Ventromedial Prefrontal-Anterior Cingulate Hyperconnectivity and Resilience to Apathy in Traumatic Brain Injury.

Apathy is a common and impairing sequela of traumatic brain injury (TBI). Yet, little is known about the neural mechanisms determining in which patients apathy does or does not develop post-TBI. We aimed to elucidate the impact of TBI on motivational neural circuits and how this shapes apathy over the course of TBI recovery. Resting-state functional magnetic resonance imaging data were collected in patients with subacute mild TBI (n = 44), chronic mild-to-moderate TBI (n = 26), and nonbrain-injured control participants (CTRL; n = 28). We measured ventromedial prefrontal cortex (vmPFC) functional connectivity (FC) as a function of apathy, using an a priori vmPFC seed adopted from a motivated decision-making study in an independent TBI study cohort. Patients reported apathy using a well-validated tool for assaying apathy in TBI. The vmPFC-to-wholebrain FC was contrasted between groups, and we fit regression models with apathy predicting vmPFC FC. Subacute and chronic TBI caused increased apathy relative to CTRL, replicating previous work suggesting that apathy has an enduring impact in TBI. The vmPFC was functionally connected to the canonical default network, and this architecture did not differ between subacute TBI, chronic TBI, and CTRL groups. Critically, in TBI, increased apathy scores predicted decreased vmPFC-dorsal anterior cingulate cortex (dACC) FC. Last, we subdivided the TBI group based on patients above versus below the threshold for "clinically significant apathy," finding that TBI patients with clinically significant apathy demonstrated comparable vmPFC-dACC FC to CTRLs, whereas TBI patients with subthreshold apathy scores demonstrated vmPFC-dACC hyperconnectivity relative to both CTRLs and patients with clinically significant apathy. Post-TBI vmPFC-dACC hyperconnectivity may represent an adaptive compensatory response, helping to maintain motivation and enabling resilience to the development of apathy after neurotrauma. Given the role of vmPFC-dACC circuits in value-based decision making, rehabilitation strategies designed to improve this ability may help to reduce apathy and improve functional outcomes in TBI.

Joint analysis of frontal theta synchrony and white matter following mild traumatic brain injury.

Some of the most disabling aspects of mild traumatic brain injury (mTBI) include lingering deficits in executive functioning. It is known that mTBI can damage white matter tracts, but it remains unknown how this structural brain damage translates into cognitive deficits. This experiment utilized theta band phase synchrony to identify the dysfunctional neural operations that contribute to cognitive problems following mTBI. Sub-acute stage (< 2 weeks) mTBI patients (N = 52) and healthy matched controls (N = 32) completed a control-demanding task with concurrent EEG. Structural MRI was also collected. While there were no performance-specific behavioral differences between groups in the dot probe expectancy task, the degree of theta band phase synchrony immediately following injury predicted the degree of symptom recovery two months later. Although there were no differences in fractional anisotropy (FA) between groups, joint independent components analysis revealed that a smaller network of lower FA-valued voxels contributed to a diminished frontal theta phase synchrony network in the mTBI group. This finding suggests that frontal theta band markers of cognitive control are sensitive to sub-threshold structural aberrations following mTBI.

Executive function predictors of delayed memory deficits after mild traumatic brain injury.

Delayed memory deficits are common for patients with mild traumatic brain injury (mTBI), according to a recent systematic review of meta-analyses (Karr et al., 2014). However, there has been little work to identify different cognitive processes that may be underpinning these delayed memory deficits for mTBI. Frontal cortex is important for delayed memory, and is implicated in the pathophysiology of mTBI; moreover, frontal lobes are typically considered the locus of executive abilities. To further explore these relationships, we sought to partly explain delayed memory deficits after mTBI by examining behavioral indicators of executive function. Results showed that sub-acute as well as chronic mTBI patients performed worse than controls on the delayed memory trial of the Hopkins Verbal Learning Test-Revised (Brandt & Benedict, 2001), recalling approximately 18% and 15% fewer words, respectively. Furthermore, worse delayed memory performance was associated with less use of the cognitive strategy of semantic clustering, and with lower scores for the executive function composite from a standardized neuropsychological battery (NIH EXAMINER; Kramer et al., 2014). In contrast, serial clustering, a memory organizational strategy thought to be less dependent on executive function, did not show strong relationships to clinical status or delayed memory performance. This exploratory work suggests novel hypotheses to be tested in future, confirmatory studies, including that general executive functions and/or semantic clustering will mediate delayed memory deficits following mTBI.

ERPs predict symptomatic distress and recovery in sub-acute mild traumatic brain injury.

Mild traumatic brain injury (mTBI) can affect high-level executive functioning long after somatic symptoms resolve. We tested if simple EEG responses within an oddball paradigm could capture variance relevant to this clinical problem. The P3a and P3b components reflect bottom-up and top-down processes driving engagement with exogenous stimuli. Since these features are related to primitive decision abilities, abnormal amplitudes following mTBI may account for problems in the ability to exert executive control. Sub-acute (<2 weeks) mTBI participants (N = 38) and healthy controls (N = 24) were assessed at an initial session as well as a two-month follow-up (sessions 1 and 2). We contrasted the initial assessment to a comparison group of participants with chronic symptomatology following brain injury (N = 23). There were no group differences in P3a or P3b amplitudes. Yet in the sub-acute mTBI group, higher symptomatology on the Frontal Systems Behavior scale (FrSBe), a questionnaire validated as measuring symptomatic distress related to frontal lobe injury, correlated with lower P3a in session 1. This relationship was replicated in session 2. These findings were distinct from chronic TBI participants, who instead expressed a relationship between increased FrSBe symptoms and a lower P3b component. In the sub-acute group, P3b amplitudes in the first session correlated with the degree of symptom change between sessions 1 and 2, above and beyond demographic predictors. Controls did not show any relationship between FrSBe symptoms and P3a or P3b. These findings identify symptom-specific alterations in neural systems that vary along the time course of post-concussive symptomatology.

