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This chapter summarizes the functional–anatomic organization of the connectivity of the basal ganglia with the thalamocortical systems and the brainstem. This connectional organization substantiates the neural basis for the wide array of functions in which the basal ganglia are involved, ranging from pure sensorimotor to cognitive–executive and emotional–motivational behaviors. Across this broad array of motor and behavioral functions, the mechanism by which the basal ganglia contribute to these functions is through “response selection.” This mechanism fits well with the arrangement of the intrinsic connections between the individual basal ganglia nuclei, supporting the selection of appropriate responses in a particular context and, at the same time, the suppression of inadequate responses. A variety of symptoms as part of neurologic movement disorders, such as Parkinson’s disease, Huntington’s disease and dystonia, or neuropsychiatric diseases like obsessive-compulsive disorder, mood disorders, and drug addiction, might be interpreted as an inadequate selection of motor, cognitive, or affective responses to internal or external stimuli.
Although Parkinson’s disease (PD) is most associated with and diagnosed by the presence of motor symptoms, non-motor symptoms (NMS) can often be the most debilitating for patients. Highly prevalent among non-motor features are neuropsychiatric symptoms (NPS), including depression, anxiety, psychosis, impulse control disorders, apathy and cognitive impairment, the latter being particularly burdensome and occurring in the majority of PD patients long term. The neurobiological underpinnings of NPS are a mix of disease-related, other neurodegenerative disease processes, PD treatment effects and psychosocial factors. NPS can be difficult to recognize and diagnose in PD patients; therefore, PD-specific assessments have been developed to better identify and treat them. Treatment strategies are a mix of those used in the general population for these conditions and those specific to PD, and are a combination of pharmacologic and non-pharmacologic interventions. Although significant advances have been made in our understanding and management of NPS in PD, etiology or biologically informed management strategies are needed to further advance the field.
Improving functioning in adults with major depressive disorder (MDD) and bipolar disorder (BD) is a priority therapeutic objective.
Methods
This retrospective post hoc secondary analysis evaluated 108 patients with MDD or BD receiving the antidepressants vortioxetine, ketamine, or infliximab. The analysis aimed to determine if changes in objective or subjective cognitive function mediated the relationship between depression symptom severity and workplace outcomes. Cognitive function was measured by the Perceived Deficits Questionnaire (PDQ-5), the Digit Symbol Substitution Test (DSST), and the Trail Making Test Part B (TMT-B). Depression symptom severity was measured by the Montgomery–Åsberg Depression Rating Scale (MADRS). Workplace function was measured by the Sheehan Disability Scale (SDS) work–school item.
Results
When co-varying for BMI, age, and sex, the association between MADRS and SDS work scores was partially mediated by PDQ-5 total scores and DSST total scores, but not DSST error scores and TMT-B time.
Limitations
This study was insufficiently powered to perform sub-group analyses to identify distinctions between MDD and BD populations as well as between antidepressant agents.
Conclusions
These findings suggest that cognitive impairment in adults with MDD and BD is a critical mediator of workplace function and reinforces its importance as a therapeutic target.
Early gut microbiome development may impact brain and behavioral development. Using a nonhuman primate model (Macaca mulatta), we investigated the association between social environments and the gut microbiome on infant neurodevelopment and cognitive function. Infant rhesus monkeys (n = 33) were either mother-peer-reared (MPR) or nursery-reared (NR). Neurodevelopmental outcomes, namely emotional responsivity, visual orientation, and motor maturity, were assessed with the Primate Neonatal Neurobehavioral Assessment (PNNA) at 14–30 days. Cognitive development was assessed through tasks evaluating infant reward association, cognitive flexibility, and impulsivity at 6–8 months. The fecal microbiome was quantified from rectal swabs via 16S rRNA sequencing. Factor analysis was used to identify “co-abundance factors” describing patterns of microbial composition. We used multiple linear regressions with AIC Model Selection and differential abundance analysis (MaAsLin2) to evaluate relationships between co-abundance factors, microbiome diversity, and neuro-/cognitive development outcomes. At 30 days of age, a gut microbiome co-abundance factor, or pattern, with high Prevotella and Lactobacillus (β = −0.88, p = 0.04, AIC Weight = 68%) and gut microbiome alpha diversity as measured by Shannon diversity (β = −1.33, p = 0.02, AIC Weight = 80%) were both negatively associated with infant emotional responsivity. At 30 days of age, being NR was also associated with lower emotional responsivity (Factor 1 model: β = −3.13, p < 0.01; Shannon diversity model: β = −3.77, p < 0.01). The infant gut microbiome, along with early-rearing environments, may shape domains of neuro-/cognitive development related to temperament.
