan children: Examining behavioral signatures

ObjectivesLead (Pb) and manganese (Mn) are confirmed neurotoxins but it is unclear to what extent low-level exposure produces a unique behavioral signature. The objective of this study was to investigate latent cognitive profiles among children (6–8 years) from Montevideo, Uruguay co-exposed to these metals. MethodAmong 345 children, blood Pb and hair Mn were measured using atomic absorption spectroscopy and ICP-MS, respectively. Sixteen measures, reflecting multiple domains of cognitive functioning were gathered: (1) three tests from Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-Extra Dimensional Shift (IED), Spatial Span (SSP) and Stockings of Cambridge (SOC), (2) ten tasks from Woodcock-Muñoz Achievement Battery, Revised (WM): Visual-Motor Integration, Verbal Comprehension (Vocabulary, Synonyms, Antonyms, Analogies), Visual-Auditory Comprehension, Concept Formation, Visual Spatial Thinking, Number Inversion and Spatial Relations, (3) Bender Gestalt task, and (4) Weschler block design task. Scores were modeled using latent profile analysis (LPA). Association between blood Pb and hair Mn on performance profiles was assessed using ordinal regression, controlling for confounders. An interaction between Pb and Mn was tested. ResultsMean ± SD of blood Pb was 4.1 ± 2.1 μg/dL and 35% of children had blood Pb ≥ 5 μg/dL. Median [5%, 95%] hair Mn level was 0.8 [0.3, 4.1] ppb. Three latent cognitive performance profiles were identified: high (n = 46, 13%), average (n = 209, 61%) and low (n = 90, 26%). Each one-unit increase in blood Pb was associated with a 28% greater likelihood of belonging to a poorer-performing profile. The association was non-linear, with the effect of Pb on profile membership strongest at lower levels of exposure. There was no meaningful interaction between Pb and Mn. ConclusionsA behavioral signature for low-level Pb & Mn exposure was not identified, but the likelihood of membership in low-performing profile was higher at lowest levels of blood Pb. There was no effect measure modification between Pb and Mn. Future research should address how complex environments created by chemical exposures and the social context relate to cognitive performance in young children.

Executive function in middle childhood and the relationship with theory of mind

ABSTRACT A group of 126 typically developing children (aged 5–12 years) completed three cool executive function tasks (spatial working memory, stop signal, intra-extra dimensional shift), two hot executive function tasks (gambling, delay of gratification), one advanced theory of mind task (strange stories with high versus low affective tone), and a vocabulary test. Older children performed better than younger children, consistent with the protracted development of hot and cool executive functions and theory of mind. Multiple regression analyses showed that hot and cool executive functions were correlated but they predicted theory of mind in different ways.

Do children adopted from British foster care show difficulties in executive functioning and social communication?

Early life experiences leave a mark on a child’s emotional, social and cognitive development. It is well established that children adopted from psychosocially depriving institutions have difficulties in executive functioning and social communication ability, but this type of research has not been replicated in children adopted from foster care. In this study, 30 primary school aged UK adoptees without a history of institutionalisation completed an assessment of their intellectual, executive functioning and social communication abilities. Compared to children of a similar age in the general population, the adopted group showed elevated emotional and behavioural difficulties on a parental report measure (Strengths and Difficulties Questionnaire, SDQ). They performed statistically poorer on two of three computerised executive functioning tests (CANTAB Intra-Extra Dimensional Shift and Spatial Working Memory) and elevated scores were observed on a parental report measure of executive functioning (Behavior Rating Inventory of Executive Functioning, BRIEF). A strong negative correlation was found between age of adoption and BRIEF scores controlling for ADHD symptoms; no other pre- or post-adoption variables strongly correlated with executive functioning. Although all participants scored below cut-off on an autism screening measure (Social Communication Questionnaire, SCQ), a moderate positive correlation was observed with age of adoption. The identified elevation in emotional, behavioural and executive functioning difficulties is in line with previous research examining children adopted from institutions; however, the observed negative correlation between BRIEF scores and age of adoption is contrary to previous evidence. Limitations and implications for future research are discussed.

Assessing Specific Cognitive Deficits Associated with Dementia in Older Adults with Down Syndrome: Use and Validity of the Arizona Cognitive Test Battery (ACTB).

