From Practice to Public Health: Broadening Neuropsychology's Reach & Value-An Introduction to the National Academy of Neuropsychology's 2022 Annual Conference Special Issue.

This special issue is centered around presentations from the National Academy of Neuropsychology 2022 Annual Conference. The theme of the conference, "From Practice to Public Health: Broadening Neuropsychology's Reach & Value" is pivotal for the field's future. With an ever-shifting technological landscape and recent changes in clinical practice post-COVID, we are left wondering how neuropsychology will develop. How will we use biomedical and technological advances, such as blood-based Alzheimer's disease biomarkers or passive digital recordings, to improve clinical care and further expand our understanding of disease mechanisms? As neuropsychologists, how can we use our expertise to empirically inform public health policy? The diagnosis and treatment of post-acute sequelae of COVID-19, the identification and characterization of post-pandemic educational setbacks, and the adaptation of new technological and diagnostic advances into clinical practice workflows represent a vital set of new challenges and opportunities poised to disrupt traditional modes of practice. The articles in this special issue convey the role of neuropsychology in addressing these emerging issues and illustrate how and why neuropsychology is well positioned to be at the forefront of clinical practice and scientific advancements.

Differential Cognitive Effects of Unilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: The aim of this study was to investigate the cognitive effects of unilateral directional versus ring subthalamic nucleus deep brain stimulation (STN DBS) in patients with advanced Parkinson's disease. METHODS: We examined 31 participants who underwent unilateral STN DBS (left n = 17; right n = 14) as part of an National Institutes of Health (NIH)-sponsored randomized, double-blind, crossover study contrasting directional versus ring stimulation. All participants received unilateral DBS implants in the hemisphere more severely affected by motor parkinsonism. Measures of cognition included verbal fluency, auditory-verbal memory, and response inhibition. We used mixed linear models to contrast the effects of directional versus ring stimulation and implant hemisphere on longitudinal cognitive function. RESULTS: Crossover analyses showed no evidence for group-level changes in cognitive performance related to directional versus ring stimulation. Implant hemisphere, however, impacted cognition in several ways. Left STN participants had lower baseline verbal fluency than patients with right implants (t [20.66 = -2.50, p = 0.02]). Verbal fluency declined after left (p = 0.013) but increased after right STN DBS (p < 0.001), and response inhibition was faster following right STN DBS (p = 0.031). Regardless of hemisphere, delayed recall declined modestly over time versus baseline (p = 0.001), and immediate recall was unchanged. INTERPRETATION: Directional versus ring STN DBS did not differentially affect cognition. Similar to prior bilateral DBS studies, unilateral left stimulation worsened verbal fluency performance. In contrast, unilateral right STN surgery increased performance on verbal fluency and response inhibition tasks. Our findings raise the hypothesis that unilateral right STN DBS in selected patients with predominant right brain motor parkinsonism could mitigate declines in verbal fluency associated with the bilateral intervention. ANN NEUROL 2024;95:1205-1219.

Neural correlates of audiovisual narrative speech perception in children and adults on the autism spectrum: A functional magnetic resonance imaging study.

Autistic individuals show substantially reduced benefit from observing visual articulations during audiovisual speech perception, a multisensory integration deficit that is particularly relevant to social communication. This has mostly been studied using simple syllabic or word-level stimuli and it remains unclear how altered lower-level multisensory integration translates to the processing of more complex natural multisensory stimulus environments in autism. Here, functional neuroimaging was used to examine neural correlates of audiovisual gain (AV-gain) in 41 autistic individuals to those of 41 age-matched non-autistic controls when presented with a complex audiovisual narrative. Participants were presented with continuous narration of a story in auditory-alone, visual-alone, and both synchronous and asynchronous audiovisual speech conditions. We hypothesized that previously identified differences in audiovisual speech processing in autism would be characterized by activation differences in brain regions well known to be associated with audiovisual enhancement in neurotypicals. However, our results did not provide evidence for altered processing of auditory alone, visual alone, audiovisual conditions or AV- gain in regions associated with the respective task when comparing activation patterns between groups. Instead, we found that autistic individuals responded with higher activations in mostly frontal regions where the activation to the experimental conditions was below baseline (de-activations) in the control group. These frontal effects were observed in both unisensory and audiovisual conditions, suggesting that these altered activations were not specific to multisensory processing but reflective of more general mechanisms such as an altered disengagement of Default Mode Network processes during the observation of the language stimulus across conditions.

