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Background This investigation examined whether aspects of attention and executive functioning differed between Parkinson's Disease (PD) patients with freezing of gait (FOG) based on responsiveness to dopamine. We also explored association of cognition with FOG severity and gait metrics. Methods Fifty-four individuals with PD completed the study protocol: 17 without freezing (PDC), 23 with dopa-responsive FOG (RFOG), and 14 with dopa-unresponsive (URFOG). Standardized neuropsychological tests assessed attention (focused and sustained), psychomotor speed, and set-switching (time and errors). FOG severity was measured using the new FOG Questionnaire (nFOG-Q). Metrics from timed up and go (TUG) tasks were obtained while “on” and “off” dopamine, with and without dual cognitive tasks. Results After controlling for clinical and demographic factors, analysis of covariance revealed a significant between-group difference for set-switching errors; planned contrasts revealed increased set-switching errors in URFOG relative to RFOG and PD control groups. Groups were not different in other cognitive domains. FOG severity was modestly associated with set-switching errors in RFOG but not URFOG. TUG performances while “on” were associated with set-switching errors in PD controls, and with focused attention in RFOG. Conclusion PD patients with dopa-unresponsive FOG are more prone to set-switching errors than those who respond to treatment. Furthermore, executive function appears relevant to FOG severity only in patients who show dopamine response. Together, these findings suggest disruption of a common dopamine-mediated pathway for FOG and ability to monitor rules while alternating cognitive processes. Consideration of dopa-response could be useful in characterizing cohorts and treating FOG in PD.

Background: Cognitive impairment is common in Parkinson’s disease (PD) and highly associated with loss of independence, caregiver burden, and assisted living placement. The need for cognitive functional capacity tools validated for use in PD clinical and research applications has thus been emphasized in the literature. The Virtual Reality Functional Capacity Assessment Tool (VRFCAT-SL) is a tablet-based instrument that assesses proficiency for performing real world tasks in a highly realistic environment. Objective: The present study explored application of the VRFCAT-SL in clinical assessments of patients with PD. Specifically, we examined associations between VRFCAT-SL performance and measures of cognition, motor severity, and self-reported cognitive functioning. Methods: The VRFCAT-SL was completed by a sample of 29 PD patients seen in clinic for a comprehensive neuropsychological evaluation. Fifteen patients met Movement Disorders Society Task Force criteria for mild cognitive impairment (PD-MCI); no patients were diagnosed with dementia. Non-parametric correlations between VRFCAT-SL performance and standardized neuropsychological tests and clinical measures were examined. Results: VRFCAT-SL performance was moderately associated with global rank on neuropsychological testing and discriminated PD-MCI. Follow-up analyses found completion time was associated with visual memory, sustained attention, and set-switching, while errors were associated with psychomotor inhibition. No clinical or motor measures were associated with VRFCAT-SL performance. Self-report was not associated with VRFCAT-SL or neuropsychological test performance. Conclusion: The VRFCAT-SL appears to provide a useful measure of cognitive functional capacity that is not confounded by PD motor symptoms. Future studies will examine utility in PD dementia.

People with essential tremor commonly experience psychological difficulties that are not addressed. The effect of stigma, i.e., negative judgement by others because of a perceived difference in this case shaky movement, is a heretofore unstudied element. This project was undertaken to develop and field test a new measure for stigma associated with essential tremor.Under guidance from a patient panel and an expert panel of neurologists and psychologists, the essential tremor stigma construct was delineated, and survey items were written to quantify three dimensions of interest: cumulative experience of stigma; related psychological distress; and resulting behavioral dysfunction. After pilot testing and revision, the essential tremor stigma measure underwent field testing by 198 essential tremor patients at two academic neurology clinics.The experience, distress and dysfunction scales were shown to have good internal consistency and test-retest reliability. Retained items demonstrated acceptable correlations and response properties. The validity of the distress scale was supported by concurrence with an existing stigma scale for neurologic disease, while a patient's openness to psychologic referral was predicted by higher scores on the dysfunction scale.This new measure is introduced to study the phenomenon of stigma associated with essential tremor. It may prove useful in assessing potential treatments for the psychological distress and maladaptive behavior that result from this stigma.

