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Psychomotor disturbances are observed across psychiatric disorders and often manifest as psychomotor slowing, agitation, disorganized behavior, or catatonia. Psychomotor function includes both cognitive and motor components, but the neural circuits driving these subprocesses and how they relate to symptoms have remained elusive for centuries. We analyzed data from the HCP-EP (Human Connectome Project for Early Psychosis), a multisite study of 125 participants with early psychosis and 58 healthy participants with resting-state functional magnetic resonance imaging and clinical characterization. Psychomotor function was assessed using the 9-hole pegboard task, a timed motor task that engages mechanical and psychomotor components of action, and tasks assessing processing speed and task switching. We used multivariate pattern analysis of whole-connectome data to identify brain correlates of psychomotor function. We identified discrete brain circuits driving the cognitive and motor components of psychomotor function. In our combined sample of participants with psychosis (n = 89) and healthy control participants (n = 52), the strongest correlates of psychomotor function (pegboard performance) (p <.005) were between a midline cerebellar region and left frontal region and presupplementary motor area. Psychomotor function was correlated with both cerebellar-frontal connectivity (r = 0.33) and cerebellar–presupplementary motor area connectivity (r = 0.27). However, the cognitive component of psychomotor performance (task switching) was correlated only with cerebellar-frontal connectivity (r = 0.19), whereas the motor component (processing speed) was correlated only with cerebellar–presupplementary motor area connectivity (r = 0.15), suggesting distinct circuits driving unique subprocesses of psychomotor function. We identified cerebellar-cortical circuits that drive distinct subprocesses of psychomotor function. Future studies should probe relationships between cerebellar connectivity and psychomotor performance using neuromodulation. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a progressive condition. Investigating the neuroimaging mechanisms in depressed adolescents with subthreshold mania (Sub MD) facilitates the early identification of BD. However, the global brain connectivity (GBC) patterns in Sub MD patients, as well as the relationship with processing speed before the onset of full-blown BD, remain unclear. The study involved 72 Sub MD , 77 depressed adolescents without subthreshold mania (nSub MD), and 69 gender- and age-matched healthy adolescents (HCs). All patients underwent a clinical follow-up ranging from six to twelve months. We calculated the voxel-based graph theory analysis of the GBC map and conducted the TMT-A test to measure the processing speed. Compared to HCs and nSub MD , Sub MD patients displayed distinctive GBC index patterns: GBC index decreased in the right Medial Superior Frontal Gyrus (SFGmed.R)/Superior Frontal Gyrus (SFG) while increased in the right Precuneus and left Postcentral Gyrus. Both patient groups showed increased GBC index in the right Inferior Temporal Gyrus. An increased GBC value in the right Supplementary Motor Area was exclusively observed in the nSub MD -group. There were opposite changes in the GBC index in SFGmed.R/SFG between two patient groups, with an AUC of 0.727. Additionally, GBC values in SFGmed.R/SFG exhibited a positive correlation with TMT-A scores in Sub MD -group. Relatively shorter follow-up duration, medications confounding, and modest sample size. These findings suggest that adolescents with subthreshold BD have specific impairments patterns at the whole brain connectivity level associated with processing speed impairments, providing insights into early identification and intervention strategies for BD. • We found distinctive alterations in global brain connectivity among depressed adolescents with subthreshold mania. The alterations include a decrease in the right Medial Superior Frontal Gyrus (SFGmed.R)/Superior Frontal Gyrus (SFG) and an increase in the right Precuneus and left Postcentral Gyrus. • Significantly, the GBC index in the SFGmed.R/SFG displayed an opposite pattern between the two patient groups compared to HCs, decreasing in Sub MD patients while increasing in nSub MD patients, demonstrating good discriminative efficacy and suggesting specific early alterations in bipolar disorder (BD). • Additionally, an increased GBC index in the right Inferior Temporal Gyrus (ITG.R) emerged as a common alteration across both patient groups, presenting a gradient in the extent of alterations with Sub MD ＞nSub MD ＞HCs. [ABSTRACT FROM AUTHOR]

We characterized the neurocognitive profile of communed-based individuals and unaffected siblings of patients with psychosis from Brazil reporting psychotic experiences (PEs). We also analyzed associations between PEs and the intra and inter-functional connectivity (FC) in the Default Mode Network (DMN), the Fronto-Parietal Network (FPN) and the Salience Network (SN) measured by functional magnetic resonance imaging. The combined sample of communed-based individuals and unaffected siblings of patients with psychosis comprised 417 (neurocognition) and 85 (FC) volunteers who were divided as having low (<75th percentile) and high (≥75th percentile) PEs (positive, negative, and depressive dimensions) assessed by the Community Assessment of Psychic Experiences. The neurocognitive profile and the estimated current brief intellectual quotient (IQ) were assessed using the digit symbol (processing speed), arithmetic (working memory), block design (visual learning) and information (verbal learning) subtests of Wechsler Adult Intelligence Scale-third edition. Logistic regression models were performed for neurocognitive analysis. For neuroimaging, we used the CONN toolbox to assess FC between the specified regions, and ROI-to-ROI analysis. In the combined sample, high PEs (all dimensions) were related to lower processing speed performance. High negative PEs were related to poor visual learning performance and lower IQ, while high depressive PEs were associated with poor working memory performance. Those with high negative PEs presented FPN hypoconnectivity between the right and left lateral prefrontal cortex. There were no associations between PEs and the DMN and SN FC. Brazilian individuals with high PEs showed neurocognitive impairments like those living in wealthier countries. Hypoconnectivity in the FPN in a community sample with high PEs is coherent with the hypothesis of functional dysconnectivity in schizophrenia. [ABSTRACT FROM AUTHOR]

This study aimed to examine the relationships among cognitive function, symptoms, prefrontal activation, basic driving skills, and collision risk factors using a hazard prediction task in simulated driving. Participants included 42 people with schizophrenia aged 20–50 years who had actual experience of driving. The Trail making test (TMT) A and TMT B, Wechsler Memory Test–Revised (WMS-R), and Zoo Map test (ZMT) were used to evaluate cognitive function. Positive and negative syndrome scale was used to assess symptoms, and brain activity was assessed by evaluating cerebral blood flow during a visual working memory task using functional near-infrared spectroscopy. Driving tasks that tested basic skills, such as brake reaction, steering wheel skills, and standard deviation of lateral position, were analyzed using multiple regression analysis. Three hazard prediction tasks were performed using discriminant analysis. Brake reaction associated with cerebral blood flow and TMT-A. Steering wheel skills associated with WMS-R, driving experience and depression. Significant differences were found between the collision and noncollision groups in the hazard prediction task, as shown by the ZMT, driving experience, and brake reaction. Brain activity in the frontal lobe during a desk task may be useful data for driving assessment. Assessment of processing speed and learning ability may be particularly important in the evaluation of basic skills for safe driving. In addition, for people with schizophrenia, foresight, as represented by proactive planning, experience, and quick braking may be an essential characteristic to anticipate danger and react quickly enough to avoid collisions. [ABSTRACT FROM AUTHOR]

Previous research in psychotic disorders discovered associations between reduced integrity of white matter (WM) in the corpus callosum (CC) and impaired cognitive functions, suggesting processing speed as a central construct. However, it is still largely unexplored to what extent disruption in callosal WM is related to cognitive deficits during the risk stage prior to psychosis. To address this gap, we measured the WM integrity in CC by fractional anisotropy (FA) and assessed cognition in 60 clinical-high risk for psychosis (CHR) patients during adolescence/young adulthood and 38 healthy control (HC) subjects. We employed tract based spatial statistics to examine group differences and associations between CC-FA and processing speed, executive function, and spatial working memory. We revealed deficits in processing speed, executive function, and spatial working memory of CHR patients, and reductions in FA of the genu and the body of the CC (p < 0.05, corrected for multiple comparisons) compared to HC. A mediation analysis using the combined sample (CHR + HC) showed that processing speed mediates the associations between the impaired CC structure and executive function and spatial working memory, respectively. Exploratory analyses between CC-FA and the cognitive domains located associations of processing speed in the genu and the body of CC with distinct spatial distributions of executive function and spatial working memory. We suggest processing speed as a subordinate cognitive factor contributing to the associations between callosal WM, executive function and working memory. These results extend findings in psychotic disorders to the prior risk stage. [ABSTRACT FROM AUTHOR]

• We examined EEG oscillatory power and functional connectivity as potential correlates of non-motor symptoms in Huntington's disease (HD). • The HD group had lower theta power, higher delta power and connectivity, and theta power was correlated with processing speed. • Our findings support the use of quantitative EEG metrics as a potential marker of processing speed for clinical research in HD. To find sensitive neurophysiological correlates of non-motor symptoms in Huntington's disease (HD), which are essential for the development and assessment of novel treatments. We used resting state EEG to examine differences in oscillatory activity (analysing the isolated periodic as well as the complete EEG signal) and functional connectivity in 22 late premanifest and early stage people with HD and 20 neurotypical controls. We then assessed the correlations between these neurophysiological markers and clinical measures of apathy and processing speed. Significantly lower theta and greater delta resting state power was seen in the HD group, as well as significantly greater delta connectivity. There was a significant positive correlation between theta power and processing speed, however there were no associations between the neurophysiological and apathy measures. We speculate that these changes in oscillatory power and connectivity reflect ongoing, frontally concentrated degenerative and compensatory processes associated with HD. Our findings support the potential utility of quantitative EEG as a proximate marker of processing speed, but not apathy in HD. [ABSTRACT FROM AUTHOR]

