Quantitative Susceptibility Mapping (QSM) is an MRI-based technique that sensitively measures in-vivo iron deposition via relaxation and magnetic susceptibility of brain tissue. Iron is essential for brain homeostasis, including oxidative metabolism, formation and maintenance of neural networks, and myelin synthesis. While increased levels of iron deposition occur during normal aging, high levels may have detrimental effects. Previous work has linked excessive brain iron accumulation to oxidative stress, beta-amyloid and tau toxicity, neurodegeneration, and cognitive dysfunction, particularly memory loss. Physical activity, on the other hand, correlates with higher synaptic integrity and memory performance, even in the presence of neuropathology. To date, it is unknown how physical activity may affect iron deposition-related cognition changes. We examined the moderating role of physical activity on the relationship between QSM hippocampal iron deposition and verbal memory in typically aging adults.

62 cognitively unimpaired older adults from the UCSF Memory and Aging Center (age mean(SD) = 78.34(7.28) years; 56% women; education mean(SD) = 17.94(1.72) years; 85% non-Hispanic White) completed neuropsychological testing and brain MRI during annual research visits, followed by Fitbit™ physical activity monitoring for 30 days. Average total daily steps were aggregated. Participants completed 3T Prisma neuroimaging with QSM, and regional iron deposition levels were quantified. All subjects also underwent diffusion tensor imaging (fractional anisotropy). Verbal memory was assessed via long delay free recall scores from the California Verbal Learning Test II (CVLT-II). Linear regression examined verbal memory as a function of hippocampal QSM (bilateral), physical activity, and their interaction. Models covaried for age, sex, and education. Additional models separately examined left and right hippocampal QSM, as well as subcortical QSM to determine lateralization and specificity of verbal memory effects to hippocampal iron deposition, respectively.

Univariably, higher bilateral hippocampal QSM correlated with worse verbal memory (r= 0.35; p= 0.015). Adjusting for demographics, physical activity moderated the relationship between bilateral hippocampal QSM and verbal memory (ß= 0.41, p= 0.011), such that at higher levels of physical activity, the negative relationship between hippocampal QSM and verbal memory was significantly attenuated. Results persisted when adjusting for DTI integrity of the uncinate fasciculus and fornix white matter tracts. Lateralization models were both significant, suggesting that results were not dominantly driven by either left (ß= 0.34, p= 0.048), or right (ß=0.31, p= 0.035) hippocampal QSM. In contrast, subcortical QSM did not correlate with memory performance (r= 0.13, p > 0.05) or interact with physical activity on verbal memory outcomes (p > 0.05).

Physical activity significantly moderated the negative relationship between hippocampal QSM and verbal memory performance. Higher exercise engagement may buffer the adverse effect of hippocampal iron deposition on memory, potentially through its role in maintenance of myelin and synaptic integrity and/or protecting against other neurotoxic events (e.g., oxidative stress, neuronal cell death). Our results support that physical activity continues to be a modifiable risk factor that may offer a protective role in neurobiological pathways of memory and cognitive decline.

In recent years, rates of alcohol consumption and alcohol use disorder have steadily increased among adults age 60 and older. Large studies have demonstrated that moderate-to-heavy alcohol consumption (>7 drinks per week) is a risk factor for developing various types of dementias. The effects of alcohol-related problems on cognition are less clear, and are particularly understudied in older adults. Similarly, while there is an established link between worse cognition and financial exploitation vulnerability in older adults, no studies have examined relationships between alcohol-related problems and financial exploitation in this population. The current study therefore explores whether alcohol-related problems are associated with neuropsychological performance and financial exploitation vulnerability in a sample of older adults.

Participants were a community sample of cognitively unimpaired adults over the age of 50 (N = 55, Age M(SD) = 69.1(6.2), 74.5% female, Years of education M(SD) = 16.8(2.3)). Interested individuals were excluded if they reported current or past substance use disorders. Participants completed a laboratory visit that included a neuropsychological assessment. Measures included the NIH Cognition toolbox, CVLT-II, Digit Span, Trails A/B, Benson Complex Figure Recall, and Verbal Fluency: Phonemic and Semantic, from the Alzheimer’s Disease Centers’ Uniform Data Set (UDS) version 3. Participants completed the CAGE Alcohol Abuse Screening Tool and the Short Michigan Alcohol Screener Test - Geriatric Version (SMAST) to assess alcohol-related problems. Both measures are used as clinical screening tools to measure likelihood of a substance use disorder and produce a summary score (0-4 for CAGE, 010 for SMAST) tabulating symptoms of alcohol-related problems. Participants also completed the Perceived Financial Vulnerability Scale (PFVS) to assess financial exploitation vulnerability. As a significant number of participants reported no drinking and therefore no alcohol-related problems, negative binomial regressions were used to test associations between neuropsychological measures, financial exploitation vulnerability, and alcohol-related problems.

After covarying for age and sex, SMAST was negatively associated with NIH toolbox total cognition (B(SE) = -.14(.07), p<.05) and marginally negatively associated with fluid cognition (B(SE) = -.07(.04), p=.06). Neither SMAST nor CAGE scores were significantly associated with performance on any other neuropsychological test (ps = .13-.99). SMAST was positively associated with financial exploitation vulnerability (B(SE) = .31(.16), p = .05); this effect remained significant after covarying for NIH total composite score in a secondary analysis.

In a community sample of cognitively unimpaired, low-drinking adults over the age of 50, more alcohol-related problems were associated with worse NIH toolbox cognition scores. Similarly, more alcohol-related problems were associated with greater financial exploitation vulnerability, and this relationship was not driven by worse cognition. These results suggest that even low amounts of drinking and alcohol-related problems may be associated with cognition and financial exploitation vulnerability in cognitively unimpaired older adults. This study also corroborates the use of the SMAST over the CAGE in older adult populations that may be more sensitive to cognitive changes.

This was a pilot study testing a cognitive enhancement program to improve rate of cognitive recovery in early substance abuse treatment. It is hypothesized that if patients were able to accelerate the rate of cognitive improvement, they may be able to better engage in substance abuse treatment and potentially have better long-term outcomes.