Despite data supporting the rapid adoption of telehealth in the delivery of clinical care in North America, the implementation of telehealth visits in clinical research studies has faced critical barriers. These challenges include: (1) variations in state licensure requirements for telehealth; (2) disparities in access to telehealth among disadvantaged populations; (3) lack of consistency among individual Investigational Review Boards (IRBs). Each barrier prevents the systematic conversion of research protocols to include telehealth visits. The Parkinson’s Foundation and members of the Parkinson Study Group submit this Comment to highlight current challenges to implementing telehealth visits for clinical research studies. Our objective is to provide a consensus statement emphasizing the urgent need for regulators to standardize adoption of telehealth practices and to propose recommendations to reduce the burden for implementation in existing research study protocols.

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.

Background Reliable detection of slowed vertical saccades may help discriminate progressive supranuclear palsy (PSP) from the subset of Parkinson’s disease patients who lack tremor (akinetic-rigid or PD-postural instability and gait disorder PIGD subtype), and from age-related oculomotor changes. We investigated the feasibility of a camera-less computerized behavioral saccade latency paradigm previously validated in PD to discriminate probable PSP-Richardson syndrome (PSP-RS) from PD-PIGD and age-matched controls. Methods In this proof-of-concept case-control study, reflexive saccade latencies were measured in 5 subjects with probable PSP-RS, 5 subjects with PD-PIGD subtype, and 5 age-matched controls using the behavioral paradigm. The battery was repeated approximately one month later. All subjects were examined off levodopa by a movement disorders neurologist and by an ophthalmologist, who also performed a dilated eye exam. Results Vertical prosaccade latencies were longer in the PSP group (median = 903 ms) relative to PD (median = 268 ms) and control groups (median = 235 ms), with no overlap between groups (100% accuracy). PSP subjects also had larger vertical-horizontal discrepancies than comparison groups. Test-retest reliability for the behavioral saccade measures was good (interclass correlation coefficient = 0.948; 95% confidence interval [0.856, 0.982]), and the measures strongly correlated with clinical ratings. Conclusions Computerized behavioral measurement of reflexive saccade latency is feasible in PSP, and potentially discriminates probable PSP-RS from the PD-PIGD subtype. Findings from this proof-of-concept study support utility of the approach for obtaining objective saccade metrics in clinical evaluations and for tracking change in future, larger trials of moderately advanced PSP. Future studies should also examine the behavioral paradigm in earlier presentations of PSP and other subtypes of PSP.

Studies have assessed omega-3 fatty acids and cognitive decline among older adults and cognitive development among children, although less is known about cognitive or neurological effects among young adults. We examined whether omega-3 supplementation from krill oil could improve cognition and resilience among young military officers compared to a control. This double-blind, placebo-controlled trial enrolled 555 officers (mean age 23.4 ± 2.8, 98.6% male) entering the United States (US) Army Infantry Basic Officer Leaders Course (IBOLC) with the intention to complete the US Ranger Course. Volunteer participants consumed eight dietary supplements daily of krill oil containing 2.3 g omega-3 or control (macadamia nut oil) over an approximate 20-week period. Cognitive functioning, resilience, and mood were assessed during a well-rested period at approximately 14 weeks and after a battlefield simulation at 16 weeks. Blood spot samples were collected to monitor compliance and dietary intake was assessed. All hypotheses were tested using both ‘Intention to Treat’ (ITT) and ‘As Per Protocol’ (APP) approaches. Of the 555 randomized individuals, 245 (44.1%) completed the study. No statistically significant group-by-time interactions indicating treatment effect were found on any outcomes. Poor compliance was indicated by lower than expected omega-3 elevations in the treatment group, and may have contributed to a failure to detect a response.

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.

Intake of nutrients fundamental for optimal neuronal function is of increasing interest. The potential importance of omega-3 highly unsaturated fatty acids (HUFAs) for optimizing emotional states, cognitive function, and mental health has been demonstrated in observational studies and randomized controlled trials. Omega-3 (HUFAs), specifically EPA (eicosapentaenoic acid) and docosahexaenoic acid (DHA), are concentrated in neural tissues and are essential for neural function, normative neurodevelopment, neurotransmitter, and neural immune functions. Omega-3 HUFAs must be obtained from the diet, predominantly from marine sources such as fish and other seafood. HUFAs also can be found in a variety of dietary supplements (omega-3 fatty acid esters, fish oil and krill oil). As dietary supplements, omega-3 HUFAs (fatty acid esters, fish and krill oils) differ substantially in their physicochemical properties and nutrient content. Here we present the design and methods for the Ranger Resilience and Improved Performance on Phospholipid bound Omega-3's (RRIPP-3) study. RRIPP-3 was a double blind, randomized, controlled trial among individuals in the United States (US) Army Infantry Basic Officer Leaders Course (IBOLC) and following US Ranger School training (RC) at Fort Benning, GA of omega-3 HUFA on krill oil versus placebo supplementation. The RRIPP-3 study sought to determine if krill oil supplementation with omega-3 HUFAs supports aspects of cognitive functioning critical to battlefield success when measured immediately after an intense combat simulation. Sub-analyses addressed basic improvements in IBOLC performance. We also describe additional outcome measures critical for interpretation of the study results, such as diet and other dietary supplement use. Keywords: Omega-3 fatty acids, Cognition, Krill oil, US Army officers, Phospholipids, Resilience