• Identifying factors that help people maintain good cognitive functions as they age is important. • We conducted a genome-wide association study of processing speed in members of families enriched for extreme human longevity. • We discovered rare variants that are associated with maintaining excellent processing speed at very old age. • These variants may help identify therapeutic targets for the preservation of cognitive function. We conducted a genome-wide association study of Digit Symbol Substitution Test scores administered in 4207 family members of the Long Life Family Study (LLFS). Genotype data were imputed to the HRC panel of 64,940 haplotypes resulting in ∼15M genetic variants with a quality score > 0.7. The results were replicated using genetic data imputed to the 1000 Genomes phase 3 reference panel from 2 Danish twin cohorts: the study of Middle Aged Danish Twins and the Longitudinal Study of Aging Danish Twins. The genome-wide association study in LLFS discovered 18 rare genetic variants (minor allele frequency (MAF) < 1.0%) that reached genome-wide significance (p -value < 5 × 10−8). Among these, 17 rare variants in chromosome 3 had large protective effects on the processing speed, including rs7623455, rs9821776, rs9821587, rs78704059, which were replicated in the combined Danish twin cohort. These SNPs are located in/near 2 genes, THRB and RARB , that belonged to the thyroid hormone receptors family that may influence the speed of metabolism and cognitive aging. The gene-level tests in LLFS confirmed that these 2 genes are associated with processing speed. [ABSTRACT FROM AUTHOR]

Deficits in functioning affect people with first-episode psychosis. Deficits in cognitive performance are common in such individuals and appear to be related to functioning. The present study examined the relationship between the domains of cognitive performance and personal and social functioning, as well as evaluating which cognitive domains are the most closely related to personal and social functioning and whether they explain variations once other clinical and sociodemographic aspects are accounted for. Ninety-four people with first-episode psychosis participated in the study; they were assessed with the MATRICS battery. Symptoms were evaluated with the Emsley factors of the positive and negative syndrome scale. Cannabis use, duration of untreated psychosis, suicide risk, perceived stress, antipsychotic doses, and premorbid intelligence quotient was accounted for. Processing speed, attention/vigilance, working memory, visual learning, reasoning and problem solving correlated to personal and social functioning. Processing speed emerged as the strongest predictor of social and personal functioning and underscores the importance of targeting this domain in treatment. Moreover, suicide risk and excited symptoms were also significant variables in functioning. Early intervention, focusing on improvement of processing speed, may be crucial to the improvement of functioning in first-episode psychosis. The relationship of this cognitive domain with functioning in first-episode psychosis should be studied further. • Processing speed emerged as the strongest predictor of social and personal functioning. • None of the other cognitive domains have a significant effect on functioning after controlling for confounding variables. • Early intervention to improve processing speed may be crucial to the improvement of functioning in first-episode psychosis. [ABSTRACT FROM AUTHOR]

Recent evidence indicates that DDR1 participates in myelination and that variants of DDR1 are associated with decreased cognitive processing speed (PS) in schizophrenia (SZ). Here, we explored whether DDR1 variants were associated with PS in subjects diagnosed with an early psychosis (EP), a condition often preceding SZ. Data from two Spanish independent samples (from Reus and Santander) including patients with EP (n = 75 and n = 312, respectively) and healthy controls (HCs; n = 57 and n = 160) were analyzed. The Trail Making Test part A was used to evaluate PS. Participants underwent genotyping to identify DDR1 variants rs1264323 and rs2267641. Cross-sectional data were analyzed with general linear models and longitudinal data were analyzed using mixed models. We examined the combined rs1264323AA-rs2267641AC/CC genotypes (an SZ-risk combination) on PS. The SZ-risk combined genotypes were associated with increased PS in EP patients but not in HCs in the cross-sectional analysis. In the longitudinal analysis, the SZ-risk combined genotypes were significantly associated with increased PS in both HCs and EP patients throughout the 10-year follow-up but no genotype × time interaction was observed. These results provide further evidence that DDR1 is involved in cognition and should be replicated with other samples. • Patients with an early psychosis carrying DDR1 schizophrenia-risk genotype had faster processing speed than the non-carriers. • Healthy controls carrying DDR1 schizophrenia-risk genotype compared to non-carriers did not show faster processing speed. • Participants carrying DDR1 schizophrenia-risk genotype had faster processing speed over a 10-year follow-up period. [ABSTRACT FROM AUTHOR]

The planned missions to the Moon and Mars will present more significant health challenges to astronauts compared to low earth orbit missions. During deep space missions, astronauts will be constantly exposed to Space radiation (SR). Multiple rodent studies suggest that < 25 cGy of SR impairs performance in executive functions, which play a key role in advanced cognitive processes, but also regulate response inhibition and impulse control. There is the possibility that SR exposure may exacerbate aberrant behaviors evoked by psychological stress related to exposure to isolated and confined (ICE) hostile environment or independently induce additional aberrant behaviors. This study has determined that female Wistar rats exposed to 10 cGy of 250 MeV/n He had an increased risk taking propensity (RTP)\compared to shams. The increased RTP of the He-exposed rats was associated with significantly increased reaction times during the trials, suggesting a SR-induced loss of processing speed. The response times of the He-exposed rats were even further reduced in trials that immediately followed a loss, raising the possibility that conflict and interference avoidance may be impaired after SR exposure. Whether these findings occur following other types of SR exposure, and/or in male rats remains to be determined. • First study to demonstrate that space radiation exposure impacts risk taking predisposition. • First definitive data that space radiation exposure impacts processing speed. • Expansion of the scope of CNS processes that space radiation exposure impacts. [ABSTRACT FROM AUTHOR]

Background: Higher anxiety levels in older adults are associated with worse executive functioning and an increased risk for dementia. In this study individual anxiety disorders and clinically relevant generalized anxiety symptoms are studied in relation to multiple cognitive domains.Method: This cross-sectional study includes 7344 community-dwelling participants of The Maastricht Study aged 40-75 years and oversampling of type 2 diabetes. Panic disorder with and without agoraphobia, agoraphobia and lifetime panic disorder were measured with the Mini International Neuropsychiatric Interview. Generalized anxiety symptoms were measured with the Generalized Anxiety Disorder 7-item scale (GAD-7). Multiple cognitive domains (executive functioning, memory and processing speed) and cognitive impairment were assessed. Multivariable linear and logistic regression analyses were used with adjustment for potential confounders. Interaction analyses were performed to test the moderation of age, sex and type 2 diabetes (due to oversampling).Results: Agoraphobia was associated with worse scores on all cognitive domains (range B = -0.12 to -0.10; range 95%CI = -0.20 to -0.04) and with higher odds of cognitive impairment (OR = 1.51, 95%CI = 1.18-1.93). High scores on the GAD-7 were associated with worse scores on processing speed (B = -0.11, 95%CI = -0.20 to -0.03) and higher odds of cognitive impairment (OR = 1.42, 95%CI = 1.02-1.97). Panic disorder was significantly associated with worse scores on memory tasks (B = -0.25, 95%CI = -0.48 to -0.02). Associations were stronger in the younger participants and for agoraphobia and GAD-7 scores also in those with type 2 diabetes.Conclusion: Multiple anxiety disorders and generalized anxiety symptoms were associated with worse cognitive functioning on several cognitive domains. [ABSTRACT FROM AUTHOR]

Background: To date, few studies have examined baseline cognitive function as a predictor of clinical outcome following treatment in bipolar disorder (BD). The aim of this analysis was therefore to examine the relationship between baseline cognitive function and treatment outcome in a sample of young adults with BD receiving Interpersonal Social Rhythm Therapy (IPSRT) or Specialist Supportive Care (SSC) with adjunctive pharmacotherapy.Methods: Eighty-six BD patients underwent baseline cognitive testing and completed 18 months of IPSRT or SCC. Univariate analyses examined the relationship between baseline cognitive function (global and individual cognitive domains) and change in mood symptom burden, and psychosocial functioning, from baseline to treatment-end.Results: Baseline global cognition was not predictive of change in mood symptom burden over 18 months of treatment. However, poorer baseline psychomotor speed performance was associated with less improvement in mood symptom burden at treatment-end. Neither baseline global cognition nor individual cognitive domain scores were associated with change in psychosocial functioning.Limitations: Due to the exploratory nature of the study, correction was not made for multiple comparisons. Data was obtained from a relatively small sample and has been the subject of prior analysis, thereby increasing the likelihood of chance findings.Conclusion: Although global cognition was not associated with outcome, when examining individual domains, poorer baseline psychomotor speed predicted less change in mood symptom burden following 18-months of psychotherapy and pharmacotherapy. This suggests that pre-treatment measures of psychomotor speed may help to identify those who require additional, and more targeted, intervention. Further large-scale research is required. [ABSTRACT FROM AUTHOR]