Participants were 47 adults newly admitted to a residential substance abuse treatment facility (74.5% male, 76.6% white, mean age=34.5 years, education=12+ years). All were post-detox. All were being treated for opioid abuse, with the majority in treatment for polysubstance abuse. Participants were randomly assigned to either the intervention group (BrainHQ research cognitive training program) or active control group (inert computer games) and completed 34 training sessions per week for a minimum of 3 weeks. NIH Toolbox cognition battery was administered at baseline and endpoint.

Regardless of study group, most participants had a significant improvement in cognitive performance across most subtests and composite scores of the NIH Toolbox cognition battery. The RAVLT and Oral Symbol Digit subtests had the greatest change (p<.001) for both groups, as well as a significant improvement (p=.002) in Cognitive Function Composite Score for both groups. The only difference between the control and intervention group was on the Pattern Comparison subtest, with the intervention group scoring significantly higher at endpoint (p=.004).

Although substance abuse is known to cause injury to the brain that may not be fully repaired by sobriety, cognitive recovery was significant in this group of patients during early inpatient treatment for opioid abuse. Although it has yielded significant effect in other patient populations, the BrainHQ program did not show a significant enhancement in cognitive recovery, compared to the active control group, in this pilot study of patients in treatment for opioid abuse. This study was limited by a small sample size and potential future variations should be considered, such as changes to intervention intensity and specific intervention exercises.

Early life adversity is strongly correlated with a number of negative health outcomes, with some of the highest risks are related to later illicit drug use and substance use disorders (SUDs). Specifically, it has been found that an ACEs score of >4 confers a 7-10-fold risk of substance abuse. Subsequent research has identified a number of neurobiological effects of childhood trauma, including structural and functional disruptions of the LHPA axis, the brain's primary stress-response system. It has been hypothesized that various trauma-induced neurobiological changes may lead to later physical health, mental health, and psychosocial problems in persons with early life adversity. One area that such changes might affect is a person's ability to stop abusing substances, with factors such as trauma-related mood, self-efficacy, or cognitive functioning as considerations in early treatment success. This study followed a group of participants in a residential substance abuse treatment program across their first month of abstinence, to assess natural change in cognitive performance as well as potential effect of early life adversity on changes in neuropsychiatric outcomes.

Participants were 37 adults (mean age=33.9 years, SD=6.7) who had completed detoxification and were first assessed during their first week of residential treatment. Follow-up assessment was completed 4 weeks later. Participants were primarily male (62%) and white (62%). They were all in treatment for opioid abuse, with a majority of participants reporting a history of polysubstance abuse. To measure adverse and protective factors, participants completed the Adverse Childhood Experiences scale and Protective And Compensatory Experiences Scale at baseline. Participants also completed the NIH Toolbox cognition battery and a set of self-report measures of cognitive functioning, mood, anxiety, and self-efficacy at baseline and follow up.

Results of paired samples t-test comparison between baseline and follow-up testing found a significant improvement in self-reported depression symptoms, anxiety symptoms, and self-efficacy (all p<.001). Interestingly, participants overall reported an increase in cognitive problems between baseline and retest, even though on objective cognitive testing (NIH Toolbox cognition battery) there was significant improvement in cognitive performance. Participants generally had a high level of childhood adversity (mean ACE score of 4.5), with an average level of childhood compensatory experiences. Considering the specific effect for childhood adversity, ACE score was found to be predictive in amount of anxiety and self-reported cognitive change but not for objective cognitive performance or change in other factors.

Consistent with previous research, these patients had a high level of past trauma, which interacted with a number of other neuropsychiatric measures and support the importance of assessing for trauma history and integrating trauma-focused treatment into substance abuse treatment programs.

Methamphetamine and cannabis are two widely used substances with possibly opposing effects on aspects of central nervous system functioning. Use of these substances is prevalent among people with HIV (PWH), though their combined effects on HIV-associated neurocognitive impairment (NCI) are unknown. Adverse effects of methamphetamine use on cognition are well documented. Cannabis may disturb cognition acutely, though its longer-term effects in PWH are not well understood. Our prior analysis of people without HIV (PWoH) found that cotemporaneous cannabis use was associated with better neurocognitive outcomes among methamphetamine users. The aim of this study was to assess how lifetime cannabis and methamphetamine use disorder relate to neurocognitive outcomes in PWH.

HIV-positive participants (n=472) were on average 45.6±11.5 years of age, male (86.4%), White (60.6%), and educated 13.9±2.5 years. Most participants were on ART (81.9%) and virally suppressed (70%). Participants were stratified by lifetime methamphetamine (M-/M+) and cannabis (C-/C+) DSM-IV abuse/dependence disorder into four groups: M-C- (n=187), M-C+ (n=68), M+C-, (n=82) and M+C+ (n=135) and completed a comprehensive neurobehavioral assessment. Demographically corrected T-scores and deficit scores were used for analyses. Group differences in global and domain NC performances (i.e., T-scores) were examined using multiple linear regression, holding constant covariates that were associated with study groups and/or cognition. Specifically, M+ participants displayed higher rates of Hepatitis C infection (p=.004), higher current depressive symptom scores (p<.001), and higher rates of detectable plasma HIV RNA (p=.014). Multiple logistic regression was used to test for group differences in probability of neurocognitive impairment (i.e., deficit scores>0.5), including the same covariates. Pooling data with a sample of HIV-negative participants (n=423), we used generalized linear mixed effect models to examine how neurocognitive performance and impairment profiles varied by methamphetamine and/or cannabis use group, HIV disease characteristics, and their interactions.

