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Objective: This study aims to estimate the extent to which anticholinergic and sedative burden is associated with cognitive ability and self-reported cognitive difficulties (SCD) in middle-aged and older adults living with HIV., Design: This cross-sectional analysis examined data from the inaugural visit of participants enrolled in the Positive Brain Health Now (BHN) study., Methods: Cognitive ability was measured using the Brief Cognitive Ability Measure (B-CAM; higher is better) and SCD using the Perceived Deficits Questionnaire (PDQ; higher is worse). Medication burden was quantified using several scoring systems, including the Anticholinergic Cognitive Burden (ACB), Anticholinergic and Sedative Burden Catalog (ACSBC), Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and the Sedative Load Model (SLM). Multivariable Ordinary Least Squares and quantile regression were utilized to estimate average effects and distribution-specific impacts, respectively., Results: Of 824 participants (mean age 53 years, 84.7% men), 41.4% used anticholinergics (ACSBC) and 39% used sedatives (SLM). High anticholinergic burden was linked to worse cognitive ability [ β = -3.81; 95% confidence interval (CI): -7.16, -0.46] and SCD ( β = 3.89; 95% CI: 1.08, 6.71). Using three or more anticholinergics worsened cognitive ability ( β = -4.45; 95% CI: -8.54, -0.35), and using three or more sedatives increased SCD ( β  = 4.35; 95% CI: 0.92-7.78). Stronger negative associations were observed in participants with lower cognitive ability and more difficulties., Conclusions: These results suggest that anticholinergic and sedative burden may contribute to cognitive impairment in people with HIV. Personalized medication management and regular cognitive assessments could mitigate these adverse effects., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Motor skill learning and performance are improved when successful actions are paired with extrinsic rewards, such as money. Positive feedback indicating successful task performance is thought to induce intrinsic reward associated with goal attainment, evidenced by increases in positive affect that correlate with neural reward signaling. However, it is not clear whether the subjective, internal reward processes elicited by positive feedback promote motor learning and performance.Here, we tested the hypothesis that intrinsic reward elicited by positive feedback promotes motor learning and performance. Participants practiced a visuomotor interception task using a joystick, and received feedback during practice indicating success or failure depending on their accuracy. During practice, the accuracy demands were adapted to control and vary the frequency of positive feedback across randomly ordered blocks of practice at either 50%, 70%, or 90%. Performance was measured for each condition as the average accuracy during practice. Learning was estimated by measuring the accuracy pre and post practice in the absence of feedback. We queried participants periodically on their enjoyment of the task to index affective responses to performance feedback.The intrinsic reward elicited by positive feedback, operationalized by the increase in enjoyment immediately following positive versus negative feedback, was positively correlated with learning from pre to post practice. However, increasing the overall amount of positive feedback by lower accuracy demands did not improve performance. These results suggest that experiencing intrinsic reward due to positive feedback benefits motor learning only when it is contingent on good performance., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Brain health is a dynamic state involving cognitive, emotional, and motor domains. Measuring brain health is a challenge owing to the uncertainty as to whether it is one or many constructs. This study aimed to contribute evidence for brain health as a unified construct by estimating the strength of relationships between and among patient-reported items related to the brain health construct in a population with brain vulnerability owing to HIV., Methods: Data for this cross-sectional analysis came from a Canadian cohort of people aging with HIV. The sample included 710 men recruited between 2014 and 2016 from five Canadian cities. A network analysis was conducted with 30 items selected from the brain-related domains of fatigue, cognition, depression, sleep, anxiety, and motivation. Node centrality measures were used to determine the most critical items in the network., Results: The network showed small-world properties, that is, most nodes can be reached from other nodes with few hops," indicating strong connectivity. The most central symptoms were "How much do you enjoy life?" and "How often do you have negative feelings?"., Conclusion: The small-world properties of the network structure indicate that brain health items are interconnected and may be influenced by shared underlying factors. The centrality indices suggest that items related to enjoyment of life and negative feelings may be particularly important for understanding brain health in this population. Future research should aim to replicate these findings in larger and more diverse samples to confirm their robustness and generalizability., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: To estimate the extent to which comorbidity, polypharmacy, and anticholinergic/sedative burden interrelate to influence cognitive ability, perceived cognitive deficits and physical frailty in people living with HIV., Design: Cross-sectional Structural Equation Modeling (SEM) of data from 824 older people living with HIV in Canada, participating in the Positive Brain Health Now study., Method: SEM was used to link observed variables, including comorbidity, polypharmacy, anticholinergic and sedative burden, to cognitive ability and two latent constructs - physical frailty and perceived cognitive deficits (PCD). The model was adjusted for age, sex, education, nadir CD4, duration of HIV, and symptoms of anxiety/depression. Maximum Likelihood with Robust standard errors and bootstrapping were used to test the robustness and significance of the model's indirect effects., Results: Anticholinergic burden had a direct significant negative relationship with cognitive ability (βstd = -0.21, p<0.05) and indirect effect on PCD (βstd = 0.16, p<0.01) and frailty (βstd = 0.06, p<0.01) through sedative burden. Sedative burden was directly associated with PCD (βstd = 0.18, p<0.01) and indirectly with frailty through PCD (βstd = 0.07, p<0.01). Comorbidity and polypharmacy exerted indirect effects on PCD and physical frailty through anticholinergic and sedative burden. The model fit the data well (CFI: 0.97, TLI: 0.94, RMSEA: 0.05, SRMR: 0.04)., Conclusion: Anticholinergic and sedative burden function as a pathway through which polypharmacy and comorbidities influence physical frailty and perceived cognitive deficits. Reducing the use of anticholinergic and sedative medications could help prevent and manage cognitive impairment and frailty in older people living with HIV., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: This study aimed to produce a patient-centered understanding of mental health symptoms of people with the post-COVID-19 syndrome (PCS)., Methods: A cross-sectional analysis of 414 participants in a longitudinal study was carried out involving people who self-identified as having symptoms of PCS. People were asked to name their most frequent and most bothersome mental health symptoms affected by PCS using the structure of the Patient Generated Index (PGI). The text threads from the PGI were grouped into topics using BERTopic analysis., Results: 20 topics were identified from 818 text threads referring to PCS mental health symptoms. 35% of threads were identified as relating to anxiety, discussed in terms of five topics: generalized/social anxiety, fear/worry, post-traumatic stress, panic, and nervous. 29% of threads were identified as relating to low mood, represented by five topics: depression, discouragement, emotional distress, sadness, and loneliness. A cognitive domain (22% of threads) was covered by four topics referring to concentration, memory, brain fog, and mental fatigue. Topics related to frustration, anger, irritability. and mood swings (7%) were considered as one domain and there were separate topics related to motivation, insomnia, and isolation., Conclusions: This novel method of digital transformation of unstructured text data uncovered different ways in which people think about classical mental health domains. This information could be used to evaluate whether existing measures cover the content identified by people with PCS, to initiate a clinical conversation, or to justify the development of a new measure of the mental health impact of PCS., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Technology is poised to bridge the gap between demand for therapies to improve gait in people with Parkinson's and available resources. A wearable sensor, Heel2Toe™, a small device that attaches to the side of the shoe and gives a sound each time the person starts their step with a strong heel strike, has been developed and pre-tested by a team at McGill University. The objective of this study was to estimate feasibility and efficacy potential of the Heel2Toe™ sensor in changing walking capacity and gait pattern in people with Parkinson's., Methods: A pilot study was carried out involving 27 people with Parkinson's randomized 2:1 to train with the Heel2Toe[TM] sensor and or to train with recommendations from a gait-related workbook., Results: A total of 21 completed the 3-month evaluation, 14 trained with the Heel2Toe[TM] sensor, and 7 trained with the workbook. Thirteen of 14 people in the Heel2Toe group improved over measurement error on the primary outcome, the 6-Minute Walk Test, (mean change 66.4 m) and 0 of the 7 in the Workbook group (mean change - 19.4 m): 4 of 14 in the Heel2Toe group made reliable change and 0 of 7 in the Workbook group. Improvements in walking distance were accompanied by improvements in gait quality. Forty percent of participants in the intervention group were strongly satisfied with their technology experience and an additional 37% were satisfied., Conclusions: Despite some technological difficulties, feasibility and efficacy potential of the Heel2Toe sensor in improving gait in people with Parkinson's was supported., (© 2024. The Author(s).)