Background: Understanding generational trends in dementia and cognitive decline is essential to quantify future healthcare needs and may help identify interventions and preventions. We aimed to determine whether individuals from more recent generations showed better neurocognitive function.Methods: This cross-sectional study combined data from 4439 participants (mean age 64 years (SD = 13); 57% were women) from the Epidemiology of Hearing Loss Study and Beaver Dam Offspring Study. We assessed participants' birth cohort (1901-1924, Greatest Generation; 1925-1945, Silent Generation; 1946-1964, Baby Boom Generation; 1965-1984, Generation X) and neurocognition (Trail-Making Tests A and B, Digit Symbol Substitution Test, Auditory Verbal Learning Test, Verbal Fluency Test). Multivariable linear regression models were utilized.Results: Adjusted for age, sex, education, and known risk factors for cognitive decline, more recent generations showed better processing speed, executive function, attention, and verbal fluency than the Greatest Generation. Largest benefits were found in the Baby Boom Generation. Compared with the Greatest Generation, individuals from the Baby Boom Generation performed better on Trail-Making Tests A (-0.21 ln(time in s); 95% confidence interval (CI) -0.29, -0.13) and B (-0.31 ln(time in s); 95% CI -0.40, -0.22), Digit Symbol Substitution Test (6.07 numbers correct; 95% CI 3.61, 8.52) and Verbal Fluency Test (8.75 numbers correct; 95% CI 5.07, 12.42 in women; 5.28 numbers correct; 95% CI 0.79, 9.78 in men), with effect sizes similar to effects of 11-15 years of less aging.Conclusions: This indicates that some benefits of younger generations might be related to yet unknown and potentially modifiable environmental, health-related or lifestyle factors and motivates research of such underlying factors to promote healthy cognitive aging. [ABSTRACT FROM AUTHOR]

This study examines how children with developmental language disorder (DLD) discriminate voiced and voiceless consonants and their processing speed. It also explores the contribution of factors like age, nonverbal intelligence, vocabulary, morphosyntactic skills, and sentence repetition in explaining speech perception abilities. Fourteen Cypriot Greek children with DLD and 14 peers with typical development (TD) aged 7; 10–10; 4 were recruited. Children were divided into four groups based on age and condition: young-DLD, young-TD, old-DLD, and old-TD. All children participated in an AX task, which measured their ability to discriminate sounds and their processing speed. They also completed a nonverbal intelligence test and a DVIQ test, which provided measures of various language abilities. The results demonstrated that the young-DLD group exhibited lower performance in discriminating consonants compared to the young-TD group, while such differences were not observed between the old-DLD and old-TD groups. Furthermore, while no significant differences in processing time were found between the DLD and TD groups, both young DLD and TD groups displayed longer processing times compared to their older counterparts. Age was the best-contributing factor to speech perception abilities in children with DLD in contrast to morphosyntax and vocabulary for children with TD. These findings highlight the role of voicing discrimination as a diagnostic marker of DLD as opposed to reaction time. Moreover, they underscore the crucial role of age in detecting DLD. The language developmental trajectories of children with TD appear distinct from those with DLD, as evidenced by variations in contributing factors between the two groups. These disparities can be attributed to the diverse nature of the DLD population, the therapies they receive, the compensatory strategies they employ, and the potential impact of other contributing factors. • Younger children with DLD exhibited poorer discrimination of voicing contrasts than younger children with TD. • Processing time did not differ between children with DLD and children with TD. • Younger children exhibited poorer discrimination of contrasts and longer response times compared to their older peers. • Age was the best contributing factor in children with DLD, unlike morphosyntax and vocabulary in their TD peers. [ABSTRACT FROM AUTHOR]

• Children with cochlear implants had below average information processing speed. • Information processing speed was associated with speech-language outcomes after implantation. • This association was greater in children with implants than in hearing peers. • The processing speed-language association was not explained by executive functioning or nonverbal intelligence. Spoken language development after pediatric cochlear implantation requires rapid and efficient processing of novel, degraded auditory signals and linguistic information. These demands for rapid adaptation tax the information processing speed ability of children who receive cochlear implants. This study investigated the association of speed of information processing ability with spoken language outcomes after cochlear implantation in prelingually deaf children aged 4–6 years. Two domain-general (visual, non-linguistic) speed of information processing measures were administered to 21 preschool-aged children with cochlear implants and 23 normal-hearing peers. Measures of speech recognition, language (vocabulary and comprehension), nonverbal intelligence, and executive functioning skills were also obtained from each participant. Speed of information processing was positively associated with speech recognition and language skills in preschool-aged children with cochlear implants but not in normal-hearing peers. This association remained significant after controlling for hearing group, age, nonverbal intelligence, and executive functioning skills. These findings are consistent with models suggesting that domain-general, fast-efficient information processing speed underlies adaptation to speech perception and language learning following implantation. Assessment and intervention strategies targeting speed of information processing may provide better understanding and development of speech-language skills after cochlear implantation. [ABSTRACT FROM AUTHOR]

The developmental cascade model, elaborated by Fry and Hale (2000) emphasizes the role of age-related increases in processing speed and working memory for the development of fluid intelligence. Given the intimate relationships between intra-subject variability and the aforementioned constructs, the present study set out to determine the role of intra-subject variability within the pathways outlined in the developmental cascade model, postulating a fundamental role of intra-subject variability for the development of processing speed, working memory and fluid intelligence. To that end, N = 403 participants aged 8–18 years took a testing battery including choice reaction time tasks to measure processing speed and intra-subject variability as well as span, operation span and coordination tasks to measure working memory within the empirical framework of Oberauer et al. (2003). Cattell's Culture Fair Test (CFT-20 R) was used to measure fluid intelligence. Our results confirm the well-known close relationships between processing speed, working memory, and fluid intelligence, and show that intra-subject variability is also closely related to these constructs. The results of the present study suggest the extension of the developmental cascade model by the inclusion of intra-subject variability as a fundamental construct. • The cascade model, elaborated by Fry and Hale (2000) , has been a highly influential model of cognitive development, emphasizing the role of processing speed (PS) and working memory (WM) for the development of fluid intelligence (gf). • In a cross-sectional study, we tested a sample of children and adolescents using a large battery of tests. • Based on a sample of N = 403 children and adolescents we confirm here the relationships between PS, WM and gf and extend this network of constructs by intra-subject variability (ISV) as another fundamental construct of an extended cascade model. [ABSTRACT FROM AUTHOR]

Developmental difficulties in many cognitive domains are common in children with sickle cell anaemia (SCA). Children with stroke are most affected but delayed or atypical cognitive function has been reported in children with SCA and silent infarcts (SCI), vasculopathy, and normal brain MRI. However, very few studies of cognition have been conducted in Africa, a continent with 75% of the SCA burden. We therefore investigated cognitive profiles in Tanzanian children with SCA and examined the impact of age, SCI, vasculopathy, and haemoglobin concentration (Hb). Children aged 6–16 years with and without SCA were eligible for this cross-sectional study. Cognitive assessment was performed using Raven's Matrices, assessing fluid, non-verbal intelligence and subtests from the Wechsler Intelligence Scales for Children (WISC-IV), assessing processing speed (PS), perceptual reasoning (PR), and working memory (WM) as these tests are less culture-bound. Magnetic resonance imaging (MRI) and angiography (MRA) were also completed to assess the presence of SCI and vasculopathy. Hb was collected in both SCA children and their non-SCA siblings. Seventy-three children with SCA and 71 healthy siblings (Mean ages 11.9, SD = 2.8 and 11.1, SD = 2.9 years respectively) were recruited. Compared with healthy siblings, children with SCA had lower PS (Mean diff 7.35 points; p =.002). Older children had higher performance scores on all tests in relation to their ages. Lowest cognitive scores were observed on the PS subtest, where patients with SCI (SCI+) had lowest mean values as compared to children with no SCI (SCI-) and healthy siblings (i.e., SCI+ < SCI- < healthy siblings, p =.028). On post-hoc analysis the difference was between SCI+ and healthy siblings SCI+ < non-SCA siblings (p =.015); there was no difference between SCI+ and SCI- patient groups. PS was significantly lower in SCA patients with no vasculopathy as compared to healthy siblings. The mean difference from healthy siblings was -8.352 and -0.752 points for VASC- and VASC + respectively (p =.004). There was a significant positive effect of Hb on PSI (p =.001) in both patients and controls and a trend level significant positive effect of Hb on PR (p =.050) and WM (p =.051). In this Tanzanian study, cognitive performance was reduced in children with SCA with or without SCI on MRI or vasculopathy. Cognitive performance improved with increasing age. Lower Hb was associated with lower cognitive performance in both patients with SCA and their non-SCA siblings. SCI and vasculopathy do not appear to have an impact on cognitive function. [ABSTRACT FROM AUTHOR]