Compared to M+C+, M+C- performed worse on measures of executive functions (ß=-3.17), learning (ß=-3.95), memory (ß=-5.58), and working memory (ß=-4.05) and were more likely to be classified as impaired in the learning (OR=2.93), memory (OR=5.24), and working memory (OR=2.48) domains. M-C- performed better than M+C+ on measures of learning (ß=3.46) and memory (ß=5.19), but worse than M-C+ on measures of executive functions (ß=-3.90), learning (ß=-3.32), memory (ß=-3.38), and working memory (ß=-3.38). Generalized linear mixed effect models indicate that detectable plasma HIV RNA (ß=-1.85) and low nadir CD4 T-cell counts (nadir CD4<200; ß=-1.07) were associated with worse neurocognitive performance, and these effects did not differ in size or direction by substance use group.

In PWH, lifetime methamphetamine use disorder and both current and legacy markers of HIV disease severity are associated with worse neurocognitive outcomes. Cannabis use disorder does not appear to exacerbate methamphetamine-related deficits in PWH. Instead, results are consistent with findings from preclinical studies that cannabis use may protect against methamphetamine’s deleterious effects. Profile analysis models showed that participants with a history of cannabis use disorder display better overall neurocognitive performance than comparison (M-C-) participants. Mechanisms underlying a potential protective effect of cannabis may be elucidated by examining the temporal relationship between cannabis and methamphetamine consumption and neurocognitive performance.

Chronic alcohol consumption has been associated with widespread cognitive deficits, including psychomotor speed. Researchers have found impairments in reaction speed, information processing, and fine-finger movement in alcoholics (Oscar-Berman et al., 2015). There have also been mixed findings on the impact of duration of alcohol use on neurocognitive functioning (Beatty et al., 2000; Oscar-Berman et al., 2004). This meta-analytical study examines: (a) the performance of abstinent alcohol-dependent individuals on psychomotor speed using the Trail Making TestA (TMT-A), and (b) the effect of duration of alcohol use on TMT-A.

As part of a larger study, two researchers independently searched eight databases, extracted required data, and calculated effect sizes on neuropsychological data in alcohol dependent (AD) individuals. Inclusion criteria for articles were: (a) comparison of abstinent alcohol-dependent patients to healthy controls, (b) matched control group on age, education, or IQ, and (c) standardized neuropsychological testing. Exclusion criteria included: (a) diagnosis of Axis I disorders (other than alcohol dependence), (b) comorbidity with other disorders that impact neuropsychological functioning, or (c) not published or translated into English. Twenty-seven articles (AD n= 840 and HC n = 881) were analyzed in this study.

The TMT-A evidenced a statistically significant and medium effect size estimate (g = 0.624, p < 0.001). The heterogeneity of TMT-A was statistically significant (Q=61.935, df=26, p=0.000) and moderate (I2=58.021%). The meta-regression analysis between duration of alcohol use in days and TMT-A was not statistically significant (Q=0.012, df=1, p=0.913).

TMT-A detects psychomotor speed deficits associated with alcohol dependence. Duration of alcohol use did not affect TMT-A performance, suggesting that other factors may have moderated this relationship. Further research should analyze other factors that affect psychomotor performance in alcohol dependent individuals.

Verbal fluency consists of semantic and phonemic fluency and is often used to detect verbal ability and executive control (Shao et al., 2014). While research has found general verbal fluency impairments in chronic alcohol use, few studies have examined semantic and phonemic fluency separately (Stavro et al., 2012; Stephan et al., 2017). This meta-analytical study examines the performance of abstinent alcohol-dependent individuals on semantic fluency (categories) and phonemic fluency (letters).

As part of a larger study, two researchers independently searched eight databases, extracted required data, and calculated effect sizes on neuropsychological data in alcohol dependent (AD) individuals. Inclusion criteria for articles were: (a) comparison of abstinent alcohol-dependent patients to healthy controls, (b) matched control group on age, education, or IQ, and (c) standardized neuropsychological testing. Exclusion criteria included: (a) diagnosis of Axis I disorders (other than alcohol dependence), (b) comorbidity with other disorders that impact neuropsychological functioning, or (c) not published or translated into English. A total of 31 articles (AD n=1,080 and HC n=1,090) was analyzed in this study.

Semantic fluency evidenced a statistically significant and medium effect size estimate (g = 0.632, p < 0.001). The heterogeneity for semantic fluency was statistically significant (Q=152.468, df=20, p=0.000). Phonemic fluency evidenced a statistically significant and medium effect size estimate (g = 0.572, p < 0.001). The heterogeneity for phonemic fluency was also statistically significant (Q=236.697, df=24, p=0.000).

Deficits in semantic and phonemic fluency are both associated with alcohol dependence. Although some previous research has reported more frontal lobe impact of alcohol, which would be expected to impact phonemic more readily than semantic fluency, this is not evident in the current data. There are many possible reasons for this failure to observe this dissociation meta-analytically. Some potential reasons include the possibility that alcohol affects multiple regions of the brain, that both these measures are affected by alcohol but miss the subtlety associated with frontal damage, or the likelihood that when studies are aggregated in meta-analysis the heterogeneity results in a regression to the mean effect size. These and other reasons are not mutually exclusive and future research should attempt to examine these and other hypotheses.

Opioid use disorder (OUD) has been declared a national public health emergency leading to increased enrollment in medication assisted treatment (MAT) programs. Cognitive deficits are seen among those with OUD which can persist even with MAT. Moreover, cognitive deficits predict poor community and treatment outcomes. Neuropsychological evaluations can identify, diagnose, and provide treatment recommendations, and are associated with improved outcomes in non-substance use patient populations. Yet, patients with OUD rarely undergo neuropsychological assessment when participating in opioid use treatment. Teleneuropsychology (TNP) may increase access to care but has not been evaluated with people with substance use disorders (SUDs). This project used a mixed-method design to evaluate the feasibility and impact of a pilot hybrid TNP service with new patients with OUDs entering a MAT program.

