Alexander A. Stevens

Cortical activation during delay discounting in abstinent methamphetamine dependent individuals

BackgroundMethamphetamine (MA)-dependent individuals prefer smaller immediate over larger delayed rewards in delay discounting (DD) tasks. Human and animal data implicate ventral (amygdala, ventral striatum, ventrolateral prefrontal cortex insula) and dorsal (dorsolateral prefrontal cortex, dorsal anterior cingulate cortex and posterior parietal cortex) systems in DD decisions. The ventral system is hypothesized to respond to the salience and immediacy of rewards while the dorsal system is implicated in the process of comparison and choice.MethodsWe used functional Magnetic Resonance Imaging to probe the neural correlates of DD in 19 recently abstinent MA-dependent patients and 17 age- and gender-matched controls.ResultsHard DD choices were associated with greatest activation in bilateral middle cingulate, posterior parietal cortex (PPC), and the right rostral insula. Control subjects showed more activation than MA patients bilaterally in the precuneus and in the right caudate nucleus, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). Magnitude of discounting was correlated with activity in the amygdala, DLPFC, posterior cingulate cortex and PPC.ConclusionsOur findings were consistent with a model wherein dorsal cognitive systems modulate the neural response of ventral regions. Patients addicted to MA, who strongly prefer smaller immediate over larger delayed rewards, activate the dorsal cognitive control system in order to overcome their preference. Activation of the amygdala during choice of delayed rewards was associated with a greater degree of discounting, suggesting that heavily discounting MA-dependent individuals may be more responsive to the negative salience of delayed rewards than controls.

The potential of ferumoxytol nanoparticle magnetic resonance imaging, perfusion, and angiography in central nervous system malignancy: a pilot study.

OBJECTIVEFerumoxytol, an iron oxide nanoparticle that targets phagocytic cells, can be used in magnetic resonance imaging of malignant brain tumors and can be administered as a bolus, allowing dynamic imaging. Our objectives were to determine the optimum time of delayed contrast enhancement of ferumoxytol, and to compare ferumoxytol and gadolinium contrast agents for magnetic resonance angiography and perfusion. METHODSTwelve patients with malignant brain tumors underwent serial magnetic resonance imaging multiple times up to 72 hours after ferumoxytol injection at both 1.5 and 3-T. The enhancement time course was determined for ferumoxytol and compared with a baseline gadolinium scan. Perfusion, time-of-flight and dynamic magnetic resonance angiography and T1-weighted scans were compared for the two agents. RESULTSThe lesions were detectable at all field strengths, even with an intraoperative 0.15-T magnet. Maximal ferumoxytol enhancement intensity was at 24 to 28 hours after administration, and the enhancing volume subsequently expanded with time into a non-gadolinium-enhancing, high T2-weighted signal region of tumor-infiltrated brain. Dynamic studies were assessed with both agents, indicating early vascular leak with gadolinium but not with ferumoxytol. CONCLUSIONOur most important finding was that gadolinium leaks out of blood vessels early after injection, whereas ferumoxytol stays intravascular in the “early” phase, thereby increasing the accuracy of tumor perfusion assessment. As a magnetic resonance imaging contrast agent, ferumoxytol visualizes brain tumors at all field strengths evaluated, with delayed enhancement peaking at 24 to 28 hours after administration.

Functional brain network modularity captures inter- and intra-individual variation in working memory capacity.

Background Cognitive abilities, such as working memory, differ among people; however, individuals also vary in their own day-to-day cognitive performance. One potential source of cognitive variability may be fluctuations in the functional organization of neural systems. The degree to which the organization of these functional networks is optimized may relate to the effective cognitive functioning of the individual. Here we specifically examine how changes in the organization of large-scale networks measured via resting state functional connectivity MRI and graph theory track changes in working memory capacity. Methodology/Principal Findings Twenty-two participants performed a test of working memory capacity and then underwent resting-state fMRI. Seventeen subjects repeated the protocol three weeks later. We applied graph theoretic techniques to measure network organization on 34 brain regions of interest (ROI). Network modularity, which measures the level of integration and segregation across sub-networks, and small-worldness, which measures global network connection efficiency, both predicted individual differences in memory capacity; however, only modularity predicted intra-individual variation across the two sessions. Partial correlations controlling for the component of working memory that was stable across sessions revealed that modularity was almost entirely associated with the variability of working memory at each session. Analyses of specific sub-networks and individual circuits were unable to consistently account for working memory capacity variability. Conclusions/Significance The results suggest that the intrinsic functional organization of an a priori defined cognitive control network measured at rest provides substantial information about actual cognitive performance. The association of network modularity to the variability in an individuals working memory capacity suggests that the organization of this network into high connectivity within modules and sparse connections between modules may reflect effective signaling across brain regions, perhaps through the modulation of signal or the suppression of the propagation of noise.