L'objectif de la présente recherche est de déterminer dans quelle mesure l'effet de fréquence du voisinage orthographique dans une tâche de catégorisation de couleur de mots est modifié lors du vieillissement lorsque la vitesse de traitement des participants est prise en compte. Deux conditions de mots colorés ont été comparées dans une tâche de catégorisation de couleurs réalisée par un groupe d'adultes jeunes (M âge = 21,62) et un groupe d'adultes âgés (M âge = 66,04). La moitié des mots ne possédaient pas de voisin orthographique (ex., pistil), l'autre moitié avaient un voisin plus fréquent (ex., tirade/tirage). Les résultats ont montré que l'effet de fréquence du voisinage sur les temps de catégorisation de couleur variait différemment dans chaque groupe d'âge selon la vitesse de traitement. Ces données sont discutées dans le cadre des théories du vieillissement cognitif et de la reconnaissance des mots écrits. The objective of this research was to determine to what extent the effect of higher-frequency orthographic neighbourhood in a word colour-categorization task is changed during aging when processing speed is taken into account. In addition, the effect of the lexicality of the stimuli on colour categorization was examined, as well as its variation according to age and processing speed. Fifty-two young adults (M age = 21.62) and 52 older adults (M age = 66.04) participated in this study. For each age group, two sub-groups were created according to the processing speed of the participants as measured by the WAIS Coding subtest. Two conditions of words (written in red, yellow, green or blue) were presented in a colour-categorization task. Half of the words did not have any orthographic neighbours (e.g., pistil [pistil]), while the other half had a higher-frequency neighbour (e.g., tirade [tirade]/TIRAGE [draw]). A control condition with a series of Xs was added to test the influence of the effect of the lexicality of words on the colour-categorization times. As a whole, the results showed slower colour-categorization times for words compared to a series of Xs, which did not vary with age and processing speed. Importantly, the results showed that orthographic neighbourhood frequency interacted with age and processing speed, on colour categorization response times. More precisely, the neighbourhood frequency effect was found to vary differently according to processing speed in each age group. For the fastest young adults, the facilitatory effect of higher-frequency orthographic neighbourhood was obtained, whereas no such effect was found for the slowest young adults. The fastest older adults did not exhibit any effect of higher-frequency orthographic neighbourhood whereas a facilitatory effect was observed for the slowest older adults. Therefore, these data suggest that both aging and the processing speed of the participants influence the interference effect of reading on colour categorization. These findings are discussed in the context of cognitive aging theories and models of written word recognition. [ABSTRACT FROM AUTHOR]

Background: Exposure to general anaesthesia in children may be related to deficits in certain areas of cognition. It is unclear if these deficits could be measured in the immediate postoperative period in young children. The goal of the current study was to evaluate the trajectory of cognitive function in the domains of processing speed, working memory, and fine motor skills amongst children aged 2.5-6 yr who underwent general anaesthesia for elective surgery.Methods: Children who were scheduled to receive general anaesthesia for surgery were recruited for assessment of cognitive function at three times: preoperatively, 1-2 weeks postoperatively, and 3 months postoperatively. Assessments included processing speed, working memory, and fine motor skills. To assess longitudinal changes in the cognitive outcomes, linear mixed models were built with visit number included as a categorical variable and subject-specific random intercepts.Results: Sixty-one children (33 girls [54%]) enrolled in the study. Twenty-three children (38%) had received general anaesthesia previously. Significant improvements in picture memory, cancellation, and the processing speed composite were found at Visit 2. The improvement in cancellation and processing speed composite remained significant at Visit 3. Statistically significant improvement in Mullen fine motor score was noticed at Visit 3 compared with Visit 1. The pattern of results did not depend upon prior anaesthesia exposure.Conclusions: General anaesthesia for elective surgery in young children was not associated with declines in working memory, processing speed, and fine motor skills in the first 3 months postoperatively, including in children with prior exposure to anaesthesia. [ABSTRACT FROM AUTHOR]

Substantial evidence supports the existence of neurocognitive endophenotypes in bipolar disorder (BD), but very few longitudinal studies have included unaffected relatives. In a 5-year, follow-up, family study, we have recently suggested that deficits in manual motor speed and visual memory could be endophenotype candidates for BD. We aimed to explore whether this also applies to processing speed. A sample of 348 individuals, including 163 BD patients, 65 unaffected first-degree relatives (BD-Rel) and 120 genetically unrelated healthy controls (HC), was assessed with the Digit Symbol Substitution Test (DSST) on two occasions over a 2-year period (T1, T2). DSST values were controlled for age, years of education, occupational status, and subsyndromic mood symptoms. Differences between groups were evaluated with ANCOVAs. At T1 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.38) and BD-Rel (p < 0.001; Cohen's d = 0.82). BD-Rel showed an intermediate performance with significant differences with HC (p < 0.01; Cohen's d = 0.50). Similarly, at T2 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.44) and BD-Rel (p < 0.01; Cohen's d = 0.51). BD-Rel performance was intermediate and significantly lower than that of HC (p < 0.01; Cohen's d = 0.97). A Repeated Measures ANOVA revealed no significant between-group differences in performance over time (p > 0.05). The results of this longitudinal, family study suggest that impaired processing speed may represent a suitable cognitive endophenotype for BD. Further research on the field is required to confirm these preliminary findings. • The endophenotypic nature of processing speed in bipolar disorder is uncertain. • Longitudinal family studies may be a suitable strategy for its identification. • Both patients and unaffected relatives showed a persistent deficit. • Impaired processing speed may be a valid endophenotype of bipolar disorder. [ABSTRACT FROM AUTHOR]

Objective: Slowed processing speed and executive dysfunction are associated with poor outcomes in Late Life Depression (LLD), though it is unclear why. We investigated whether these variables interfere with the development of positive treatment expectancies in an antidepressant trial.Methods: Depressed older subjects were randomized to Open (intended to increase patient expectancy) or Placebo-controlled (termed 'Hidden,' intended to decrease expectancy) administration of antidepressant medication for 8 weeks. Analysis of covariance analyzed the between-group difference on expectancy (Credibility and Expectancy Scale [CES]) and depression (Hamilton Rating Scale for Depression [HRSD], Clinical Global Impressions [CGI] Severity). Moderator analyses examined whether these Open versus Hidden differences varied based on higher versus lower processing speed and executive function.Results: Among the 108 participants, a significant between-group difference was observed on expectancy (effect size [ES, Cohen's d] = 0.51 on CES Item 2; ES = 0.64 on Item 4), indicating the manipulation was effective. Processing speed as measured by the Stroop Color-Word Test (number color-words named in congruent condition) was a significant moderator of the Open versus Hidden effect on expectancy. Depressive symptom improvement was greater on average for Open versus Hidden participants who received active drug (CGI-severity ES = 1.25, HRSD ES = 0.41), but no neurocognitive moderators of the between-group difference reached statistical significance.Conclusions: Slowed processing speed impairs the development of expectancies in antidepressant trials for LLD, which may help explain lower antidepressant response among older adults. Future studies may address whether interventions to optimize treatment expectancies are capable of improving treatment outcomes. [ABSTRACT FROM AUTHOR]

After stroke, patients can experience visual hypersensitivity, an increase in their sensitivity for visual stimuli as compared to their state prior to the stroke. Candidate behavioural mechanisms for these subjective symptoms are atypical bottom-up sensory processing and impaired selective attention, but empirical evidence is currently lacking. In the current study, we aimed to investigate the relationship between post-stroke visual hypersensitivity and sensory thresholds, sensory processing speed, and selective attention using computational modelling of behavioural data. During a whole/partial report task, participants (51 stroke patients, 76 orthopedic patients, and 77 neurotypical adults) had to correctly identify a single target letter that was presented alone (for 17–100 ms) or along a distractor (for 83ms). Performance on this task was used to estimate the sensory threshold, sensory processing speed, and selective attention abilities of each participant. In the stroke population, both on a group and individual level, there was evidence for impaired selective attention and -to a lesser extent- lower sensory thresholds in patients with post-stroke visual hypersensitivity as compared to neurotypical adults, orthopedic patients, or stroke patients without post-stroke sensory hypersensitivity. These results provide a significant advancement in our comprehension of post-stroke visual hypersensitivity and can serve as a catalyst for further investigations into the underlying mechanisms of sensory hypersensitivity after other types of acquired brain injury as well as post-injury hypersensitivity for other sensory modalities. • Stroke survivors often report an increased sensitivity to visual stimuli. • The behavioural mechanisms of post-stroke visual hypersensitivity remain unclear. • This study links post-stroke visual hypersensitivity to impaired selective attention. • Our results also suggest an association with lower sensory thresholds. • Understanding post-stroke sensory hypersensitivity can improve symptom treatment. [ABSTRACT FROM AUTHOR]

• Predictors of driving safety in Veterans referred for driving evaluation are explored. • Poor attention and processing speed linked to higher on-road test failure rates. • Age and referral diagnosis were in contrast not linked to driving performance. Introduction: Veterans are at heightened risk of being in a motor-vehicle crash and many fail on-road driving evaluations, particularly as they age. This may be due in part to the high prevalence of age-associated conditions impacting cognition in this population, including neurodegenerative diseases (e.g., Alzheimer's Disease) and acquired neurological conditions (e.g., cerebrovascular accident). However, understanding of the impact of referral diagnosis, age and cognition on Veterans' on-road driving performance is limited. Methods: 109 Veterans were referred for a driving evaluation (mean age = 72.0, SD = 11.5) at a driving assessment clinic at the Minneapolis Veterans Affairs Healthcare System. Of the 109 Veterans enrolled, 44 were referred due to a neurodegenerative disease, 37 due to an acquired neurological condition, and 28 due to a non-neurological condition (e.g., vision loss). Veterans completed collection of health history information and administration of cognitive tests assessing visual attention, processing speed, and executive functioning, as well as a standardized, on-road driving evaluation. Results: A total of 17.9% of Veterans failed the on-road evaluation. Clinical diagnostic group was not associated with failure rate. Age was not associated with failure rates in the full sample or within diagnostic groups. After controlling for age, poorer processing speed and selective/divided attention were associated with higher failure rates in the full sample. No cognitive tests were associated with failure rates within diagnostic groups. Conclusion: Referral diagnosis and age alone are not reliable predictors of Veterans' driving performance. Cognitive performance, specifically speed of processing and attention, may be helpful in screening Veterans' driving safety. Practical Applications : Clinicians tasked with assessing Veterans' driving safety should take into account cognitive performance, particularly processing speed and attention, when making decisions regarding driving safety. Age and referral diagnosis, while helpful information, are insufficient to predict outcomes on driving evaluations. [ABSTRACT FROM AUTHOR]

