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OBJECTIVE: Neuropsychological assessment is integral to the pre-surgical deep brain stimulation (DBS) workup for patients with movement disorders. The COVID-19 pandemic quickly affected care access and shifted healthcare delivery, and neuropsychology has adapted successfully to provide tele-neuropsychological (teleNP) DBS evaluations during this time, thus permanently changing the landscape of neuropsychological practice. Method: In this paper, we discuss the lessons learned from the pandemic and we offer care management guidelines for teleNP and in-person evaluations of pre-DBS populations, with exploration of the feasibility of the different approaches for uninterrupted care access. Results: We summarize the strengths and weaknesses of these care models and we provide future directions for the state of clinical neuropsychological practice for DBS programs, with implications for broader patient populations. Conclusions: A better understanding of these dynamics will inform and educate the DBS team and community regarding the complexities of performing DBS neuropsychological evaluations during COVID-19 and beyond.

The evaluation and management of patients with movement disorders has evolved considerably due to the COVID-19 pandemic, including the assessment of candidates for deep brain stimulation (DBS) therapy. Members of the Neuropsychology Focus Group from the Parkinson Study Group Functional Neurosurgical Working Group met virtually to discuss current practices and solutions, build consensus, and to inform the DBS team and community regarding the complexities of performing DBS neuropsychological evaluations during COVID-19. It is our viewpoint that the practice of neuropsychology has adapted successfully to provide tele-neuropsychological pre-DBS evaluations during the global pandemic, thus permanently changing the landscape of neuropsychological services.

Objective Judgment of Line Orientation (JOLO) test is widely used in assessing visuospatial deficits in Parkinson's disease (PD). The neuropsychological assessment battery (NAB) offers the Visual Discrimination test, with age and education correction, parallel forms, and co-normed standardization sample for comparisons within and between domains. However, NAB Visual Discrimination has not been validated in PD, and may not measure the same construct as JOLO. Method A heterogeneous sample of 47 PD patients completed the JOLO and NAB Visual Discrimination within a broader neuropsychological evaluation. Pearson correlations assessed relationships between JOLO and NAB Visual Discrimination performances. Results Raw and demographically corrected scores from JOLO and Visual Discrimination were only weakly correlated. NAB Visual Discrimination subtest was moderately correlated with overall cognitive functioning, whereas the JOLO was not. Conclusions Despite apparent virtues, results do not support NAB Visual Discrimination as an alternative to JOLO in assessing visuospatial functioning in PD.

Ability to identify change is crucial for measuring response to interventions and tracking disease progression. Beyond psychometrics, investigations of Parkinson's disease with mild cognitive impairment (PD-MCI) must consider fluctuating medication, motor, and mental status. One solution is to employ 90% reliable change indices (RCIs) from test manuals to account for account measurement error and practice effects. The current study examined robustness of 90% RCIs for 19 commonly used executive function tests in 14 PD-MCI subjects assigned to the placebo arm of a 10-week randomized controlled trial of atomoxetine in PD-MCI. Using 90% RCIs, the typical participant showed spurious improvement on one measure, and spurious decline on another. Reliability estimates from healthy adults standardization samples and PD-MCI were similar. In contrast to healthy adult samples, practice effects were minimal in this PD-MCI group. Separate 90% RCIs based on the PD-MCI sample did not further reduce error rate. In the present study, application of 90% RCIs based on healthy adults in standardization samples effectively reduced misidentification of change in a sample of PD-MCI. Our findings support continued application of 90% RCIs when using executive function tests to assess change in neurological populations with fluctuating status.