Information on the time spent completing cognitive testing is often collected, but such data are not typically considered when quantifying cognition in large-scale community-based surveys. We sought to evaluate the added value of timing data over and above traditional cognitive scores for the measurement of cognition in older adults.
Method:
We used data from the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) study (N = 4,091), to assess the added value of timing data over and above traditional cognitive scores, using item-specific regression models for 36 cognitive test items. Models were adjusted for age, gender, interviewer, and item score.
Results:
Compared to Quintile 3 (median time), taking longer to complete specific items was associated (p < 0.05) with lower cognitive performance for 67% (Quintile 5) and 28% (Quintile 4) of items. Responding quickly (Quintile 1) was associated with higher cognitive performance for 25% of simpler items (e.g., orientation for year), but with lower cognitive functioning for 63% of items requiring higher-order processing (e.g., digit span test). Results were consistent in a range of different analyses adjusting for factors including education, hearing impairment, and language of administration and in models using splines rather than quintiles.
Conclusions:
Response times from cognitive testing may contain important information on cognition not captured in traditional scoring. Incorporation of this information has the potential to improve existing estimates of cognitive functioning.
This study aimed to investigate the prevalence and nature of cognitive impairment among severely ill COVID-19 patients and the effectiveness of the Montreal Cognitive Assessment (MoCA) in detecting it.
Method:
We evaluated cognition in COVID-19 patients hospitalized during the first wave (March to June 2020) from six Dutch hospitals, nine months post-discharge, using a comprehensive multi-domain neuropsychological test battery. Test performance was corrected for sex, age, and education differences and transformed into z-scores. Scores within each cognitive domain were averaged and categorized as average and above (z-score ≥ −0.84), low average (z-score −1.28 to −0.84), below average (z-score −1.65 to −1.28), and exceptionally low (z-score < −1.65). Patients were classified with cognitive impairment if at least one domain’s z-score fell below −1.65. We assessed the MoCA’s accuracy using both the original cutoff (<26) and an “optimal” cutoff determined by Youden’s index.
Results:
Cognitive impairment was found in 12.1% (24/199) of patients, with verbal memory and mental speed most affected (6.5% and 7% below −1.65, respectively). The MoCA had an area under the curve of 0.84. The original cutoff showed sensitivity of 83% and specificity of 66%. Using the identified optimal cutoff of <24, maintained sensitivity while improving specificity to 81%.
Conclusions:
Cognitive impairment prevalence in initially hospitalized COVID-19 patients is lower than initially expected. Verbal memory and processing speed are primarily affected. The MoCA is a valuable screening tool for these impairments and lowering the MoCA cutoff to <24 improves specificity.
Van Breukelen offers a promising method for modeling both response speed and response accuracy. However, the underlying conception of both dependent measures is somewhat flawed, leading the author to conclude that the approach possesses limitations that, under revised assumptions, may not hold. The central misconception, and a set of related misconceptions, is addressed, and it is suggested that this approach holds a good deal of promise for application in the perceptual and cognitive sciences.
This study explored cognitive effects on narrative macrostructure in both languages of 38 Russian-German bilinguals aged 4;6 to 5;1‚ while controlling for demographic factors (sex, socioeconomic status) and language proficiency. Macrostructure was operationalised as story structure (SS) and story complexity (SC) using the Multilingual Assessment Instrument for Narratives. Nonverbal cognitive subtasks assessing shifting (Figure Ground), visual memory (Form Completion), and inhibition (Attention Divided) were administered. None of the cognitive skills influenced SS; however, they differentially impacted SC: Figure Ground affected Russian SC, while Form Completion affected German SC. Findings advance our understanding of how cognition affects oral narratives in bilingual preschoolers.