Objective: Computational models provide information about cognitive components underlying behavior. When applied to psychopathology-relevant processes, they offer additional insight to observed differences in behavioral performance. Drift diffusion models have been successfully applied to investigate processing efficiency during binary choice tasks. Using these models, we examine the association between psychopathology (irritability and inattention/hyperactivity) and processing efficiency under different attentional demands.Method: A total of 187 youths with attention-deficit/hyperactivity disorder (ADHD), disruptive mood dysregulation disorder (DMDD), both disorders, or no major psychopathology (age, mean ± SD, 13.09 ± 2.55 y, 34% female) completed an Eriksen Flanker task. Of these, 87 youths provided complete data on dimensional measures of the core symptom of DMDD (irritability) and those of ADHD (inattention and hyperactivity).Results: In a categorical diagnosis-based analysis (n = 187), we found significant interactive effects among ADHD, DMDD, and task condition on processing efficiency, whereby changes in processing efficiency between conflict and nonconflict conditions were larger in youths without psychopathology compared with patients. Analysis of symptom severity (n = 87) across diagnoses similarly revealed an interaction between symptom dimensions and task condition on processing efficiency. Irritability moderated the magnitude of association between inattention symptoms and difference in processing efficiency between conflict and nonconflict conditions.Conclusion: Adapting processing efficiency to cognitive demands may represent a shared cognitive endophenotype for both ADHD and DMDD. Highly irritable and/or inattentive youth may have difficulty adjusting processing efficiency to changing task demands, possibly reflecting impairments in cognitive flexibility. [ABSTRACT FROM AUTHOR]

Cognitive impairment is a feature of severe mental illness (SMI; schizophrenia, bipolar disorder, major depressive disorder). Psychotic forms of SMI may be associated with greater cognitive impairment, but it is unclear if this differential impairment pre-dates illness onset or whether it reflects a consequence of the disorder. To establish if there is a developmental impairment related to familial risk of psychotic SMI, we investigated cognition in offspring of parents with psychotic and non-psychotic SMI. Participants included 360 children and youth (mean age 11.10, SD 4.03, range 6–24), including 68 offspring of parents with psychotic SMI, 193 offspring of parents with non-psychotic SMI, and 99 offspring of control parents. The cognitive battery assessed a range of functions using standardized tests and executive function tasks from the Cambridge Automated Neuropsychological Test Battery. Compared to controls, offspring of parents with psychotic SMI performed worse on overall cognition (β = −0.32; p < 0.001) and 6 of 15 cognitive domains, including verbal intelligence, verbal working memory, processing speed, verbal learning and memory, verbal fluency, and sustained attention. Offspring of parents with non-psychotic SMI performed worse than controls on 3 of the 15 domain specific cognitive tests, including verbal intelligence, visual memory and decision-making. Widespread mild-to-moderate cognitive impairments are present in young offspring at familial risk for transdiagnostic psychotic SMI. Offspring at familial risk for non-psychotic SMI showed fewer and more specific impairments in the domains of verbal intelligence, visual memory and decision-making. [ABSTRACT FROM AUTHOR]

To investigate early and late effects of planned surgically acquired homonymous hemianopias on visual search in children and adolescents. This prospective study included five patients (5y 5 m–18y 0 m; 2 girls) with pharmaco-refractory epilepsies in whom one visual hemifield was sacrificed as part of the surgical strategy, and, as controls, seven patients (5y 11 m–18y 0 m; 6 girls) undergoing epilepsy surgeries not affecting the visual fields. Visual search was studied using the "Table Test", which is an everyday life-like visual search test. General processing speed was studied using a standard IQ subtest. All five patients with newly acquired homonymous hemianopias showed a relative disadvantage of visual search times for objects in their newly blind hemifields immediately after the surgery. Six months later, this relative disadvantage had recovered completely in all patients. Nevertheless, compared with the preoperative situation, overall search times were still prolonged in the hemianopic patients, but this effect could be mitigated or even overcompensated by improvements in processing speed. Children with homonymous hemianopias inflicted by epilepsy surgery develop effective compensation strategies to minimize the relative disadvantage of visual search in their blind hemifields. For changes in overall visual search times between the preoperative and the six-month follow-up examination, we could demonstrate overlapping effects of (a) deterioration by hemianopia and (b) amelioration by improved processing speed as part of the cognitive improvements achieved by amelioration of the epilepsy. • Prospective study (pre/post) on visual search in newly acquired iatrogenic hemianopia. • New hemianopia causes visual search disadvantage in the newly blind hemifield. • Six months later, this relative disadvantage is compensated. [ABSTRACT FROM AUTHOR]

Background: Cognitive deficits, particularly in processing speed, are widely recognized as a critical feature of schizophrenia, and are also present across schizophrenia spectrum disorders. A number of important confounders, however, such as hospitalization effects and antipsychotic medication, have been shown to affect processing speed, causing debate as to the core cognitive deficits of schizophrenia. The study of individuals who are not clinically psychotic but have schizotypal traits allows investigation of cognitive deficits associated with both positive and negative schizotypy dimensions while excluding potential confounds.Methods: A population-based community sample of 242 healthy adult volunteers assessed using the Structured Interview of Schizotypy - Revised (SIS-R) scale, and a neuropsychological testing battery that included measures of verbal ability, visual and verbal memory, verbal fluency, working memory, executive functions and processing speed. Participants were classified in High or Low Positive Schizotypy (H-PST or L-PST), High or Low Paranoia-like traits (H-PAR or L-PAR) and High or Low Negative Schizotypy (H-NST or L-NST) groups, respectively.Results: Individuals with H-PST performed significantly (p < 0.05) worse than L-PST on measures of processing speed and executive functions. Processing speed deficits were also observed in individuals with H-PAR compared to L-PAR (p < 0.05). There were no statistically significant differences in neuropsychological performance between H-NST and L-NST on any measure.Conclusions: In a population-based community sample, individuals with high positive schizotypal traits or paranoia-like traits show impairments in processing speed. Consistent with a dimensional view of psychosis, this supports the hypothesis that processing speed represents a core deficit of schizophrenia-like mental states. [ABSTRACT FROM AUTHOR]

Objective: Despite the losses commonly associated with aging, older adults seem to possess particularly preserved emotional regulation. To further understand this phenomenon, the authors examined longitudinal trajectories between age, depressive symptoms, brain structure, and cognition.Methods: Seven hundred and sixteen functionally intact older adults (age M = 67.9, 56.8% female), followed longitudinally (visit range: 1-13, M = 2.5), completed cognitive testing and the Geriatric Depression Scale (GDS). A subset (N = 327) underwent 3T brain MRI. Mixed-effects linear regression models were conducted controlling for sex, education, and total intracranial volume.Results: There was a significant interaction between age and time on GDS, such that GDS improved with increasing age over time, but attenuated around age 71 (age*time b = 0.10, p <0.001). Fractional anisotropy (FA) and mean diffusivity interacted with age to predict longitudinal changes in GDS (FA: b = -0.02, p = 0.01; MD: b = 0.03, p = 0.007), such that age-related benefits on GDS were attenuated in those with declining FA. Executive function (EF) and processing speed also interacted with age to predict longitudinal changes in GDS (EF: b = -0.04, p = 0.03; speed: b = 0.04, p = 0.04). Again, the positive effect of age on GDS attenuated in those with worsening EF and speed. There were no associations with memory, semantic fluency, or gray matter (p values >0.05).Conclusion: EF, processing speed, and white matter integrity moderated the longitudinal relationship between age and mood. Previous studies demonstrate the link between positivity and better cognitive control, leading to improved mood in older adults. Our results are not only consistent, but establish a potential neurobiological correlate. Future research further exploring biological mechanisms driving psychological processes may have important therapeutic implications. [ABSTRACT FROM AUTHOR]

There is growing interest in understanding the behavioral and neural mechanisms of catatonia. Here, we examine cognition and brain structure in schizophrenia spectrum disorder (SSD) patients with a history of catatonia. A total of 172 subjects were selected from a data repository; these included SSD patients with (n = 43) and without (n = 43) a history of catatonia and healthy control subjects (n = 86). Cognitive functioning was assessed using the Screen for Cognitive Impairment in Psychiatry (SCIP) and brain structure was assessed using voxel-based morphometry (VBM) in the CAT12 toolbox. SSD patients with a history of catatonia showed worse performance on tests of verbal fluency and processing speed compared to SSD patients without such a history, even after controlling for current antipsychotic and benzodiazepine use. No differences were found between patients with and without a history of catatonia in terms of brain structure. Both patient groups combined showed significantly smaller grey matter volumes compared to healthy control subjects in brain regions consistent with prior studies, including the anterior cingulate, insular, temporal, and medial frontal cortices. The results highlight a cognitive-motor impairment in SSD patients with a history of catatonia. Challenges and limitations of examining brain structure in patients with a history of catatonia are discussed. [ABSTRACT FROM AUTHOR]