Background: Post-COVID syndrome (PCS) causes lasting symptoms like fatigue and cognitive issues. PCS treatment is nonspecific, focusing on symptom management, potentially increasing the risk of polypharmacy., Objectives: To describe medication use patterns among patients with Post-COVID Syndrome (PCS) and estimate the prevalence of polypharmacy, potential drug-drug interactions, and anticholinergic/sedative burden., Methods: A cross-sectional analysis of baseline data from the Quebec Action for Post-COVID cohort, consisting of individuals self-identifying with persistent COVID-19 symptoms beyond 12 weeks. Medications were categorized using Anatomical Therapeutic Classification (ATC) codes. Polypharmacy was defined as using 5 or more concurrent medications. The Anticholinergic and Sedative Burden Catalog assessed anticholinergic and sedative loads. The Lexi-Interact checker identified potential drug-drug interactions, which were categorized into 3 severity tiers., Results: Out of 414 respondents, 154 (average age 47.7 years) were prescribed medications related to persistent COVID-19 symptoms. Drugs targeting the nervous system were predominant at 54.5%. The median number of medications was 2, while 11.7% reported polypharmacy. Over half of the participants prescribed medications used at least 1 anticholinergic or sedative medication, and 25% had the potential risk for clinically significant drug-drug interactions, primarily needing therapy monitoring., Conclusions: Our study reveals prescription patterns for PCS, underscoring the targeted management of nervous system symptoms. The risks associated with polypharmacy, potential drug-drug interactions, and anticholinergic/sedative burden stress the importance of judicious prescribing. While limitations like recall bias and a regional cohort are present, the findings underscore the imperative need for vigilant PCS symptom management., Competing Interests: Disclosure The authors also declare that they have no conflicts of interest to disclose., (Copyright © 2024 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to estimate the structure and relationships between four h ypothesized frailty dimensions (physical, emotional, cognitive, and social) and the extent to which personal and HIV-related factors and comorbidity associate with these frailty dimensions. This is a secondary analysis of an existing dataset arising from Positive Brain Health Now study ( n = 856) in people aging with HIV (mean age: 52.3 ± 8.1 years). Structural equation modeling (SEM) models were applied to two cross-sections of the data: one at study entry and one at second visit, 9-month apart. Multidimensional frailty was modeled based on the combined Wilson-Cleary and International Classification of Functioning, Disability and Health framework. Four dimensions were operationalized with patient-reported and self-report measures from standardized questionnaires. The SEM model from the first visit was replicated using data from the second visit, testing measurement invariance. The proposed model showed acceptable fit at both visits (including no violation of measurement invariance). The final model for the first visit showed that sex, body mass index, HIV diagnosis pre-1997, current or nadir CD4 counts, and comorbidity did not associate with any frailty dimension; however, age (β range: 0.12-0.25), symptoms (β range: -0.35 to -0.58), and measured cognition (β range: 0.10-0.24) directly associated with all frailty dimensions. The model remained stable across the two visits. This study contributes evidence for operationalizing multidimensional frailty. Evidence-based interventions are available for many of the measures considered here, offering opportunities to improve the lives of people with frailty in the context of HIV.

Objective: This study aimed to estimate the strength of the association between anticholinergic/sedative burden and concurrent physical frailty in people aging with HIV., Design: This cross-sectional analysis examined baseline data from 824 adults with a mean age of 53 enrolled in the Positive Brain Health Now study., Methods: Anticholinergic medications were identified using four methods: Anticholinergic Cognitive Burden (ACB) Scale, Anticholinergic Risk Scale (ARS), Anticholinergic Drug Scale (ADS), and the anticholinergic list of the Anticholinergic and Sedative Burden Catalog (ACSBC). Sedatives were identified using the Sedative Load Model (SLM) and the sedative list of the ACSBC. Physical frailty was assessed using a modified Fried Frailty Phenotype (FFP) based on self-report items. Multivariable logistic regression models, adjusted for sociodemographic factors, lifestyle considerations, HIV-related variables, comorbidities, and co-medication use, were used to estimate odds ratios (ORs)., Results: Anticholinergic burden demonstrated associations with frailty across various methods: total anticholinergic burden (OR range: 1.22-1.32; 95% confidence interval (CI) range: 1.03-1.66), sedative burden (OR range: 1.18-1.24; 95% CI range: 1.02-1.45), high anticholinergic burden (OR range: 2.12-2.74; 95% CI range: 1.03-6.19), and high sedative burden (OR range: 1.94-2.18; 95% CI: 1.01-4.34)., Conclusion: The anticholinergic and sedative burdens may represent modifiable risk factors for frailty in people aging with HIV. Future studies should evaluate the effects of reducing anticholinergic and sedative burdens on frailty outcomes and explore the prognostic value of diverse scoring methods., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To identify the contexts in which goal setting has been used in chronic disease management interventions and to estimate the magnitude of its effect on improvement of health outcomes., Methods: The strength of evidence and extent of potential bias in the published systematic reviews of goal setting interventions in chronic conditions were summarized using AMSTAR2 quality appraisal tool, number of participants, 95% prediction intervals, and between-study heterogeneity. Components of goal setting interventions were also extracted., Results: Nine publications and 35 meta-analysis models were identified, investigating 25 health outcomes. Of the 35 meta-analyses, none found strong evidence and three provided some suggestive evidence on symptom reduction and perceived well-being. There was weak evidence for effects on eight health outcomes (HbA1c, self-efficacy, depression, anxiety, distress, medication adherence, health-related quality of life and physical activity), with the rest classified as non-significant. Half of the meta-analyses had high level of heterogeneity., Conclusion: Goal setting by itself affects outcomes of chronic diseases only to a small degree. This is not unexpected finding as changing outcomes in chronic diseases requires a complex and individualized approach. Implementing goal setting in a standardized way in the management of chronic conditions would seem to be a way forward.IMPLICATIONS FOR REHABILITATIONThe link between goal setting and health outcomes seems to be weak.Some levels of positive behavioural change could be of benefits to patients as seen by improved self-efficacy, patients' satisfaction and overall quality of life.Systematic and consistent application of personalized goal-oriented interventions considering patient's readiness to change could better predict improved outcomes.Incorporation of various goal setting components while actively engaging patient and/or their care givers in the process could appraise how goal setting could help with challenges in faced by people living with chronic conditions in different areas.