Maturing Thalamocortical Functional Connectivity Across Development

Recent years have witnessed a surge of investigations examining functional brain organization using resting-state functional connectivity MRI (rs-fcMRI). To date, this method has been used to examine systems organization in typical and atypical developing populations. While the majority of these investigations have focused on cortical–cortical interactions, cortical–subcortical interactions also mature into adulthood. Innovative work by Zhang et al. (2008) in adults have identified methods that utilize rs-fcMRI and known thalamo-cortical topographic segregation to identify functional boundaries in the thalamus that are remarkably similar to known thalamic nuclear grouping. However, despite thalamic nuclei being well formed early in development, the developmental trajectory of functional thalamo-cortical relations remains unexplored. Thalamic maps generated by rs-fcMRI are based on functional relationships, and should modify with the dynamic thalamo-cortical changes that occur throughout maturation. To examine this possibility, we employed a strategy as previously described by Zhang et al. to a sample of healthy children, adolescents, and adults. We found strengthening functional connectivity of the cortex with dorsal/anterior subdivisions of the thalamus, with greater connectivity observed in adults versus children. Temporal lobe connectivity with ventral/midline/posterior subdivisions of the thalamus weakened with age. Changes in sensory and motor thalamo-cortical interactions were also identified but were limited. These findings are consistent with known anatomical and physiological cortical–subcortical changes over development. The methods and developmental context provided here will be important for understanding how cortical–subcortical interactions relate to models of typically developing behavior and developmental neuropsychiatric disorders.

Premotor functional connectivity predicts impulsivity in juvenile offenders

Teenagers are often impulsive. In some cases this is a phase of normal development; in other cases impulsivity contributes to criminal behavior. Using functional magnetic resonance imaging, we examined resting-state functional connectivity among brain systems and behavioral measures of impulsivity in 107 juveniles incarcerated in a high-security facility. In less-impulsive juveniles and normal controls, motor planning regions were correlated with brain networks associated with spatial attention and executive control. In more-impulsive juveniles, these same regions correlated with the default-mode network, a constellation of brain areas associated with spontaneous, unconstrained, self-referential cognition. The strength of these brain–behavior relationships was sufficient to predict impulsivity scores at the individual level. Our data suggest that increased functional connectivity of motor-planning regions with networks subserving unconstrained, self-referential cognition, rather than those subserving executive control, heightens the predisposition to impulsive behavior in juvenile offenders. To further explore the relationship between impulsivity and neural development, we studied functional connectivity in the same motor-planning regions in 95 typically developing individuals across a wide age span. The change in functional connectivity with age mirrored that of impulsivity: younger subjects tended to exhibit functional connectivity similar to the more-impulsive incarcerated juveniles, whereas older subjects exhibited a less-impulsive pattern. This observation suggests that impulsivity in the offender population is a consequence of a delay in typical development, rather than a distinct abnormality.

Preparatory activity in occipital cortex in early blind humans predicts auditory perceptual performance

Early onset blindness leads to a dramatic alteration in the way the world is perceived, a change that is detectable in the organization of the brain. Several studies have confirmed that blindness leads to functional alterations in occipital cortices that normally serve visual functions. These reorganized brain regions respond to a variety of tasks and stimuli, but their specific functions are unclear. In sighted individuals, several studies have reported preparatory activity in retinotopic areas, which enhances perceptual sensitivity. “Baseline shifts,” changes in activity associated with a cue predicting an upcoming event, provides a marker for attentional modulation. Here we demonstrate that, in early blind subjects, medial occipital areas produced significant blood oxygenation level-dependent (BOLD) responses to a cue signaling an auditory discrimination trial but not to a cue indicating a no-trial period. Furthermore, the amplitude of the BOLD response in the anterior calcarine sulcus of early blind subjects correlated with their discrimination performance on the auditory backward masking task. Preparatory BOLD responses also were present in auditory cortices, although they were more robust in blind than sighted control subjects. The pattern of response in visual areas is similar to preparatory effects observed during visual selective attention in sighted subjects and consistent with the hypothesis that the mechanisms implicated in visual attention continue to modulate occipital cortex in the early blind. A possible source of this top-down modulation may be the frontoparietal circuits that retain their connectivity with the reorganized occipital cortex and as a result influence processing of nonvisual stimuli in the blind.