Does Olfactory Training Improve Brain Function and Cognition? A Systematic Review.

Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning/memory. OT is also associated with increases in the volume/size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.

An Exploratory Pilot Study of Neuropsychological Performance in Two Huntington Disease Centers of Excellence Clinics.

OBJECTIVES: To describe the characteristics of patients receiving a clinical referral for neuropsychological evaluation in two Huntington's Disease Society of America Centers of Excellence (HDSA COE). In this exploratory pilot study, we used an empirically supported clinical neuropsychological battery to assess differences in cognitive performance between premanifest and manifest HD patient groups (compared with each other and normative expectations). METHOD: Clinical data from 76 adult genetically confirmed patients referred for neuropsychological evaluations was retrospectively collected from two HDSA COEs. ANOVA and Chi-square tests were used to compare variables between pre-manifest (n = 14) and manifest (n = 62) groups for demographic, cognitive, neuropsychiatric, and disease severity variables. RESULTS: Our clinics serviced a disproportionate number of motor manifest patients. Six measures were excluded from analyses due to infrequent administration. The full WAIS-IV Digit Span was disproportionately administered to the manifest group. The premanifest group showed stronger cognitive performance with effect sizes in the large range on subtests of the WAIS-IV Digit Span, HVLT-R, SDMT, and verbal fluency. CONCLUSIONS: This is the first study to assess an empirically supported neuropsychological research battery in a clinical setting with a relatively large sample size given the rarity of HD. The battery adequately captured areas of impairment across the disease spectrum. Application of the current battery with larger premanifest samples is warranted.

Huntington Study Group's Neuropsychology Working Group: Implementing Non-Motor Diagnostic Criteria.

Background: The clinical diagnosis of manifest Huntington's disease (HD) relies on a high level of clinical confidence (99% confidence) of HD-consistent motor signs. Longitudinal data have reliably identified cognitive and behavioral dysfunction predating clinical motor diagnosis by up to 15 years. Reliance on motor signs to establish a diagnosis of HD increases risk of early misdiagnosis or delayed diagnosis. Clinical neuropsychologists are uniquely positioned to advise on the clinical application of the Movement Disorder Society Task Force's recently proposed non-motor diagnostic criteria for HD. Objectives: To provide (1) a recommended clinical approach toward non-motor diagnostic criteria in persons with HD and facilitation of accurate diagnosis; (2) recommended practices for medical treatment providers to screen and longitudinally monitor non-motor signs of HD. Methods: The Huntington Study Group re-established the Neuropsychology Working Group, then recruited a multi-disciplinary group of neuropsychologists, neurologists, and psychiatrists to conduct an unstructured literature review and discuss expert opinions on practice, to facilitate an informal consensus opinion to accomplish the objectives. Results: The opinion and an example protocol for medical treatment providers to screen, monitor, and triage non-motor signs and symptoms of Huntington's disease is provided. Conclusions: Clinical diagnosis of non-motor HD is empirically justified and clinically important. Screening and triage by non-neuropsychologist clinicians can aid in detecting and monitoring non-motor Huntington's disease manifestation. The Neuropsychology Working Group consensus advances good clinical practice, clinical research, and quality of life. A companion position paper presenting the details of our consensus opinion regarding evidence-based guidelines for neuropsychological practice is forthcoming.

Within-Person Test Score Distributions: How Typical Is "Normal"?