Participants were >18 years old and new patients enrolling in MAT for OUD. Participants were excluded if they planned to move out of town within six months or were pending incarceration. Participants were identified by triage questions at MAT intake based on frequency of relevant co-occurring conditions indicating those with greatest need. Positively triaged individuals were referred to the TNP service which was conducted by a hybrid approach (i.e., patient presents to the clinic and is evaluated from a separate room using video-teleconferencing technology). We aimed to schedule participants within two-weeks of 30-days from intake to the MAT program. Consented participants completed questionnaires of feasibility and acceptability (e.g., satisfaction, usefulness) after undergoing a screening TNP evaluation and feedback of the results and recommendations. Participants also were invited to undergo a brief qualitative interview to further assess facilitators and barriers.

Of 57 individuals screened positive, 51 were referred, and 14 were reached to offer TNP. Ten (71.4%) agreed to the TNP evaluation and scheduled an appointment, though 50% had the first appointment scheduled within two weeks of 30-days after intake to MAT. Seven (70%) did not keep the first appointment (no show or cancellation) or were rescheduled due to clinic scheduling. Three were reached to reschedule. All three were unable to keep the appointment, but one did reschedule and keep the third appointment. Of the 4 who attended TNP, only 1 (25%) was within two weeks of 30-days after intake. Of those who attended the TNP appointment, 100% completed the protocol, 75% were satisfied with the evaluation overall, 75% found the evaluation useful, and 67% would recommend TNP to others (one participant did not respond to this question).

Neuropsychological assessment may provide valuable information to improve treatment for those with OUDs. This pilot project revealed that individuals with OUDs can tolerate and are satisfied with a screening TNP evaluation and find the evaluation useful. The primary barrier was reaching referred patients. Treatment engagement among those with SUDs is a common challenge. Those with counselors who coordinated with the clinic schedulers were more likely to be reached and scheduled, suggesting support for regular case management. Other lessons learned and potential future steps are discussed.

Executive functions (EF) are a primary mediator of both typical and atypical functioning, influencing the progression of psychopathology due to their role in supporting self-monitoring/regulation and top-down control of cognitive processes. According to recent models, EF impairments may contribute to the functional decline of patients with substance use disorder (SUD), exacerbating secondary affective and social symptoms. Despite these potential implications, the tools now commonly used to outline neurocognitive, and specifically EF, impairments in patients with addiction are not tailored to this clinical population, having been developed to assess cognitive or dysexecutive deficits in neurology or geriatric patients. Because of their different clinical focus, such tools are frequently unable to fully delineate the dysfunctional EF profile of addiction patients. We here present the development and validation of a novel specific screening battery for executive disorders in addiction: Battery for Executive Functions in Addiction (BFE-A).

151 SUD patients and 55 control persons were recruited for the validation of the BFE-A battery. The battery consists of two computerized neurocognitive tasks (Stroop and Go/No-go tasks) and five digitalized neuropsychological tests (focus: short/long-term memory, working memory, focused attention, verbal/non-verbal cognitive flexibility). The tests are designed to assess executive control, inhibition mechanisms, and attention bias toward drugs of abuse.

In tests of verbal memory, focused attention, and cognitive flexibility, as well as in computerized tasks, inferential statistical analyses revealed lower performance in SUD patients compared to control participants, indicating a lack of inhibitory processes and dysfunctional management of cognitive resources. The investigation of Cohen’s d values has revealed that inhibitory control, verbal/nonverbal fluency, and short/long-term memory are the areas with the most significant impairments.

While the evaluation of EF dysfunctions associated to addiction is a currently underrepresented component of the diagnostic procedure in drug assistance/treatment programs, is also is an essential step for both profiling of patients and design of rehabilitation protocols. Clinical interviews should be complemented by early assessment of cognitive weaknesses and preserved EF skills in order to establishing personalized therapy strategy and perhaps organizing a concurrent phase of cognitive rehabilitation.

Since seminal work by Sherrington, the term interoception refers to the ability to sense modifications of internal bodily states as opposed to the ability to sense stimuli coming from outside the body itself. Despite conceptual changes regarding the afferent signals subserving this type of inner perception, the core of this definition is still valid and widely accepted. The critical contribution of internal state perception to self-regulation as well as higher-order cognitive processes has led to the development of psychometric and observational measures trying to capture individual interoceptive skills, focusing especially on the ability to orient attention to internal sensations. Nonetheless, despite growing interest in interoceptive attention (IAtt), little is known about neurofunctional correlates of our ability to redirect attention to internal sensations and consciously process them, as well as on potential objective biomarkers of IAtt performance.

This study included 36 volunteers who were asked to complete a heart-beat counting task (HCT), a common IAtt task. During both resting-state and HCT, central electrophysiological (EEG, 32 electrodes) and cardiovascular activity (ECG, I lead) were recorded. eLORETA was used to estimate both task-related and resting-state intracortical sources of EEG signals. Statistical non-parametric mapping (SnPM) was used to draw and investigate contrast statistical maps between rest- and task-related cortical current density.

Contrast analyses comparing HCT and resting revealed higher Alpha frequency current density estimates during the task, with primary cortical seed in the right parahippocampal gyrus. Regression analyses of the relationship between IAtt scores and task-related changes in intracortical current density during HCT revealed a positive relationship for the Beta frequency bands with primary cortical seeds in the cingulate gyrus and insula.

Findings add to available literature by further specifying the electrophysiological signature of interoceptive attentiveness, and suggest specific electrophysiological markers as objective measures of individual IAtt skills.

Neuronal dysfunction of the locus coeruleus (LC), the primary producer of norepinephrine, has been identified as a biomarker of early Alzheimer's disease (AD) pathophysiology. Norepinephrine has been implicated in attentional control, and its reduced cortical circulation in AD may be associated with selective attentional difficulties. Additionally, greater pupil dilation indicates greater effort needed to perform a cognitive task, and greater compensatory effort to perform the digit span task has been found in individuals at risk for AD. In this study, we examined associations between a neuroimaging biomarker of the LC and pupil dilation during the Stroop task as a sensitive measure of attentional control.