We adapt our movements to new and changing environments through multiple processes. Sensory error-based learning counteracts environmental perturbations that affect the sensory consequences of movements. Sensory errors also cause the upregulation of reflexes and muscle co-contraction. Reinforcement-based learning enhances the selection of movements that produce rewarding outcomes. Although some findings have identified dissociable neural substrates of sensory error- and reinforcement-based learning, correlative methods have implicated dorsomedial frontal cortex in both. Here, we tested the causal contributions of dorsomedial frontal to adaptive motor control, studying people with chronic damage to this region. Seven human participants with focal brain lesions affecting the dorsomedial frontal and 20 controls performed a battery of arm movement tasks. Three experiments tested: (i) the upregulation of visuomotor reflexes and muscle co-contraction in response to unpredictable mechanical perturbations, (ii) sensory error-based learning in which participants learned to compensate predictively for mechanical force-field perturbations, and (iii) reinforcement-based motor learning based on binary feedback in the absence of sensory error feedback. Participants with dorsomedial frontal damage were impaired in the early stages of force field adaptation, but performed similarly to controls in all other measures. These results provide evidence for a specific and selective causal role for the dorsomedial frontal in sensory error-based learning., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Purpose: In research people are often asked to fill out questionnaires about their health and functioning and some of the questions refer to serious health concerns. Typically, these concerns are not identified until the statistician analyses the data. An alternative is to use an individualized measure, the Patient Generated Index (PGI) where people are asked to self-nominate areas of concern which can then be dealt with in real-time. This study estimates the extent to which self-nominated areas of concern related to mood, anxiety and cognition predict the presence or occurrence of brain health outcomes such as depression, anxiety, psychological distress, or cognitive impairment among people aging with HIV at study entry and for successive assessments over 27 months., Methods: The data comes from participants enrolled in the Positive Brain Health Now (+ BHN) cohort (n = 856). We analyzed the self-nominated areas that participants wrote on the PGI and classified them into seven sentiment groups according to the type of sentiment expressed: emotional, interpersonal, anxiety, depressogenic, somatic, cognitive and positive sentiments. Tokenization was used to convert qualitative data into quantifiable tokens. A longitudinal design was used to link these sentiment groups to the presence or emergence of brain health outcomes as assessed using standardized measures of these constructs: the Hospital Anxiety and Depression Scale (HADS), the Mental Health Index (MHI) of the RAND-36, the Communicating Cognitive Concerns Questionnaire (C3Q) and the Brief Cognitive Ability Measure (B-CAM). Logistic regressions were used to estimate the goodness of fit of each model using the c-statistic., Results: Emotional sentiments predicted all of the brain health outcomes at all visits with adjusted odds ratios (OR) ranging from 1.61 to 2.00 and c-statistics > 0.73 (good to excellent prediction). Nominating an anxiety sentiment was specific to predicting anxiety and psychological distress (OR 1.65 & 1.52); nominating a cognitive concern was specific to predicting self-reported cognitive ability (OR 4.78). Positive sentiments were predictive of good cognitive function (OR 0.36) and protective of depressive symptoms (OR 0.55)., Conclusions: This study indicates the value of using this semi-qualitative approach as an early-warning system in predicting brain health outcomes., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: While many everyday choices are between multi-attribute options, how attribute values are integrated to allow such choices remains unclear. Recent findings suggest a distinction between elemental (attribute-by-attribute) and configural (holistic) evaluation of multi-attribute options, with different neural substrates. Here, we asked if there are behavioral or gaze pattern differences between these putatively distinct modes of multi-attribute decision-making., Methods: Thirty-nine healthy men and women learned the monetary values of novel multi-attribute pseudo-objects (fribbles) and then made choices between pairs of these objects while eye movements were tracked. Value was associated with individual attributes in the elemental condition, and with unique combinations of attributes in the configural condition. Choice, reaction time, gaze fixation time on options and individual attributes, and within- and between-option gaze transitions were recorded., Results: There were systematic behavioral differences between elemental and configural conditions. Elemental trials had longer reaction times and more between-option transitions, while configural trials had more within-option transitions. The effect of last fixation on choice was more pronounced in the configural condition., Discussion: We observed differences in gaze patterns and the influence of last fixation location on choice in multi-attribute value-based choices depending on how value is associated with those attributes. This adds support for the claim that multi-attribute option values may emerge either elementally or holistically, reminiscent of similar distinctions in multi-attribute object recognition. This may be important to consider in neuroeconomics research that involve visually-presented complex objects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ryan-Lortie, Pelletier, Pilgrim and Fellows.)

Background: Gut damage allows translocation of bacterial lipopolysaccharide (LPS) and fungal β-D-glucan (BDG) into the blood. This microbial translocation contributes to systemic inflammation and risk of non-AIDS comorbidities in people living with HIV, including those receiving antiretroviral therapy (ART). We assessed whether markers of gut damage and microbial translocation were associated with cognition in ART-treated PLWH., Methods: Eighty ART-treated men living with HIV from the Positive Brain Health Now Canadian cohort were included. Brief cognitive ability measure (B-CAM) and 20-item patient deficit questionnaire (PDQ) were administered to all participants. Three groups were selected based on their B-CAM levels. We excluded participants who received proton pump inhibitors or antiacids in the past 3 months. Cannabis users were also excluded. Plasma levels of intestinal fatty acid binding protein (I-FABP), regenerating islet-derived protein 3 α (REG3α), and lipopolysaccharides (LPS = were quantified by ELISA, while 1-3-β-D-glucan BDG) levels were assessed using the Fungitell assay. Univariable, multivariable, and splines analyses were performed., Results: Plasma levels of I-FABP, REG3α, LPS and BDG were not different between groups of low, intermediate and high B-CAM levels. However, LPS and REG3α levels were higher in participants with PDQ higher than the median. Multivariable analyses showed that LPS association with PDQ, but not B-CAM, was independent of age and level of education. I-FABP, REG3α, and BDG levels were not associated with B-CAM nor PDQ levels in multivariable analyses., Conclusion: In this well characterized cohort of ART-treated men living with HIV, bacterial but not fungal translocation was associated with presence of cognitive difficulties. These results need replication in larger samples., (© 2023. The Author(s).)