We evaluated within-person variability across a cognitive test battery by analyzing the shape of the distribution of each individual's scores within a battery of tests. We hypothesized that most healthy adults would produce test scores that are normally distributed around their own personal battery-wide, within-person (wp) mean. Using cross-sectional data from 327 neurologically healthy adults, we computed each person's mean, standard deviation, skew, and kurtosis for 30 neuropsychological measures. Raw scores were converted to T-scores using three degrees of calibration: (a) none, (b) age, and (c) age, sex, race, education, and estimated premorbid IQ. Regardless of calibration, no participant showed abnormal within-person skew (wpskew) and only 10 (3.1%) to 16 (4.9%) showed wpkurtosis greater than 2. If replicated in other samples and measures, these findings could illuminate how healthy individuals are endowed with different cognitive abilities and provide the foundation for a new method of inference in clinical neuropsychology.

Cognitive intra-individual variability in breast cancer survivors: A systematic review.

Subjective and objective cognitive impairments in Breast Cancer Survivors (BCS) often do not correlate. One important contribution to the reported disparities may be the reliance on mean-based cognitive performance. Cognitive intra-individual variability (IIV) may provide important insights into these reported disparities. Cognitive IIV refers to the fluctuation in performance for an individual on either one cognitive task across a trial or dispersed across tasks within a neuropsychological test battery. The purpose of this systematic review was to search for and examine the literature on cognitive IIV in BCS. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach was used to search for all articles related to cognitive IIV in BCS. MEDLINE (via PubMed), Embase, and Scopus databases were searched using detailed search terms and strategies. Initially, 164 articles were retrieved but only 4 articles met the criteria for this systematic review. BCS differed from healthy controls in similar ways across the four studies, generally demonstrating similar performance but showing increased cognitive IIV for the more difficult tasks. Differences were enhanced later during chemotherapy. The four studies provide support for cognitive IIV as a useful measure to detect the subtle objective cognitive change often reported by BCS but frequently not detected by standard normed-based cognitive testing. Unexpectedly, measures of cognitive IIV were not consistently associated with self-reported measures of cognition.

Huntington study group's neuropsychology working group position on best practice recommendations for the clinical neuropsychological evaluation of patients with Huntington disease.

Objective: Neuropsychological evaluation is critical to detection and management of cognitive and neuropsychiatric changes associated with Huntington disease (HD). Accurate assessment of non-motor complications of HD is critical given the prominent impact on functional disability, frequently commensurate with or exceeding that of motor symptoms. The increasing emphasis on developing disease-modifying therapies targeting cognitive decline in HD requires consensus on clinical neuropsychological assessment methods. The Neuropsychology Working Group (NPWG) of the Huntington Study Group (HSG) sought to provide evidence and consensus-based, practical guidelines for the evaluation of cognitive and neuropsychiatric symptoms associated with HD. Method: The NPWG recruited a multi-disciplinary group of neuropsychologists, neurologists, and psychiatrists to inform best practices in assessing, diagnosing, and treating the non-motor symptoms in HD. A review was circulated among the NPWG, and in an iterative process informed by reviewed literature, best practices in neuropsychological evaluation of patients with HD were identified. Results: A brief review of the available literature and rational for a clinical consensus battery is offered. Conclusion: Clinical neuropsychologists are uniquely positioned to both detect and characterize the non-motor symptoms in HD, and further, provide neurologists and allied health professions with clinically meaningful information that impacts functional outcomes and quality of life. The NPWG provides guidance on best practices to clinical neuropsychologists in this statement. A companion paper operationalizing clinical application of previous research-based non-motor diagnostic criteria for HD is forthcoming, which also advises on non-motor symptom screening methods for the non-neuropsychologist working with HD.

A rationale and framework for addressing physician cognitive impairment.

