The relationship between performance validity testing, external incentives, and cognitive functioning in long COVID.

INTRODUCTION: Performance validity test (PVT) failures occur in clinical practice and at higher rates with external incentives. However, little PVT research has been applied to the Long COVID population. This study aims to address this gap. METHODS: Participants were 247 consecutive individuals with Long COVID seen for neuropsychological evaluation who completed 4 PVTs and a standardized neuropsychological battery. The sample was 84.2% White and 66% female. The mean age was 51.16 years and mean education was 14.75 years. Medical records were searched for external incentive (e.g., disability claims). Three groups were created based on PVT failures (Pass [no failures], Intermediate [1 failure], and Fail [2+ failures]). RESULTS: A total of 8.9% participants failed 2+ PVTs, 6.4% failed one PVT, and 85% passed PVTs. From the full sample, 25.1% were identified with external incentive. However, there was a significant difference between the rates of external incentives in the Fail group (54.5%) compared to the Pass (22.1%) and Intermediate (20%) groups. Further, the Fail group had lower cognitive scores and higher frequency of impaired range scores, consistent with PVT research in other populations. External incentives were uncorrelated with cognitive performance. CONCLUSIONS: Consistent with other populations, results suggest Long COVID cases are not immune to PVT failure and external incentives are associated with PVT failure. Results indicated that individuals in the Pass and Intermediate groups showed no evidence for significant cognitive deficits, but the Fail group had significantly poorer cognitive performance. Thus, PVTs should be routinely administered in Long COVID cases and research.

Outcomes in post-acute sequelae of COVID-19 (PASC) at 6 months post-infection Part 1: Cognitive functioning.

OBJECTIVE: Long-term cognitive sequelae of COVID-19 have not been extensively studied. This study provides initial results on cognitive outcomes in Post-Acute Sequelae of COVID-19 (PASC).Participants and Methods: This study examined 53 consecutive outpatients diagnosed with COVID-19. Four participants were excluded due to performance validity test failure. All participants had positive COVID-19 tests, reported cognitive concerns, and completed neuropsychological tests to assess performance validity, attention/working memory, processing speed, memory, language, visual-spatial, executive functioning, motor, and emotional functioning. The sample was mostly white (89.8%), female (83.7%), and never hospitalized (69.4%) for COVID-19. RESULTS: Analyses indicated no mean scores in the Impaired range (>2 standard deviations [SD] below normative mean) on objective cognitive testing and a low base rate of Impaired test scores. Higher (>20%) base rates of Borderline performance (1-2 SDs below normative mean) were found on some measures. There was also evidence for frequently elevated mean scores on mood measures which correlated with some cognitive measures and the number of Borderline scores per participants. CONCLUSIONS: The results were noteworthy for infrequent Impaired scores, and significant correlations between cognition and mood/anxiety measures, but not between cognitive performance and premorbid vascular risk factors, psychiatric diagnoses, or COVID-19 disease severity. Results suggest that psychological distress was prominent in PASC and related to objective cognitive performance, but objective cognitive performance was unrelated to cognitive complaints. Other contributing factors may include fatigue/sleep issues. Neurologically based cognitive deficits were not suggested by the results.

Outcomes in post-acute sequelae of COVID-19 (PASC) at 6 months post-infection part 2: Psychological functioning.

Limited research investigating the long-term psychological and emotional correlates of COVID-19 infection has been completed. The current study begins to address this limitation in patients experiencing Post-Acute Sequelae SARS-CoV-2 (PASC; e.g. "Long COVID").Participants were 43 consecutive neuropsychological outpatients diagnosed with PASC and who completed the Personality Assessment Inventory (PAI). The sample was predominantly female (n = 36) and white (n = 32). Effect sizes compared to the normative mean T scores and base rates of elevated (T > 69) scores were calculated.PAI scales measuring somatic preoccupation and depression had large effect sizes and the highest base rates of scale elevations, with the mean T score at approximately the normative cutoff for clinical significance (T = 70). The Schizophrenia Thought Disorder subscale (SCZ-T) also had a large effect size and high base rate of elevation, likely reflecting cognitive concerns. Scales measuring anxiety had medium effect sizes. The other PAI scales generally had small to negligible effect sizes. There were no significant differences between hospitalized and non-hospitalized participants on the PAI.Overall, PAI scales measuring psychological distress, particularly somatic preoccupation and depression, were the most frequently elevated in the participants. The specific reasons for somatic preoccupation could not be determined in this study. Potential explanations include a vulnerability to distress in Long COVID patients, premorbid somatic preoccupation perhaps motivating these patients to seek clinical attention, or socioenvironmental factors leading some COVID patients to be somatically preoccupied with minor physiological changes and attribute those changes to COVID-19.