Study objectives Working memory (WM) has been described as a multicomponent process, comprised of the following: attention-driven encoding, maintenance and rehearsal of information, and encoding to and retrieval from episodic memory. Impairments can affect higher-order cognitive processes and many everyday functions. The impact of sleep changes on these cognitive processes across the life span needs to be investigated. The aim of the current study is to examine the effects of sleep deprivation on component processes of WM, comparing younger and older adults across verbal and visuospatial modalities. Methods Thirty-one younger adults (19-38 years) and 33 older adults (59-82 years) attended two counterbalanced sleep protocols: a regular night of sleep followed by testing the next day (normally rested condition), and 36 hr of total sleep deprivation (TSD), followed by testing (TSD condition). Participants completed matched versions of verbal and visuospatial WM tasks across conditions. Results Younger adults significantly outperformed older adults on encoding and displacement component processes, for both verbal and visuospatial WM. Following TSD, younger adults showed a significantly larger drop compared with older adults in verbal encoding and in visuospatial displacement. A main effect of condition was observed for verbal displacement. Conclusions Differences were observed in the performance of younger and older adults on component processes of WM following TSD. This suggests that TSD can have differential effects on each component process when younger and older adults are compared, in both verbal and visuospatial tasks. Understanding this profile of changes is important for the development of possible compensatory strategies or interventions and the differentiation of clinical and healthy populations.

Objective Comorbidity and symptom overlap between traumatic brain injury and posttraumatic stress disorder (PTSD) in veterans returning from deployment present challenges with respect to differential diagnosis and treatment. Both conditions frequently manifest with attention and working memory deficits, though the underlying neuropsychological basis differs. This study evaluated whether hyperarousal symptoms explain the relationship between subjective and objective measures of cognition in a veteran sample. Participants and procedures One-hundred three veterans completed the military version of the PTSD Checklist (PCL), the Neurobehavioral Symptom Inventory, and the Wechsler Memory Scale, 3rd edition digit span task with adequate effort. Results Hierarchical regression suggested that hyperarousal, but not other PTSD symptoms, explained the relationship between neurobehavioral symptoms and cognitive functioning. This relationship was present regardless of whether veterans met full PTSD diagnostic criteria or screened positive on a traumatic brain injury screener and was robust to other moderators. Conclusion These findings highlight the importance of considering traumatic brain injury and PTSD symptom overlap, particularly the relationship between hyperarousal symptoms and attention and working memory deficits, in conceptualizing cases and treatment planning.

Speed and control of saccades are related to disease progression and cognitive functioning in Parkinson's disease (PD). Traditional eye-tracking complexities encumber application for individual evaluations and clinical trials. The authors examined psychometric properties of standalone tasks for reflexive prosaccade latency, volitional saccade initiation, and saccade inhibition (antisaccade) in a heterogeneous sample of 65 PD patients. Demographics had minimal impact on task performance. Thirty-day test-retest reliability estimates for behavioral tasks were acceptable and similar to traditional eye tracking. Behavioral tasks demonstrated concurrent validity with traditional eye-tracking measures; discriminant validity was less clear. Saccade initiation and inhibition discriminated PD patients with cognitive impairment. The present findings support further development and use of the behavioral tasks for assessing latency and control of saccades in PD.

Patients who exert inadequate effort on neuropsychological examination might not receive accurate diagnoses and recommendations, and might not cooperate fully with other aspects of healthcare. This study examined whether inadequate effort is associated with increased healthcare utilization. Of 355 patients seen for routine, clinical neuropsychological examination at a VA Medical Center, 283 (79.7%) showed adequate effort and 72 (20.3%) showed inadequate effort, as determined at time of evaluation using the Word Memory Test and/or Test of Memory Malingering. Utilization data included number of Emergency Department (ED) visits and inpatient hospitalizations in the year following evaluation. Patients who had shown inadequate effort on examination had more Emergency Department visits, more inpatient hospitalizations, and more days of inpatient hospitalization in the year after evaluation, compared to patients who had exerted adequate effort. This finding was not attributable to group differences in age or med...