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.

Many randomized controlled trials (RCTs) of neuropsychiatric conditions involve cognitive outcome measures; however, validity of cognitive data relies on adequate effort during testing, and such screening is seldom performed. Given well-established rates of 10 to 30% poor effort in clinical settings, this is not a trivial concern. This preliminary study evaluated effort during cognitive testing in an RCT of omega-3 supplementation to reduce suicidality in a high-risk psychiatric population. An interim analysis of sustained attentions measures from the Connors Performance Test (CPT-2) at baseline for the first 60 participants was conducted. Previously validated cut points to detect insufficient effort on the CPT-2 were applied. At baseline, 12% (7) were identified as giving poor effort. Follow-up analyses indicated less psychiatric distress and suicidality among those who gave poor effort. RESULTS suggest comparable likelihood of a poor effort on cognitive testing in clinical and RCT participation. Reduced psychiatric distress in the poor effort group raises concern regarding interpretation of other measures. The importance of screening cognitive data for effort in RCTs is highlighted. Future studies will examine effort at follow-up visits, and explore relationships to attrition, adherence, and response to treatment.Copyright © 2016 John Wiley & Sons, Ltd. Language: en

OBJECTIVES/GOALS: This study uses diffusion kurtosis imaging (DKI) to investigate the structural profiles of basal ganglia (BG) motor circuitry in Vascular Parkinsonism (VP), Parkinson’s disease (PD), and healthy aging controls (HC). VP is a clinical diagnosis of lower body predominant parkinsonism without significant benefit from levodopa. VP is distinct from PD, yet the concept of VP remains debated due to the inability of prior studies to identify specific causative changes. One reason for this may be limitations in measuring intricate BG connectivity in vivo. Given the predominant lower body parkinsonism symptoms in VP, we hypothesized that VP would be associated with decreased connectivity specifically within the BG motor loop. METHODS/STUDY POPULATION: We obtained DKI brain imaging in subjects with VP (N = 7), PD (N = 21), and HCs (N = 58), the latter of which had cardiovascular risk factors but no neurological symptoms. The VP and PD groups were evaluated by a parkinsonism-focused motor exam and brief cognitive testing. We compared BG motor loop connectivity between groups and investigated for correlation between connectivity and clinical scores. To account for differences in fiber counts due to the different imaging scanners and protocols between cohorts, we used a BG motor loop proportion, which was the ratio of the BG motor loop fiber count over a control loop, the visual processing pathway. We used Kruskal-Wallis rank sum test with post-hoc Dunn tests to assess imaging findings between subject groups, and Pearson’s correlation to look for correlation between clinical scores and fiber counts. RESULTS/ANTICIPATED RESULTS: The whole brain connectome showed the fewest number of fibers in VP, followed by PD, and then HC (p

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.

Many randomized controlled trials (RCTs) of neuropsychiatric conditions involve cognitive outcome measures; however, validity of cognitive data relies on adequate effort during testing, and such screening is seldom performed. Given well‐established rates of 10 to 30% poor effort in clinical settings, this is not a trivial concern. This preliminary study evaluated effort during cognitive testing in an RCT of omega‐3 supplementation to reduce suicidality in a high‐risk psychiatric population. An interim analysis of sustained attentions measures from the Connors Performance Test (CPT‐2) at baseline for the first 60 participants was conducted. Previously validated cut points to detect insufficient effort on the CPT‐2 were applied. At baseline, 12% (7) were identified as giving poor effort. Follow‐up analyses indicated less psychiatric distress and suicidality among those who gave poor effort. Results suggest comparable likelihood of a poor effort on cognitive testing in clinical and RCT participation. Reduced psychiatric distress in the poor effort group raises concern regarding interpretation of other measures. The importance of screening cognitive data for effort in RCTs is highlighted. Future studies will examine effort at follow‐up visits, and explore relationships to attrition, adherence, and response to treatment. Copyright © 2016 John Wiley & Sons, Ltd.

