Benjamin S. McKenna

The Effects of One Night of Sleep Deprivation on Known-Risk and Ambiguous-Risk Decisions

Sleep deprivation has been shown to alter decision‐making abilities. The majority of research has utilized fairly complex tasks with the goal of emulating ’real‐life’ scenarios. Here, we use a Lottery Choice Task (LCT) which assesses risk and ambiguity preference for both decisions involving potential gains and those involving potential losses. We hypothesized that one night of sleep deprivation would make subjects more risk seeking in both gains and losses. Both a control group and an experimental group took the LCT on two consecutive days, with an intervening night of either sleep or sleep deprivation. The control group demonstrated that there was no effect of repeated administration of the LCT. For the experimental group, results showed significant interactions of night (normal sleep versus total sleep deprivation, TSD) by frame (gains versus losses), which demonstrate that following as little as 23 h of TSD, the prototypical response to decisions involving risk is altered. Following TSD, subjects were willing to take more risk than they ordinarily would when they were considering a gain, but less risk than they ordinarily would when they were considering a loss. For ambiguity preferences, there seems to be no direct effect of TSD. These findings suggest that, overall, risk preference is moderated by TSD, but whether an individual is willing to take more or less risk than when well‐rested depends on whether the decision is framed in terms of gains or losses.

Eye Tracking Reveals Abnormal Visual Preference for Geometric Images as an Early Biomarker of an Autism Spectrum Disorder Subtype Associated With Increased Symptom Severity

BACKGROUND Clinically and biologically, autism spectrum disorder (ASD) is heterogeneous. Unusual patterns of visual preference as indexed by eye tracking are hallmarks; however, whether they can be used to define an early biomarker of ASD as a whole or leveraged to define a subtype is unclear. To begin to examine this issue, large cohorts are required. METHODS A sample of 334 toddlers from six distinct groups (115 toddlers with ASD, 20 toddlers with ASD features, 57 toddlers with developmental delay, 53 toddlers with other conditions [e.g., premature birth, prenatal drug exposure], 64 toddlers with typical development, and 25 unaffected toddlers with siblings with ASD) was studied. Toddlers watched a movie containing geometric and social images. Fixation duration and number of saccades within each area of interest and validation statistics for this independent sample were computed. Next, to maximize power, data from our previous study (n = 110) were added for a total of 444 subjects. A subset of toddlers repeated the eye-tracking procedure. RESULTS As in the original study, a subset of toddlers with ASD fixated on geometric images >69% of the time. Using this cutoff, sensitivity for ASD was 21%, specificity was 98%, and positive predictive value was 86%. Toddlers with ASD who strongly preferred geometric images had 1) worse cognitive, language, and social skills relative to toddlers with ASD who strongly preferred social images and 2) fewer saccades when viewing geometric images. Unaffected siblings of ASD probands did not show evidence of heightened preference for geometric images. Test-retest reliability was good. Examination of age effects suggested that this test may not be appropriate with children >4 years old. CONCLUSIONS Enhanced visual preference for geometric repetition may be an early developmental biomarker of an ASD subtype with more severe symptoms.

Overlapping prefrontal systems involved in cognitive and emotional processing in euthymic bipolar disorder and following sleep deprivation: a review of functional neuroimaging studies.

Prefrontal cortex (PFC) mediated cognitive and emotional processing deficits in bipolar disorder lead to functional limitations even during periods of mood stability. Alterations of sleep and circadian functioning are well-documented in bipolar disorder, but there is little research directly examining the mechanistic role of sleep and/or circadian rhythms in the observed cognitive and emotional processing deficits. We systematically review the cognitive and emotional processing deficits reliant upon PFC functioning of euthymic patients with bipolar disorder and in healthy individuals deprived of sleep. The evidence from two parallel lines of investigation suggests that sleep and circadian rhythms may be involved in the cognitive and emotional processing deficits seen in bipolar disorder through overlapping neurobiological systems. We discuss current models of bipolar highlighting the PFC-limbic connections and discuss inclusion of sleep-related mechanisms. Sleep and circadian dysfunction is a core feature of bipolar disorder and models of neurobiological abnormalities should incorporate chronobiological measures. Further research into the role of sleep and circadian rhythms in cognition and emotional processing in bipolar disorder is warranted.