Background Mild cognitive impairment in Parkinson's disease (PD-MCI) is associated with diminished norepinephrine from the locus coeruleus to the prefrontal cortex. Atomoxetine is a specific norepinephrine reuptake inhibitor that has been approved by the US Food and Drug Administration to treat attention deficit hyperactivity disorder in adults. The authors hypothesized that atomoxetine would improve attention and executive functioning in patients with PD-MCI. Methods Thirty participants who met Movement Disorder Society Task Force Level I criteria for PD-MCI were enrolled in a randomized controlled trial of atomoxetine. Cognitive evaluations were performed at baseline and after 10 weeks of treatment or placebo. A safety visit was performed at Week 12. A global statistical test was used to examine treatment effects on standardized tests of attention, working memory, processing speed, and set shifting (primary outcome measure). Secondary outcomes included cognitive measures hypothesized to be insensitive to atomoxetine, the Conners Adult Attention Deficit Hyperactivity Disorder Rating Scale, and safety measures. Results Fifteen participants were randomized to each arm. Groups were similar on medical and demographic variables and baseline cognition. Three serious adverse events occurred; 2 on atomoxetine (syncope, isolated episode of atrial fibrillation) and 1 on placebo (atrial fibrillation). The global statistical test of primary outcome measures did not reveal a significant difference between groups. However, significant improvements were observed for atomoxetine but not placebo on subjective measures of attention and impulsivity (Conners Adult Attention Deficit Hyperactivity Disorder Rating Scale). Conclusions Atomoxetine treatment produced subjective, but not objective, improvements in PD-MCI. Failure to detect objective differences may be due to insensitivity of cognitive tests or severity of cognitive deficits in the study participants.

As parametric cognitive models become more commonly used to measure individual differences, the construct validity of the interpretation of individual model parameters needs to be well established. The validity of the interpretation of 2 parameters of a formal model of the Continuous Recognition Memory Test (CRMT) was investigated in 2 experiments. The 1st study found that manipulating the percentage of trials on the CRMT for which degraded pseudowords were presented altered the model's stimulus encoding parameter but not the working memory displacement parameter. The 2nd experiment showed that manipulating the number of syllables forming a pseudoword altered the model's working memory displacement parameter for each syllable added to the pseudoword. Findings from both experiments supported the construct representation of the model parameters, supporting the construct validity of the model's use to interpret CRMT performance. Combining parametric models with the manipulation of factors that theory predicts are related to model parameters provides an approach to construct validation that bridges experimental and individual difference methods of studying human cognition.

Objective This study tested whether patients who were given a handout based on deterrence theory, immediately prior to evaluation, would provide invalid data less frequently than patients who were simply given an informational handout. Method All outpatients seen for clinical evaluation in a VA Neuropsychology Clinic were randomly given one of the two handouts immediately prior to evaluation. The "Intervention" handout emphasized the importance of trying one's hardest, explicitly listed consequences of valid and invalid responding and asked patients to sign and initial it. The "Control" handout provided general information about neuropsychological evaluation. Examiners were blinded to condition. Patients were excluded from analyses if they were diagnosed with major neurocognitive disorder or could not read the handout. Medical Symptom Validity Test (MSVT) was used to determine performance validity. Results Groups did not differ on age, education, or litigation status. For the entire sample (N = 251), there was no effect of handout on passing versus failing MSVT. However, among patients who were seeking disability benefits at the time of evaluation (n = 70), the Intervention handout was associated with lower frequency of failing MSVT than the Control handout. Conclusions This brief, theory-based, cost-free intervention was associated with lower frequency of invalid data among patients seeking disability benefits at the time of clinical evaluation. We suggest methodological modifications that might produce a more potent intervention that could be effective with additional subsets of patients.

Broca's area is crucial for speech production. Several recent studies have suggested that it has an additional role in visual speech perception. This conclusion remains tenuous, as earlier studies used tasks requiring active processing of visual speech movements, which may have elicited conscious subvocalizations. To study whether Broca's area is modulated during passive viewing of speech movements, we conducted a functional MRI experiment where participants detected rare and brief visual targets that were briefly superimposed on two task irrelevant conditions: passive viewing of silent speech versus nonspeech (gurning) facial movements. Comparison revealed Broca's area to be more active when observing speech. These findings provide further support for Broca's area in speech perception and have clear implications for rehabilitation of aphasia.

