Callosal Function in Pediatric Traumatic Brain Injury Linked to Disrupted White Matter Integrity.

Traumatic brain injury (TBI) often results in traumatic axonal injury and white matter (WM) damage, particularly to the corpus callosum (CC). Damage to the CC can lead to impaired performance on neurocognitive tasks, but there is a high degree of heterogeneity in impairment following TBI. Here we examined the relation between CC microstructure and function in pediatric TBI. We used high angular resolution diffusion-weighted imaging (DWI) to evaluate the structural integrity of the CC in humans following brain injury in a sample of 32 children (23 males and 9 females) with moderate-to-severe TBI (msTBI) at 1-5 months postinjury, compared with well matched healthy control children. We assessed CC function through interhemispheric transfer time (IHTT) as measured using event-related potentials (ERPs), and related this to DWI measures of WM integrity. Finally, the relation between DWI and IHTT results was supported by additional results of neurocognitive performance assessed using a single composite performance scale. Half of the msTBI participants (16 participants) had significantly slower IHTTs than the control group. This slow IHTT group demonstrated lower CC integrity (lower fractional anisotropy and higher mean diffusivity) and poorer neurocognitive functioning than both the control group and the msTBI group with normal IHTTs. Lower fractional anisotropy-a common sign of impaired WM-and slower IHTTs also predicted poor neurocognitive function. This study reveals that there is a subset of pediatric msTBI patients during the post-acute phase of injury who have markedly impaired CC functioning and structural integrity that is associated with poor neurocognitive functioning. SIGNIFICANCE STATEMENT: Traumatic brain injury (TBI) is the primary cause of death and disability in children and adolescents. There is considerable heterogeneity in postinjury outcome, which is only partially explained by injury severity. Imaging biomarkers may help explain some of this variance, as diffusion weighted imaging is sensitive to the white matter disruption that is common after injury. The corpus callosum (CC) is one of the most commonly reported areas of disruption. In this multimodal study, we discovered a divergence within our pediatric moderate-to-severe TBI sample 1-5 months postinjury. A subset of the TBI sample showed significant impairment in CC function, which is supported by additional results showing deficits in CC structural integrity. This subset also had poorer neurocognitive functioning. Our research sheds light on postinjury heterogeneity.

The Warrington Recognition Memory Test for words as a measure of response bias: total score and response time cutoffs developed on "real world" credible and noncredible subjects.

Several studies have examined the usefulness of the Warrington Recognition Memory Test-Words as a measure to detect suspect effort, although samples have generally been small and/or comprised of simulators rather than "real world" credible and noncredible patients. The current study examined the Warrington Recognition Memory Test-Words total score and response time of "real world" noncredible patients (as determined by motive to feign, failure on > or =2 independent measures of response bias, low cognitive scores inconsistent with normal ADLs; n = 190) versus credible patients (as determined by no motive to feign, failure of < or =1 measure of response bias; n = 124) derived from an archival database of individuals from the Harbor-UCLA Medical Center, Department of Psychiatry, Outpatient Neuropsychology Service, and the private practice of the second author. Noncredible patients obtained significantly lower total scores and longer times to complete the task. A total correct cutoff of < or =42 was found to have excellent specificity (91.9%) and sensitivity (88.9%), whereas a time cutoff of > or =207'' was associated with 65.5% sensitivity at 90.7% specificity, and when the time cut-score was used in combination with the total score cutoff, an additional 5% of the noncredible participants were captured, raising overall sensitivity to 93.7% (at 87.1% specificity). Thus, the Warrington Recognition Memory Test-Words, although not originally created for the purposes of measuring suspect effort, appears to be an excellent measure for detecting response bias on neuropsychological testing.

Examination of various WMS-III logical memory scores in the assessment of response bias.