Background: Declining function in dopamine circuits is implicated in normal aging and late-life depression (LLD). Dopamine augmentation recently has shown therapeutic promise, but predictors of response are unknown.Methods: Depressed elders with slowed gait underwent baseline magnetic resonance imaging (MRI) and [11C]raclopride positron emission tomography (PET). Subjects then received open treatment with carbidopa/levodopa (L-DOPA) for three weeks. Linear regressions examined relationships between baseline MRI measures, [11C]raclopride binding, and behavioral outcomes.Results: Among N = 16 participants aged 72.5 ± 6.8 years, higher left superior temporal gyrus volume was associated with higher processing speed at baseline, while cortical thinning in a processing speed network was associated with greater improvement following L-DOPA. Greater volume and cortical thickness in brain regions associated with mobility were associated with higher baseline gait speed. Higher baseline white matter hyperintensity volume predicted less post-L-DOPA improvement on dual task gait speed and IDS-SR scores. Higher [11C]raclopride binding in the associative striatum was associated with cortical thickness in some, but not all, processing speed brain regions, while higher binding in sensorimotor striatum was significantly associated with left caudate volume.Limitations: Limiting the conclusions drawn from this pilot study are the small sample size and open administration of L-DOPA.Conclusions: Greater baseline brain volumes and cortical thickness in regions supporting cognition and gait were associated with higher behavioral performance, while lower structural integrity was associated with increased responsivity to L-DOPA. If substantiated in larger studies, these findings could facilitate the targeting of dopaminergic treatments to those LLD patients most likely to respond. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) are autoimmune disorders that may lead to cognitive impairment. This study aimed to compare the neuropsychological profiles of patients with MS, and MS and coexisting SLE features. We included a total of 90 participants, divided into 3 groups: 30 patients with clinically definite relapsing remitting MS, 30 with coexisting MS and incomplete SLE (overlap group) and 30 healthy controls (HC). All participants underwent neuropsychological assessment with the Montreal Cognitive Assessment (MoCA), Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Selective Reminding Test (SRT). Both groups scored lower on the MoCA compared to the HC (p <.001). The overlap group showed the lowest performance on the SDMT and PASAT compared to the other two groups (p <.01), while the MS group scored similarly to the HC in the PASAT (p >.05). Regarding the learning rate and long-term recall, the overlap group had lower scores compared to both the MS and HC (p <.001), but it outperformed both groups in the retention efficacy score (p <.001). The MS group did not differ significantly from the HC in these memory domains (p >.05). The overlap group exhibited a broader range of impairments, including slower processing speed, decreased working memory, reduced learning rate, and long-term retrieval deficits. Their retention ability remained intact. The coexistence of MS with SLE pathology had additive impacts on cognitive function. • People with overlapping RRMS and SLE pathology display more extensive impairments in working memory and processing speed. • The MS patients struggle with initial learning, but their long-term retention and recall of information were not affected, indicating intact potential compensation mechanisms. • The patients with MS and SLE characteristics demonstrated superior retention, suggesting that cognitive deficits may be related to complex cognitive processes rather than permanent deficits. • In RRMS with overlapping SLE features, concurrent impairments in processing speed, and working memory may lead to more pronounced cognitive deficits, particularly in verbal learning processes. Retention and consolidation of information do not appear to be primarily affected. [ABSTRACT FROM AUTHOR]

• Baseline hand dexterity predicts changes in executive function and processing speed. • Baseline maximum gait speed predict changes in executive function over time. • Baseline executive function predicts hand dexterity and maximum gait speed changes. • Baseline processing speed associates with longitudinal changes in hand dexterity. • Trajectories of hand dexterity and high-level cognitive domains are associated. Whether age-related decline in the musculoskeletal system may contribute to a decline in cognitive performance or vice versa is unclear. Understanding the direction of their associations and the extent to which upper and lower extremities similarly predict subtle changes in high-level cognitive performance will help elucidate their mechanisms, especially that of the hand dexterity. We evaluated the bidirectional associations of motor performance and high-level cognitive domains in 165 highly cognitively and physically healthy older adults. Motor performance tests consisted of handgrip strength, hand dexterity, assessed with the Purdue Pegboard Test (PPT), and usual and maximum gait speeds. High-level cognitive measures included executive function and information processing speed. The Trail Making Test (TMT)B and the letter and category fluency tests (LFT and CFT) evaluated executive function, while the TMTA and Digit Symbol assessed processing speed. Measurements were taken at baseline and at 2-, 5- and 7-year follow-up. Generalized linear mixed-effect models showed that baseline hand dexterity and its trajectory predicted changes in TMTB, CFT, TMTA, and Digit Symbol over time, and vice versa. Baseline maximum gait speed was associated with LFT over time and vice versa. No associations were found for handgrip and usual gait speed. The positive bidirectional association observed both in hand dexterity and maximum gait speed with executive function performance and that of hand dexterity with processing speed over time highlights a reciprocal relationship where each factor affects the other and both factors are dependent on each other, suggesting commonality in their neural basis. [ABSTRACT FROM AUTHOR]

• Neurocognitive aging research using BOLD fMRI assumes age-equivalence of neural-vascular coupling mechanisms. • Research with animal models suggests that most components of neural-vascular signaling are disrupted with age. • Age-related changes in neural-vascular coupling provide a plausible physiologic basis for cognitive decline in older adults. Theories of neurocognitive aging rely heavily on functional magnetic resonance imaging (fMRI) to test hypotheses regarding the brain basis of age-differences in cognition. This technique is based on the blood-oxygen level dependent signal (BOLD) that arises from the coordinated neural-vascular coupling that leads to increased blood flow following an increase in neural activity. Here we review the literature and current controversies regarding the mechanisms by which blood flow and neural activity are coupled, and how they change in the aging process. This literature suggests that neural-vascular coupling is a complex of processes, involving dynamic signaling between neurons, glia, and blood vessels. Nearly every component of this process is affected in aging leading to changes in BOLD and pervasive age-related cognitive changes. [ABSTRACT FROM AUTHOR]

Although metabolic syndrome and cognitive inefficiencies are well-described common complications of schizophrenia, their association remains inconsistent, potentially due to poorly understood mechanisms underlying their relationship. Variability in the endothelial nitric oxide synthase (eNOS) gene, specifically the T-786C variant, has been separately associated with cognition and metabolic syndrome, with worse outcomes for eNOS- 786C carriers likely occurring via negative effects on blood vessel functioning. However, the interaction between eNOS and metabolic syndrome in cognition among adults with schizophrenia is unknown. This study aimed to test the main and interaction effects of the eNOS- 786C allele in cognition using hierarchical regression analyses controlling for age, sex, education, race, and antipsychotic exposure. Metabolic syndrome, eNOS T-786C genotype, and cognitive performance were assessed in 226 community-dwelling participants with chronic schizophrenia-spectrum disorders. Results demonstrated a significant interaction between metabolic syndrome and the eNOS- 786C allele. Specifically, among eNOS- 786C carriers only, metabolic syndrome was independently associated with lower scores in processing speed and verbal fluency, and predicted 12.5% and 15.8% of variance in performance, respectively. These results suggest that the additive negative effects of eNOS- 786C and metabolic syndrome on blood vessel functioning may be severe enough to negatively impact cognition. The finding that metabolic syndrome is associated with worse cognition only in the presence of the eNOS- 786C allele may clarify extant inconsistencies in the literature. These findings provide preliminary evidence that may inform interventions to reduce cognitive morbidity among adults with schizophrenia. [ABSTRACT FROM AUTHOR]

A high-risk subgroup of older patients with depression has slowed processing and gait speeds. This study examined whether carbidopa/levodopa (L-DOPA) monotherapy increased dopamine availability, increased processing/gait speed, and relieved depressive symptoms. Adult outpatients with depression >59 years old underwent baseline [11C]raclopride positron emission tomography followed by open L-DOPA for 3 weeks (1 week each of 150 mg, 300 mg, and 450 mg). Generalized estimating equations tested the pre- and post-L-DOPA differences in processing and gait speed measures, depressive symptoms, and reported side effects. The decrease in binding potential between the pre- and posttreatment scans indexed enhanced synaptic dopamine availability induced by L-DOPA treatment. Thirty-six subjects participated (age, 75.3 ± 7.5 years; 44.4% male). Significant, dose-dependent increases in processing and gait speed were observed with L-DOPA (450-mg dose: processing speed factor score effect size = 0.41, p =.001; dual-task gait speed effect size = 0.43, p =.002). [11C]raclopride decrease in binding potential was significantly different from 0 in sensorimotor (t 24 = −4.85, p <.001) and associative striatum (t 24 = −2.52, p =.019) but not in limbic striatum (t 24 = 0.265, p =.793). Depressive symptoms decreased significantly on the Hamilton Rating Scale for Depression (effect size = −0.37, p =.002). Dropout rate was 8.3%, and nausea was the most frequently reported side effect. By enhancing availability of dopamine, L-DOPA improved processing and gait speed in older adults with depression and significantly decreased [11C]raclopride binding in selected striatal subregions. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates systemic biological dysregulations in patients with psychosis that have been conceptualized as the "allostatic load" (AL) index. We aimed to investigate the AL index in 37 subjects at familial high risk of psychosis (FHRP), 42 first-episode psychosis (FEP) patients, 25 acutely relapsed schizophrenia (SCZ-AR) patients and 42 healthy controls (HCs), taking into account psychopathology and cognitive impairment. The AL index was calculated based on 15 biomarkers (cardiovascular markers, anthropometric measures, inflammatory markers, glucose homeostasis parameters, lipids and steroids). Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The AL index was significantly higher in patients with psychosis and FHR-P individuals compared to HCs. Patients with FEP and FHR-P individuals had similar AL index. Moreover, the AL index was significantly higher in SCZ-AR patients compared to other groups of participants. Higher AL index was associated with more severe general psychopathology and depressive symptoms, lower scores of attention (total score, digit span and digit coding tasks) and semantic fluency, as well as worse general functioning in patients with psychosis. There was a significant negative correlation between the AL index and the scores of attention (total score and digit coding task) in FHR-P individuals. No significant correlations between the AL index and cognition were found in HCs. Our results indicate that biological dysregulations, captured by the AL index, appear already in FHR-P individuals and progress with psychotic exacerbations. Elevated AL index might contribute to cognitive impairments in FHR-P individuals and patients with psychosis. [ABSTRACT FROM AUTHOR]