Established in the early 1980s, Word Grammar is the first theory of grammar that was cast in the terms of cognitive linguistics. This book surveys the groundbreaking contribution of WG to a number of disciplines both within and outside of linguistics. It illustrates the benefits of thinking beyond traditional phrase-structural notions of syntax, and beyond encapsulated theories of cognition, by exploring how key problems in theoretical linguistics and historical linguistics can be approached from alternative perspectives. It provides examples of how theoretical linguistic notions and constructs of WG can be applied to bilingual language use, as well as a variety of typologically different languages including English, Chinese, German and Swedish. It also explores the relationship between language and social cognition and dependency distance as a universal measure of syntactic complexity. It is essential reading for linguists seeking creative ideas on how to advance explanations of language, language variation and change.
Cognitive impairment is a core feature of psychosis, which adversely affects global functioning and quality of life and has been consistently reported from the early stages of illness. Patients with first-episode psychosis (FEP) exhibit deficits in processing speed, short-term memory, attention, working memory, and executive functioning, which respond poorly to psychotropic drugs. Among non-pharmacological approaches, physical activity has shown promise in improving cognitive functioning in schizophrenia spectrum disorders. However, current evidence lacks specific data on individuals with FEP. In this review, we aim to explore the potential role of physical activity-based interventions in ameliorating the cognitive functions of people with FEP.
Methods
The literature search was conducted on PubMed, PsycINFO, and Web of Science in March 2024, identifying 127 de-duplicated records. One additional article was identified by screening the reference lists of the included studies. A total of six studies fulfilled the inclusion criteria and were reviewed. They all analyzed the effect of structured physical activity interventions on the cognitive functioning of patients with FEP.
Results
Preliminary findings suggest that physical activity interventions enhance memory, attention, and executive functions of patients with FEP but not social cognition and motor function.
Conclusions
Study differences in sample characteristics, design, and intervention protocols prevent firm conclusions about the cognitive-boosting effects of the interventions in FEP. Further studies using more rigorous methodologies are needed to understand the durability of these effects and the underlying mechanisms.
Validated computerized assessments for cognitive functioning are crucial for older individuals and those at risk of cognitive decline. The National Institutes of Health (NIH) Toolbox Cognition Battery (NIHTB-CB) exhibits good construct validity but requires validation in diverse populations and for adults aged 85+. This study uses data from the Assessing Reliable Measurement in Alzheimer’s Disease and cognitive Aging study to explore differences in the factor structure of the NIHTB-CB for adults 85 and older, Black participants versus White participants, and those diagnosed as amnestic Mild Cognitive Impairment (aMCI) vs cognitively normal (CN).
Method:
Subtests from the NACC UDS-3 and NIHTB-CB were administered to 503 community-dwelling Black and White adults ages 55–99 (367 CN; 136 aMCI). Confirmatory factor analyses were used to investigate the original factor structure of NIHTB-CB that forms the basis for NIHTB-CD Index factor scores.
Results:
Factor analyses for all participants and some participant subsets (aMCI, White, 85+) substantiated the two anticipated factors (Fluid and Crystallized). However, while Black aMCI participants had the expected two-factor structure, for Black CN participants, the List Sorting Working Memory and Picture Sequence tests loaded on the Crystallized factor.
Conclusions:
Findings provide psychometric support for the NIHTB-CB. Differences in factor structure between Black CN individuals and Black aMCI individuals suggest potential instability across levels of cognitive impairment. Future research should explore changes in NIHTB-CB across diagnoses in different populations.