64 older adults without dementia were recruited from the San Diego community (mean [SD] age = 74.3 [6.3]; 39 cognitively unimpaired and 25 with mild cognitive impairment). All participants underwent magnetic resonance imaging of the LC and generated behavioral data from a computerized Stroop task that included 36 incongruent trials (e.g., GREEN presented in red ink), 36 congruent trials (e.g., GREEN presented in green ink), and 32 neutral trials (e.g., LEGAL presented in green ink) in a randomized presentation. Mean pupil dilation for each trial (change relative to baseline at the start of each trial) was measured at 30 Hz using the Tobii X2-30 system (Tobii, Stockholm, Sweden) and averaged within each Stroop condition. Paired t-tests assessed for differences in mean pupil dilation across incongruent and congruent Stroop conditions. Iterative re-weighted least squares regression was used to assess the association between a rostral LC contrast ratio measure derived from manually marked ROIs and mean pupil dilation during incongruent trials divided by congruent trials, adjusting for age, sex, and education. Follow-up analyses also assessed the association of these variables with mean reaction time (RT) for incongruent trials divided by congruent trials.

Mean pupil dilation significantly differed across conditions (t = 3.74, mean difference = .13, 95% CI [.06, .20]) such that dilation was higher during the incongruent condition (mean [SD] dilation = .18 [.38] mm) relative to the congruent condition (mean [SD] dilation = .05 [.35] mm). A significant association was observed between pupil dilation and LC contrast ratio, such that increased levels of mean dilation during incongruent trials relative to congruent trials were observed at lower levels of LC contrast ratio (i.e., lower LC integrity; r = -.37, 95% CI [-.55, -.13]). This association was not observed for mean dilation during only congruent trials (r = -.08, 95% CI [-.31, .18]). Additionally, neither LC contrast ratio [r = .24, 95% CI [-.02, .46]) nor mean incongruent/congruent pupil dilation (r = .14, 95% CI [-.13, .37]) were associated with incongruent/congruent RT.

Findings suggest that increased pupil dilation during a demanding attentional task is indicative of increased compensatory effort needed to achieve the same level of performance for individuals with reduced LC biomarker integrity. Pupillometry assessment offers a low-cost, non-invasive, and scalable biomarker of LC dysfunction that may be indicative of preclinical AD.

Delayed speech and language development is one of the main diagnostic criteria for autism spectrum disorders (ASD) and is found almost in all children with ASD. Language development in children with ASD may differ from the norm both quantitatively (delayed speech development, reduced vocabulary, scarcity of speech and limitation in its use) and qualitatively (echolalias, violation of speech grammatical structure, difficulties in the communicative use of speech). Studying different aspects of language development in ASD is very important as it provides opportunities for finer diagnostics, as well as for targeted correction of communication disorders.

The study included 34 primary-school-aged children, who were diagnosed ASD using ADOS-2, diagnostic groups included “autism” (24 children) and “autism spectrum” (8 children). Speech development was assessed using the “Korablik” test on 9 parameters: distinguishing sounds; understanding and generating nouns, verbs and syntax; text understanding; sentences repetition. Kaufman test battery (KABC-II) and the Wechsler test (WISC-III) were used to assess non-verbal intelligence. The sample was divided into two subgroups according to an educational program recommended by PMPC (Psychological, Medical and Pedagogical Commission). Group 1 included 15 children, attending program 8.1, which is recommended for children with ASD who reach developmental milestones before starting study. Group 2 included 19 children attending program 8.2, which is recommended for children with ASD who do not reach developmental milestones before starting study.

In general, all children were the best successful in understanding and generating nouns, understanding verbs, and the least successful in understanding text and searching for sound in the word. Comparing subgroups using Mann-Whitney test revealed significant differences in all measured speech parameters, except for word repetition and noun generation. Group 2 demonstrated uneven results for separate subtests - minimum scores in some subtests coexisted with maximum in others. The group also showed uneven scores distribution inside the subtests, for example, half of the children did not cope with the task to determine a sound in a word, while the rest successfully completed at least 83% of the task. A significant positive correlation between all speech subtests was found in the group. Correlation analysis for parameters of speech development, severity of autistic manifestations and non-verbal intelligence revealed a significant direct relationship between the total scores of impressive and expressive speech and IQ and an inverse relationship with the severity of autistic manifestations and disorders of social and communicative behavior. No relationships like described above were found for group 1.

Obtained results indicate variability of reasons for delayed development of various language aspects in children with ASD.

An individual with dementia suffers from cognitive decline affecting not only memory but at least one of the other domains, such as personality, praxis, abstract thought, language, executive functioning, attention, and social skills. Further, the severity of the decline must be significant enough to interfere with daily functions. It is currently unknown whether any of the causes of dementia can be cured. Many challenges confront patients and their families, including a lack of knowledge about dementia and associated treatments; therefore, it is essential to study illness perception regarding dementia-related symptoms in order to improve psychoeducation and lower barriers to seeking assistance. How individuals perceive and make sense of early dementia symptoms can significantly impact their help-seeking behaviors (HS). Exploring illness-perception regarding dementia-related symptoms may contribute to the development of strategies for increasing HS, early diagnosis, and intervention. The objective of this study is to describe aspects of illness perception in cognitively healthy older adults and examine potential correlations with demographic variables, including age, gender, and education.

The cohort comprised 55 cognitively healthy older adults enrolled in a study examining Subjective Cognitive Decline. All participants performed > -1.5 SD on clinical neuropsychological testing. Participants were 70% female and 30% male; and self-identified as White = 78%, Black = 16%, Asian = 2%, Other = 4% and Non-Hispanic = 98%. Participants read a short vignette describing a person experiencing significant memory issues representative of an individual with mild dementia and answered seven follow-up questions regarding the cause of memory problems, the likely course of memory problems, and potential treatments for memory problems. Chi-square analyses examined the endorsement of items in relation to age, gender, and education.