Both working memory capacity (WMC) and processing speed (PS) have been discussed as important covariates of individual differences in intelligence. Recent results indicated that especially latencies of ERP components associated with higher-order processing (P2, N2, and P3) may share up to 80% of variance with individual differences in intelligence. WMC has a similar predictive power and thus these two processes cannot explain individual differences in intelligence independently. The current study explores in how far individual differences in executive functions (EFs) may bridge the gap between WMC and PS as predictors of intelligence. We recruited 101 participants who completed three EF tasks – one for each of the three executive functions shifting, updating, and inhibition. Additionally, we assessed participants' intelligence, WMC, and PS. Results showed that only variance of behavioral RTs consistent across manipulations in the EF tasks was related to WMC, PS, and intelligence. The variance specific to the manipulations in EF tasks was small and showed no consistent correlations with each other or with any of the three covariates. These results suggest that EF tasks capture mostly manipulation-unspecific cognitive processes. Hence, individual differences in the impairment due to additional executive processing demands cannot explain why WMC and PS are related predictors of individual differences in intelligence. • We recruited a community sample of 101 participants. • Participants performed three executive function (EF) tasks. • Additionally, intelligence, working memory capacity, and processing speed were assessed. • Individual differences in EFs were not related to intelligence, working memory capacity, and processing speed. • EFs did not integrate working memory capacity and processing speed as inter-related predictors of intelligence. [ABSTRACT FROM AUTHOR]

Divergent thinking (DT) ability (i.e., the ability to come up with creative ideas) is a complex cognitive construct that has been associated with several specific components of the Cattel-Horn-Carroll (CHC) model. In this study, we employed a nested latent variable approach to examine the specific role of mental speed (Gs) and general retrieval ability (Gr) in DT ability, which was assessed by DT tasks that instructed to be creative and were scored for creative quality. Specifically, Gs was assumed to facilitate both Gr and DT, and Gr was assumed to contribute to DT. Successive latent variable models with orthogonal factors were tested to reflect these nested cognitive basic abilities. The proposed model of nested factors fit the data well: Latent Gs accounted for variation in Gs, Gr, and DT creative quality scores, latent Gr predicted performance in Gr and DT scores beyond Gs, and latent DT explained variation in DT scores beyond Gs and Gr. In addition, we related the resulting orthogonal latent variables to the external criteria of school grades to illustrate the explanatory power of the modeling approach. This study provides evidence that divergent thinking performance relies on mental speed and retrieval ability, as well as cognitive abilities unique to divergent thinking. We discuss consequences for the understanding of divergent thinking ability in the context of the CHC model. • A set of nested basic cognitive abilities underlying creative ideation in divergent thinking was proposed. • A nested cognitive abilities structural model had excellent fit to the data. • Mental speed, broad retrieval ability, and divergent thinking were all measured within the verbal domain. • The proposed model is more effective for prediction of real-life criteria as compared to a classic three-dimensional CFA model. • The used modeling approach allows to disentangle relevant cognitive components in the multipart concept of divergent thinking. [ABSTRACT FROM AUTHOR]

Learning and memory performance have been reported to be impaired in patients with Major Depressive Disorder (MDD). Impairments are associated with diminished psychosocial functioning. Based on the processing-speed theory, we aimed to examine whether processing speed mediates the relationship between depression status and verbal, visuo-spatial and working memory impairment. A neuropsychological test-battery was administered to 106 patients with current MDD, 119 patients with remitted MDD and 120 healthy controls to assess processing speed, learning and memory performance. To examine the impact of diagnosis status and processing speed on learning and memory performance, simple mediation models were computed. Currently depressed patients with MDD showed partially slowed processing speed, impaired short-term verbal and visuo-spatial memory performance compared to healthy controls. A basic deficit in processing speed mediated the relationship between depression status and verbal, visuo-spatial, and working memory impairment. However, there was no processing speed or memory impairment in patients with remitted MDD. Processing speed is an important factor regarding learning and memory impairment in patients with current MDD. Thereby, our results highlight novel targets for treatment of diminished learning and memory performance via enhancement of processing speed using pharmacological as well as therapeutic interventions. • Impaired short-term verbal and visuo-spatial memory performance in currently depressed patients with MDD • No processing speed or memory impairment in patients with remitted MDD • Processing speed mediated the relationship between depression status and verbal, visuo-spatial, and working memory [ABSTRACT FROM AUTHOR]

Cognitive impairments are considered core features of schizophrenia and are recognized as the most important predictors of functional outcome and quality of life. A better study of the mechanisms underlying the cognition is of extreme relevance. Literature has shown that several genetic and environmental factors affect cognitive performance. In particular, the interaction between Catechol-O-Methyltransferase (COMT) gene and cannabis use has gained increasing attention in the past years. Based on these premises, the present study, aimed to analyze the interplay between cannabis use and COMT polymorphism on cognitive performance in a sample of 135 patients with chronic schizophrenia. Patients were assessed for neurocognitive measures with a broad battery, genotyped for COMT Val158Met polymorphism from peripheral blood sample, and evaluated with a semi-structured interview in order to establish the history of cannabis abuse. Results showed a significant interaction effect between COMT polymorphism and cannabis use on verbal fluency and speed of processing. The analysis revealed significant differences between subjects COMT Val/Val homozygous and Met carriers with history of cannabis use, with a better performance on both tasks among the Met carriers group. These data are in line with literature on healthy subjects that suggests a more detrimental effect of cannabis among subjects with Val/Val genotype. In conclusions, results highlight the need to better disentangle the biological pathways in which cannabis use and COMT are converging, as possible treatment targets, as well as the importance to assess these factors in clinical to optimize individualized interventions. • Cognition is a core feature of schizophrenia and is recognized as the most important predictor of functional outcome. • The interplay between cannabis use and COMT Val158Met polymorphism on cognition in schizophrenia. • A significant interaction effect between COMT polymorphism and cannabis use on verbal fluency and speed of processing. [ABSTRACT FROM AUTHOR]

Age-related cognitive decline is a public health problem but highly diverse and difficult to predict. We captured nonoverlapping cognitive phenotypes in high-functioning adults and identified baseline factors differentiating trajectories. Three hundred fourteen functionally normal adults (M = 69 y) completed 2+ visits. Participants with sample-based longitudinal slopes in memory or processing speed less than −1 SD were classified as "declining" on that measure; 29 and 50 individuals had slopes less than −1 SD on processing speed or memory, respectively; 2.5% met criteria for both, who were excluded. At baseline, speed decliners demonstrated greater age, inflammation, and cognitive complaints compared with speed-stable adults; memory decliners were more likely to be male and had lower depressive symptoms, gray matter volumes, and white matter hyperintensities compared with memory-stable adults. Baseline speed, TNFα, and cognitive complaints accurately classified 96.3% of future speed decliners; baseline memory, sex, precuneal volume, and white matter hyperintensities accurately classified 88.5% of future memory decliners. There are discrete cognitive aging phenotypes reflecting nonoverlapping vulnerabilities in high-functioning adults. Early markers can predict cognition even within the "normal" spectrum and underscore therapeutic targets. • Are there unique, predictable cognitive trajectories in typical aging? • We identified a declining memory or processing speed phenotype with <3% overlap. • Unique baseline predictors differentiated speed or memory decliners with >88% accuracy. • "Normal" cognitive aging is not a singular entity and may be a misnomer. • Early markers can predict "normal" aging phenotypes and highlight therapy targets. [ABSTRACT FROM AUTHOR]

• Processing speed deficits are common in secondary progressive multiple sclerosis. • Little is known about the neural correlates of this function in this disease. • Frontal white matter integrity supports this function in this disease. • Associative and callosal tracts with information integration roles are involved. • These white matter tracts are crucial to support fast cognitive computations. Processing speed (PS) deficits have been consistently observed in secondary progressive multiple sclerosis (SPMS). However, the underlying neural correlates have not been clarified yet. The present study aimed to investigate the relationship between macrostructural and microstructural white matter (WM) integrity and performance on different cognitive measures with prominent PS load. Thirty-one patients with SPMS were recruited and underwent neurological, neuropsychological, and MRI assessments. The associations between a composite index of PS abilities and scores on various tests with prominent PS load and T1-weighted and diffusion tensor image parameters were tested. Analyses were carried out using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS). VBM results showed that only the semantic fluency task correlated with grey matter (GM) volume in a range of cortical and subcortical areas bilaterally as well as the corpus callosum and the superior longitudinal fasciculus. TBSS analysis revealed consistent results across all the cognitive measures investigated, showing a prominent role of commissural and frontal associative WM tracts in supporting PS-demanding cognitive operations. In patients with SPMS, PS abilities are mainly dependent on the degree of both macrostructural and microstructural WM integrity. Preservation of associative WM tracts that support information integration seems crucial to sustain performance in tasks requiring fast cognitive processes. [ABSTRACT FROM AUTHOR]