Loneliness has been shown to be a predictor of poor health and early mortality in the general population. Older men living with human immunodeficiency virus (HIV) are at heightened risk of experiencing loneliness. Here, we aim to describe the lived experience of loneliness in older men living with HIV and identify targets for intervention. We used grounded theory with a theoretical framework of narrative phenomenology to focus data collection and analysis on significant experiences related to loneliness. Based on individual narrative interviews with 10 older men living with HIV, experiences of loneliness related to "multiple losses," "being invisible" and "hiding out" as emergent themes. Participants also described living with loneliness by "finding meaning," "creating social experiences," "pursuing interests and things to 'live for'" and attending events in which "everyone is welcome." The discussion situates experiences of loneliness within the accumulation of losses and stigmas over time and how the participants strategies for living with loneliness could inform interventions to reduce loneliness in older men living with HIV at individual and societal levels., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Austin-Keiller et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: The overall aim of this study was to develop a method of measuring change in cognitive ability from the person's perspective., Methods: Cognitive change items came from an item pool that was used to develop the Communicating Cognitive Concerns Questionnaire (C3Q). The change items were administered to a test sample of 211 people with HIV + and a sample of 484 people drawn from the general population (HIV- sample). Rasch analysis was used to identify items that formed a linear continuum and correlations with measures of related constructs were used to support the interpretability of the new measure., Results: Eleven of the original 12 change items fit the unidimensional Rasch model in both samples with a near similar ordering of the items. The average value for cognitive change of the HIV + sample was greater than that of the HIV- sample. Values on C3Q-Change correlated most highly (> 0.7) with current self-reported cognitive status and measures of depression and anxiety (> 0.6). The lowest correlation was with performance-based cognitive ability (r = 0.2)., Conclusion: The items of C3Q-Change fit a strong measurement model and related to converging constructs in an expected way. Further work needs to be done to assess the meaning of self-reported cognitive change in relationship to measured change and to examine sources of differential item functioning., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: To estimate among people living with chronic HIV, to what extent providing feedback on their health outcomes will affect the number and specificity of patient-formulated self-management goals., Methods: A personalized feedback profile was produced for individuals enrolled in a Canadian HIV Brain Health Now study. Goal specificity was measured by total number of specific words (matched to a domain-specific developed lexicon) per person-words using text mining techniques., Results: Of 176 participants enrolled and randomly assigned to feedback and control groups, 110 responses were received. The average number of goals was similar for both groups (3.7 vs 3.9). The number of specific words used in the goals formulated by the feedback and control group were 642 and 739, respectively. Specific nouns and actionable verbs were present to some extent and "measurable" and "time-bound" words were mainly missing. Negative binomial regression showed no difference in goal specificity among groups (RR = 0.93, 95% CI 0.78-1.10). Goals set by both groups overlapped in 8 areas and had little difference in rank., Conclusion: Personalized feedback profile did not help with formulation of high-quality goals. Text mining has the potential to help with difficulties of goal evaluation outside of the face-to-face setting. With more data and use of learning models automated answers could be generated to provide a more dynamic platform., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

(1) Background: The aim of this project was to develop a short, HIV-specific, health-related quality of life measure with a scoring system based on patient preferences for the different dimensions of the Preference-Based HIV Index (PB-HIV). (2) Methods: This study is a cross-sectional analysis of data from the Canadian Positive Brain Health Now cohort (n = 854; mean age 53 years). Items from the standardized measures were mapped to the areas from the Patient-Generated Index and formed the domains. A Rasch analysis was used to identify the best performing item to represent each dimension. Each item was then regressed on self-rated health (scored 0 to 100) and the regression parameters were used as scaling weights to form an index score for the prototype measure. (3) Results: Seven independent dimensions with three declarative statements ordered as response options formed the PB-HIV Index (pain, fatigue, memory/concentration, sleep, physical appearance/body image, depression, motivation). Regression parameters from a multivariable model yielded a measure with a scoring range from 0 (worst health) to 100 (perfect health). (4) Conclusions: Preference-based measures are optimal, as the total score reflects gains in some dimensions balanced against losses in others. The PB-HIV Index is the first HIV-specific preference-based measure.

Lesion research classically maps behavioral effects of focal damage to the directly injured brain region. However, such damage can also have distant effects that can be assessed with modern imaging methods. Furthermore, the combination and comparison of imaging methods in a lesion model may shed light on the biological basis of structural and functional networks in the healthy brain. We characterized network organization assessed with multiple MRI imaging modalities in 13 patients with chronic focal damage affecting either superior or inferior frontal gyrus (SFG, IFG) and 18 demographically matched healthy Controls. We first defined structural and functional network parameters in Controls and then investigated grey matter (GM) and white matter (WM) differences between patients and Controls. Finally, we examined the differences in functional coupling to large-scale resting state networks (RSNs). The results suggest lesions are associated with widespread within-network GM loss at distal sites, yet leave WM and RSNs relatively preserved. Lesions to either prefrontal region also had a similar relative level of impact on structural and functional networks. The findings provide initial evidence for causal contributions of specific prefrontal regions to brain networks in humans that will ultimately help to refine models of the human brain., (© 2022. The Author(s).)

Goal Management Training® (GMT) teaches strategies to reduce cognitive load and improve focus in everyday tasks. The aim of this study was to ascertain feasibility, acceptability, and efficacy potential of GMT for people (≥50 years) with stable HIV infection scoring low on tests of cognitive ability. A two-sample, parallel, controlled trial was carried out. Feasibility was demonstrated, as 21/30 participants in the GMT group attended ≥8 of the 9 sessions and completed at least half of the homework. There was no change on the primary performance-based cognitive outcomes in the GMT group or in the control group (n = 23). There was a meaningful improvement in self-reported cognition in those adherent to the intervention. GMT is a promising intervention for people aging with HIV who are dealing with cognitive difficulties affecting their everyday life and should be further investigated., Competing Interests: Nancy Mayo declares she has no conflict of interest. Dr. Brian Levine is the developer of Goal Management Training® Marie-Josée Brouillette declares she has no conflict of interest. Delphine Bélanger declares she has no conflict of interest. Lesley Fellows declares she has no conflict of interest., (© 2022 Published by Elsevier Inc.)

Apathy, a clinical disorder characterized by low motivation, is prevalent in people living with Human Immunodeficiency Virus (HIV). It affects mental and physical health-related quality-of-life, medication adherence, and is associated with cognitive decline. However, the causes of apathy and the underlying brain mechanisms in HIV are unknown. Brain responses to reward may be relevant to understanding apathy and might serve as biomarkers for diagnosis or treatment response. Electroencephalogram (EEG) responses to gain and loss feedback in simple guessing tasks have been related to apathy in neurodegenerative conditions and healthy individuals. The primary aim of this study is to contribute evidence regarding the relationship between two EEG correlates of reward processing, the Reward Positivity, and the Feedback-P300, and real-world motivated behavior indicated by self-reported hours engaged in goal-directed leisure activities per week, in older individuals with well-controlled HIV infection. High-density EEG was collected from 75 participants while they performed a guessing task with gain or loss feedback. We found that a later component of reward processing, the Feedback-P300, was related to real-world engagement, while the earlier Reward Positivity was not. The Feedback-P300 measured with EEG holds promise as a biomarker for motivated behavior in older people living with HIV. These findings lay the groundwork for a better understanding of the neurobiology of apathy in this condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Castaneda, Fernandez Cruz, Brouillette, Mayo and Fellows.)