BackgroundDown syndrome is associated with specific cognitive deficits. Alongside this, older adults with Down syndrome are a high risk group for dementia. The Arizona Cognitive Test Battery (ACTB), a cognitive assessment battery specifically developed for use with individuals with Down syndrome, has been proposed for use as outcome measures for clinical trials in this population. It has not been validated in older adults with Down syndrome. This study aims to assess the use and validity of the ACTB in older adults with Down syndrome.MethodsParticipants with Down syndrome aged 45 and over were assessed using the ACTB, standard tabletop tests and informant ratings.ResultsAssessment outcomes of 49 participants were analysed. Of these, 19 (39%) had a diagnosis of dementia or possible dementia. Most participants were able to attempt most of the tasks, although some tasks had high floor effects (including CANTAB Intra-Extra Dimensional shift stages completed and Modified Dots Task). Of the ACTB tasks, statistically significant differences were observed between the dementia and no dementia groups on CANTAB Simple Reaction Time median latency, NEPSY Visuomotor Precision—Car and Motorbike and CANTAB Paired Associates Learning stages completed. No significant differences were observed for CANTAB Intra-Extra Dimensional Shift, Modified Dots Task, Finger Sequencing, NEPSY Visuomotor precision—Train and Car and CANTAB Paired Associates Learning first trial memory score. Several of the tasks in the ACTB can be used in older adults with Down syndrome and have mild to moderate concurrent validity when compared to tabletop tests and informant ratings, although this varies on a test by test basis.ConclusionsOverall, scores for a number of tests in the ACTB were similar when comparing dementia and no dementia groups of older adults with Down syndrome, suggesting that it would not be an appropriate outcome measure of cognitive function for clinical trials of dementia treatments without further modification and validation.

Strategy use, planning, and rule acquisition deficits in spinocerebellar ataxia type 2 patients.

Our goal was to improve spinocerebellar ataxia type 2 (SCA2) cognitive profile characterization by testing the hypothesis that strategy, planning and rule acquisition capacities are affected in SCA2. Forty one patients with SCA2 were evaluated with the Spatial Working Memory (SWM), the Stockings of Cambridge (SOC), and the Intra-Extra Dimensional Shift (IED) tests of the Executive module of the Cambridge Neuropsychological Testing Automated Battery (CANTAB). Paired Associates Learning (PAL) and Delayed Matching to Sample (DMS) from the CANTAB memory module were also assessed to corroborate previous findings. Motor deterioration was measured using the Scale for the Assessment and Rating of Ataxia (SARA). We found significant SCA2 related deficits in strategy, planning, and rule acquisition. Our results also corroborated significant memory deficits in these patients with SCA2. Further analysis also showed that patients with large motor deterioration had poorer associative learning and spatial planning scores. Patients with SCA2 show strategy, planning, and rule acquisition deficits as revealed with the CANTAB battery. These deficits should be noted when planning an effective therapy for these patients.

Repeated Detoxification of Alcohol-Dependent Patients Impairs Brain Mechanisms of Behavioural Control Important in Resisting Relapse

Alcohol abuse is frequently characterised by cycles of heavy drinking, detoxification, and relapse. We review evidence that multiple detoxifications are associated with impaired ability to control reward seeking, and with exaggerated responses to negative emotional stimuli. Under conditions of incentive conflict and in intra-extra dimensional shift and reversal tasks, deficits are found that are consistent with impaired executive control of behaviour by prefrontal cortical mechanisms. Correspondingly, alcoholics who have undergone multiple detoxifications show loss of grey matter in prefrontal regions associated with accurate performance of these tasks, the extent correlating with numbers of detoxifications. The ability to respond appropriately to certain emotional stimuli (e.g., fearful faces) is also impaired following multiple detoxifications. Such impairments are associated with reduced connectivity between insula and prefrontal areas but increased connectivity between insula and subcortical regions (colliculus), and between amygdala and other subcortical regions (bed nucleus of stria terminalis, BNST). Such changes may increase vulnerability to stress-induced relapse, and disrupt social abilities, contributing to social isolation.

Early-Stage Primary School Children Attending a School in the Malawian School Feeding Program (SFP) Have Better Reversal Learning and Lean Muscle Mass Growth Than Those Attending a Non-SFP School1,2

In developing countries, schoolchildren encounter a number of challenges, including failure to complete school, poor health and nutrition, and poor academic performance. Implementation of school feeding programs (SFPs) in less developed countries is increasing and yet there is mixed evidence regarding their positive effects on nutrition, education, and cognition at the population level. This study evaluated cognitive and anthropometric outcomes in entry-level primary school children in Malawi with the aim of generating evidence for the ongoing debate about SFPs in Malawi and other developing countries. A total of 226 schoolchildren aged 6–8 y in 2 rural Malawian public primary schools were followed for one school year. Children attending one school (SFP school) received a daily ration of corn-soy blend porridge, while those attending the other (non-SFP school) did not. Baseline and post-baseline outcomes included the Cambridge Neurological Test Automated Battery cognitive tests of paired associate learning, rapid visual information processing and intra-extra dimensional shift, and anthropometric measurements of weight, height, and mid-upper arm circumference (MUAC). At follow-up, the SFP subcohort had a greater reduction than the non-SFP subcohort in the number of intra-extra predimensional shift errors made (mean 18.5 and 24.9, respectively; P-interaction = 0.02) and also showed an increase in MUAC (from 16.3 to 17.0; P-interaction <0.0001). The results indicate that the SFP in Malawi is associated with an improvement in reversal learning and catch-up growth in lean muscle mass in children in the SFP school compared with children in the non-SFP school. These findings suggest that the Malawian SFP, if well managed and ration sizes are sustained, may have the potential to improve nutritional and cognitive indicators of the most disadvantaged children.

