Mary K. Askren

Behavioral and neural correlates of delay of gratification 40 years later

We examined the neural basis of self-regulation in individuals from a cohort of preschoolers who performed the delay-of-gratification task 4 decades ago. Nearly 60 individuals, now in their mid-forties, were tested on “hot” and “cool” versions of a go/nogo task to assess whether delay of gratification in childhood predicts impulse control abilities and sensitivity to alluring cues (happy faces). Individuals who were less able to delay gratification in preschool and consistently showed low self-control abilities in their twenties and thirties performed more poorly than did high delayers when having to suppress a response to a happy face but not to a neutral or fearful face. This finding suggests that sensitivity to environmental hot cues plays a significant role in individuals’ ability to suppress actions toward such stimuli. A subset of these participants (n = 26) underwent functional imaging for the first time to test for biased recruitment of frontostriatal circuitry when required to suppress responses to alluring cues. Whereas the prefrontal cortex differentiated between nogo and go trials to a greater extent in high delayers, the ventral striatum showed exaggerated recruitment in low delayers. Thus, resistance to temptation as measured originally by the delay-of-gratification task is a relatively stable individual difference that predicts reliable biases in frontostriatal circuitries that integrate motivational and control processes.

Contrasting brain patterns of writing-related DTI parameters, fMRI connectivity, and DTI-fMRI connectivity correlations in children with and without dysgraphia or dyslexia.

Based on comprehensive testing and educational history, children in grades 4–9 (on average 12 years) were diagnosed with dysgraphia (persisting handwriting impairment) or dyslexia (persisting word spelling/reading impairment) or as typical writers and readers (controls). The dysgraphia group (n = 14) and dyslexia group (n = 17) were each compared to the control group (n = 9) and to each other in separate analyses. Four brain region seed points (left occipital temporal gyrus, supramarginal gyrus, precuneus, and inferior frontal gyrus) were used in these analyses which were shown in a metaanalysis to be related to written word production on four indicators of white matter integrity and fMRI functional connectivity for four tasks (self-guided mind wandering during resting state, writing letter that follows a visually displayed letter in alphabet, writing missing letter to create a correctly spelled real word, and planning for composing after scanning on topic specified by researcher). For those DTI indicators on which the dysgraphic group or dyslexic group differed from the control group (fractional anisotropy, relative anisotropy, axial diffusivity but not radial diffusivity), correlations were computed between the DTI parameter and fMRI functional connectivity for the two writing tasks (alphabet and spelling) by seed points. Analyses, controlled for multiple comparisons, showed that (a) the control group exhibited more white matter integrity than either the dysgraphic or dyslexic group; (b) the dysgraphic and dyslexic groups showed more functional connectivity than the control group but differed in patterns of functional connectivity for task and seed point; and (c) the dysgraphic and dyslexic groups showed different patterns of significant DTI–fMRI connectivity correlations for specific seed points and written language tasks. Thus, dysgraphia and dyslexia differ in white matter integrity, fMRI functional connectivity, and white matter–gray matter correlations. Of clinical relevance, brain differences were observed in dysgraphia and dyslexia on written language tasks yoked to their defining behavioral impairments in handwriting and/or in word spelling and on the cognitive mind wandering rest condition and composition planning.

Dimensionality of brain networks linked to life-long individual differences in self-control

The ability to delay gratification in childhood has been linked to positive outcomes in adolescence and adulthood. Here we examine a subsample of participants from a seminal longitudinal study of self-control throughout a subject’s lifespan. Self control, first studied in children at age 4, is now reexamined 40 years later, on a task that required control over the contents of working memory. We examine whether patterns of brain activation on this task can reliably distinguish participants with consistently low and high self-control abilities (low vs. high delayers). We find that low delayers recruit significantly higher-dimensional neural networks when performing the task compared to high delayers. High delayers are also more homogeneous as a group in their neural patterns compared to low delayers. From these brain patterns we can predict with 71% accuracy, whether a participant is a high or low delayer. The present results suggest that dimensionality of neural networks is a biological predictor of self-control abilities.