Objective: To estimate the extent to which comorbidity and lifestyle factors were associated with physical frailty in middle-aged and older Canadians living with HIV., Design: Cross-sectional analysis of 856 participants from the Canadian Positive Brain Health Now cohort., Methods: The frailty indicator phenotype was adapted from Fried's criteria using self-report items. Univariate logistic regression and classification and regression tree (CaRT) models were used to identify the most relevant independent contributors to frailty., Results: In all, 100 men (14.0%) and 26 women (19.7%) were identified as frail (≥ 3/5 criteria) for an overall prevalence of 15.2%. Nine comorbidities showed an influential association with frailty. The most influential comorbidities were hypothyroidism [odds ratio (OR) = 2.55, 95% confidence interval (CI): 1.29-5.03] and arthritis (OR = 2.54, 95% CI: 1.58-4.09). Additionally, tobacco (OR = 1.79, 95% CI: 1.05-3.04) showed an association. Any level of alcohol consumption showed a protective effect for frailty. The CaRT model showed nine pathways that led to frailty. Arthritis was the most discriminatory variable followed by alcohol, hypothyroidism, tobacco, cancer, cannabis, liver disease, kidney disease, osteoporosis, lung disease and peripheral vascular disease. The prevalence of physical frailty for people with arthritis was 27.4%; with additional cancer or tobacco and alcohol the prevalence rates were 47.1% and 46.1%, respectively. The protective effect of alcohol consumption evident in the univariate model appeared again in the CaRT model, but this effect varied. Cognitive frailty (19.5% overall) and emotional frailty (37.9% overall) were higher than the prevalence of physical frailty., Conclusions: Specific comorbidities and tobacco use were implicated in frailty, suggesting that it is comorbidities causing frailty. However, some frailty still appears to be HIV-related. The higher prevalence of cognitive and emotional frailty highlights the fact that physical frailty should not be the only focus in HIV., (© 2022 British HIV Association.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Older adults living with HIV may be at increased risk of experiencing distress during the coronavirus disease 2019 (COVID-19) pandemic. We took advantage of a cohort study in older adults living with HIV in Canada (The Positive Brain Health Now [+BHN]) to study the psychological impact of the first wave of the COVID-19 pandemic. A longitudinal study was conducted in which participants in the +BHN study who had access to the internet and agreed to be contacted were queried on symptoms of psychological distress and its predictors each week between mid-April and the end of June 2020. Evolution of distress, measured with the Hospital Anxiety and Depression Scale (HADS), was modeled using Group Based Trajectory Analysis and logistic regression was used to identify factors predictive of psychological distress in the clinical range. The study was approved by the Research Ethics Board of the McGill University Health Center and all participants provided informed consent. The 77 +BHN participants who took part in this study were mostly men (92%) and on average 57.3 years of age. Over the study period, 32.5% experienced psychological distress in the clinical range at one or more weekly surveys. In the transition between the pre-COVID-19 and the COVID-19 periods, the HADS scores followed five distinct trajectories: (1) 39.5 % of the sample, with normal HADS scores in the several months preceding the pandemic, experienced an increase in HADS scores; (2) 30.6% of the sample had normal prepandemic HADS scores, remained stable; and (3) 29.9%, with prepandemic presence of distress, had a decrease in HADS scores. During the first wave of COVID-19, some attenuation in distress was seen over time. Feeling lonely and financial insecurity were associated with distress. Presence of psychological distress during the first wave of the COVID-19 pandemic was not universal among older adults with HIV, with as many as one third of the participants reporting an improvement in mental health. Distress was predicted by loneliness and financial insecurity.

Purpose: The purpose of this study is to estimate the extent to which people aging with HIV meet criteria for successful aging as operationalized through HRQL and maintain this status over time. A second objective is to identify factors that place people at promise for continued successful aging, including environmental and resilience factors., Methods: Participants were members of the Positive Brain Health Now (BHN) cohort. People ≥ 50 years (n = 513) were classified as aging successfully if they were at or above norms on 7 or 8 of 8 health-related quality of life domains from the RAND-36. Group-based trajectory analysis, regression tree analysis, a form of machine learning, and logistic regression were applied to identify factors predicting successful aging., Results: 73 (14·2%) met criteria for successful aging at entry and did not change status over time. The most influential factor was loneliness which split the sample into two groups with the prevalence of successful aging 28·4% in the "almost never" lonely compared to 4·6% in the "sometimes/often" lonely group. Other influential factors were feeling safe, social network, motivation, stigma, and socioeconomic status. These factors identified 17 sub-groups with at least 30 members with the proportions classified as aging successfully ranging from 0 to 79·4%. The nine variables important to classifying successful aging had a predictive accuracy of 0.862. Self-reported cognition but not cognitive test performance improved this accuracy to 0.895. The two groups defined by successful aging status did not differ on age, sex or viral load, nadir and current., Conclusion: The results indicate the important role of social determinants of health in successful aging among people living with HIV., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: In the neuroHIV literature, cognitive reserve has most often been operationalized using education, occupation, and IQ. The effects of other cognitively stimulating activities that might be more amenable to interventions have been little studied. The purpose of this study was to develop an index of cognitive reserve in people with HIV, combining multiple indicators of cognitively stimulating lifetime experiences into a single value., Methods: The data set was obtained from a Canadian longitudinal study (N = 856). Potential indicators of cognitive reserve captured at the study entry included education, occupation, engagement in six cognitively stimulating activities, number of languages spoken, and social resources. Cognitive performance was measured using a computerized test battery. A cognitive reserve index was formulated using logistic regression weights. For the evidence on concurrent and predictive validity of the index, the measures of cognition and self-reported everyday functioning were each regressed on the index scores at study entry and at the last follow-up [mean duration: 25.9 months (SD 7.2)], respectively. Corresponding regression coefficients and 95% confidence intervals (CIs) were computed., Results: Professional sports [odds ratio (OR): 2.9; 95% CI 0.59-14.7], visual and performance arts (any level of engagement), professional/amateur music, complex video gaming and competitive games, and travel outside North America were associated with higher cognitive functioning. The effects of cognitive reserve on the outcomes at the last follow-up visit were closely similar to those at study entry., Conclusion: This work contributes evidence toward the relative benefit of engaging in specific cognitively stimulating life experiences in HIV.

Research on the psychosocial impact of COVID-19 has found significant levels of distress among the general population, and among those especially vulnerable due to chronic social or health challenges. Among these are individuals aging with HIV infection, who are encountering COVID-19 as a new infectious threat to their health and wellbeing. In a longitudinal observational study of the psychosocial impact of COVID-19 in middle-aged and older people living with HIV, we identified a subset of participants who expressed heightened levels of distress and were referred for clinical intervention. This paper describes the supportive and contemporary cognitive-behavioral interventions that were provided and presents data on changes in distress in this case series. This work provides a model for identifying people in at-risk groups in acute need of psychological intervention and for implementing an individualized clinical response that can be safely delivered in the context of COVID-19 and future crisis situations., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© Springer Nature Switzerland AG 2021.)