When asked about the likely cause of memory problems, 65% of participants endorsed neurologic disease, 53% of participants endorsed normal aging, 26% endorsed stress, 25% endorsed genes, 4% endorsed fate/luck, and 16% endorsed "Don't know" for likely cause of symptoms. 64% of participants responded "will get worse", 18% "will go up and down", 16% "Don't know", and 2% "Other" in response to the progression of memory problems over time. For "Can he do anything to help [memory problems]?", only 2% responded "No" while 76% responded "Yes" and 22% endorsed "Don't know". On a follow-up question regarding ways an individual could improve his cognitive difficulties, 78% "Social Engagement", 73% "Exercise", 64% endorsed "Medication", 48% "Diet", 42% Psychological Treatment", 29% "Rehabilitation", 9%" Don't know" and 15% "Other." Lastly, 58% of participants reported "Independence", 33% "Identity," 4% "Friends," 4% "Respect," and 1% "Don't know" for things he may risk losing due to memory problems. Age, gender, and education were not associated with any of the above responses (p > .05).

Older adults demonstrate a range of ideas about the cause, course, and potential treatment for memory disorders. Understanding how and what factors impact illness perception is a pivotal step in improving illness perception and ultimately narrowing the gap in health disparities and HS. Further work in a large demographically representative sample is needed on illness perception and how socioeconomic factors, ethnicity, and other mediators interact with its impact on HS for dementia-related symptoms.

Cognitive fatigue (CF) is a common, yet poorly understood symptom in neurological disorders (e.g., multiple sclerosis, Parkinson’s disease, stroke). Studies show that reward plays a central role in CF. For instance, introducing or increasing reward often improves task performance. It is less clear, however, how reward affects subjective (self-reported) CF (SCF). This study examined the effect of reward type (monetary or performance feedback) and frequency (infrequent or frequent) on SF.

In an online between-subjects study, 400 participants completed a computerized cognitive switching task and were randomly grouped into one of the five possible groups based on reward condition: [1] infrequent monetary reward, [2] frequent monetary reward, [3] infrequent performancefeedback reward, [4] frequent performance feedback reward, and [5] a no-reward group. SCF was assessed using the Visual Analog Scale of Fatigue (VAS-F) during the task. Mixed effects models were used to estimate the influence of reward type and frequency on task performance and SCF.

We found that the monetary groups were significantly faster (p<.001) compared to the feedback and no-reward groups, and that the frequent group was faster (p=.05) compared to the infrequent group. Reward type and frequency did not have a significant effect on VAS-F scores. However, when we looked at each reward group, we found that the monetary-infrequent reward group was associated with a decrease in VAS-F scores on average compared to the no-reward group (p=.04).

The type and frequency of reward influence aspects of task performance (response time but not accuracy). Findings suggest that money had a greater effect on response time and may decrease SCF in cognitively healthy individuals when provided infrequently. Future studies should examine how these findings translate to clinical populations. Continued work is needed to understand how and which specific behavioral reward manipulations reduce fatigue, which could eventually lead to improved assessment and our ability to target fatigue across clinical populations.

Gliomas are a group of CNS neoplasms arising from neuroglial cells with various degrees of aggressiveness. Resection of brain tumors is complex to perform without neurological sequelae due to the diffuse nature of the tumors. This study aimed to design a neuropsychological battery to examine pre surgical cognitive deficits in a case series of patients with LGG and to determine the post-surgical effects after resection.

11 adult patients aged 19-65 years (38 ±DS:15.5) with a diagnosis of LGG without cognitive complaint were evaluated with a selection of specific neuropsychological tests to identify possible baseline cognitive deficits and their evolution after tumor resection. All participants completed a comprehensive neuropsychological evaluation assessing memory, language, attention, executive functions, visuospatial functions, social cognition, praxis, agnosias, functionality, mood, and quality of life. The neuropsychological battery design was based on a systematic review of the literature on surgical interventions in low-grade gliomas.

Despite not reporting subjective cognitive complaints, patients showed deficits in multiple cognitive domains in the pre-surgical evaluation when comparing their performance with normative values adjusted for age, sex, and education. Deficits in executive functions and attention were observed: 36% presented failures in graphomotor speed (TMT A), 27% of subjects presented failures in attentional span (Direct Digit Span), working memory (Inverse Digit Span), and cognitive flexibility (Wisconsin Card Sorting Test) and 9% presented difficulties in processing speed (Trail Making Test A) and inhibitory capacity (Stroop Test). Memory: 18% of the patients showed deficits in immediate logical memory and 9% in delayed memory (Craft Story 21). Likewise, 18% of the patients presented compromise in immediate auditory-verbal learning and 27% in delayed auditory-verbal learning (Rey Auditory-Verbal Test). Language: 18% showed failures in naming (Boston 60) and 9% in comprehension (Token Test). Likewise, 27% of the patients presented difficulties in social cognition (Mind in the Eyes Test). Finally 41% of the patients reported symptoms of depression and/or anxiety in the neuropsychiatric questionnaires.

The results highlight the importance of strategically designed pre-surgical cognitive assessment for the detection and follow-up of cognitive and mood disorders associated with the location of the space-occupying lesion (LOE). The patients assessed in this study will be evaluated three months after surgery to document changes in baseline cognitive symptoms. Furthermore, in patients with lesions in the left hemisphere, an intraoperative evaluation will be performed to minimize subsequent deficits, assessing these functions during surgery and emphasizing language.

Socioeconomic status (SES) has been recognized as an important factor in psychological research within the last few decades. Past literature recognizes that having lower SES can have a negative impact on many aspects of one’s health, especially in diseases related to brain aging. A recent avenue for research regarding SES and the brain-behavior relationship suggests that socioeconomic status can act as a moderator for brain activation during task performance. The hypothesis for this project was that there will be a negative correlational relationship between brain activity and SES when controlling for participants’ age, sex, and performance on the episodic memory tasks, but a positive correlation between task performance and SES was expected.

With 100 middle-aged healthy adults from the Reference Ability Neural Network (RANN) study (53 male and 47 female, age M=48.0 +/- 7.55 years), three episodic memory fMRI tasks were performed and studied in relation to SES and age. The tasks were Logical Memory, Word Order, and Pair Associates tasks that involved episodic memory for story details, order of words presented, and pairing of words, respectively. We quantified memory performance with average accuracy from performance of the three tasks. We used the FSL software to preprocess and perform voxel-wise group analysis. All brain activation analyses were corrected for multiple comparison using cluster thresholds in FSL.