Abstract Recent research (Myszkowski, Çelik, & Storme, 2018) has suggested that the ability to form accurate visual aesthetic judgments – an ability referred to as aesthetic sensitivity (Child, 1964), or "good taste" (Eysenck, 1983) – could be explained by the extent to which one taps into extensive processing strategies when facing aesthetic objects. Because individual differences in processing extensiveness may lead to different processing speed, we hypothesize that individuals with high visual aesthetic sensitivity present slower responding to visual aesthetic sensitivity tasks – even without time constraints. 201 adults took the Visual Aesthetic Sensitivity Test-Revised (Myszkowski & Storme, 2017), and their responses and response times were analyzed through joint hierarchical item-response theory modeling (van der Linden & Fox, 2016). As hypothesized, latent speed was negatively correlated at −0.47 (95% HPD [−0.61, −0.32]) with latent accuracy. Similar findings were obtained, accounting for guessing or not, including aberrant response patterns or not. In addition, more difficult items were also more time intensive. These findings are discussed as a substantiation that an important explanation for individual differences in visual aesthetic sensitivity lies in how much individuals are disposed to extensively process aesthetic objects. Highlights • We hypothesize that speed impacts accuracy in aesthetic sensitivity tests. • 201 adults responded the VAST-R while the response times were recorded. • Joint hierarchical item-response theory modeling is used. • Latent speed correlated significantly negatively and strongly with ability. • This finding is obtained with or without accounting for guessing. [ABSTRACT FROM AUTHOR]

Background: Computerized cognitive training (CCT) has previously improved cognition and mood in people with depression. Existing research has not determined if the benefits following CCT are specific to the content of CCT or are a function of participation in an engaging activity. In this double-blind randomized controlled trial, we tested whether executive functioning and processing speed (EF/PS)-focused CCT could outperform verbal ability-focused CCT.Methods: 46 young adults with at least mild depressive symptoms (HDRS ≥ 10) were recruited from the community and randomized to either EF/PS CCT or verbal ability CCT. Participants trained on their mobile device 5 days per week for 8 weeks. Depressive severity, everyday functioning, and cognition were evaluating pre and post-training.Results: The EF/PS group had greater gains in executive functioning and processing speed than the verbal group. There were no differences between groups in mood or everyday functioning improvement, though the EF/PS obtained equivalent improvement with half the training time. Both groups saw significant improvements in self and clinician-rated depressive severity, everyday functioning, and cognition.Limitations: There was no waitlist control condition and the sample consisted of individuals with mild depressive symptoms and not diagnosed major depressive disorder.Conclusions: CCT is associated with improved mood, cognition, and everyday functioning, though the type of CCT content does not differentially impact depressive symptom change. EF/PS focused CCT has greater impact on processing speed and executive functioning and leads to equivalent mood/everyday functioning gains as verbal-focused CCT more efficiently. Common factors remain plausible drivers of CCT's therapeutic effects. [ABSTRACT FROM AUTHOR]

Objectives: Patients with schizophrenia commonly suffer from impairments in various aspects of cognition. These deficits were shown to have detrimental effects on daily life functioning and might also impair car driving. This study is the first to examine driving behaviour of patients with schizophrenia using an advanced driving simulator, and to explore the role of cognitive abilities of people with schizophrenia for driving.Methods: Non-acute patients with schizophrenia (n = 31) and healthy comparison participants (n = 31) performed a comprehensive neuropsychological assessment and driving simulator rides. Neuropsychological and driving performances were compared between groups. Moreover, associations were explored between cognitive functions and driving behaviour in the entire group.Results: Patients with schizophrenia revealed impairments in multiple aspects of cognition. In the driving simulator, patients with schizophrenia showed no indication of deviant driving in terms of number of collisions or reacting to critical situations, and even showed better lane control compared to healthy individuals. However, patients with schizophrenia drove significantly slower than healthy individuals, and caused more hindrance to the car behind while merging on the motorway. Slower driving was associated with lower test scores on attention and processing speed. Hindering the car behind was associated with test performance on planning and inhibition.Conclusions: It is concluded that driving of patients with schizophrenia is characterized by a relatively slow speed, and can also be impaired in certain aspects, i.e. hindering a car behind while merging. Cognitive functions are crucial for driving, and should be target of treatment. [ABSTRACT FROM AUTHOR]

Objective: To identify neuropsychological and motor changes from adolescence to early adulthood in young people with psychotic experiences (PE).Methods: A community-based sample of 56 young people attended the study over a 9 year follow-up period. Participants were assessed over 3 time-points at T1, T2 and T3 aged x¯ = 11.69, x¯ = 15.80 and x¯ = 18.80 years respectively. PE were assessed using the Kiddie Schedule for Affective and Depressive Symptoms (K-SADS). Neuropsychological assessments, including subtests of the MATRICS battery, and motor assessments were examined at T2 and T3. Two groups were compared: those who ever reported PE during their adolescence or early adulthood (n = 21) and a healthy control group (n = 35). Further group analysis was conducted within the PE group subdividing into those with transient PE (n = 10) and those with persistent PE (n = 11).Results: At T3, a significant group difference was found between the PE and control groups in the fine motor skill task, the Pegboard task (F = 4.8, p = .03) and the processing speed task, the Digit-Symbol Coding task (F = 5.36, p = .03). Furthermore, a significant group difference was found between the transient PE and control groups on the Digit-Symbol Coding task (F = 5.61, p = .02), while a significant group difference was found between the persistent PE and control groups on the Pegboard task (F = 7.84, p = .01).Conclusion: This study shows that fine motor skill and processing speed deficits persist in young people who report PE, even in those with transient PE. The current research advances the knowledge about the trajectory and precursors of sub-clinical symptoms of psychosis in young people. [ABSTRACT FROM AUTHOR]

Abstract We used structural equation modeling to study individual age-related differences in working memory, processing speed, and the general ability of intelligence. The study took advantage of the Italian Wechsler Adult Intelligence Scale 4th edition (WAIS-IV) standardization sample (N = 2174) to obtain separate measures of working memory, processing speed, and general ability. Core and supplemental subtests were administered to 16–90 years old participants to ensure breadth of cognitive assessment and broad age coverage. Both linear and quadratic ages were associated with processing speed and working memory, which entirely accounted for the relationship between participants' age and general ability. Specific indirect relationships revealed that age-related differences in working memory weighed more than cognitive speed in predicting individual differences in general ability. Processing speed and working memory sharply decreased after 34 and 44 years of age, respectively. Like working memory, general ability decreased after 44 years of age. Bearing in mind the cognitive changes across adulthood and old age, our findings support the view that working memory is a more proximal source of age-related differences in intelligence than the cognitive processing speed. [ABSTRACT FROM AUTHOR]

Abstract The neural factors that account for the visual processing speed reduction in aging are incompletely understood. Based on previous reports of age-related decreases in the intrinsic functional connectivity (iFC) within the cingulo-opercular network and its relevance for processing speed, we hypothesized that these decreases are associated with age-related reductions in visual processing speed. We used a whole-report task and modeling based on Bundesen's "theory of visual attention" to parameterize visual processing speed in 91 healthy participants aged from 20 to 77 years. iFC was estimated using independent component analysis of resting-state functional magnetic resonance imaging data. From the clusters within the cingulo-opercular network exhibiting age-related decreased iFC, we found a cluster in the left insula to be particularly associated with visual processing speed and to mediate the age effect on visual speed. This mediation was not observed for age-related decreased iFC in other networks or for other attentional parameters. Our results point to the iFC in the cingulo-opercular network, represented by the left insula, as being a relevant marker for visual processing speed changes in aging. [ABSTRACT FROM AUTHOR]

Highlights • Different types of physical activity are strongly associated with motor and cognitive improvements. • There is a dose–response relationship between physical activity and physiological improvements. • An average of 6.2 years of physical activity had favorable effects on motor functions. • An active lifestyle in adulthood is likely to prevent aging-related motor and cognitive decline. Abstract Background There is a poor understanding of the dose–response relationship between years of physical activity and motor and cognitive function. We determined the dose–response effects of physical activity duration in years on motor and cognitive function and their relationship in healthy old females. Objectives To determine the dose-effects of physical activity duration in years on motor and cognitive function and their relationship in health aging adults. Methods We conducted a retrospective observational study with 201 old (age 69 years; SD = 5.9) and 12 young (mean age 21 years; SD = 1.9) females, with sub-groups based on number of years of self-reported physical activity. Aerobic capacity, mobility, functional reach, standing balance, global cognition, episodic memory, executive function, and processing speed were assessed with performance-based tests. We analyzed sub-group differences quantitatively and qualitatively and performed regression and mediation analyses to determine predictors and mediators of physical activity effects. Results Based on physical activity of minimal (0.3 y, n = 29), short (2.4 y, n = 77), moderate (6.2 y, n = 36) and long (16.6 y, n = 59) duration, physical activity for at least 2.4 years affords old adults benefits in body mass index with peak dose-effects present in aerobic capacity and mobility at 6.2 years without additional benefits after 16.6 years of physical activity. Physical activity for any duration had no effects on functional reach, balance, executive function, episodic memory, and processing speed. Although weakly mobility predicted global cognition and executive function. Conclusion Performing physical activity up to 6.2 years on average had favorable effects on body mass index, aerobic capacity and mobility. The data strengthen current recommendations for an active lifestyle in adulthood to prevent aging-related motor and cognitive decline. [ABSTRACT FROM AUTHOR]