Background: The impact of HIV duration on exercise adaptations has not yet been studied. Moreover, the age at which subjects living with HIV are the most responsive to exercise is not clear., Aims: Investigate the effect of a mixed exercise training program on physical performance changes in individuals living with HIV and explore if age or HIV duration influence these adaptations in men., Methods: In this feasibility study, participants followed a 12-week mixed exercise training program, three times/week, 45 min/session. Physical performance including functional capacities (normal 4-m walking test, 6min walking test), grip strength (hand dynamometer), muscle power, body composition (android and gynoid fat masses, appendicular lean mass) were evaluated pre- and post-intervention. Subgroup analysis according to the median age of the participants (age<50yrs vs. age≥50yrs) and median HIV duration (HIV<20yrs vs. HIV≥20yrs) were performed in men., Results: A total of 27 participants (age: 54.5±6.8yrs, men: 85%; HIV duration: 19.3±7.6yrs) were included. At the end of the intervention, significant increases compared to baseline were seen in grip strength (p=0.017), leg power (p<0.001), normal walking speed (p<0.001) and 6-min walking distance (p=0.003). Following the intervention, parameters improved similarly in both age groups. However improvement was greater in those with HIV>20yrs than those with a shorter infection duration, with change (%) on total (p<0.001), android (p=0.02), and gynoid (p=0.05) fat masses as well as appendicular lean mass index (p=0.03)., Conclusion: Mixed exercise training seems to be an effective intervention to improve physical performance in individuals living with HIV. In addition, this study suggests that neither age nor HIV duration has influence on the effect of mixed training in this population., Competing Interests: We have no Conflict of Interest.

This review addresses functional interactions between the primate prefrontal cortex (PFC) and the amygdala, with emphasis on their contributions to behavior and cognition. The interplay between these two telencephalic structures contributes to adaptive behavior and to the evolutionary success of all primate species. In our species, dysfunction in this circuitry creates vulnerabilities to psychopathologies. Here, we describe amygdala-PFC contributions to behaviors that have direct relevance to Darwinian fitness: learned approach and avoidance, foraging, predator defense, and social signaling, which have in common the need for flexibility and sensitivity to specific and rapidly changing contexts. Examples include the prediction of positive outcomes, such as food availability, food desirability, and various social rewards, or of negative outcomes, such as threats of harm from predators or conspecifics. To promote fitness optimally, these stimulus-outcome associations need to be rapidly updated when an associative contingency changes or when the value of a predicted outcome changes. We review evidence from nonhuman primates implicating the PFC, the amygdala, and their functional interactions in these processes, with links to experimental work and clinical findings in humans where possible., (© 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021.)

Importance: Given the importance of apathy for stroke, we felt it was time to scrutinize the psychometric properties of the commonly used Starkstein Apathy Scale (SAS) for this purpose. Objectives: The objectives were to: (i) estimate the extent to which the SAS items fit a hierarchical continuum of the Rasch Model; and (ii) estimate the strength of the relationships between the Rasch analyzed SAS and converging constructs related to stroke outcomes. Methods: Data was from a clinical trial of a community-based intervention targeting participation. A total of 857 SAS questionnaires were completed by 238 people with stroke from up to 5 time points. SAS has 14 items, rated on a 4-point scale with higher values indicating more apathy. Psychometric properties were tested using Rasch partial-credit model, correlation, and regression. Items were rescored so higher scores are interpreted as lower apathy levels. Results: Rasch analysis indicated that the response options were disordered for 8/14 items, pointing to unreliability in the interpretation of the response options; they were consequently reduced from 4 to 3. Only 9/14 items fit the Rasch model and therefore suitable for creating a total score. The new rSAS was deemed unidimensional (residual correlations: < 0.3), reasonably reliable (person separation index: 0.74), with item-locations uniform across time, age, sex, and education. However, 30% of scores were > 2 SD above the standardized mean but only 2/9 items covered this range (construct mistargeting). Apathy (rSAS/SAS) was correlated weakly with anxiety/depression and uncorrelated with physical capacity. Regression showed that the effect of apathy on participation and health perception was similar for rSAS/SAS versions: R 2 participation measures ranged from 0.11 to 0.29; R 2 for health perception was ∼0.25. When placed on the same scale (0-42), rSAS value was 6.5 units lower than SAS value with minimal floor/ceiling effects. Estimated change over time was identical (0.12 units/month) which was not substantial (1.44 units/year) but greater than expected assuming no change (t: 3.6 and 2.4). Conclusion: The retained items of the rSAS targeted domains of behaviors more than beliefs and results support the rSAS as a robust measure of apathy in people with chronic stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hum, Fellows, Lourenco and Mayo.)

Introduction: Low motivation is frequent in older people with HIV, yet poorly understood. Effort-cost decision-making (ECDM) tasks inspired by behavioral economics have shown promise as indicators of motivation or apathy. These tasks assess the willingness to exert effort to earn a monetary reward, providing an estimate of the subjective "cost" of effort for each participant. Here we sought evidence for a relationship between ECDM task performance and self-reported motivation in a cross-sectional study involving 80 middle-aged and older people with well-controlled HIV infection, a chronic health condition with a high burden of mental and cognitive health challenges., Methods: Participants attending a regular follow-up visit for a Canadian longitudinal study of brain health in HIV completed a computerized ECDM task and a self-report measure of motivation. Other brain health measures were available, collected for the parent study (cognition, depression, anxiety, and vitality, as well as self-reported time spent on real-world leisure activities)., Results: Contrary to our hypothesis, we found no relationship between ECDM performance and self-reported motivation. However, those willing to accept higher effort in the ECDM task also reported more time engaged in real-world activities. This association had a small-to-moderate effect size., Conclusions: The behavioral economics construct of subjective cost of effort, measured with a laboratory ECDM task, does not relate to motivation in people living with chronic HIV. However, the task shows some relationship with real-world goal-directed behavior, suggesting this construct has potential clinical relevance. More work is needed to understand how the subjective cost of effort plays out in clinical symptoms and everyday activities.

Although exercise has been shown to improve cardiorespiratory and metabolic outcomes in people with HIV, its effect on cognitive ability remains understudied. Our study aimed to estimate the feasibility and efficacy potential of a 12-week aerobic and resistance training program on cognitive and physical performance outcomes. This is an externally controlled, two time-point, feasibility study within a larger study using a cohort multiple randomized controlled design yielding 3 groups: intervention group; comparison group and refusers. The intervention consisted of high-intensity interval training and resistance exercises 3 days/week. Specific feasibility and brain health outcomes were evaluated. Cognitive ability was ascertained by the Brief Cognitive Ability Measure (B-CAM) in all three groups. Standardized tests of physical performance were performed in the intervention group. Effect size, 95% confidence intervals, responder status analyses and reliable change indices were computed. Adherence to the intervention schedule and acceptability outcomes were good. There was no reliable change on B-CAM in the exercise group. Most physical performance measures benefited from the exercise training (effect sizes: 0.2 - 1.5). Although the 12-week exercise program improved physical capacity, it did not yield gains in cognitive ability in HIV. Further research is required to determine the exercise parameters that could benefit cognition.