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.

Suicide remains the 10th leading cause of death among adults in the United States (U.S.). Annually, approximately 30 per 100,000 U.S. military Veterans commit suicide, compared to 14 per 100,000 U.S. civilians. Symptoms associated with suicidality can be treatment resistant and proven-effective pharmaceuticals may have adverse side-effects. Thus, a critical need remains to identify effective approaches for building psychological resiliency in at-risk individuals. Omega-3 highly unsaturated fatty acids (n-3 HUFAs) are essential nutrients, which must be consumed in the diet. N-3 HUFAs have been demonstrated to reduce symptoms of depression, anxiety, and impulsivity - which are associated with suicide risk. Here we present the design and methods for the Better Resiliency Among Veterans and non-Veterans with Omega-3's (BRAVO) study, which is a double blind, randomized, controlled trial among individuals at risk of suicide of an n-3 HUFA versus placebo supplementation in the form of all natural fruit juice beverages. The BRAVO study seeks to determine if dietary supplementation with n-3 HUFAs reduces the risk for serious suicidal behaviors, suicidal thinking, negative emotions, and symptoms associated with suicide risk. Sub-analyses will evaluate efficacy in reducing depressive symptoms, alcohol, and nicotine use. A sub-study utilizes functional magnetic resonance imaging (fMRI) to evaluate the neuropsychological and neurophysiological effects of n-3 HUFAs. We also outline selection of appropriate proxy outcome measures for detecting response to treatment and collection of ancillary data, such as diet and substance use, that are critical for interpretation of results.

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 medical/psychiatric comorbidities. Thus, patients who exerted inadequate effort showed greater healthcare utilization in the year following evaluation. Such patients might use more resources since diagnostic evaluations are inconclusive. Inadequate effort on examination might also serve as a "marker" for more general failure to cooperate fully in one's healthcare, possibly resulting in greater utilization.

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.

Individuals with Parkinson's disease (PD) exhibit higher rates of depression and anxiety than the general and other medically disabled populations. Evidence suggests that mood and anxiety symptoms are related to disease pathology. Rates of depression and anxiety in PD vary depending on how these symptoms are measured, but they are estimated to occur in up to 40% of patients. These conditions have adverse effects on patient and caregivers' quality of life, level of disability, and mortality, with several studies suggesting greater contribution than motor symptom severity. Pharmacological and psychotherapeutic interventions, particularly in combination, have demonstrated efficacy in treating depression and anxiety in PD. However, additional randomized controlled trials are needed to better delineate when and how to best treat these disabling symptoms.

Many veterans live in rural areas distant from Veterans Affairs Medical Centers (VAMCs) and receive primary medical care from community-based outpatient clinics (CBOCs). These veterans often must travel great distances to the nearest VAMC for neuropsychological evaluations, resulting in poor access to care, travel reimbursement costs, fee-basis evaluations of uncontrolled quality, and driving safety concerns. Return trips for feedback compound complications. Accordingly, we initiated a pilot trial of neuropsychological evaluation and feedback via telemedicine (i.e., clinical videoconferencing).Participants were veterans referred for neuropsychological evaluation from a rural CBOC 115 miles from the regional VAMC. All veterans were given the choice to undergo evaluation at the CBOC via telemedicine or in-person at the VAMC. Telemedicine equipment allowed presentation of digitized material with simultaneous patient observation. Testing materials were organized in numbered folders and given to veterans by CBOC clerks immediately prior to evaluation. Clerks returned completed materials via facsimile.Fifteen veterans from the rural CBOC were seen for neuropsychological evaluation. Eight chose telemedicine evaluation. Groups based on evaluation modality appeared similar on demographics, referral basis, resulting neuropsychiatric diagnoses, and follow-through on recommendations. No significant technical or clinical difficulties were encountered, and veterans reported satisfaction with telemedicine. All veterans requested feedback via telemedicine.Neuropsychological evaluation via telemedicine is feasible and appears comparable to in-person evaluation. Experiences are encouraging and consistent with the broader literature on the acceptance of and satisfaction with clinical videoconferencing. Future studies will assess possible psychometric issues in clinical populations.

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.