Associations between circadian activity rhythms and functional brain abnormalities among euthymic bipolar patients: a preliminary study.

BACKGROUND Working memory and underlying functional brain deficits have been observed in euthymic bipolar disorder (BD) patients, though there is heterogeneity in the degree of deficits. Sleep/circadian rhythm abnormalities are thought to be a core component of BD and may explain some of the heterogeneity in functional abnormalities. This preliminary study examined associations between sleep/circadian rhythm abnormalities and functional magnetic resonance imaging (fMRI) brain response on a working memory task among BD patients. METHODS Fourteen euthymic medicated BD patients wore an actigraph for 7 days before undergoing fMRI with a working memory task. Two matched healthy comparison (HC) groups were used (14 in each sample). One group completed the actigraphy portion and the other completed the fMRI portion of the study. Circadian activity rhythm and sleep variables were calculated and compared between BD and HC participants. Variables that significantly differed were used to examine the association between activity rhythms/sleep abnormalities and fMRI working memory brain response in anatomically defined regions. RESULTS Sleep efficiency and the rhythm robustness, mesor, and amplitude-to-width ratio were significantly abnormal in BD patients. Individual variability in all the sleep/circadian variables was significantly associated with the degree of abnormality of brain response in the dorsolateral prefrontal cortex and supramarginal gyri. LIMITATIONS Small sample size and multiple comparison groups limit the interpretability of these findings. CONCLUSIONS BD patients have abnormal activity rhythms and sleep efficiency, which are associated with abnormal working memory brain response. These preliminary findings support the notion that the sleep/circadian system is important in the functional brain deficits among BD patients.

Neural Predictors of Initiating Alcohol Use During Adolescence

OBJECTIVE Underage drinking is widely recognized as a leading public health and social problem for adolescents in the United States. Being able to identify at-risk adolescents before they initiate heavy alcohol use could have important clinical and public health implications; however, few investigations have explored individual-level precursors of adolescent substance use. This prospective investigation used machine learning with demographic, neurocognitive, and neuroimaging data in substance-naive adolescents to identify predictors of alcohol use initiation by age 18. METHOD Participants (N=137) were healthy substance-naive adolescents (ages 12-14) who underwent neuropsychological testing and structural and functional magnetic resonance imaging (sMRI and fMRI), and then were followed annually. By age 18, 70 youths (51%) initiated moderate to heavy alcohol use, and 67 remained nonusers. Random forest classification models identified the most important predictors of alcohol use from a large set of demographic, neuropsychological, sMRI, and fMRI variables. RESULTS Random forest models identified 34 predictors contributing to alcohol use by age 18, including several demographic and behavioral factors (being male, higher socioeconomic status, early dating, more externalizing behaviors, positive alcohol expectancies), worse executive functioning, and thinner cortices and less brain activation in diffusely distributed regions of the brain. CONCLUSIONS Incorporating a mix of demographic, behavioral, neuropsychological, and neuroimaging data may be the best strategy for identifying youths at risk for initiating alcohol use during adolescence. The identified risk factors will be useful for alcohol prevention efforts and in research to address brain mechanisms that may contribute to early drinking.

Bridging the bench to bedside gap: validation of a reverse-translated rodent continuous performance test using functional magnetic resonance imaging.

Vigilance, which requires attending to relevant while ignoring irrelevant stimuli, is a cognitive domain impacted by schizophrenia and bipolar disorder. Various continuous performance tests (CPT) have been used to examine neural correlates of vigilance within people with and without severe mental illness, though there are limited cross-species paradigms available. The 5-choice CPT (5C-CPT) was designed for use in rodents as a cross-species translational paradigm. Here, we evaluate construct validity of a reverse-translated human analog of the 5C-CPT in assessing the neural correlates of vigilance. Functional magnetic resonance imaging during the 5C-CPT was used to examine activation of healthy individuals during target and non-target trials separately. We found activation in brain regions implicated in sustained attention processes including premotor cortex, inferior parietal lobe, basal ganglia, and thalamus during target trials. For non-target trials, we found expected activation in inferior frontal cortex, premotor cortex, presupplementary motor area, and inferior parietal lobe. Results support the construct validity of the 5C-CPT in measuring attentional and inhibitory systems within a single task paradigm enabling the assessment of vigilance across species. This task can be used for powerful parallel human and animal investigations of the biological basis of vigilance deficits in populations with severe mental illness.