Objective: (1) To develop a personalized health outcome profile as a feedback tool to improve self-management in people living with chronic conditions such as HIV and (2) to evaluate the interpretability and usefulness of the feedback tool for setting specific goals., Methods: The development of "My Personal Brain Health Dashboard" was inspired by the knowledge-to-action framework. A health outcome profile was computer generated in SAS from the outcome measures, at first and last recorded visits, of each person enrolled in the +BHN cohort from five sites in Canada. The Wilson-Cleary model framed the outcome measurement strategy. Single actionable items with evidence of life impact were chosen. The response option from the original item was the person's value and the optimal level was provided to help persons compare their results to an optimal target. Cognitive interviews were conducted with members of HIV community. Appropriateness of the Dashboard for goal-setting was tested by asking participants to write specific goals according to the Dashboard they were given., Results: Fifteen respondents were recruited from Montreal and Vancouver. Items most endorsed to be changed were cognition, pain, and body mass index. 80% found the Dashboard useful for setting health-related goals. A total of 85 goals were set, the text of which was mined to create a lexicon for scoring goal quality in future endeavours., Conclusion: This study was the preparatory phase for a future trial on a method to stimulate setting specific goals. The future trial would provide a thorough understanding of the quality of person-defined goals., (© 2020. Springer Nature Switzerland AG.)

Objective: The ability to work is amongst the top concerns of people living with well treated HIV. Cognitive impairment has been reported in many otherwise asymptomatic persons living with HIV and even mild impairment is associated with higher rates of occupational difficulties. There are several classification algorithms for HIV-associated neurocognitive disorder (HAND) as well as overall scoring methods available to summarize neuropsychological performance. We asked which method best explained work status and productivity., Design: Participants (N = 263) drawn from a longitudinal Canadian cohort underwent neuropsychological testing., Methods: : Several classification algorithms were applied to establish a HAND diagnosis and two summary measures (NPZ and Global Deficit Score) were computed. Self-reported work status and productivity was assessed at each study visit (four visits, 9 months apart). The association of work status with each diagnostic classification and summary measure was estimated using logistic regression. For those working, the value on the productivity scale was regressed within individuals over time, and the slopes were regressed on each neuropsychological outcome., Results: The application of different classification algorithms to the neuropsychological data resulted in rates of impairment that ranged from 28.5 to 78.7%. Being classified as impaired by any method was associated with a higher rate of unemployment. None of the diagnostic classifications or summary methods predicted productivity, at time of testing or over the following 36 months., Conclusion: Neuropsychological diagnostic classifications and summary scores identified participants who were more likely to be unemployed, but none explained productivity. New methods of assessing cognition are required to inform optimal workforce engagement., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Lifestyle changes can protect or improve brain health in older adults. However, sustained lifestyle change is difficult for everyone and may be more difficult for those with executive dysfunction, including some people living with HIV. Thus, the key question is how we can improve adherence to the most promising interventions among people living with HIV experiencing cognitive difficulties. Goal management training is a cognitive rehabilitation program that targets executive dysfunction by teaching goal-directed behaviour and self-management. It is a promising means to improve adherence to lifestyle interventions., Objective: To estimate the extent to which goal management training before a healthy lifestyle program is associated with greater adherence to health recommendations, achievement of health-related goals, and better brain health and health outcomes compared to the healthy lifestyle program alone among people living with HIV., Methods: Brain Health Now cohort participants with cognitive difficulties or are not aging successfully are eligible. All participants will be given health resources, a health coach, a goal-setting digital application, and access to an online goal-setting workshop. The intervention group will participate in nine 2-h goal management training sessions and then will enter the healthy lifestyle program. Control participants will enter the healthy lifestyle program directly. A total sample of 100 participants will participate for 12 months. The main outcome is adherence to the healthy lifestyle program, defined as the number of weeks where physical activity adherence targets were met (150 min per week, measured with an activity monitor). Weekly social activities will be captured via self-report with confidential photo validation. We will send weekly health state reports to the participants. Downstream outcomes include cognitive ability, health-related quality of life, mobility, vascular risk profile, and social network size. We will analyze the data using a linear regression model., Discussion: This project is the first to test whether goal management training can augment adherence to health recommendations among individuals with cognitive difficulties. If successful, behavioural interventions such as goal management training could be implemented as an adjunct to lifestyle interventions in other clinical populations., Trial Registration: This trial was registered on clinicaltrials.gov (NCT04345484) on April 14, 2020, https://clinicaltrials.gov/ct2/show/NCT04345484?term=NCT04345484&draw=2&rank=1 ., (© 2021. The Author(s).)

The frontal lobes have long been implicated in inhibitory control, but a full understanding of the underlying mechanisms remains elusive. The stop-signal task has been widely used to probe instructed response inhibition in cognitive neuroscience. The processes involved have been modeled and related to putative brain substrates. However, there has been surprisingly little human lesion research using this task, with the few existing studies implicating different prefrontal regions. Here, we tested the effects of focal prefrontal damage on stop-signal task performance in a large sample of people with chronic focal damage affecting the frontal lobes (n = 42) and demographically matched healthy individuals (n = 60). Patients with damage to the left lateral, right lateral, dorsomedial, or ventromedial frontal lobe had slower stop-signal RT compared to healthy controls. There were systematic differences in the patterns of impairment across frontal subgroups: Those with damage to the left or right lateral and dorsomedial frontal lobes, but not those with ventromedial frontal damage, were slower than controls to "go" as well as to stop. These findings suggest that multiple prefrontal regions make necessary but distinct contributions to stop-signal task performance. As a consequence, stop-signal RT slowing is not strongly localizing within the frontal lobes., (© 2020 Massachusetts Institute of Technology.)

[Figure: see text].

Objective: This study used converging methods to examine the neural substrates of cognitive ability in middle-aged and older men with well-controlled HIV infection., Methods: Seventy-six HIV+ men on antiretroviral treatment completed an auditory oddball task and an inhibitory control (Simon) task while time-locked high-density EEG was acquired; 66 had usable EEG data from one or both tasks; structural MRI was available for 43. We investigated relationships between task-evoked EEG responses, cognitive ability and immunocompromise. We also explored the structural correlates of these EEG markers in the sub-sample with complete EEG and MRI data (N = 27)., Results: EEG activity was associated with cognitive ability at later (P300) but not earlier stages of both tasks. Only the oddball task P300 was reliably associated with HIV severity (nadir CD4). Source localization confirmed that the tasks engaged partially distinct circuits. Thalamus volume correlated with oddball task P300 amplitude, while globus pallidus volume was related to the P300 in both tasks., Interpretation: This is the first study to use task-evoked EEG to identify neural correlates of individual differences in cognition in men living with well-controlled HIV infection, and to explore the structural basis of the EEG markers. We found that EEG responses evoked by the oddball task are more reliably related to cognitive performance than those evoked by the Simon task. We also provide preliminary evidence for a subcortical contribution to the effects of HIV infection severity on P300 amplitudes. These results suggest brain mechanisms and candidate biomarkers for individual differences in cognition in HIV., Competing Interests: The authors have declared that no competing interests exist.