Negative modulation of GABAA α5 receptors by RO4938581 attenuates discrete sub-chronic and early postnatal phencyclidine (PCP)-induced cognitive deficits in rats

A growing body of evidence suggests that negative modulation of γ-aminobutyric acid (GABA) GABA(A) α5 receptors may be a promising strategy for the treatment of certain facets of cognitive impairment; however, selective modulators of GABA(A) α5 receptors have not yet been tested in "schizophrenia-relevant" cognitive assay/model systems in animals. The objectives of this study were to investigate the potential of RO4938581, a negative modulator of GABA(A) α5 receptors, and to attenuate cognitive impairments induced following sub-chronic (sub-PCP) and early postnatal PCP (neo-PCP) administration in the novel object recognition (NOR) and intra-extradimensional shift (ID/ED) paradigms in rats. Complementary in vitro, ex vivo and in vivo studies were performed to confirm negative modulatory activity of RO4938581 and to investigate animal model validity, concept validity and potential side effect issues, respectively. In vitro studies confirmed the reported negative modulatory activity of RO4938581, whilst immunohistochemical analyses revealed significantly reduced parvalbumin-positive cells in the prefrontal cortex of sub-PCP- and neo-PCP-treated rats. RO4938581 (1 mg/kg) ameliorated both sub-PCP- and neo-PCP-induced cognitive deficits in NOR and ID/ED performance, respectively. In contrast, QH-II-066 (1 and 3 mg/kg), a GABA(A) α5 receptor positive modulator, impaired cognitive performance in the NOR task when administered to vehicle-treated animals. Additional studies revealed that both RO4938581 (1 mg/kg) and QH-II-066 (1 and 3 mg/kg) attenuated amphetamine-induced hyperactivity in rats. Taken together, these novel findings suggest that negative modulation of GABA(A) α5 receptors may represent an attractive treatment option for the cognitive impairments, and potentially positive symptoms, associated with schizophrenia.

Fish consumption and prenatal methylmercury exposure: Cognitive and behavioral outcomes in the main cohort at 17 years from the Seychelles child development study

IntroductionPeople worldwide depend upon daily fish consumption as a major source of protein and other nutrients. Fish are high in nutrients essential for normal brain development, but they also contain methylmercury (MeHg), a neurotoxicant. Our studies in a population consuming fish daily have indicated no consistent pattern of adverse associations between prenatal MeHg and children's development. For some endpoints we found performance improved with increasing prenatal exposure to MeHg. Follow up studies indicate this association is related to the beneficial nutrients present in fish. ObjectivesTo determine if the absence of adverse outcomes and the presence of beneficial associations between prenatal MeHg and developmental outcomes previously reported persists into adolescence. MethodsThis study was conducted on the Main Cohort of the Seychelles Child Development Study (SCDS). We examined the association between prenatal MeHg exposure and subjects’ performance at 17 years of age on 27 endpoints. The test battery included the Wisconsin Card Sorting Test (WCST), the California Verbal Learning Test (CVLT), the Woodcock-Johnson (W-J-II) Achievement Test, subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB), and measures of problematic behaviors. Analyses for all endpoints were adjusted for postnatal MeHg, sex, socioeconomic status, maternal IQ, and child's age at testing and the child's IQ was added for problematic behavioral endpoints. ResultsMean prenatal MeHg exposure was 6.9ppm. There was no association between prenatal MeHg and 21 endpoints. Increasing prenatal MeHg was associated with better scores on four endpoints (higher W-J-II math calculation scores, reduced numbers of trials on the Intra-Extradimensional Shift Set of the CANTAB), fewer reports of substance use and incidents of and referrals for problematic behaviors in school. Increasing prenatal MeHg was adversely associated with one level of referrals to a school counselor. ConclusionsAt age 17 years there was no consistent pattern of adverse associations present between prenatal MeHg exposure and detailed domain specific neurocognitive and behavioral testing. There continues to be evidence of improved performance on some endpoints as prenatal MeHg exposure increases in the range studied, a finding that appears to reflect the role of beneficial nutrients present in fish as demonstrated previously in younger subjects. These findings suggest that ocean fish consumption during pregnancy is important for the health and development of children and that the benefits are long lasting.