Abnormalities of brain response during encoding into verbal working memory among euthymic patients with bipolar disorder

Individuals with bipolar disorder (BD) have trait‐like deficits in attention and working memory (WM). A fundamental dissociation for most verbal WM theories involves the separation of sensory‐perceptual encoding, reliant upon attention, from the maintenance of this information in WM proper. The present study examined if patients with BD demonstrate differential neural changes in encoding and maintenance WM processes that underlie cognitive impairment.

Fusing Functional MRI and Diffusion Tensor Imaging Measures of Brain Function and Structure to Predict Working Memory and Processing Speed Performance among Inter-episode Bipolar Patients.

Evidence for abnormal brain function as measured with diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) and cognitive dysfunction have been observed in inter-episode bipolar disorder (BD) patients. We aimed to create a joint statistical model of white matter integrity and functional response measures in explaining differences in working memory and processing speed among BD patients. Medicated inter-episode BD (n=26; age=45.2±10.1 years) and healthy comparison (HC; n=36; age=46.3±11.5 years) participants completed 51-direction DTI and fMRI while performing a working memory task. Participants also completed a processing speed test. Tract-based spatial statistics identified common white matter tracts where fractional anisotropy was calculated from atlas-defined regions of interest. Brain responses within regions of interest activation clusters were also calculated. Least angle regression was used to fuse fMRI and DTI data to select the best joint neuroimaging predictors of cognitive performance for each group. While there was overlap between groups in which regions were most related to cognitive performance, some relationships differed between groups. For working memory accuracy, BD-specific predictors included bilateral dorsolateral prefrontal cortex from fMRI, splenium of the corpus callosum, left uncinate fasciculus, and bilateral superior longitudinal fasciculi from DTI. For processing speed, the genu and splenium of the corpus callosum and right superior longitudinal fasciculus from DTI were significant predictors of cognitive performance selectively for BD patients. BD patients demonstrated unique brain-cognition relationships compared to HC. These findings are a first step in discovering how interactions of structural and functional brain abnormalities contribute to cognitive impairments in BD.

Linking mathematical modeling with human neuroimaging to segregate verbal working memory maintenance processes from stimulus encoding.

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.

BOLD response to working memory not related to cortical thickness during early adolescence.

BACKGROUND Significant cortical thinning and neural resource allocation changes emerge during adolescence; however, little is known of how morphometric changes influence neural response to cognitive demands. This study used a novel multimodal imaging registration technique to examine the relationship between brain structure and function during adolescence. METHODS 156 healthy 12-14 year-olds (44% female) participants underwent structural and functional magnetic resonance imaging. Cortical surface reconstruction was performed via FreeSurfer, and neural activation was measured from a blood oxygen level dependent (BOLD) contrast during visual working memory (VWM) via AFNI. AFNI Surface Mapper aligned segmented volumetric and functional datasets to a common template space. Hierarchical linear regressions determined the effect of cortical thickness on VWM BOLD contrast in brain regions that activated during the VWM task, controlling for age, pubertal development, gender, IQ, and intracranial volume. RESULTS Power analyses suggest this study was able to detect small effect sizes. However, in no region was cortical thickness related to BOLD activation (ps>.01; R(2)Δ<.02). Gender did not moderate effects. CONCLUSIONS Cortical thickness, although variable across individuals, was not related to BOLD response, suggesting that structural and functional maturation do not have the same developmental trajectory during early adolescence. These findings are important, as imaging studies that report group differences in regards to cortical thickness should not necessarily assume co-occurring behavioral or functional changes. The methodology used in this study could be of interest to other developmental neuroimaging researchers using multimodal imaging to understand adolescent brain development.