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4 Neurophenotypes and recovery trajectories following laboratory-confirmed SARS-CoV-2 infection
- Divya Prabhakaran, Gregory S Day, Bala Munipalli, Beth Rush, Lauren Pudalov, Shehzad Niazi, Emily Brennan, Harry R Powers, Arjun Athreya, Karen Blackmon
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 877-879
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Objective:
Cognitive sequelae are reported in 20-25% of patients following SARS-CoV-2 infection. It remains unclear whether post-infection sequelae cluster into a uniform cognitive syndrome. In this cohort study, we characterized post-COVID neuropsychological outcome clusters, identified factors associated with cluster membership, and examined 6-month recovery trajectories by cluster.
Participants and Methods:The Mayo Clinic Institutional Review Board approved study protocols. Informed consent was obtained from all participants. Participants (> 18 years old) were recruited from a hospital-wide registry of Mayo Clinic Florida patients who tested positive for SARS-CoV-2 infection from July 2020 to Feb 2022. We abstracted participant health history and COVID-19 disease severity (NIAID score) from the electronic health record and retrieved Area Deprivation Index (ADI) scores as a measure of neighborhood socioeconomic disadvantage. We assessed objective cognitive performance with the CNS Vital-Signs (CNSVS) and subjective neuropsychological symptoms with the Neuropsych Questionnaire-45 (NPQ-45). Results were used as input features in a K-means clustering analysis to derive neurophenotypes. Chi-square and analysis of variance (AnOvA) tests were used to identify clinical and sociodemographic factors associated with cluster membership. Participants repeated the CNS Vital Signs, NPQ-45, as well as the Medical Outcomes Survey (MOS SF-36) and a posttraumatic stress disorder (PTSD) checklist (PCL-C 17) 6 months following initial testing. Repeated-measures ANOVA was used to assess change in neurocognitive performance over time by cluster. Significance was set at P < 0.05.
Results:Our cohort consisted of 205 participants (171 ambulatory, 34 hospitalized) who completed post-acute outcome assessment a mean of 5.7 (± 3.8) weeks following testing positive for SARS-CoV-2. K-means clustering with elbow method fitting identified three subgroups (see figure). The first cluster (N = 31) is characterized by executive dysfunction, greater socioeconomic disadvantage, and higher rates of obesity. The second cluster (N = 32) is characterized by memory and speed impairment, higher COVID severity, prevalent anosmia (70%), and greater severity of memory complaints, depression, anxiety, and fatigue. The third and largest cluster (N = 142) is absent cognitive impairment. Approximately 39% of participants completed the 6-month outcome assessment (N=79). Regardless of cluster membership, verbal memory, psychomotor speed, and reaction time scores improved over time. Regardless of timepoint, cluster 1 (dysexecutive) showed lower scores on cognitive flexibility and complex attention and cluster 2 (memory-speed impaired) showed lower scores on verbal memory, psychomotor speed, and reaction time. Modeling of cluster by timepoint interactions showed a steeper slope of improvement in complex attention and cognitive flexibility in cluster 1 (dysexecutive). Cluster 3 (normal) showed significant improvement in fatigue while cluster 2 (memory-speed impaired) continued to report moderate-severe fatigue, worse medical outcomes, and higher PTSD symptom severity scores at six months.
Conclusions:Most participants were cognitively normal or experienced cognitive recovery following SARS-CoV-2 infection. The 25-30% of participants who showed cognitive impairment cluster into two different neurophenotypes. The dysexecutive phenotype was associated with socioeconomic factors and medical comorbidities that are non-specific to COVID-19, while the amnestic phenotype was associated with COVID-19 severity and anosmia. These results suggest that cognitive sequelae following SARS-CoV-2 infection are not uniform. Deficits may be influenced by distinct patient- and disease-specific factors, necessitating differentiated treatment approaches.
1 Psychometric Characteristics of the Grenada Learning and Memory Scale: An Innovative Tool for Preschool Memory Assessment in Resource-Limited Regions
- Roberta Evans, Lauren Mohammed, Kemi S Burgen, Rashida Isaac, Toni Murray, Patricia Kandle, Mira E Cheng, Randall Waechter, Barbara Landon, Karen Blackmon
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 209-210
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Objective:
Neuropsychological assessment of preschool children is essential for early detection of delays and referral for intervention prior to school entry. This is especially relevant in low-and middle-income countries (LMICs), which are disproportionately impacted by micronutrient deficiencies and teratogenic exposures. There are limited options for assessment of preschool learning and memory, developed and validated in resource-limited regions. The Grenada Learning and Memory Scale (GLAMS) was created for use in the Caribbean using an indigenous “ground-up” approach, with feedback from regional stakeholders at various stages of development. The GLAMS contains two subtests - a verbal list-learning task, which imagines a trip to the shop to buy culturally familiar items, and a face-name associative learning task using locally-drawn faces of Caribbean children. There are two versions: a 4-item version for 3-year-olds and a 6-item version for 4 and 5-year-olds. Here we present descriptive data and psychometric features for the GLAMS from an initial preschool sample.