Correlation between SES and memory performance was found to be marginally significant (R=.188, p=.061). All tasks had areas of positively correlated activation for age. The Logical Memory task had multiple areas of brain activation that were positively correlated with age, particularly at the lateral occipital cortex, lingual gyrus, and the occipital fusiform gyrus, all areas that underlie visual processing. There were no areas of correlated brain activation for SES, sex, and task performance for the Pair Associates and Logical Memory tasks. Brain activation for the Word order task in the left precuneous cortex and the right middle frontal gyrus, left lateral occipital cortex, left occipital fusiform gyrus, and parts of the lingual gyrus was positively correlated with memory performance when controlled for age, sex, and SES.

The hypothesis was not entirely supported by the results of this study, but the marginal effect between SES and memory performance can suggest that SES may affect memory performance within middle-aged adults. While we did not find a brain association with SES in this age group, we observed regions that underlie task performance. Further research can be done on possible moderating effects of Socioeconomic Status on memory and executive function with structural neuroimaging to further investigate the effects of SES on cognition.

Veterans from the 1991 Gulf War (GW) experienced several neurotoxicant exposures, including chemical weapons, pesticide sprays and creams, oil well fires and pyridostigmine bromide anti-nerve gas pills during the war. Research has shown these exposures to affect cognition and mood. Moreover, MR diffusion imaging has shown microstructural changes in the white matter that may be related to psychomotor slowing. Over a third of all GW veterans suffer from a chronic multi-symptom disorder called Gulf War Illness (GWI). The Kansas Criteria for GWI consists of six distinct criteria including symptoms of fatigue/sleep problems, pain symptoms, neurologic/cognitive/mood symptoms, gastrointestinal symptoms, respiratory symptoms, and skin symptoms. The Boston Gulf War Illness Consortium (GWIC) was a multi-site study designed to assess symptoms of GWI. After the conclusion of the GWIC study, the Boston Biorepository Recruitment and Integrative Network for Gulf War Illness (BBRAIN) was developed to harmonize retrospectively collected GW Veteran data while simultaneously collecting Time 2 data and samples from GW veterans who participated in the original study. This analysis includes the first 58 participants who have completed the GWIC study and the BBRAIN study.

We conducted a longitudinal analysis of cognitive outcomes from the BBRAIN data repository. Verbal learning, memory, attention, and executive functioning were assessed using neuropsychological tests including the Continuous Performance Test (CPT3), Trail Making Test A, Delis-Kaplan Executive Function System (DKEFS), California Verbal Learning Test (CVLT-II). A total of 58 participants were re-evaluated from the original GWIC cohort with a total of 47 cases and 11 controls. Paired t-tests for the cognitive measures were completed separately for GWI cases and healthy GW veteran controls for each of the neuropsychological test measures. Average time between assessments was four years.

The overall sample was on average 56 years old, 84% male and 75% White. The average level of education was 15 years. GWI cases showed significantly more commission errors and slower reaction times on the CPT3 at Time 2 compared to Time 1 (p < 0.05). Cases also showed a slowing in time to completion on Trails A at the second time point (p<0.05). On the other hand, controls only showed significantly slower reaction times on the CPT3 at Time 2 (p<0.05).

These results showed that veterans with GWI are showing more decline over time in cognitive functioning particularly on psychomotor slowing and impulsivity than control veterans. It is important to document illness trajectories for veterans with GWI in order to devise strategies for interventions and treatments. The importance of studying longitudinal cohorts is to document changes in the same individuals over time. The next steps are to assess if this accelerated aging develops into neurodegenerative conditions by using brain imaging and other biomarkers in addition to cognitive evaluations. This could identify individuals who should be the focus of targeted treatment strategies while there is still time to intervene.

Translatability of preclinical results remains a major obstacle in neuropsychiatric research. Even when cognitive tests in preclinical models show translational validity for human testing, with sensitivity to clinical deficits, there remains the issue of heterogeneity among human participants. Norming of performance on cognitive tasks enable corrections for any differences in performance that may arise from the influence of socioeconomic factors, and thus a more direct comparison with preclinical testing results. The 5-choice continuous performance task (5C-CPT) is a test sensitive to changes in sustained attention and cognitive control in rodent manipulations and clinical populations, including schizophrenia and bipolar disorder. Herein, we present normed results of 5C-CPT data from a cohort of human participants, enabling greater comparison to future clinical and rodent testing.

5C-CPT data were generated from a range of participants from the Translational Methamphetamine AIDS Research Center (n=82) and a study of bipolar disorder (n=45). Participant demographics were as follows: Age M=38.5, SD=16.7, Education: M=14.5, SD=1.9, 45% female, 10% Asian, 17% African American, 27% Hispanic, and 46% non-Hispanic White. We used the test2norm R-package to create norms for each of the major outcomes from the 5C-CPT. Non-normally distributed raw scores were transformed to generate more normally distributed data needed for the norming process. Raw scores were first converted into uniform scaled scores that range from 0-20 where a higher score indicated better performance. We then generated T-score formulas, which are standardized residuals and scaled to have a mean of 50 and standard deviation of 10. The residuals are obtained from regressions, modeled using multiple fractional polynomial method (MFP), which regresses scaled scores on demographic variables, which a user wishes to control for (gender, age, education, ethnicity, etc.). MFP models allow to fit non-linear effects for numeric demographic factors (e.g., age), if such effects exist.

New, demographically corrected T-score formulas were calculated for each major outcome of the 5C-CPT: reaction time (MCL), reaction time variability (VarRT), dprime, hit rate (HR) and false-alarm rate (FAR). MFP models showed that age had a significant effect on MCL, VarRT, dprime, and HR (all p<0.01), while gender only showed a significant effect for MCL and VarRT (all p<0.05). Interestingly, education and ethnicity did not show a significant effect for any MFP model and none of the demographic factors (age, education, gender, ethnicity) were significant in the model for FAR. As defined in the test2norm package, all scaled scores had a mean of 10 and SD of 3 and all T-scores had a mean of 50 and SD of 10.