Emerging evidence suggests a potential association between “leaky gut syndrome” and low-grade systemic inflammation in individuals with psychiatric disorders, such as schizophrenia. Gut dysbiosis could increase intestinal permeability, allowing the passage of toxins and bacteria into the systemic circulation, subsequently triggering immune-reactive responses. This study delves into understanding the relationship between plasma markers of intestinal permeability and symptom severity in schizophrenia. Furthermore, the influence of lifestyle habits on these intestinal permeability markers was determined.
Methods
Biomarkers of intestinal permeability, namely lipopolysaccharide-binding protein (LBP), lipopolysaccharides (LPS), and intestinal fatty acid binding protein (I-FABP), were analyzed in 242 adult schizophrenia patients enrolled in an observational, cross-sectional, multicenter study from four centers in Spain (PI17/00246). Sociodemographic and clinical data were collected, including psychoactive drug use, lifestyle habits, the Positive and Negative Syndrome Scale to evaluate schizophrenia symptom severity, and the Screen for Cognitive Impairment in Psychiatry to assess cognitive performance.
Results
Results revealed elevated levels of LBP and LPS in a significant proportion of patients with schizophrenia (62% and 25.6%, respectively). However, no statistically significant correlation was observed between these biomarkers and the overall clinical severity of psychotic symptoms or cognitive performance, once confounding variables were controlled for. Interestingly, adherence to a Mediterranean diet was negatively correlated with I-FABP levels (beta = −0.186, t = −2.325, p = 0.021), suggesting a potential positive influence on intestinal barrier function.
Conclusions
These findings underscore the importance of addressing dietary habits and promoting a healthy lifestyle in individuals with schizophrenia, with potential implications for both physical and psychopathological aspects of the disorder.
Older age significantly increases risk for cognitive decline. A growing number of older adults (≥ 65 years) experience cognitive decline that compromises immediate and/or long-term health. Interventions to mitigate cognitive decline are greatly needed. Intermittent fasting aligned with innate circadian rhythms is associated with health benefits and improved circadian rhythms; here, we explore impacts on cognition and cardiometabolic outcomes.
Methods:
We conducted a single-group, pre-/post-pilot study to explore an 8-week prolonged nightly fasting intervention (14 h fasting/night) among adults 65+ years with self-reported memory decline. We explored changes in cognitive function, insomnia, and cardiometabolic risk factors. Intervention engagement/adherence were assessed. The intervention was delivered fully remotely; participants completed their fasting protocol at home and were not required to come into the lab.
Results:
In total, 20 individuals signed consent and 18 participants completed the study. Participants were mean age 69.7 years, non-Hispanic White (89%), predominantly female (95%), married (50%), and employed (65%). Paired t-tests indicated an increase in cognitive function (Memory and Attention Phone Screener) (p = 0.02) with a medium effect size (Cohen’s d = 0.58) and a decrease in insomnia (Insomnia Severity Index) (p = 0.04) with a medium effect size (Cohen’s d = 0.52). Changes in BMI or diet quality were not observed. Engagement (66%–77%) and adherence (70%–100%) were high.
Conclusion:
These pilot findings suggest that prolonged nightly fasting, targeted to align food intake with circadian rhythms, may improve cognitive function and sleep among older adults. Fully powered, randomized controlled trials to test the efficacy of this non-pharmacological, low cost-to-burden ratio intervention are needed.
This chapter considers Irish Murdoch’s torn feelings about the role of philosophy in fiction. Such ambivalence, I argue, expresses her broader concerns about the role of ‘ideas’ both in art and in life. Murdochs’s novels are often embarrassed by their own conceptuality and yearn for a more brute contact with the world that has no recourse to the mediating role of ideas and theories. But this wish is also exposed as a fantasy in her work. Literature in Murdoch is a form of thought and is subject to its limitations. Not only does it rely on concepts, it is also pulled between different aspects of thinking: between particular and general viewpoints and inner and outer perspectives. As I show, the friction between these modes of thought accounts for the uneven form and philosophical power of Murdoch’s fiction.
Immune dysregulation appears involved in affective disorder pathophysiology. Inflammatory biomarkers have been linked with the cognitive impairment observed in people with bipolar disorders and as such are candidate markers that may improve with, and/or predict outcomes to, cognitive remediation therapies (CRT).
