Gregory C. Burgess

Function in the human connectome: task-fMRI and individual differences in behavior.

The primary goal of the Human Connectome Project (HCP) is to delineate the typical patterns of structural and functional connectivity in the healthy adult human brain. However, we know that there are important individual differences in such patterns of connectivity, with evidence that this variability is associated with alterations in important cognitive and behavioral variables that affect real world function. The HCP data will be a critical stepping-off point for future studies that will examine how variation in human structural and functional connectivity play a role in adult and pediatric neurological and psychiatric disorders that account for a huge amount of public health resources. Thus, the HCP is collecting behavioral measures of a range of motor, sensory, cognitive and emotional processes that will delineate a core set of functions relevant to understanding the relationship between brain connectivity and human behavior. In addition, the HCP is using task-fMRI (tfMRI) to help delineate the relationships between individual differences in the neurobiological substrates of mental processing and both functional and structural connectivity, as well as to help characterize and validate the connectivity analyses to be conducted on the structural and functional connectivity data. This paper describes the logic and rationale behind the development of the behavioral, individual difference, and tfMRI batteries and provides preliminary data on the patterns of activation associated with each of the fMRI tasks, at both group and individual levels.

Neural Mechanisms of Interference Control Underlie the Relationship between Fluid Intelligence and Working Memory Span.

Fluid intelligence (gF) and working memory (WM) span predict success in demanding cognitive situations. Recent studies show that much of the variance in gF and WM span is shared, suggesting common neural mechanisms. This study provides a direct investigation of the degree to which shared variance in gF and WM span can be explained by neural mechanisms of interference control. The authors measured performance and functional magnetic resonance imaging activity in 102 participants during the n-back WM task, focusing on the selective activation effects associated with high-interference lure trials. Brain activity on these trials was correlated with gF, WM span, and task performance in core brain regions linked to WM and executive control, including bilateral dorsolateral prefrontal cortex (middle frontal gyrus; BA9) and parietal cortex (inferior parietal cortex; BA 40/7). Interference-related performance and interference-related activity accounted for a significant proportion of the shared variance in gF and WM span. Path analyses indicate that interference control activity may affect gF through a common set of processes that also influence WM span. These results suggest that individual differences in interference-control mechanisms are important for understanding the relationship between gF and WM span.

Anxiety and cognitive efficiency: differential modulation of transient and sustained neural activity during a working memory task.

According to the processing-efficiency hypothesis (Eysenck, Derakshan, Santos, & Calvo, 2007), anxious individuals are thought to require greater activation of brain systems supporting cognitive control (e.g., dorsolateral prefrontal cortex; DLPFC) in order to maintain equivalent performance to nonanxious subjects. A recent theory of cognitive control (Braver, Gray, & Burgess, 2007) has proposed that reduced cognitive efficiency might occur as a result of changes in the temporal dynamics of DLPFC recruitment. In this study, we used a mixed blocked/ event-related fMRI design to track transient and sustained activity in DLPFC while high- and low-anxious participants performed a working memory task. The task was performed after the participants viewed videos designed to induce neutral or anxiety-related moods. After the neutral video, the high-anxious participants had reduced sustained but increased transient activation in working memory areas, in comparison with low-anxious participants. The high-anxious group also showed extensive reductions in sustained activation of “default-network” areas (possible deactivation). After the negative video, the low-anxiety group shifted their activation dynamics in cognitive control regions to resemble those of the high-anxious group. These results suggest that reduced cognitive control in anxiety might be due to a transient, rather than sustained, pattern of working memory recruitment. Supplementary information for this study may be found at www.psychonomic.org/archive.

Affective personality differences in neural processing efficiency confirmed using fMRI

To test for a relation between individual differences in personality and neural-processing efficiency, we used functional magnetic resonance imaging (fMRI) to assess brain activity within regions associated with cognitive control during a demanding working memory task. Fifty-three participants completed both the self-report behavioral inhibition sensitivity (BIS) and behavioral approach sensitivity (BAS) personality scales and a standard measure of fluid intelligence (Raven’s Advanced Progressive Matrices). They were then scanned as they performed a three-back working memory task. A mixed blocked/ event-related fMRI design enabled us to identify both sustained and transient neural activity. Higher BAS was negatively related to event-related activity in the dorsal anterior cingulate, the lateral prefrontal cortex, and parietal areas in regions of interest identified in previous work. These relationships were not explained by differences in either behavioral performance or fluid intelligence, consistent with greater neural efficiency. The results reveal the high specificity of the relationships among personality, cognition, and brain activity. The data confirm that affective dimensions of personality are independent of intelligence, yet also suggest that they might be interrelated in subtle ways, because they modulate activity in overlapping brain regions that appear to be critical for task performance.

MSM: a new flexible framework for Multimodal Surface Matching.

Surface-based cortical registration methods that are driven by geometrical features, such as folding, provide sub-optimal alignment of many functional areas due to variable correlation between cortical folding patterns and function. This has led to the proposal of new registration methods using features derived from functional and diffusion imaging. However, as yet there is no consensus over the best set of features for optimal alignment of brain function. In this paper we demonstrate the utility of a new Multimodal Surface Matching (MSM) algorithm capable of driving alignment using a wide variety of descriptors of brain architecture, function and connectivity. The versatility of the framework originates from adapting the discrete Markov Random Field (MRF) registration method to surface alignment. This has the benefit of being very flexible in the choice of a similarity measure and relatively insensitive to local minima. The method offers significant flexibility in the choice of feature set, and we demonstrate the advantages of this by performing registrations using univariate descriptors of surface curvature and myelination, multivariate feature sets derived from resting fMRI, and multimodal descriptors of surface curvature and myelination. We compare the results with two state of the art surface registration methods that use geometric features: FreeSurfer and Spherical Demons. In the future, the MSM technique will allow explorations into the best combinations of features and alignment strategies for inter-subject alignment of cortical functional areas for a wide range of neuroimaging data sets.

