Influence of age and education on a performance-based measure of everyday functioning.

Sociodemographic variables, such as age and education, influence the determination of impairment on neuropsychological tests, but their influence on impairment determinations for tests of everyday functioning is less well defined. Existing studies suggest that older age and lower education levels are associated with worse everyday functioning when assessed by self- or collateral-report. This relationship, however, has not been thoroughly investigated with performance-based methods of everyday functioning. This study aimed to determine the influence of sociodemographic factors on the Functional Impact Assessment (FIA), a performance-based measure of everyday functioning that includes measures of both accuracy and speed. Seventy-three healthy individuals, ages 42 - 88 years, completed the FIA and an additional everyday functioning self-report questionnaire (Functional Activities Questionnaire). Using a multiple regression statistical approach, age and education predicted overall FIA accuracy, while age alone predicted FIA speed. Sociodemographic variables continued to predict FIA performance when controlling for overall cognitive functioning. Sociodemographic variables were unrelated to FAQ scores. These findings indicate that age and education are associated with scores on a performance-based test of everyday functioning. Demographic corrections may improve accuracy in determining functional impairment, but more research is needed given the complex relationships among demographic factors, healthy aging, and dementia risk.

Use of Medical Cannabis to Treat Traumatic Brain Injury.

There is not a single pharmacological agent with demonstrated therapeutic efficacy for traumatic brain injury (TBI). With recent legalization efforts and the growing popularity of medical cannabis, patients with TBI will inevitably consider medical cannabis as a treatment option. Pre-clinical TBI research suggests that cannabinoids have neuroprotective and psychotherapeutic properties. In contrast, recreational cannabis use has consistently shown to have detrimental effects. Our review identified a paucity of high-quality studies examining the beneficial and adverse effects of medical cannabis on TBI, with only a single phase III randomized control trial. However, observational studies demonstrate that TBI patients are using medical and recreational cannabis to treat their symptoms, highlighting inconsistencies between public policy, perception of potential efficacy, and the dearth of empirical evidence. We conclude that randomized controlled trials and prospective studies with appropriate control groups are necessary to fully understand the efficacy and potential adverse effects of medical cannabis for TBI.

Associations and Heritability of Auditory Encoding, Gray Matter, and Attention in Schizophrenia.

BACKGROUND: Auditory encoding abnormalities, gray-matter loss, and cognitive deficits are all candidate schizophrenia (SZ) endophenotypes. This study evaluated associations between and heritability of auditory network attributes (function and structure) and attention in healthy controls (HC), SZ patients, and unaffected relatives (UR). METHODS: Whole-brain maps of M100 auditory activity from magnetoencephalography recordings, cortical thickness (CT), and a measure of attention were obtained from 70 HC, 69 SZ patients, and 35 UR. Heritability estimates (h2r) were obtained for M100, CT at each group-difference region, and the attention measure. RESULTS: SZ patients had weaker bilateral superior temporal gyrus (STG) M100 responses than HC and a weaker right frontal M100 response than UR. Abnormally large M100 responses in left superior frontal gyrus were observed in UR and SZ patients. SZ patients showed smaller CT in bilateral STG and right frontal regions. Interrelatedness between 3 putative SZ endophenotypes was demonstrated, although in the left STG the M100 and CT function-structure associations observed in HC and UR were absent in SZ patients. Heritability analyses also showed that right frontal M100 and bilateral STG CT measures are significantly heritable. CONCLUSIONS: Present findings indicated that the 3 SZ endophenotypes examined are not isolated markers of pathology but instead are connected. The pattern of auditory encoding group differences and the pattern of brain function-structure associations differ as a function of brain region, indicating the need for regional specificity when studying these endophenotypes, and with the presence of left STG function-structure associations in HC and UR but not in SZ perhaps reflecting disease-associated damage to gray matter that disrupts function-structure relationships in SZ.

Neurocognitive Correlates of Successful Treatment of PTSD in Female Veterans.