A successful class of models link decision-making to brain signals by assuming that evidence accumulates to a decision threshold. These evidence accumulation models have identified neuronal activity that appears to reflect sensory evidence and decision variables that drive behavior. More recently, an additional evidence-independent and time-variant signal, called urgency, has been hypothesized to accelerate decisions in the face of insufficient evidence. However, most decision-making paradigms tested with fMRI or EEG in humans have not been designed to disentangle evidence accumulation from urgency. Here we use a face-morphing decision-making task in combination with EEG and a hierarchical Bayesian model to identify neural signals related to sensory and decision variables, and to test the urgency-gating model. Forty females and 34 males took part (mean age, 23.4 years). We find that an evoked potential time locked to the decision, the centroparietal positivity, reflects the decision variable from the computational model. We further show that the unfolding of this signal throughout the decision process best reflects the product of sensory evidence and an evidence-independent urgency signal. Urgency varied across subjects, suggesting that it may represent an individual trait. Our results show that it is possible to use EEG to distinguish neural signals related to sensory evidence accumulation, decision variables, and urgency. These mechanisms expose principles of cognitive function in general and may have applications to the study of pathologic decision-making such as in impulse control and addictive disorders. SIGNIFICANCE STATEMENT Perceptual decisions are often described by a class of models that assumes that sensory evidence accumulates gradually over time until a decision threshold is reached. In the present study, we demonstrate that an additional urgency signal impacts how decisions are formed. This endogenous signal encourages one to respond as time elapses. We found that neural decision signals measured by EEG reflect the product of sensory evidence and an evidence-independent urgency signal. A nuanced understanding of human decisions, and the neural mechanisms that support it, can improve decision-making in many situations and potentially ameliorate dysfunction when it has gone awry., (Copyright © 2021 the authors.)

Everyday decision-making commonly involves assigning values to complex objects with multiple value-relevant attributes. Drawing on object recognition theories, we hypothesized two routes to multiattribute evaluation: assessing the value of the whole object based on holistic attribute configuration or summing individual attribute values. In two samples of healthy human male and female participants undergoing eye tracking and functional magnetic resonance imaging (fMRI) while evaluating novel pseudo objects, we found evidence for both forms of evaluation. Fixations to and transitions between attributes differed systematically when the value of pseudo objects was associated with individual attributes or attribute configurations. Ventromedial prefrontal cortex (vmPFC) and perirhinal cortex were engaged when configural processing was required. These results converge with our recent findings that individuals with vmPFC lesions were impaired in decisions requiring configural evaluation but not when evaluating the sum of the parts. This suggests that multiattribute decision-making engages distinct evaluation mechanisms relying on partially dissociable neural substrates, depending on the relationship between attributes and value. SIGNIFICANCE STATEMENT Decision neuroscience has only recently begun to address how multiple choice-relevant attributes are brought together during evaluation and choice among complex options. Object recognition research makes a crucial distinction between individual attribute and holistic/configural object processing, but how the brain evaluates attributes and whole objects remains unclear. Using fMRI and eye tracking, we found that the vmPFC and the perirhinal cortex contribute to value estimation specifically when value was related to whole objects, that is, predicted by the unique configuration of attributes and not when value was predicted by the sum of individual attribute values. This perspective on the interactions between subjective value and object processing mechanisms provides a novel bridge between the study of object recognition and reward-guided decision-making., (Copyright © 2021 the authors.)

Decision neuroscience research has consistently implicated orbitofrontal and adjacent ventromedial prefrontal cortex in value-based decision-making. These areas are thought to reflect subjective value, a generic indicator of the personal motivational relevance of different options that allows them to be compared on a common scale. There are a number of unanswered questions arising from this model. We review findings from studies in patients with focal damage to the ventral frontal lobe that led us to reconsider how decision options are evaluated, applying perspectives from research on object recognition in the ventral visual stream. While decision-making is often approached from an abstract economic perspective in the lab, most of our everyday decisions, whether about food, goods, or people, are between directly perceived complex objects made up of multiple value-predictive attributes. It is not clear how multiple attributes are integrated to produce a global value estimate. We know the objects themselves are represented in the ventral visual stream at different levels of complexity, ranging from individual features to unique combinations of such features, but what about the values of those objects? Here, we suggest distinctions between configural and elemental evaluation echoing distinctions in visual processing. We discuss evidence that orbitofrontal-ventromedial prefrontal cortex is not required for all value-based decisions, but rather is specifically critical for recognizing value when it is predicted by configural relationships between attributes. We also consider how this perspective connects with emerging views of orbitofrontal cortex as an abstract cognitive map, and the debate on whether subjective value is a neurobiologically meaningful construct. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Purpose: People living with HIV may experience some degree of mild cognitive impairment. They are best placed to report on their cognitive symptoms, but no HIV-specific questionnaire exists to elicit these concerns. This study aimed to validate a set of items to form a measure METHODS: 48 items were tested on an initial sample of 204 people with HIV. Rasch analysis was used to identify those that fit a hierarchical continuum. The hierarchy was validated on a new sample of 703 people with HIV and a sample of 484 people without HIV., Results: 18 items fit the model and formed the Communicating Cognitive Concerns Questionnaire (C3Q). The items spanned the full range of cognitive ability, distinguished between people working and not working, and correlated with other self-report outcomes such as mental health (0.56) and work productivity (0.60), although showed a low correlation with cognitive test performance., Conclusion: The C3Q is the first questionnaire specifically developed for use among people with HIV. While not strongly associated with cognitive test performance, it reflects real-life concerns of people and is associated with mood, work, and work productivity. It is a needed step in assessing cognition in this population.

Current models of decision-making assume that the brain gradually accumulates evidence and drifts toward a threshold that, once crossed, results in a choice selection. These models have been especially successful in primate research; however, transposing them to human fMRI paradigms has proved it to be challenging. Here, we exploit the face-selective visual system and test whether decoded emotional facial features from multivariate fMRI signals during a dynamic perceptual decision-making task are related to the parameters of computational models of decision-making. We show that trial-by-trial variations in the pattern of neural activity in the fusiform gyrus reflect facial emotional information and modulate drift rates during deliberation. We also observed an inverse-urgency signal based in the caudate nucleus that was independent of sensory information but appeared to slow decisions, particularly when information in the task was ambiguous. Taken together, our results characterize how decision parameters from a computational model (i.e., drift rate and urgency signal) are involved in perceptual decision-making and reflected in the activity of the human brain., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)