Aims
Nine candidate biomarkers were examined as putative mediators and/or moderators to improvements following CRT compared with treatment as usual (TAU) from a randomised controlled trial.
Method
Euthymic adults with bipolar disorders who had been randomised to CRT (n = 23) or TAU (n = 21) underwent blood testing before and after a 12 week intervention period. Five cytokines and four growth factor proteins, selected a priori, were examined in association with global cognition and psychosocial functioning outcomes.
Results
CRT attenuated a reduction in the brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor and vascular endothelial growth factor-C compared to TAU. For the BDNF, lower baseline levels predicted better functional outcomes across the sample but was more pronounced in TAU versus CRT participants and indicated larger CRT effects in those with a higher BDNF. A moderation effect was also apparent for tumour necrosis factor-β and interleukin-16, with greater CRT versus TAU effects on functioning for participants with lower baseline levels.
Conclusions
Although preliminary, results suggest that CRT may exert some protective biological effects, and that people with lower levels of neurotrophins or cytokines may benefit more from CRT. We note an absence of associations with cognitive (versus functional) outcomes. These findings require further examination in large well-controlled studies.
Cognitive impairment constitutes a prevailing issue in the schizophrenia spectrum, severely impacting patients' functional outcomes. A global cognitive score, sensitive to the stages of the spectrum, would benefit the exploration of potential factors involved in the cognitive decline.
Methods
First, we performed principal component analysis on cognitive scores from 768 individuals across the schizophrenia spectrum, including first-degree relatives of patients, individuals at ultra-high risk, who had a first-episode psychosis, and chronic schizophrenia patients, alongside 124 healthy controls. The analysis provided 10 g-factors as global cognitive scores, validated through correlations with intelligence quotient and assessed for their sensitivity to the stages on the spectrum using analyses of variance. Second, using the g-factors, we explored potential mechanisms underlying cognitive impairment in the schizophrenia spectrum using correlations with sociodemographic, clinical, and developmental data, and linear regressions with genotypic data, pooled through meta-analyses.
Results
The g-factors were highly correlated with intelligence quotient and with each other, confirming their validity. They presented significant differences between subgroups along the schizophrenia spectrum. They were positively correlated with educational attainment and the polygenic risk score (PRS) for cognitive performance, and negatively correlated with general psychopathology of schizophrenia, neurodevelopmental load, and the PRS for schizophrenia.
Conclusions
The g-factors appeared as valid estimators of global cognition, enabling discerning cognitive states within the schizophrenia spectrum. Educational attainment and genetics related to cognitive performance may have a positive influence on cognitive functioning, while general psychopathology of schizophrenia, neurodevelopmental load, and genetic liability to schizophrenia may have an adverse impact.
This chapter focuses on emotions and affects in Greek epic. Leven demarcates the difference between emotion and affect in this context: emotions are defined as complex phenomena that involve embodied minds, gendered individuals and their societies, as well as instincts, cognition and values; and affects are understood as more ineffable feelings, which lie ‘beneath’ the surface: the innumerable microevents that bodies and selves undergo in their experience of the world around them, rarely indexed in conventional language. The chapter then starts by outlining the main questions that have divided scholarship on ancient emotions in general, and epic emotions in particular, with special focus on two cases, anger and fear. It then turns to episodes featuring what Leven calls ‘scenes of affect’ and argues, first, that epic is not in fact solely dominated by ‘big emotions’ but is rather shaped by a multitude of affects. Focusing on representative passages of the Odyssey, the Argonautica, and the Posthomerica, the chapter ultimately shows that epic provides its own tools to conceptualise these affects.
Higher white matter hyperintensity (WMH) volume is a marker of cardiovascular disease (CVD) risk. CVD risk factors increase risk for Alzheimer’s disease and related dementias (ADRD). Mexican Americans (MA) and individuals of other Hispanic/Latino heritages have higher risk for CVD and ADRD. However, knowledge of associations between WMH volume and cognition in these groups remains limited.