Working memory (WM) was studied in 82 healthy volunteers, 43 schizophrenia patients, and 81 bipolar patients. Schizophrenia patients were impaired on verbal and figural WM tasks that possessed similar test discriminating power. Bipolar patients performed similarly to healthy volunteers. A mathematical model of WM performance revealed a primary role for reduced WM span in accounting for the impaired verbal WM of schizophrenia patients and a primary role for diminished attention in accounting for impaired figural WM. Although WM impairment in schizophrenia is due neither to the general effects of severe mental illness nor to the specific type of material studied, the microarchitecture of abnormal WM in schizophrenia may depend on the stimulus material presented.

The current investigation examined changes in working memory (WM) component processes following total sleep deprivation (TSD) in a sample of healthy young persons. Forty subjects were administered a verbal form of a continuous recognition test (CRT) before and after 42 hr of TSD. Parameters of a computational model of the CRT reflecting attention, WM span, and rate of episodic memory encoding were estimated for each individual. Subjects made more errors on the test following sleep deprivation. Analysis of model parameters revealed statistically independent declines in both the attention and WM span parameters, with a larger effect observed for the decline in WM span. Examination of individual profiles suggested that the effects of TSD on verbal WM component processes vary from person to person. Declines in global verbal WM functioning appear to be primarily driven by reduced WM span and attention; however, these effects may be individual-specific. Further applications of the computational model for examining WM component processes with sleep deprivation and other clinical populations are discussed.

Objectives: Epidermal Growth Factor (EGF) is a candidate biomarker for cognitive functioning in Parkinson’s disease (PD). Relationships between EGF and cognition were explored in progressed PD. Methods: EGF levels were obtained from a heterogeneous sample of PD patients referred for clinical neuropsychological evaluation. Correlation and effect size analyses evaluated relationships between EGF and cognitive measures. Results: EGF was associated with measures of executive functioning and memory. Conclusion: EGF corresponds to cognition in progressed PD. Findings are consistent with previous studies, and support further investigation of EGF’s utility as a biomarker for cognitive functioning in PD

The aim of this study was to evaluate the objective value of neuropsychological evaluation (NPE) through reduction in Emergency Room (ER) visits and hospitalizations. Retrospective analysis examined trends in ER visits and hospitalizations in 440 U.S. veterans who completed NPE between the years of 2003 and 2010. Within-subjects comparisons showed significant decreases in incidence of hospitalization and length of hospitalization in the year after evaluation compared to the year prior. Mean number of hospitalizations declined from 0.31 (SD = 0.64) pre-NPE to 0.22 (SD = 0.59) post-NPE; there were a total of 41 fewer hospitalizations in the year following NPE. Mean length of hospitalization decreased from 1.9 days (SD = 5.6) pre-NPE to 1.06 days (SD = 3.9) post-NPE; there were a total of 368 fewer days of hospitalization post-NPE. This reduction was not attributable to age or time. Incidence of ER visits also decreased from pre-NPE (M = 0.74, SD = 1.3) to post-evaluation (M = 0.69, SD = 1.3), though this was not significant. These findings provide preliminary evidence of the clinical and potential economic value of neuropsychological services within a medical setting. Follow-up studies should examine individual and exam-specific factors that may contribute to reduced utilization.

OBJECTIVE A fundamental dissociation for most working memory (WM) theories involves the separation of sensory-perceptual encoding of stimulus information from the maintenance of this information. The present paper reports tests of this separability hypothesis for visually presented pseudowords at both mathematical and neuroimaging levels of analysis. METHOD Levels of analysis were linked by two experimental manipulations-visual degradation and pseudoword length variation-that coupled findings from a mathematical modeling study of WM performed in a separate sample to findings from an event-related functional MRI (fMRI) study reported in the present paper. Results from the mathematical modeling study generated parametric signatures of stimulus encoding and WM rehearsal and displacement. These signatures led to specific predictions about neurophysiological responses to study manipulations in a priori regions of interest (ROI). RESULTS Results demonstrated predicted dissociations of activation signatures in several ROIs. Significant patterns of brain response mirroring the encode signature were observed only during the task encode interval and only in the visual cortex and posterior fusiform gyrus. In contrast, significant brain response mirroring the rehearsal/displacement signature was observed only in the dorsolateral prefrontal cortex, inferior frontal gyrus, and supramarginal gyrus. CONCLUSIONS Present findings support the separability hypothesis insofar as brain regions that underlie sensory-perceptual processes demonstrated encode signatures whereas brain regions that support WM maintenance demonstrated the rehearsal/displacement signature. These results also provide evidence for the utility of combining mathematical modeling with fMRI to integrate information across cognitive and neural levels of analysis.