BACKGROUND: The influence of psychotherapy on neurocognition in post-traumatic stress disorder (PTSD) has not been examined methodically. This is despite evidence that pre-treatment learning and memory has been associated with treatment success and that executive function theories emphasize weak executive functions (especially inhibition/switching) are associated with PTSD. OBJECTIVES: To determine (1) if higher pre-treatment learning/memory, inhibition/switching, or both predict treatment success; and (2) if treatment success is associated with specific improvement in inhibition/switching and not learning/memory or working memory, another aspect of executive function. METHODS: Pre-treatment neurocognition and neurocognitive changes (inhibition/switching, learning/memory, working memory) were examined in female veterans with PTSD. They were evaluated before and after 16-weeks of group psychotherapy for PTSD that included three counterbalanced modules (cognitive restructuring therapy, exposure therapy, skills training) with fidelity checks for therapist adherence. RESULTS: Only pre-treatment learning/memory predicted better treatment outcome. Treatment success was associated with improvement in inhibition/switching only, even after controlling for mild traumatic brain injury, and changes in depressive symptoms, working memory, and learning/memory. CONCLUSIONS: Our finding that learning/memory predicted treatment success is consistent with previous studies. We extended these studies by showing that the effect was restricted to learning/memory, which is contrary to the executive function theory of PTSD. In contrast, the fact that only inhibition/switching significantly improved with better treatment success is consistent with its potential importance in maintaining PTSD symptoms. Future research should determine whether inhibition/switching abilities are a risk for development and maintenance of PTSD or whether such abilities have a broader reciprocal relationship with PTSD symptom change. (JINS, 2016, 22, 643-651).

Frontal slow-wave activity as a predictor of negative symptoms, cognition and functional capacity in schizophrenia.

BACKGROUND: Increased temporal and frontal slow-wave delta (1-4 Hz) and theta (4-7 Hz) activities are the most consistent resting-state neural abnormalities reported in schizophrenia. The frontal lobe is associated with negative symptoms and cognitive abilities such as attention, with negative symptoms and impaired attention associated with poor functional capacity. AIMS: To establish whether frontal dysfunction, as indexed by slowing, would be associated with functional impairments. METHOD: Eyes-closed magnetoencephalography data were collected in 41 participants with schizophrenia and 37 healthy controls, and frequency-domain source imaging localised delta and theta activity. RESULTS: Elevated delta and theta activity in right frontal and right temporoparietal regions was observed in the schizophrenia v. CONTROL GROUP: In schizophrenia, right-frontal delta activity was uniquely associated with negative but not positive symptoms. In the full sample, increased right-frontal delta activity predicted poorer attention and functional capacity. CONCLUSIONS: Our findings suggest that treatment-associated decreases in slow-wave activity could be accompanied by improved functional outcome and thus better prognosis.

Clinical utility of the Neuropsychological Assessment Battery (NAB) after unilateral stroke.

The NAB is a comprehensive battery assessing five cognitive domains (Attention, Language, Memory, Spatial, Executive Function). Despite the advantage of co-normative domain data, its clinical utility is not well established because few studies have reported full-battery findings. The aim of this study was to determine if the NAB was sensitive to well documented hemispheric differences in language and spatial skills after unilateral stroke. We compared demographically matched control participants (n = 52) and individuals after left (LHD, n = 36) or right (RHD, n = 33) hemisphere damage due to stroke on the NAB, parts of the Western Aphasia Battery, and traditional visuospatial tasks. Both stroke groups showed impaired NAB Attention, Spatial, and Executive Functions relative to controls, while the LHD group was more impaired than control and RHD groups on Language and Memory modules. LHD patients with aphasia on traditional measures performed worse than control and non-aphasic LHD patients on all NAB domains. RHD patients with spatial impairment on traditional measures performed worse than controls, but not RHD patients without spatial impairment, on the NAB Spatial domain. Findings suggest the NAB is generally comparable to traditional language and visuospatial measures, and it sufficiently detects attention and executive deficits.

Performance-based everyday functioning after stroke: relationship with IADL questionnaire and neurocognitive performance.