Medical error is costly, in terms of the health and wellbeing of the patient, their family, and the financial burden placed on the medical system. Reducing medical error is paramount to minimizing harm and improving outcomes. One potential source of medical error is physician cognitive impairment. Determining how to effectively assess and mange physician cognitive impairment is an important, albeit difficult problem to address. There have been calls and attempts to implement age-based cognitive screening, but this approach is not optimal. Instead, we propose that neuropsychological assessment is the gold standard for fitness-for-duty evaluations and that there is a need for the development of physician-based, normative data to improve these evaluations. Here, we outline the framework of our research protocol in a large, academic medical center, in partnership with hospital leadership and legal counsel, which can be modeled by other medical centers. With high rates of physician burnout and an aging physician population, the United States is facing a looming public health crisis that requires proactive management.

Alternative patterns of deep brain stimulation in neurologic and neuropsychiatric disorders.

Deep brain stimulation (DBS) is a widely used clinical therapy that modulates neuronal firing in subcortical structures, eliciting downstream network effects. Its effectiveness is determined by electrode geometry and location as well as adjustable stimulation parameters including pulse width, interstimulus interval, frequency, and amplitude. These parameters are often determined empirically during clinical or intraoperative programming and can be altered to an almost unlimited number of combinations. Conventional high-frequency stimulation uses a continuous high-frequency square-wave pulse (typically 130-160 Hz), but other stimulation patterns may prove efficacious, such as continuous or bursting theta-frequencies, variable frequencies, and coordinated reset stimulation. Here we summarize the current landscape and potential clinical applications for novel stimulation patterns.

Differential cognitive effects of unilateral left and right subthalamic nucleus deep brain stimulation for Parkinson disease.

Objective: To investigate hemispheric effects of directional versus ring subthalamic nucleus (STN) deep brain stimulation (DBS) surgery on cognitive function in patients with advanced Parkinson's disease (PD). Methods: We examined 31 PD patients (Left STN n = 17; Right STN n = 14) who underwent unilateral subthalamic nucleus (STN) DBS as part of a NIH-sponsored randomized, cross-over, double-blind (ring vs directional) clinical trial. Outcome measures were tests of verbal fluency, auditory-verbal memory, and response inhibition. First, all participants were pooled together to study the effects of directional versus ring stimulation. Then, we stratified the groups by surgery hemisphere and studied the longitudinal changes in cognition post-unilateral STN DBS. Results: Relative to pre-DBS cognitive baseline performances, there were no group changes in cognition following unilateral DBS for either directional or ring stimulation. However, assessment of unilateral DBS by hemisphere revealed a different pattern. The left STN DBS group had lower verbal fluency than the right STN group (t(20.66 = -2.50, p = 0.02). Over a period of eight months post-DBS, verbal fluency declined in the left STN DBS group (p = 0.013) and improved in the right STN DBS group over time (p < .001). Similarly, response inhibition improved following right STN DBS (p = 0.031). Immediate recall did not significantly differ over time, nor was it affected by implant hemisphere, but delayed recall equivalently declined over time for both left and right STN DBS groups (left STN DBS p = 0.001, right STN DBS differ from left STN DBS p = 0.794). Conclusions: Directional and ring DBS did not differentially or adversely affect cognition over time. Regarding hemisphere effects, verbal fluency decline was observed in those who received left STN DBS, along with the left and right STN DBS declines in delayed memory. The left STN DBS verbal fluency decrement is consistent with prior bilateral DBS research, likely reflecting disruption of the basal-ganglia-thalamocortical network connecting STN and inferior frontal gyrus. Interestingly, we found an improvement in verbal fluency and response inhibition following right STN DBS. It is possible that unilateral STN DBS, particularly in the right hemisphere, may mitigate cognitive decline.

Predictors of an Active Lifestyle in Middle-Aged and Older Adults with HIV in the United States Deep South.