Neurocognitive deficits in severe COVID-19 infection: Case series and proposed model.

Objective: To date, very few studies investigating neurocognitive deficits in COVID-19 have been published. This case series addresses cognition in post-COVID-19 patient by describing three patients in acute rehabilitation to inform a model of cognitive sequelae of COVID-19. Methods: Three English-speaking inpatients with severe symptoms and long-term intensive care unit (ICU) treatment are described. All patients had a premorbid history of hypertension and hyperlipidemia and experienced delirium and hypoxemia when hospitalized. Patient 1 is a 62-year-old male with 15 years of education with additional history of obstructive sleep apnea and type 2 diabetes. Patient 2 is a 73-year-old female with 12 years of education with a premorbid medical history of alcohol use disorder and Guillain-Barre syndrome. Patient 3 is a 75-year-old male with 14 years of education. No patients had premorbid psychiatric histories. Results: The three patients demonstrated deficits on formal neuropsychological testing, particularly with encoding and verbal fluency. Memory measures improved with a more structured story memory task compared to a less-structured verbal list-learning task, suggesting executive dysfunction impacted learning. None of the patients demonstrated rapid forgetting of information. Two patients endorsed new depressive and/or anxiety symptoms. Conclusions: The results suggest evidence for neurocognitive deficits after severe COVID-19 infection, particularly in encoding and verbal fluency. These results were interpreted with caution given the limited number of patients and the telephone-based battery. The specific mechanism that caused these cognitive deficits in these individuals remains unclear. A proposed three-stage model of cognitive dysfunction is described to help guide future research.

Neuropsychological characterization of three adolescent females with anti-NMDA receptor encephalitis in the acute, post-acute, and chronic phases: an inter-institutional case series.

OBJECTIVE: Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is an acute, immune-mediated paraneoplastic syndrome that often presents with psychobehavioral changes, abnormal movements, autonomic instability, seizures, and cognitive dysfunction. While the disease continues to be more readily identified and appropriately treated, the course of cognitive deficits from the acute to post-acute to chronic phase has not been well described, particularly in the pediatric population. This case series describes the neuropsychological functioning of three adolescent females with anti-NMDA receptor encephalitis from its early presentation to long-term follow-up. METHOD: All three cases are adolescent females with antibody-confirmed anti-NMDA receptor encephalitis. A review of the literature is provided summarizing the disorder and its known cognitive sequelae, pathophysiology, treatment, and prognostic factors, as well as each patient's relevant history, symptom presentation, and disease course. Neuropsychological functioning of each patient was evaluated from her initial inpatient hospitalization to long-term follow-up (3.5-12 months after acute evaluation). RESULTS: All three patients demonstrated clear improvement in cognitive functioning during the course of their recovery, though selected deficits in executive functioning, fine motor dexterity, language, and memory were observed at long-term follow-up in some of our patients. CONCLUSIONS: Findings are consistent with studies in adults that found cognitive deficits following anti-NMDA receptor encephalitis. Though gradual recovery was noted over time, all three patients reported no clinically significant difficulties during their final evaluation, despite showing mild impairment in some areas, emphasizing the importance of ongoing neuropsychological follow-up.

Brain Network Theory Can Predict Whether Neuropsychological Outcomes Will Differ from Clinical Expectations.

OBJECTIVE: Theories of brain-network organization based on neuroimaging data have burgeoned in recent years, but the predictive power of such theories for cognition and behavior has only rarely been examined. Here, predictions from clinical neuropsychologists about the cognitive profiles of patients with focal brain lesions were used to evaluate a brain-network theory (Warren et al., 2014). METHOD: Neuropsychologists made predictions regarding the neuropsychological profiles of a neurological patient sample (N = 30) based on lesion location. The neuropsychologists then rated the congruence of their predictions with observed neuropsychological outcomes, in regard to the "severity" of neuropsychological deficits and the "focality" of neuropsychological deficits. Based on the network theory, two types of lesion locations were identified: "target" locations (putative hubs in a brain-wide network) and "control" locations (hypothesized to play limited roles in network function). RESULTS: We found that patients with lesions of target locations (N = 19) had deficits of greater than expected severity that were more widespread than expected, whereas patients with lesions of control locations (N = 11) showed milder, circumscribed deficits that were more congruent with expectations. CONCLUSIONS: The findings for the target brain locations suggest that prevailing views of brain-behavior relationships may be sharpened and refined by integrating recently proposed network-oriented perspectives.

Network measures predict neuropsychological outcome after brain injury.