Auditory perceptual consolidation in early-onset blindness

Early-onset blindness (EB) produces measurable advantages in auditory perception, attention, memory and language. Neville and Bavelier [Neville, H. J., & Bavelier, D. (2001) Variability of developmental plasticity. In J. L. McClelland, R. S. Siegler (Eds.) Mechanisms of cognitive development: Behavioral andellon symposia on cognition (pp. 271-301)] hypothesized that faster temporal processing underlies many auditory compensatory effects in the blind. We tested this hypothesis by comparing early-onset blind individuals and sighted counterparts (SC) by assessing their rates of perceptual consolidation, the accurate perceptual representation of auditory stimuli. Firstly, we first tested both groups on a temporal-order judgment task (TOJ). EB subjects had significantly lower TOJ thresholds than the SC subjects. Secondly, we assessed perceptual consolidation speed using auditory backward masking tasks, taking into account individual TOJ thresholds. Discrimination performance was unaffected at all mask delays in the EB group while the SC subjects needed a mask delay of 160 ms to perform comparably. A backward masking task using single tone stimuli found no differences between the EB and SC groups any mask delay. A simultaneous masking task demonstrated that the mask effectively impaired discrimination in EB subjects at sensory stages. These results suggest that advantages in perceptual consolidation may reflect a mechanism responsible for the short response times and better performance reported in early blind individuals across a number of complex auditory tasks.

Attention and Sensory Interactions within the Occipital Cortex in the Early Blind: An fMRI Study

Visual deprivation early in life results in occipital cortical responsiveness across a broad range of perceptual and cognitive tasks. In the reorganized occipital cortex of early blind (EB) individuals, the relative lack of specificity for particular sensory stimuli and tasks suggests that attention effects may play a prominent role in these areas. We wished to establish whether occipital cortical areas in the EB were responsive to stimuli across sensory modalities (auditory, tactile) and whether these areas maintained or altered their activity as a function of selective attention. Using a three-stimulus oddball paradigm and event-related functional magnetic resonance imaging, auditory and tactile tasks presented separately demonstrated that several occipital regions of interest (ROIs) in the EB, but not sighted controls (SCs), responded to targets and task-irrelevant distracter stimuli of both modalities. When auditory and tactile stimuli were presented simultaneously with subjects alternating attention between sensory streams, only the calcarine sulcus continued to respond to stimuli in both modalities. In all other ROIs, responses to auditory targets were as large or larger than those observed in the auditory-alone condition, but responses to tactile targets were attenuated or abolished by the presence of unattended auditory stimuli. Both auditory and somatosensory cortices responded consistently to auditory and tactile targets, respectively. These results reveal mechanisms of orienting and selective attention within the visual cortex of EB individuals and suggest that mechanisms of enhancement and suppression interact asymmetrically on auditory and tactile streams during bimodal sensory presentation.

Orienting Auditory Spatial Attention Engages Frontal Eye Fields and Medial Occipital Cortex in Congenitally Blind Humans

What happens in vision-related cortical areas when congenitally blind (CB) individuals orient attention to spatial locations? Previous neuroimaging of sighted individuals has found overlapping activation in a network of frontoparietal areas including frontal eye fields (FEF), during both overt (with eye movement) and covert (without eye movement) shifts of spatial attention. Since voluntary eye movement planning seems irrelevant in CB, their FEF neurons should be recruited for alternative functions if their attentional role in sighted individuals is only due to eye movement planning. Recent neuroimaging of the blind has also reported activation in medial occipital areas, normally associated with visual processing, during a diverse set of non-visual tasks, but their response to attentional shifts remains poorly understood. Here, we used event-related fMRI to explore FEF and medial occipital areas in CB individuals and sighted controls with eyes closed (SC) performing a covert attention orienting task with endogenous verbal cues and spatialized auditory targets. We found robust stimulus-locked FEF activation of all CB subjects, similar to and stronger than in SC, suggesting that FEF plays a role in endogenous orienting of covert spatial attention even in individuals in whom voluntary eye movements are irrelevant. We also found robust activation in bilateral medial occipital cortex in CB but not in SC subjects. The response decreased below baseline following endogenous verbal cues but increased following auditory targets, suggesting that the medial occipital area in CB does not directly engage during cued orienting of attention but may be recruited for processing of spatialized auditory targets.

Mechanisms underlying heightened risk taking in adolescents as compared with adults

Self-report surveys and behavioral tasks indicate greater risk-taking behavior in adolescents as compared with adults. However, the underlying causes of these behavioral differences remain unclear. The present study examined the possibility that adolescents may be more susceptible to immediate positive and negative outcomes than adults. We compared the behavior of adolescents and adults on a modified version of the Balloon Analogue Risk Task (Lejuez et al., 2002). The task required that participants press a button to“inflate” a series of balloons on a computer screen. Balloons inflated until either the participant released the button (“saved” balloons) or the balloon“burst.” Accumulated points increased as the duration of the buttonpress increased; however, simultaneously, the likelihood that the balloon would burst also increased. Adolescents inflated balloons to a larger size prior to saving them than adults did, suggesting relatively higher levels of risk taking, although the adolescents’ behavior was not uniformly risk prone. Further, in comparison with adults, behavior in adolescents was more influenced by whether a balloon was saved or had burst on the preceding trial, suggesting that sensitivity to immediate consequences is one mechanism that underlies the observed difference in risk taking.