The assessment of response validity during neuropsychological evaluation is an integral part of the testing process. Research has increasingly focused on the use of "embedded" effort measures (derived from standard neuropsychological tasks) because they do not require additional administration time and are less likely to be identified as effort indicators by test takers because of their primary focus as measures of cognitive function. The current study examined the clinical utility of various WMS-III Logical Memory scores in detecting response bias, as well as the Rarely Missed Index, an embedded effort indicator derived from the WMS-III Logical Memory Delayed Recognition subtest. The Rarely Missed Index cut-off only identified 24.1% of 63 non-credible participants (at >/=90% specificity in 125 credible patients), and cut-offs for other Logical Memory variables were in fact found to be more sensitive to non-credible performance. A new indicator, consisting of the weighted combination of the two most sensitive Logical Memory subtest scores (Logical Memory II raw score and Logical Memory Delayed Recognition raw score), was associated with 53% to 60% sensitivity, and thus may be an effective adjunct when utilized in conjunction with other validated effort indicators and collateral information in identifying non-credible performance.

The role of proopiomelanocortin (POMC) in sequentially dependent self-injurious behavior.

Self-injuring behavior (SIB) is a life-threatening behavior exhibited by many species, including humans, and has no known cause and no agreed upon treatment. The role of the stress axis in the maintenance of this mysterious behavior was examined in subjects with life-long SIB. Over a 6-year period, 40 hr of direct observations of behavior and the environment were recorded on palmtop computers while 36 residential subjects (28 target and 8 control subjects) conducted their daily activities. Blood samples were collected in morning and evening for all subjects and within minutes after a self-injuring act in 28 target subjects who exhibited SIB to determine levels of ACTH and B-endorphin (BE). Self-injuring events in the patient group were significantly sequentially dependent (i.e., the only predictor of a self-injuring act was an antecedent self-injuring act). Higher morning levels of BE relative to ACTH predicted [r(df=27) = .57, p < .001] the sequentially dependent pattern of SIB. This effect was validated in a subgroup retested several months later [r(df=22) = .60, p < .001]. A subgroup of seven subjects exhibiting sequentially dependent patterns were administered an opiate blocker (naltrexone) in a double-blind, crossover design with an additional 14 hr/week of observation for 7 weeks. Naltrexone challenge interrupted the sequential pattern (improved behavior) in subjects with elevated BE immediately following SIB (r = .85, p < .01). The pattern of results supported the conclusion that the stress axis played a significant role in the maintenance of complex episodes of self-injury.

Age-associated predictors of medication adherence in HIV-positive adults: health beliefs, self-efficacy, and neurocognitive status.

OBJECTIVE: Although most agree that poor adherence to antiretrovirals is a common problem, relatively few factors have been shown to consistently predict treatment failure. In this study, a theoretical framework encompassing demographic characteristics, health beliefs/attitudes, treatment self-efficacy, and neurocognitive status was examined in relationship to highly active antiretroviral therapy adherence. DESIGN: Prospective, cross-sectional observational design. MAIN OUTCOME MEASURES: Neuropsychological test performance, health beliefs and attitudes, and medication adherence tracked over a 1-month period using electronic monitoring technology (Medication Event Monitoring System caps). RESULTS: The rate of poor adherence was twice as high among younger participants than with older participants (68% and 33%, respectively). Results of binary logistic regression revealed that low self-efficacy and lack of perceived treatment utility predicted poor adherence among younger individuals, whereas decreased levels of neurocognitive functioning remained the sole predictor of poor adherence among older participants. CONCLUSION: These data support components of the health beliefs model in predicting medication adherence among younger HIV-positive individuals. However, risk of adherence failure in those ages 50 years and older appears most related to neurocognitive status.

Drug use and medication adherence among HIV-1 infected individuals.

This longitudinal study examined the impact of drug use and abuse on medication adherence among 150 HIV-infected individuals, 102 who tested urinalysis positive for recent illicit drug use. Medication adherence was tracked over a 6-month period using an electronic monitoring device (MEMS caps). Over the 6-month study drug-positive participants demonstrated significantly worse medication adherence than did drug-negative participants (63 vs. 79%, respectively). Logistic regression revealed that drug use was associated with over a fourfold greater risk of adherence failure. Stimulant users were at greatest risk for poor adherence. Based upon within-participants analyses comparing 3-day adherence rates when actively using versus not using drugs, this appears to be more a function of state rather than trait. These data suggest that it is the acute effects of intoxication, rather than stable features that may be characteristic of the drug-using populace, which leads to difficulties with medication adherence.