An everyday activity as a treatment for depression: The benefits of expressive writing for people diagnosed with major depressive disorder

BACKGROUND The benefits of expressive writing have been well documented among several populations, but particularly among those who report feelings of dysphoria. It is not known, however, if those diagnosed with Major Depressive Disorder (MDD) would also benefit from expressive writing. METHODS Forty people diagnosed with current MDD by the Structured Clinical Interview for DSM-IV participated in the study. On day 1 of testing, participants completed a series of questionnaires and cognitive tasks. Participants were then randomly assigned to either an expressive writing condition in which they wrote for 20 min over three consecutive days about their deepest thoughts and feelings surrounding an emotional event (n=20), or to a control condition (n=20) in which they wrote about non-emotional daily events each day. On day 5 of testing, participants completed another series of questionnaires and cognitive measures. These measures were repeated again 4 weeks later. RESULTS People diagnosed with MDD in the expressive writing condition showed significant decreases in depression scores (Beck Depression Inventory and Patient Health Questionnaire-9 scores) immediately after the experimental manipulation (Day 5). These benefits persisted at the 4-week follow-up. LIMITATIONS Self-selected sample. CONCLUSIONS This is the first study to demonstrate the efficacy of expressive writing among people formally diagnosed with current MDD. These data suggest that expressive writing may be a useful supplement to existing interventions for depression.

Cerebral perfusion and cortical thickness indicate cortical involvement in mild Parkinson's disease.

Cortical dysfunction in Parkinsons disease (PD) may be caused by disruption to ascending systems or by intrinsic cortical neuropathology. We introduce and conduct a joint analysis of metabolism and atrophy capable of identifying whether metabolic disruption occurs in mild PD without cortical atrophy, to determine the extent and spatial pattern of cortical involvement in mild PD. The design was observational, studying 23 cognitively normal participants with mild PD (mean Hoehn & Yahr stage 2) and 21 healthy controls. Cortical thickness (obtained from analysis of structural magnetic resonance imaging [MRI] with FreeSurfer) and cerebral perfusion measures (obtained from arterial spin labeling [ASL]) analyzed independently and then together in a joint multiple factorial analysis to identify spatial patterns of perfusion and cortical thickness. We identify a pattern of changes in perfusion and cortical thickness characterized by symmetric parietal cortical thinning and reduced precuneus perfusion, with relative preservation of thickness and perfusion in the anterior cingulate cortex (ACC), right prefrontal gyrus, and medial frontal gyrus. The expression of this pattern is correlated with motor system symptoms and speed of processing. A spatial pattern of joint parietal cortical thinning and disproportionate reduction in perfusion occurs in our nondemented PD sample. We found no PD‐related components of reduced perfusion without cortical thinning. This suggests that PD affects the cortex itself, even when symptoms are relatively mild.

Using Make for Reproducible and Parallel Neuroimaging Workflow and Quality-Assurance

The contribution of this paper is to describe how we can program neuroimaging workflow using Make, a software development tool designed for describing how to build executables from source files. A makefile (or a file of instructions for Make) consists of a set of rules that create or update target files if they have not been modified since their dependencies were last modified. These rules are processed to create a directed acyclic dependency graph that allows multiple entry points from which to execute the workflow. We show that using Make we can achieve many of the features of more sophisticated neuroimaging pipeline systems, including reproducibility, parallelization, fault tolerance, and quality assurance reports. We suggest that Make permits a large step toward these features with only a modest increase in programming demands over shell scripts. This approach reduces the technical skill and time required to write, debug, and maintain neuroimaging workflows in a dynamic environment, where pipelines are often modified to accommodate new best practices or to study the effect of alternative preprocessing steps, and where the underlying packages change frequently. This paper has a comprehensive accompanying manual with lab practicals and examples (see Supplemental Materials) and all data, scripts, and makefiles necessary to run the practicals and examples are available in the “makepipelines” project at NITRC.

The suppression of scale-free fMRI brain dynamics across three different sources of effort: aging, task novelty and task difficulty

There is growing evidence that fluctuations in brain activity may exhibit scale-free (“fractal”) dynamics. Scale-free signals follow a spectral-power curve of the form P(f ) ∝ f−β, where spectral power decreases in a power-law fashion with increasing frequency. In this study, we demonstrated that fractal scaling of BOLD fMRI signal is consistently suppressed for different sources of cognitive effort. Decreases in the Hurst exponent (H), which quantifies scale-free signal, was related to three different sources of cognitive effort/task engagement: 1) task difficulty, 2) task novelty, and 3) aging effects. These results were consistently observed across multiple datasets and task paradigms. We also demonstrated that estimates of H are robust across a range of time-window sizes. H was also compared to alternative metrics of BOLD variability (SDBOLD) and global connectivity (Gconn), with effort-related decreases in H producing similar decreases in SDBOLD and Gconn. These results indicate a potential global brain phenomenon that unites research from different fields and indicates that fractal scaling may be a highly sensitive metric for indexing cognitive effort/task engagement.