Neuropsychologists frequently are asked to comment on everyday functioning, but the research relies mostly on questionnaire-based assessment of daily functioning. While performance-based assessment of everyday functioning has many advantages over commonly used questionnaires, there are few empirically validated comprehensive performance-based measures. We present data here on a performance-based battery of daily living skills, the Functional Impact Assessment (FIA) in 47 unilateral stroke patients and 37 matched healthy controls. The FIA was validated by comparing it to performance on the self- and informant-report version of the Functional Activities Questionnaire (FAQ). We also examined the relationship between the FIA and cognitive functioning using the Neuropsychological Assessment Battery (NAB). The stroke group's performance on the FIA, FAQ (self and informant), and NAB (total and domain scores) was significantly (d's ≥ .80) lower than the control group. The NAB total score and all domain scores were highly correlated with the FIA in the stroke group (r's > .7), and only one NAB domain score (visuospatial) was a unique predictor. This may be due to the fact that most of the NAB domains have a statistical problem of multicollinearity, which may explain why only the spatial domain was a unique predictor. While the informant FAQ was significantly correlated with FIA total score (r = .48, p < .01), the NAB total score was a significantly better predictor (r = .83, p < .001) than the informant FAQ. NAB total scaled score of less than 86 predicted impairment on the FIA with 92% sensitivity and 84% specificity. Our findings argue that the FIA is sensitive to deficits associated with stroke and is highly associated with all neuropsychological domains (attention, executive functions, language and spatial skills, and memory).

A baseline for the multivariate comparison of resting-state networks.

As the size of functional and structural MRI datasets expands, it becomes increasingly important to establish a baseline from which diagnostic relevance may be determined, a processing strategy that efficiently prepares data for analysis, and a statistical approach that identifies important effects in a manner that is both robust and reproducible. In this paper, we introduce a multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing. We demonstrate the utility of this mega-analytic approach by identifying the effects of age and gender on the resting-state networks (RSNs) of 603 healthy adolescents and adults (mean age: 23.4 years, range: 12-71 years). Data were collected on the same scanner, preprocessed using an automated analysis pipeline based in SPM, and studied using group independent component analysis. RSNs were identified and evaluated in terms of three primary outcome measures: time course spectral power, spatial map intensity, and functional network connectivity. Results revealed robust effects of age on all three outcome measures, largely indicating decreases in network coherence and connectivity with increasing age. Gender effects were of smaller magnitude but suggested stronger intra-network connectivity in females and more inter-network connectivity in males, particularly with regard to sensorimotor networks. These findings, along with the analysis approach and statistical framework described here, provide a useful baseline for future investigations of brain networks in health and disease.

Utility of the Neuropsychological Assessment Battery in detecting cognitive impairment after unilateral stroke.

This study evaluated the clinical utility of the Neuropsychological Assessment Battery (NAB) in a stroke sample by examining the NAB's ability to differentiate a chronic stroke group with radiologically confirmed unilateral damage (n = 42) and a demographically matched healthy control (HC) group (n = 36). The stroke group performed more poorly than the control group across NAB Total score and all five Domain scores. Receiver operator curves (ROC) were derived and area under the curve (AUC) showed moderate diagnostic effectiveness (AUC .70 to .90) for NAB Total score, all five Domain scores, a motor composite, and a Global Deficit Score (GDS) that has been shown to closely approximate clinical ratings of neuropsychological impairment. The NAB Total, GDS, and motor composite had comparable clinical utility, whereas the Attention and Executive domain scores demonstrated better classification utility compared with the Memory domain. Because 90.5% of our stroke sample had middle cerebral artery territory strokes, the comparison of motor and cognitive classification utility may be biased. However, follow-up analyses showed that the NAB accounted for additional variance even when motor composite was included in the model. Sensitivity, specificity, and odds ratios at various clinical cutoffs are provided. These results suggest that the NAB is a useful clinical tool for detection of cognitive deficits in individuals with chronic unilateral stroke, although lenient clinical cutoffs appear warranted to maximize sensitivity.

Persistent neuropsychological impairment associated with West Nile virus infection.

West Nile virus infection can result in prolonged subjective complaints of cognitive and functional decline even in the absence of a neuroinvasive form of infection. Persistent cognitive and functional complaints could be a result of general somatic symptoms, emotional distress, or residual central nervous system damage or dysfunction. Most studies of cognition in postacute West Nile virus infection rely on self-report. This descriptive study aimed to document cognitive deficits in a sample of the 2003 infected population reported in New Mexico. Patients with clinically defined neuroinvasive disease or who were impaired on brief mental status screening were seen for comprehensive neuropsychological assessment. We found that one year after symptom onset, more than half of the sample had objectively measurable neuropsychological impairment in at least two cognitive domains. Impairment was not related to subjective complaints of physical or emotional distress, or premorbid intellectual abilities. Persistent cognitive impairment in West Nile virus infection may be due to prolonged or permanent damage to the central nervous system.