Background and Purpose: An active lifestyle is important for health maintenance and disease prevention. This study was to examine what factors predict an active lifestyle in HIV+ and HIV- adults from the United States Deep South. Methods: The sample included 279 participants (174 HIV+ and 105 HIV-) who completed a comprehensive assessment. An active lifestyle composite was created using variables of employment status, level of social support, level of physical activity, and diet. Correlations and regression analyses were conducted between the active lifestyle composite and possible predictors for all (HIV+ and HIV-), HIV+, and HIV- participants, respectively. Results: Lower levels of depression, higher socioeconomic status (SES), and younger age were significant predictors of a more active lifestyle for the full sample, HIV+, and HIV- participants, respectively. Conclusion: SES and depression represent important factors influencing engagement in an active lifestyle in PLWH. Such factors should be considered when developing and implementing lifestyle interventions.

Longitudinal associations of anticholinergic medications on cognition and possible mitigating role of physical activity.

BACKGROUND: Many older adults take at least one prescription medication with anticholinergic (ACH) activity, which can impact the central nervous system and can lead to cognitive decline and impairment especially in an aging population susceptible to cognitive changes. We examined this relationship between ACH burden and cognitive function in middle-aged and older adults. We further determined if increased activity levels mitigated the relationships between ACH burden and cognition. METHODS: Data from The Reasons for Geographic and Racial Differences in Stroke project were used. We included 20,575 adults aged ≥45 years with longitudinal cognitive testing. The anticholinergic cognitive burden (ACB) scale was used to assess for ACH use and overall burden. Cognitive data included an overall composite score, a memory, and verbal fluency composites. Mixed effects models were conducted to determine if cognitive function worsened over time for participants with higher ACB (>3) scores. The full model adjusted for age, sex, race, education, diabetes, hypertension, cardiovascular disease, congestive heart failure, and dyslipidemia, self-reported physical activity (PA) and depressive symptoms. RESULTS: A significant relationship between ACH burden and composite cognitive scores was found (p = <0.001), with those with higher ACB showing more rapid cognitive decline over time. There was an effect of age for participants with higher ACB (>3) scores and ACB as a continuous variable. Baseline PA level was associated with less cognitive decline over time and this effect was greater in older cohorts. CONCLUSIONS: We observed an effect of ACHs on cognition in adults ≥45 years old that worsened with age. ACH users showed more cognitive effects, whereas PA emerged as a possible mitigating factor.

Formal Neuropsychological Testing: Test Batteries, Interpretation, and Added Value in Practice.

Neuropsychologists evaluate patients for cognitive decline and dementia, using validated psychometric tests, along with behavioral observation, record review, clinical interview, and information about psychological functioning, to evaluate brain-behavior relationships and aid in differential diagnosis and treatment planning. Also considered are premorbid functioning, education, sex, socioeconomic status, primary language, culture, and race-related health disparities when selecting tests, interpreting performance, and providing a diagnostic impression. Neuropsychologists provide diagnostic clarity, explain symptoms and likely disease course to patients and family members, and assist the family with future planning, behavioral management strategies, and ways to mitigate caregiver burden.

A Pilot Study of Self-Rated and Psychophysical Olfactory Dysfunction in Men Living with HIV.

Background: Olfactory loss is associated with poor quality of life, malnutrition, and increased risk of depression, yet few studies have examined unawareness of olfactory dysfunction in men living with HIV (MLWH). Method: MLWH (n = 51) completed olfaction self-ratings, psychophysical odor identification testing, cognitive measures, and questionnaires assessing smell habits, mood, cognitive failures, and quality of life. The sensitivity and specificity of olfactory self-ratings was calculated, and t-tests were used to examine factors contributing to discordance between self-rated and psychophysical olfaction dysfunction. Results: We found that 33.3% (17 of 51 MLWH) of our sample demonstrated discordance between self-reported and psychophysical olfactory scores. Those unaware of olfaction dysfunction reported using less scented products in daily life but showed no other differences across demographic, clinical, or cognitive indices. Conclusions: Our results cohere with prior studies of cognitively normal older adults, traumatic brain injury, and Parkinson's disease, which found that olfactory self-ratings may inadequately capture the full range of a person's olfactory status. Our work extends these findings to MLWH, with discordance rates ranging from 35 to 61% for self-rated and psychophysical olfactory dysfunction. Implications: Given the differing rates of self-rated and psychophysical olfaction in our sample, psychophysical olfactory measures may be useful to consider in the neuropsychological assessment and clinical care of PLWH. Supplementary Information: The online version contains supplementary material available at 10.1007/s12078-022-09305-x.