The Mattis Dementia Rating Scale (DRS) is widely used to assess cognition and screen for dementia in Parkinson's disease (PD). In 2008, Llebaria and colleagues reported excellent sensitivity and specificity detecting dementia in PD using a DRS total score cutoff of 123. However, this study used a sample with rather low mean educational achievement (8.9 years). The 123 cutoff score was cross-validated in a sample of 51 PD patients with a rather high mean educational achievement (14.84 years). A total score cutoff of 123 correctly classified 60.7% of the sample, with 20% sensitivity and 100% specificity. Use of age- and education-corrected scaled scores improved classification accuracy, but these cutoffs corresponded to the 25th percentile. Optimal classification of 82.4% accuracy was achieved using a raw total score cutoff of 133, corresponding roughly to the 16th percentile. Neither age nor education evinced a strong correlation to DRS total score in our sample. Results suggest caution in applying the DRS-2 total score cutoff of 123 and highlight the importance of comprehensive neuropsychological evaluations for clinical diagnosis of dementia in PD.

ObjectiveTo compare patients with posttraumatic stress disorder (PTSD) to patients without psychiatric or cognitive disorders on neuropsychological measures of attention.MethodsThe sample included 19 patients with PTSD and 22 participants with no cognitive or psychiatric diagnosis. All had been referred for clinical neuropsychological evaluation at a VA Medical Center. None were diagnosed with dementia, delirium, or current substance dependence except nicotine or caffeine, and none had a history of stroke or of traumatic brain injury with loss of consciousness. Patients were excluded if they failed to exert adequate effort on testing.ResultsPTSD patients performed significantly more poorly than patients without psychiatric diagnoses on Digit Span.ConclusionPTSD patients were impaired relative to participants without psychiatric diagnoses on a measure of focused attention. Several factors, including the small sample size, suggest that the results should be considered preliminary.

Initiation and inhibition of saccadic eye movements has been shown to be impaired in patients with Huntington's disease (HD) and premanifest gene carriers (PMGC), and may provide biomarkers useful in tracking phenotypic change. Computerized behavioral tests of prosaccade latency and disinhibition presented to 31 non–gene carriers (NGC), 25 PMGC, and 12 HD patients. These tests provided quantitative performance measures without use of eye-tracking equipment. Significant differences on saccade tests were found, with PMGC intermediate between NGC and HD patients. Saccade latency discriminated PMGC from NGC, whereas saccade disinhibition discriminated PMGC from HD patients. Results suggest utility of behavioral saccade measures as premanifest indicators of phenoconversion in HD.

Amlodipine is a calcium-channel antagonist with neuropharmacological properties believed to be protective against cerebral hypoperfusion, microinfarcts, and excitoxic cell death. Based on its pharmacological properties, we hypothesized that amlodipine would be associated with improved attention, processing speed, memory, and executive functioning at treatment follow-up in 84 cocaine-dependent individuals enrolled in a 12-week, placebo-controlled, double-blind clinical trial of amlodipine. We also hypothesized that better cognitive functioning at baseline would be associated with reduced cocaine use (negative urine drug screens) and longer treatment retention (last session attended). Results indicated that amlodipine produced no measurable benefit in cognitive functioning. Percent perseverative errors on Wisconsin Card Sorting Test was negatively correlated with treatment retention (n = 84, r = -.350, p < .01). No other findings were significant. Thus, cocaine-dependent individuals who repeated mistakes and benefited less from corrective feedback on a problem-solving task discontinued treatment earlier. Notably, no other cognitive measures predicted treatment outcome. The observed relationship implicates the relevance of executive functioning to treatment outcome for cocaine dependence.