Arm use after left or right hemiparesis is influenced by hand preference.

BACKGROUND AND PURPOSE: Despite strong evidence for hand preference and its impact on motor performance, its influence on stroke rehabilitation has not been routinely considered. Previous research demonstrates that patients with hemiparetic stroke use their ipsilesional, nonparetic arm 5 to 6 times more frequently than their paretic arm, but it is unknown if such use varies with laterality of hemiparesis. The purpose of our study was to determine if the right arm is used more frequently in right-handed patients with stroke. METHODS: We assessed relative use of the right, left, and both arms with wrist accelerometers on patients with unilateral, paretic stroke matched for degree of paresis (12 with right hemisphere damage, 17 with left hemisphere damage) and 25 neurologically intact control participants as they performed the Arm Motor Ability Test. RESULTS: We showed: (1) ipsilesional arm use was greater after right hemisphere damage than left hemisphere damage; (2) the left hemisphere damage group used both arms together more often than the right hemisphere damage group but less often than the control group; and (3) both stroke groups used their contralesional, paretic arm to the same degree. CONCLUSIONS: These findings emphasize the influence of hand preference on arm use after stroke for the ipsilesional but not the contralesional arm. Although both stroke groups used their ipsilesional more than their contralesional arm, the difference was greater for the right hemisphere damage group who used their ipsilesional arm 4 times more frequently than their contralesional arm, whereas the left hemisphere damage group used their ipsilesional arm 2 times more frequently than their contralesional arm.

The impact of neuropsychological functioning and depressed mood on functional complaints in HIV-1 infection and methamphetamine dependence.

Diagnosis of neurobehavioral syndromes associated with HIV infection requires the determination that neuropsychological (NP) deficits are present, are not caused by any comorbid (e.g., psychiatric) condition, and significantly affect everyday functioning. Methamphetamine (Meth) dependence and depression are common comorbid conditions with HIV and may complicate diagnosis of HIV-associated neurobehavioral syndromes. The current study examined the complex relationships between depression and NP impairment, and self-report of problems with everyday functioning, in 362 adults with HIV infection or Meth dependence, or both. Everyday functioning was measured with questionnaires of instrumental activities of daily living (IADLs) and reported cognitive difficulties. Results indicate that comorbid HIV and Meth did not increase the likelihood of complaints regarding everyday functioning, beyond what was seen with either single risk factor. Across all groups, depressive symptoms predicted greater IADL decline and cognitive complaints, while NP impairment predicted cognitive complaints more than IADL decline. Both IADL decline and cognitive complaints were associated with higher rates of unemployment and worse clinician ratings of overall functioning (Karnofsky ratings), even when depressive symptoms were controlled. These results suggest that depressive symptoms should not be used to dismiss subjective complaints related to everyday functioning even though depressive symptoms account for significant variance in self-reported complaints. Additional research is needed to clarify the potentially reciprocal causal relationships between depressive symptoms and impairment in everyday functioning.

Work-related abilities in schizophrenia and HIV infection.

Schizophrenia and human immunodeficiency virus (HIV) infection both are associated with high rates of neurocognitive impairment. These impairments predict unemployment in both disorders, independent of other disease-related factors that may affect employment. In this study, we investigated work-related abilities and previous employment patterns in 27 unemployed patients with schizophrenia, 27 demographically matched unemployed HIV-infected participants, and 27 nonmatched employed HIV seropositive (HIV+) participants. All subjects were administered a computerized and hands-on assessment of vocational abilities and a comprehensive work history interview. Compared with the employed HIV+ group, the two unemployed groups had lower estimates of maximal lifetime job functioning. In terms of current vocational abilities, the employed HIV+ subjects generally performed best, followed by the unemployed HIV+ subjects and the patients with schizophrenia. Although the unemployed schizophrenia subjects had the most decline in vocational abilities (from estimated lifetime maximum level), the patterns of decline were similar in the two unemployed groups and were suggestive of parallel impairments in frontal-subcortical functioning.