Neuropsychological Functioning in Primary Dystonia: Updated and Expanded Multidomain Meta-Analysis.

BACKGROUND: Primary dystonia is conventionally considered as a motor disorder, though an emerging literature reports associated cognitive dysfunction. OBJECTIVES: Here, we conducted meta-analyses on studies comparing clinical measures of cognition in persons with primary dystonia and healthy controls (HCs). METHODS: We searched PubMed, Embase, Cochrane Library, Scopus, and PsycINFO (January 2000-October 2020). Analyses were modeled under random effects. We used Hedge's g as a bias-corrected estimate of effect size, where negative values indicate lower performance in dystonia versus controls. Between-study heterogeneity and bias were primarily assessed with Cochran's Q, I2 , and Egger's regression. RESULTS: From 866 initial results, 20 studies met criteria for analysis (dystonia n = 739, controls n = 643; 254 effect sizes extracted). Meta-analysis showed a significant combined effect size of primary dystonia across all studies (g = -0.56, P < 0.001), with low heterogeneity (Q = 25.26, P = 0.15, I2  = 24.78). Within-domain effects of primary dystonia were motor speed = -0.84, nonmotor speed = -0.83, global cognition = -0.65, language = -0.54, executive functioning = -0.53, learning/memory = -0.46, visuospatial/construction = -0.44, and simple/complex attention = -0.37 (P-values <0.01). High heterogeneity was observed in the motor/nonmotor speed and learning/memory domains. There was no evidence of publication bias. Moderator analyses were mostly negative but possibly underpowered. Blepharospasm samples showed worse performance than other focal/cervical dystonias. Those with inherited (ie, genetic) disease etiology demonstrated worse performance than acquired. CONCLUSIONS: Dystonia patients consistently demonstrated lower performances on neuropsychological tests versus HCs. Effect sizes were generally moderate in strength, clustering around -0.50 SD units. Within the speed domain, results suggested cognitive slowing beyond effects from motor symptoms. Overall, findings indicate dystonia patients experience multidomain cognitive difficulties, as detected by neuropsychological tests. © 2022 International Parkinson and Movement Disorder Society.

Diverse experiences and approaches to tele neuropsychology: Commentary and reflections over the past year of COVID-19.

Objectives: In response to the coronavirus disease 2019 (COVID-19) pandemic, neuropsychologists rapidly adopted teleneuropsychology (TeleNP) services to ensure continued clinical care. Prior to COVID-19, TeleNP was not widely used nor was it included in the majority of traditional practice or training models across graduate, internship, and postdoctoral programs. Out of necessity, the pandemic was a catalyst that promoted greater adoption of TeleNP services. In response, neuropsychological guidelines for modified assessments were developed and further empirical studies have been published. Numerous surveys in response to service delivery changes during COVID-19 now exist, but what follows is a commentary based on neuropsychologists' experiences with adapting clinical practice to TeleNP. Methods: Co-authors represent settings across academic medical centers, Veterans Affairs hospitals, and private practices that serve multiculturally diverse pediatric, adult, and geriatric populations in the United States. Results: The perspectives within this commentary aim to highlight the growth of TeleNP and highlight lessons learned from implementation across practice settings. Conclusions: Our goal is to help foster the development of further empirical studies through candid discussion of various TeleNP experiences and approaches. Through this reflective process, TeleNP presents both opportunities and challenges but it ultimately has potential to reduce healthcare disparities and enhance patient care.