Human Connectome Project informatics: quality control, database services, and data visualization.

The Human Connectome Project (HCP) has developed protocols, standard operating and quality control procedures, and a suite of informatics tools to enable high throughput data collection, data sharing, automated data processing and analysis, and data mining and visualization. Quality control procedures include methods to maintain data collection consistency over time, to measure head motion, and to establish quantitative modality-specific overall quality assessments. Database services developed as customizations of the XNAT imaging informatics platform support both internal daily operations and open access data sharing. The Connectome Workbench visualization environment enables user interaction with HCP data and is increasingly integrated with the HCPs database services. Here we describe the current state of these procedures and tools and their application in the ongoing HCP study.

Attentional Control Activation Relates to Working Memory in Attention-Deficit/Hyperactivity Disorder

BACKGROUND Attentional control difficulties in individuals with attention-deficit/hyperactivity disorder (ADHD) might reflect poor working memory (WM) ability, especially because WM ability and attentional control rely on similar brain regions. The current study examined whether WM ability might explain group differences in brain activation between adults with ADHD and normal control subjects during attentional demand. METHODS Participants were 20 adults with ADHD combined subtype with no comorbid psychiatric or learning disorders and 23 control subjects similar in age, IQ, and gender. The WM measures were obtained from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-Revised. Brain activation was assessed with functional magnetic resonance imaging (fMRI) while performing a Color-Word Stroop task. RESULTS Group differences in WM ability explained a portion of the activation in left dorsolateral prefrontal cortex (DLPFC), which has been related to the creation and maintenance of an attentional set for task-relevant information. In addition, greater WM ability predicted increased activation of brain regions related to stimulus-driven attention and response selection processes in the ADHD group but not in the control group. CONCLUSIONS The inability to maintain an appropriate task set in young adults with combined type ADHD, associated with decreased activity in left DLPFC, might in part be due to poor WM ability. Furthermore, in individuals with ADHD, higher WM ability might relate to increased recruitment of stimulus-driven attention and response selection processes, perhaps as a compensatory strategy.

Cognitive control in adolescence: neural underpinnings and relation to self-report behaviors.

Background Adolescence is commonly characterized by impulsivity, poor decision-making, and lack of foresight. However, the developmental neural underpinnings of these characteristics are not well established. Methodology/Principal Findings To test the hypothesis that these adolescent behaviors are linked to under-developed proactive control mechanisms, the present study employed a hybrid block/event-related functional Magnetic Resonance Imaging (fMRI) Stroop paradigm combined with self-report questionnaires in a large sample of adolescents and adults, ranging in age from 14 to 25. Compared to adults, adolescents under-activated a set of brain regions implicated in proactive top-down control across task blocks comprised of difficult and easy trials. Moreover, the magnitude of lateral prefrontal activity in adolescents predicted self-report measures of impulse control, foresight, and resistance to peer pressure. Consistent with reactive compensatory mechanisms to reduced proactive control, older adolescents exhibited elevated transient activity in regions implicated in response-related interference resolution. Conclusions/Significance Collectively, these results suggest that maturation of cognitive control may be partly mediated by earlier development of neural systems supporting reactive control and delayed development of systems supporting proactive control. Importantly, the development of these mechanisms is associated with cognitive control in real-life behaviors.

The neural basis of sustained and transient attentional control in young adults with ADHD.

Differences in neural activation during performance on an attentionally demanding Stroop task were examined between 23 young adults with ADHD carefully selected to not be co-morbid for other psychiatric disorders and 23 matched controls. A hybrid blocked/single-trial design allowed for examination of more sustained vs. more transient aspects of attentional control. Our results indicated neural dysregulation across a wide range of brain regions including those involved in overall arousal, top-down attentional control, response selection, and inhibition. Furthermore, this dysregulation was most notable in lateral regions of DLPFC for sustained attentional control and in medial areas for transient aspects of attentional control. Because of the careful selection and matching of our two groups, these results provide strong evidence that the neural systems of attentional control are dysregulated in young adults with ADHD and are similar to dysregulations seen in children and adolescents with ADHD.

Individual differences in amygdala activity predict response speed during working memory.

The human amygdala has classically been viewed as a brain structure primarily related to emotions and dissociated from higher cognition. We report here findings suggesting that the human amygdala also has a role in supporting working memory (WM), a canonical higher cognitive function. In a first functional magnetic resonance imaging (fMRI) study (n = 53), individual differences in amygdala activity predicted behavioral performance in a 3-back WM task. Specifically, higher event-related amygdala amplitude predicted faster response time (RT; r = −0.64), with no loss of accuracy. This relationship was not contingent on mood state, task content, or personality variables. In a second fMRI study (n = 21), we replicated the key finding (r = −0.47) and further showed that the correlation between the amygdala and faster RT was specific to a high working memory load condition (3-back) compared with a low working memory load condition (1-back). These results support models of amygdala function that can account for its involvement not only in emotion but also higher cognition.