Hubs are network components that hold positions of high importance for network function. Previous research has identified hubs in human brain networks derived from neuroimaging data; however, there is little consensus on the localization of such hubs. Moreover, direct evidence regarding the role of various proposed hubs in network function (e.g., cognition) is scarce. Regions of the default mode network (DMN) have been frequently identified as "cortical hubs" of brain networks. On theoretical grounds, we have argued against some of the methods used to identify these hubs and have advocated alternative approaches that identify different regions of cortex as hubs. Our framework predicts that our proposed hub locations may play influential roles in multiple aspects of cognition, and, in contrast, that hubs identified via other methods (including salient regions in the DMN) might not exert such broad influence. Here we used a neuropsychological approach to directly test these predictions by studying long-term cognitive and behavioral outcomes in 30 patients, 19 with focal lesions to six "target" hubs identified by our approaches (high system density and participation coefficient) and 11 with focal lesions to two "control" hubs (high degree centrality). In support of our predictions, we found that damage to target locations produced severe and widespread cognitive deficits, whereas damage to control locations produced more circumscribed deficits. These findings support our interpretation of how neuroimaging-derived network measures relate to cognition and augment classic neuroanatomically based predictions about cognitive and behavioral outcomes after focal brain injury.

Personality disturbances in amyotrophic lateral sclerosis: a case study demonstrating changes in personality without cognitive deficits.

Patients with amyotrophic lateral sclerosis (ALS) often show deficits on neuropsychological tests that tap functions related to the integrity of the prefrontal lobes. Various aspects of personality are also known to be mediated by prefrontal regions, particularly ventromedial prefrontal cortex (vmPFC). Other than apathy, personality changes have not been widely reported in patients with ALS, although clinical observations indicate such changes might be relatively common. Here, we report on a middle-aged woman with bulbar onset ALS (diagnosed 06/2011, examined in Spring, 2012) whose neuropsychological exam did not reveal cognitive deficits. She performed normally on tests of executive functioning. Self-report measures of mood and personality were unremarkable. However, significant personality changes subsequent to disease onset were reported by her husband and two daughters, and these changes were quantified with the Iowa Scales of Personality Change. Results show that personality disturbance may manifest in the absence of notable cognitive changes in ALS, and careful assessment of personality may be important for documenting early neurobehavioral changes in some ALS patients. Findings also show that patients with ALS may not have good insight into personality changes, underscoring the importance of acquiring collateral information. More generally, the results provide further evidence that ALS may compromise the integrity of ventromedial prefrontal regions.

The left temporal pole is a heteromodal hub for retrieving proper names.

The left temporal pole (LTP) has been posited to be a heteromodal hub for retrieving proper names for semantically unique entities. Previous investigations have demonstrated that LTP is important for retrieving names for famous faces and unique landmarks. However, whether such a relationship would hold for unique entities apprehended through stimulus modalities other than vision has not been well established, and such evidence is critical to adjudicate claims about the "heteromodal" nature of the LTP. Here, we tested the hypothesis that the LTP would be important for naming famous voices. Individuals with LTP lesions were asked to recognize and name famous persons speaking in audio clips. Relative to neurologically normal and brain damaged comparison participants, patients with LTP lesions were able to recognize famous persons from their voices normally, but were selectively impaired in naming famous persons from their voices. The current results extend previous research and provide further support for the notion that the LTP is a convergence region serving as a heteromodal hub for retrieving the names of semantically unique entities.

The role of age of acquisition on past tense generation in Spanish-English bilinguals: an fMRI study.

At its most basic sense, the sensorimotor/emergentist (S/E) model suggests that early second language (L2) learning is preferentially reliant upon sensory and motor processes, while later L2 learning is accomplished by greater reliance on executive abilities. To investigate the S/E model using fMRI, neural correlates of L2 age of acquisition were examined by employing a past-tense generation task on 22 L2 proficient bilinguals. Early bilinguals preferentially recruited left hemisphere sensorimotor regions involved in motoric control and articulation. In contrast, later learners, to a greater degree, engaged regions involved in executive cognitive control and lexical access. The data support the notion that early L2 learners devote neural resources to motor control during lexical retrieval. In contrast, later L2 learners recruit executive control mechanisms to generate the past tense. These data are consistent with the S/E model of bilingual language learning, and serve as an extension of cognitive control theories.

The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI): II. Reliability and convergent validity.

A standardized measure of neurological dysfunction specifically designed for TBI currently does not exist and the lack of assessment of this domain represents a substantial gap. To address this, the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) was developed for TBI outcomes research through the addition to and modification of items specifically relevant to patients with TBI, based on the National Institutes of Health Stroke Scale. In a sample of 50 participants (mean age = 33.3 years, SD = 12.9)