The functional connectivity landscape of the human brain.

Functional brain networks emerge and dissipate over a primarily static anatomical foundation. The dynamic basis of these networks is inter-regional communication involving local and distal regions. It is assumed that inter-regional distances play a pivotal role in modulating network dynamics. Using three different neuroimaging modalities, 6 datasets were evaluated to determine whether experimental manipulations asymmetrically affect functional relationships based on the distance between brain regions in human participants. Contrary to previous assumptions, here we show that short- and long-range connections are equally likely to strengthen or weaken in response to task demands. Additionally, connections between homotopic areas are the most stable and less likely to change compared to any other type of connection. Our results point to a functional connectivity landscape characterized by fluid transitions between local specialization and global integration. This ability to mediate functional properties irrespective of spatial distance may engender a diverse repertoire of cognitive processes when faced with a dynamic environment.

A Low-Cost, Computer-Interfaced Drawing Pad for fMRI Studies of Dysgraphia and Dyslexia

We have developed a pen and writing tablet for use by subjects during fMRI scanning. The pen consists of two jacketed, multi-mode optical fibers routed to the tip of a hollowed-out ball-point pen. The pen has been further modified by addition of a plastic plate to maintain a perpendicular pen-tablet orientation. The tablet is simply a non-metallic frame holding a paper print of continuously varying color gradients. The optical fibers are routed out of the MRI bore to a light-tight box in an adjacent control room. Within the box, light from a high intensity LED is coupled into one of the fibers, while the other fiber abuts a color sensor. Light from the LED exits the pen tip, illuminating a small spot on the tablet, and the resulting reflected light is routed to the color sensor. Given a lookup table of position for each color on the tablet, the coordinates of the pen on the tablet may be displayed and digitized in real-time. While simple and inexpensive, the system achieves sufficient resolution to grade writing tasks testing dysgraphic and dyslexic phenomena.

Hippocampal contribution to context encoding across development is disrupted following early-life adversity

Context can drastically influence responses to environmental stimuli. For example, a gunshot should provoke a different response at a public park than a shooting range. Little is known about how contextual processing and neural correlates change across human development or about individual differences related to early environmental experiences. Children (N = 60; 8–19 years, 24 exposed to interpersonal violence) completed a context encoding task during fMRI scanning using a delayed match-to-sample design with neutral, happy, and angry facial cues embedded in realistic background scenes. Outside the scanner, participants completed a memory test for context-face pairings. Context memory and neural correlates of context encoding did not vary with age. Larger hippocampal volume was associated with better context memory. Posterior hippocampus was recruited during context encoding, and greater activation in this region predicted better memory for contexts paired with angry faces. Children exposed to violence had poor memory of contexts paired with angry faces, reduced hippocampal volume, and atypical neural recruitment on encoding trials with angry faces, including reduced hippocampal activation and greater functional connectivity between hippocampus and ventrolateral prefrontal cortex (vlPFC). Greater hippocampus-vlPFC connectivity was associated with worse memory for contexts paired with angry faces. Posterior hippocampus appears to support context encoding, a process that does not exhibit age-related variation from middle childhood to late adolescence. Exposure to dangerous environments in childhood is associated with poor context encoding in the presence of threat, likely due to greater vlPFC-dependent attentional narrowing on threat cues at the expense of hippocampus-dependent processing of the broader context. SIGNIFICANCE STATEMENT The ability to use context to guide reactions to environmental stimuli promotes flexible behavior. Remarkably little research has examined how contextual processing changes across development or about influences of the early environment. We provide evidence for posterior hippocampus involvement in context encoding in youth and lack of age-related variation from middle childhood to late adolescence. Children exposed to interpersonal violence exhibited poor memory of contexts paired with angry faces and atypical neural recruitment during context encoding in the presence of threatening facial cues. Heightened attention to threat following violence exposure may come at the expense of encoding contextual information, which may ultimately contribute to pathological fear expressed in safe contexts.