Association Between Executive Functioning and Functional Impairment Among Pediatric Cancer Survivors and Controls.

OBJECTIVE: To examine the impact of cancer treatment upon neurocognitive and functional impairment; and to explore the relationship between these constructs in pediatric cancer survivors compared to controls. METHOD: A cross-sectional cohort of survivors (n = 26) and controls (n = 53) was included. Survivors were off treatment an average of 6.35 years (SD = 5.38; range 1-15 years) and demonstrated an average "medium" Central Nervous System (CNS) treatment intensity score. Participants completed measures of neurocognitive functions including intellectual assessment (RIST) and executive functions (NIH Examiner), while parents reported on children's functional impairment (BIS). RESULTS: Survivors were similar to controls in neurocognitive ability, including intellectual and executive functions, and functional impairment. Regardless of group membership, NIH Examiner performance and functional impairment increased with age. Increased impairment was associated with different neurocognitive variables for survivors versus controls. CONCLUSIONS: Research regarding functional impairment of cancer survivors and the association between neurocognitive deficits and functional impairment has been limited. Our results demonstrate that, while low treatment intensity may confer relative sparing of neurocognitive and executive functioning among survivors, functional impairment continues to be a potential risk. In conclusion, pediatric cancer survivors should be screened for functional difficulties, particularly in the areas of interpersonal relations and self-care.

Impact of Erythropoiesis-Stimulating Agents on Behavioral Measures in Children Born Preterm.

OBJECTIVE: To evaluate the impact of erythropoiesis-stimulating agents (ESAs) administered during initial hospitalization and family demographic factors on behavior at 3.5-4 years of age. STUDY DESIGN: Children were enrolled who had previously participated in a randomized study of ESAs (n = 35) or placebo (n = 14) in infants born preterm with birth weights of 500-1250 g. A term healthy control group (n = 22) also was recruited. Behavior was evaluated by parent report with the Behavioral Assessment System of Children-2. Principal component analyses identified 2 demographic factors, a Socioeconomic Composite (SEC) and a Family Stress Composite. A multivariate general linear model evaluated the impact of study group and sex on the 4 composite scales of the Behavioral Assessment System of Children-2. Demographic factors were treated as covariates and interactions with study group (ESA, placebo, and term) were examined. RESULTS: The ESA group had significantly better scores than the placebo group on behavioral symptoms (P = .04) and externalizing scales (P = .04). An interaction was observed between study group and SEC (P = .001). A beneficial effect of ESAs was maximal in the children with lower SEC scores. CONCLUSIONS: The beneficial effects of ESAs on childhood behavior were maximal in children with lower SEC scores. ESAs seemed to ameliorate the adverse impact of lower SEC on behavioral domains seen in the placebo group. This effect was independent of the beneficial effect of ESAs on global cognition we reported previously. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01207778 and NCT00334737.

Maternal touch and infant affect in the Still Face Paradigm: A cross-cultural examination.

Touch between mother and infant plays an important role in development starting from birth. Cross-cultural differences surrounding rearing practices have an influence on parent-infant interaction, including types of touch used and the development of emotional regulation. This study was designed to investigate maternal touch and infant emotional regulation in infant-mother dyads from Ecuador (n=25) and Hispanic dyads from the United States (US) (n=26). Mothers and their 4-month-old full-term infants participated in the Still Face Paradigm. Second-by-second coding of maternal touch and infant affect was completed. Overall the analyses showed that Ecuadorian mothers used more nurturing and accompaniment touch and less attention seeking touch than US Hispanic mothers during the pre-stressor (baseline) episode. Lagged multilevel models were used to investigate the effect of the different types of touch on infant emotional regulation in the groups for the episodes. The data suggest that playful touch had a significant increase in infant affect, whereas accompaniment and attention-seeking touch had a significant decrease in infant affect. Overall, this study provides support for the role of touch in mother-infant synchronicity in relation to infant's emotional regulation. Identifying touch that is more calming is important to foster emotional regulation in infancy, which can have important implications for development.

"What's wrong with grandma?": depictions of Alzheimer's disease in children's storybooks.

Alzheimer's disease (AD) affects the entire family system, including young children. Yet there are few resources to help children understand AD. Storybooks are used to educate children about other diseases and may be useful in AD as well. In this study, we examined the depiction of AD in 33 English-language children's storybooks written specifically about AD. As a group, storybooks present AD as a brain disease, but provide little information about the diagnostic process or treatments. Clinical presentations are diverse among characters with AD, and no single book presents a comprehensive depiction of the cognitive, behavioral, affective, and functional symptoms of the disease. In fact, the prevalence of some symptoms in this "population" of storybook characters diverges substantially from epidemiological reports. Books designed to familiarize children about AD should be comprehensive and accurate. Current resources, while useful, could be improved to ensure health literacy about AD in young children.