Retrograde amnesia in dementia: comparison of HIV-associated dementia, Alzheimer's disease, and Huntington's disease.

Remote memory was assessed in persons with HIV-associated dementia (HIV-D), probable Alzheimer's disease (AD), and Huntington's disease (HD) and in healthy controls. The clinical groups were similar in overall dementia severity. Each clinical group exhibited impairments on remote memory tests relative to controls; however, temporally graded memory loss with selective preservation of older information was observed in the AD group but not the HD or HIV-D group. Analysis of cued retrieval indicated a preferential cuing benefit for the HIV-D and HD groups relative to the AD group. The similar pattern of remote memory performance demonstrated by the HIV-D and HD groups is a novel finding and suggests a subcortically mediated retrograde amnesia in HIV-D. The temporally graded pattern and the abnormal cued retrieval performance in the AD group are consistent with a consolidation deficit associated with extrahippocampal (cortical) and hippocampal damage.

Left and right basal ganglia and frontal activity during language generation: contributions to lexical, semantic, and phonological processes.

fMRI was used to determine the frontal, basal ganglia, and thalamic structures engaged by three facets of language generation: lexical status of generated items, the use of semantic vs. phonological information during language generation, and rate of generation. During fMRI, 21 neurologically normal subjects performed four tasks: generation of nonsense syllables given beginning and ending consonant blends, generation of words given a rhyming word, generation of words given a semantic category at a fast rate (matched to the rate of nonsense syllable generation), and generation of words given a semantic category at a slow rate (matched to the rate of generating of rhyming words). Components of a left pre-SMA-dorsal caudate nucleus-ventral anterior thalamic loop were active during word generation from rhyming or category cues but not during nonsense syllable generation. Findings indicate that this loop is involved in retrieving words from pre-existing lexical stores. Relatively diffuse activity in the right basal ganglia (caudate nucleus and putamen) also was found during word-generation tasks but not during nonsense syllable generation. Given the relative absence of right frontal activity during the word generation tasks, we suggest that the right basal ganglia activity serves to suppress right frontal activity, preventing right frontal structures from interfering with language production. Current findings establish roles for the left and the right basal ganglia in word generation. Hypotheses are discussed for future research to help refine our understanding of basal ganglia functions in language generation.

Semantic monitoring of words with emotional connotation during fMRI: contribution of anterior left frontal cortex.

Previous studies showed that cortex in the anterior portions of the left frontal and temporal lobes participates in generating words with emotional connotations and processing pictures with emotional content. If these cortices process the semantic attribute of emotional connotation, they should be active whenever processing emotional connotation, without respect to modality of input or mode of output. Thus, we hypothesized that they would activate during monitoring of words with emotional connotations. Sixteen normal subjects performed semantic monitoring of words with emotional connotations, animal names, and implement names during fMRI. Cortex in the anterior left frontal lobe demonstrated significant activity for monitoring words with emotional connotations compared to monitoring tone sequences, animal names, or implement names. Together, the current and previous results implicate cortex in the anterior left frontal lobe in semantic processing of emotional connotation, consistent with connections of this cortex to paralimbic association areas. Current findings also indicate that neural substrates for processing emotional connotation are independent of substrates for processing the categories of living and nonliving things.

Functional neuroimaging in neurology and psychiatry.

How can functional neuroimaging be applied to clinical neurology and psychiatry? This article reviews selected contributions of functional neuroimaging to the clinical neurosciences. We review selected technical aspects of positron emission tomography, single photon emission tomography, and functional magnetic resonance imaging with a focus on the relative strengths and weaknesses of these techniques. Consumers of functional neuroimaging research are encouraged to consider the limitations of imaging techniques and theoretical pitfalls of cognitive task design when interpreting results of functional imaging studies. Then, we selectively review the contributions of functional neuroimaging to neurology and psychiatry, including the areas of epilepsy, stroke, chronic pain, schizophrenia, depression, and obsessive-compulsive disorder. Future directions of functional neuroimaging research are offered, with the emphasis that the best conclusions are informed by a convergence of research from functional neuroimaging, neurophysiological, and lesion studies.