Method:
We conducted a cross-sectional study of associations between WMH volume and neuropsychological performance (attention/executive functioning, memory) in MA (n = 851) and non-Hispanic White (NHW; n = 747) adults in the Health and Aging Brain Study: Health Disparities.
Results:
The MA group (mean age = 63.72 ± 7.90 years; 66.3% female) had higher rates of consensus diagnoses of hypertension and diabetes, whereas the NHW group (mean age = 69.18 ± 8.65 years; 55.2% female) had higher rates of diagnosed CVD (ps < .01). WMH volumes were higher among individuals with CVD risk factors/conditions (ps < .01). There were differential associations between WMH and neuropsychological performance across ethnoracial groups (ps < .001), wherein associations were steeper in the NHW group than in the MA group. Lower educational level was associated with higher WMH volume in the NHW group (p < .001), but no association was seen in the MA group (p > .05).
Conclusions:
Negative effects of pathological changes in the form of WMH on cognition may be less robust or consistent for MA adults than NHW adults. Furthermore, the impact of WMH on cognition in NHW adults may be mitigated by cognitive reserve related to educational attainment.
Being married may protect late-life cognition. Less is known about living arrangement among unmarried adults and mechanisms such as brain health (BH) and cognitive reserve (CR) across race and ethnicity or sex/gender. The current study examines (1) associations between marital status, BH, and CR among diverse older adults and (2) whether one’s living arrangement is linked to BH and CR among unmarried adults.
Method:
Cross-sectional data come from the Washington Heights-Inwood Columbia Aging Project (N = 778, 41% Hispanic, 33% non-Hispanic Black, 25% non-Hispanic White; 64% women). Magnetic resonance imaging (MRI) markers of BH included cortical thickness in Alzheimer’s disease signature regions and hippocampal, gray matter, and white matter hyperintensity volumes. CR was residual variance in an episodic memory composite after partialing out MRI markers. Exploratory analyses stratified by race and ethnicity and sex/gender and included potential mediators.
Results:
Marital status was associated with CR, but not BH. Compared to married individuals, those who were previously married (i.e., divorced, widowed, and separated) had lower CR than their married counterparts in the full sample, among White and Hispanic subgroups, and among women. Never married women also had lower CR than married women. These findings were independent of age, education, physical health, and household income. Among never married individuals, living with others was negatively linked to BH.
Conclusions:
Marriage may protect late-life cognition via CR. Findings also highlight differential effects across race and ethnicity and sex/gender. Marital status could be considered when assessing the risk of cognitive impairment during routine screenings.
Cognitive and psychiatric symptoms have been increasingly reported after severe acute respiratory syndrome coronavirus 2 infection, developing soon after infection and possibly persisting for several months. We aimed to study this syndrome and start implementing strategies for its assessment.
Methods
Consecutive patients, referred by the infectious disease specialist because of cognitive complaints after COVID-19, were neurologically evaluated. Neurological evaluation included a cognitive screening test (Montreal Cognitive Assessment, MoCA). Moreover, patients were invited to fill out a general symptom questionnaire and a self-administered multidimensional assessment of psychiatric symptoms, followed by a full psychiatric assessment if scores were above validated cutoffs.
Results
Of 144 referred patients, 101 (mean age 55.2±13.1, 63.4% females) completed the cognitive screening and the self-administered psychiatric questionnaire. Acute infection severity was low for most patients and the most common persisting symptoms were fatigue (92%), sleep problems (69.5%), and headache (52.4%). MoCA outlined cognitive deficits in ≥1 cognitive domain in 34% of patients, mainly in memory and attention. About 60% of patients presented depressive, anxiety, or stress-related symptoms. Psychiatric scale scores significantly correlated with overall symptom burden and MoCA score. No significant correlation was found between MoCA scores and overall symptom burden.
Conclusion
We hypothesize that persistent cognitive complaints after COVID-19 might reflect a concomitant or reactive psychopathological condition, possibly coupled with an infection-related impact on cognitive functions. The application of a combined neurological and psychiatric assessment seems crucial to appraise the nature of post-COVID-19 condition.