The 5C-CPT is a test of attention and cognitive control available for human testing, reverse-translated from rodent studies. The normative data generated here will enable future comparisons of data without the need for additional control studies. Furthermore, comparing these normative data to manipulations will enable further comparisons to rodent testing, with manipulations relative to baseline becoming more meaningful. Thus, the 5C-CPT is a viable tool for conducting cross-species translational research toward developing novel therapeutics that treat dysfunctional attentional and cognitive control.

Subjective Cognitive Decline (SCD) is the self-reported experience of one’s own declining cognition prior to objective impairment on clinical neuropsychological testing. While SCD is a promising marker of preclinical Alzheimer’s disease (AD), information is needed to determine which cognitive complaints reflect typical aging versus prodromal degenerative disease. The objective of the current study was to examine the extent to which specific cognitive complaints were associated with two clinical outcomes including: 1) lower performance on cognitive tasks sensitive to preclinical AD; and 2) seeking help (i.e., medical attention) for cognitive difficulties.

The current sample consisted of 175 healthy older adults (56 Male, 119 Female), aged 51 to 90 (M=72.67, SD=7.12) with a mean education of 16 years (SD=2.3 years) who performed > -1.5 SD on clinical neuropsychological testing. 26.8% of the sample self-reported as race/ethnic minorities (e.g., Hispanic or Non-Hispanic, Black, Asian, Other.) Participants completed a 20-item SCD questionnaire assessing perceived cognitive difficulties in comparison to same aged peers, and tests shown to be sensitive to preclinical AD including the Face Name Associative Learning Test and the Loewenstein-Acevedo Scales for Semantic Interference and Learning. Participants were coded as having sought help for SCD (39%) if they entered the current study from a clinical referral source, OR if they entered through a non-clinical referral stream but indicated that they had previously seen a doctor specifically for memory concerns or spoken to their doctor about memory concerns. Chi square tests were used to examine relationships between SCD item endorsement and help-seeking; ANOVAs were used to the extent to which item endorsement was associated with performance on cognitive tests. Results were considered significant at p < .05.

Three SCD items were associated with both lower cognitive test scores and having sought help for SCD (p values ranged from < .001 to .02). Items included difficulty remembering the date or day of the week and remembering a few shopping items without a list. One non-memory item was also associated with both outcomes including difficulty thinking ahead. In contrast, six items were not related to either outcome of interest. Such items included difficulty remembering appointments, remembering where you put things like keys, following a map to a new location, doing two things at once, understanding what you read, or understanding what people say to you. The remaining eleven items explore the extent to which selective associations exist with either help-seeking or cognitive performance.

Patients and clinicians alike are often unsure about which cognitive difficulties are typical for aging and which may be the cause for further workup. Current results suggest that certain complaints among cognitively healthy older adults may be cause for more thorough evaluation or monitoring. These complaints include specific memory and nonmemory concerns. Future work is needed to determine if these complaints predict future cognitive decline or conversion to Mild Cognitive Impairment.

Hearing consists of peripheral components (outer and middle ear, cochlea) and the central auditory system (cochlear nuclei to the auditory cortex). Speech perception relies on peripheral hearing abilities (i.e., pure-tone thresholds) and central auditory processing (CAP) and cognitive functioning. Specifically, working memory, executive function, attention, and verbal functioning allow for speech understanding. As a result, CAP deficits are also influenced by peripheral hearing sensitivity and cognitive functioning. Assessing CAP deficits can be difficult because of these complex interactions. Prior work has shown persons living with HIV (PWH) are at higher risk for sensorineural hearing loss compared to persons living without HIV (PWOH) after adjusting for age, sex, and noise exposure. Further, HIV is a risk factor for cognitive impairment, one example being Alzheimer's disease (AD) and its precursor, Mild Cognitive Impairment (MCI), with auditory dysfunction occurring in earlier stages of AD. Therefore, the purpose of this study was to evaluate: 1) the peripheral hearing sensitivity and CAP in PWH and PWOH; and 2) the association between cognitive function measures and CAP in PWH and PWOH.

Participants included 59 PWH (39 men and 20 women, mean age=66.7 years [SD=4.4 years]) and 27 PWOH (13 men and 14 women, mean age=71.9 years [SD=7.1 years]). Participants completed a standard neuropsychological battery assessing the domains of learning, recall, executive function, working memory, verbal fluency, processing speed and motor. Raw scores were transformed to demographically corrected, domain T-scores. Cognitive function was normal for 39 (66.1%) PWH and 16 (59.3%) PWOH while 43 (72.9%) PWH and 17 (63.0%) PWOH were determined to have MCI. Participants with dementia were excluded. Participants also completed a hearing assessment, a portion of which consisted of pure-tone thresholds, peripheral hearing measure, and dichotic digits testing (DDT), a CAP measure. Pure-tone air-conduction thresholds were obtained at octave frequencies from 0.25 through 8 kHz, including 3 and 6 kHz. A pure-tone average (PTA) was calculated from 0.5, 1, 2, and 4 kHz thresholds for each ear. The DDT involves the presentation of numbers from 1 to 10, excluding 7, in which two different digits are presented to one ear while two other digits are simultaneously presented to the opposite ear. The outcome of DDT is percent correct.

PWH had slightly lower (i.e., better) mean PTAs in both ears compared to PWOH, but this was not statistically significant. Conversely, PWH had lower percent correct DDT results compared to PWOH, but this difference was also not statistically significant. Participants with impairment in verbal fluency, executive functioning, and working memory had significantly worse DDT results by approximately 10%, but only for right ear data.

PWH in our sample had better hearing than PWOH, which can be explained by PWH having a lower mean age. PWH had poorer DDT results, however, indicative of CAP deficits rather than peripheral hearing problems. Poor right ear DDT was associated with impairments specifically in frontal-based cognitive processes with an executive component.