Participants and Methods:Participants were recruited from a social-emotional intervention study (SGU IRB#14099) in Grenada between 2019-2021. Children were between 36 and 72 months of age, primarily English-speaking, and had no known history of neurodevelopmental disorders. Trained Early Childhood Assessors administered the GLAMS and NEPSY-II in public preschools and homes across Grenada. Exploratory descriptive statistics characterized participant sociodemographics and test score distributions. Spearman correlations, MannWhitney U, and Kruskal-Wallis tests examined the impact of sociodemographics on test scores. Internal reliability was assessed with coefficient alpha. NEPSY-II subtests were used to assess convergent validity, with the prediction that the highest correlations would be observed for NEPSY-II Sentence Repetition. Test engagement (as reflected by “zero-learning”, “some learning”, and “positive learning curves”) was assessed across each age bracket (in 6-month increments). We assessed and summarized barriers to engagement qualitatively.
Results:The sample consisted of 304 children (152 males,152 females). Participants were predominantly Afro-Caribbean and Indo-Caribbean. Parent education and household income (Mdn=$370-740 USD per month) were consistent with the general population. GLAMS internal consistency was reliable (a=0.713). There were age effects on list-learning (rs=0.51; p<0.001), list recall (rs=0.51; p<0.001), face-name learning (rs=0.30;p<0.001), and face-name recall (rs=0.25; p<0.001). There were gender effects on list-learning (p=0.02) and list recall (p=0.01) but not face-name learning or recall. All GLAMS subtests were correlated with NEPSY Sentence Repetition (rs=0.22-0.34; p<0.001). There was sufficient sampling of males and females across all 6 age brackets. As age increased, a higher proportion of children showed a positive learning curve (and fewer “zero-scores”) on verbal learning (X2 =30.88, p<0.001) and face-name learning (X2=22.19, p=0.014), demonstrating increased task engagement as children mature. There were various qualitative observations of why children showed “zero-scores”, ranging from environmental distractions to anxiety and inattention.
Conclusions:As far as we know, the GLAMS is the first preschool measure of learning and memory developed indigenously from within the Caribbean. It shows reliable internal consistency, expected age and gender effects and convergent validity. These initial results are encouraging and support continued efforts to establish test-retest and inter-rater reliability. Plans include validation in clinical samples, scale-up to other Caribbean countries, and eventual adaptation across global LMICs.
Musical hallucinations: a brief review of functional neuroimaging findings
- Francesco Bernardini, Luigi Attademo, Karen Blackmon, Orrin Devinsky
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- CNS Spectrums / Volume 22 / Issue 5 / October 2017
- Published online by Cambridge University Press:
- 19 December 2016, pp. 397-403
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Musical hallucinations are uncommon phenomena characterized by intrusive and frequently distressful auditory musical percepts without an external source, often associated with hypoacusis, psychiatric illness, focal brain lesion, epilepsy, and intoxication/pharmacology. Their physiological basis is thought to involve diverse mechanisms, including “release” from normal sensory or inhibitory inputs as well as stimulation during seizures, or they can be produced by functional or structural disorders in diverse cortical and subcortical areas. The aim of this review is to further explore their pathophysiology, describing the functional neuroimaging findings regarding musical hallucinations. A literature search of the PubMed electronic database was conducted through to 29 December 2015. Search terms included “musical hallucinations” combined with the names of specific functional neuroimaging techniques. A total of 18 articles, all clinical case reports, providing data on 23 patients, comprised the set we reviewed. Diverse pathological processes and patient populations with musical hallucinations were included in the studies. Converging data from multiple studies suggest that the superior temporal sulcus is the most common site and that activation is the most common mechanism. Further neurobiological research is needed to clarify the pathophysiology of musical hallucinations.
Volume of the Human Septal Forebrain Region Is a Predictor of Source Memory Accuracy
- Tracy Butler, Karen Blackmon, Laszlo Zaborszky, Xiuyuan Wang, Jonathan DuBois, Chad Carlson, William B. Barr, Jacqueline French, Orrin Devinsky, Ruben Kuzniecky, Eric Halgren, Thomas Thesen
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- Journal:
- Journal of the International Neuropsychological Society / Volume 18 / Issue 1 / January 2012
- Published online by Cambridge University Press:
- 09 December 2011, pp. 157-161
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Septal nuclei, components of basal forebrain, are strongly and reciprocally connected with hippocampus, and have been shown in animals to play a critical role in memory. In humans, the septal forebrain has received little attention. To examine the role of human septal forebrain in memory, we acquired high-resolution magnetic resonance imaging scans from 25 healthy subjects and calculated septal forebrain volume using recently developed probabilistic cytoarchitectonic maps. We indexed memory with the California Verbal Learning Test-II. Linear regression showed that bilateral septal forebrain volume was a significant positive predictor of recognition memory accuracy. More specifically, larger septal forebrain volume was associated with the ability to recall item source/context accuracy. Results indicate specific involvement of septal forebrain in human source memory, and recall the need for additional research into the role of septal nuclei in memory and other impairments associated with human diseases. (JINS, 2012, 18, 157–161)