Scott A. Huettel

Males and females use different distal cues in a virtual environment navigation task

The study of navigational ability in humans is often limited by the restricted availability and inconvenience of using large novel environments. In the present study we use a computer-generated virtual environment to study sex differences in human spatial navigation. Adult male and female participants navigated through a virtual water maze where both landmarks and room geometry were available as distal cues. Manipulation of environmental characteristics revealed that females rely predominantly on landmark information, while males more readily use both landmark and geometric information. We discuss these results as a possible link between recent human research reporting hippocampal activation in spatial tasks and animal work showing sex differences in both spatial ability and hippocampal development.

Decisions under Uncertainty: Probabilistic Context Influences Activation of Prefrontal and Parietal Cortices

Many decisions are made under uncertainty; that is, with limited information about their potential consequences. Previous neuroimaging studies of decision making have implicated regions of the medial frontal lobe in processes related to the resolution of uncertainty. However, a different set of regions in dorsal prefrontal and posterior parietal cortices has been reported to be critical for selection of actions to unexpected or unpredicted stimuli within a sequence. In the current study, we induced uncertainty using a novel task that required subjects to base their decisions on a binary sequence of eight stimuli so that uncertainty changed dynamically over time (from 20 to 50%), depending on which stimuli were presented. Activation within prefrontal, parietal, and insular cortices increased with increasing uncertainty. In contrast, within medial frontal regions, as well as motor and visual cortices, activation did not increase with increasing uncertainty. We conclude that the brain response to uncertainty depends on the demands of the experimental task. When uncertainty depends on learned associations between stimuli and responses, as in previous studies, it modulates activation in the medial frontal lobes. However, when uncertainty develops over short time scales as information is accumulated toward a decision, dorsal prefrontal and posterior parietal contributions are critical for its resolution. The distinction between neural mechanisms subserving different forms of uncertainty resolution provides an important constraint for neuroeconomic models of decision making.

Diffusion tensor imaging of adult age differences in cerebral white matter: relation to response time.

Diffusion tensor imaging (DTI) measures the displacement of water molecules across tissue components, thus providing information regarding the microstructure of cerebral white matter. Fractional anisotropy (FA), the degree to which diffusion is directionally dependent, is typically higher for compact, homogeneous fiber bundles such as the corpus callosum. Previous DTI studies in adults have demonstrated an age-related decline in white matter FA, but whether the relation between FA and behavioral performance varies as a function of age has not been determined. We investigated adult age differences in FA, and age-related changes in the relation between FA and response time (RT), in a visual target-detection task. The results confirmed that, independently of age, FA is higher in the corpus callosum than in other brain regions. We also observed an age-related decline in FA that did not vary significantly across the brain regions. For both age groups, a lower level of integrity of the cerebral white matter (as indexed by FA), in specific brain regions, was associated with slower responses in the visual task. An age-related change in this relation was evident, however, in that the best predictor of RT for younger adults was FA in the splenium of the corpus callosum, whereas for older adults the best predictor was FA in the anterior limb of the internal capsule. This pattern is consistent with measures of the task-related cortical activation obtained from these same individuals and suggests an age-related increase in the attentional control of responses mediated by corticostriatal or corticothalamic circuits.

The effects of aging upon the hemodynamic response measured by functional MRI.

We comparedthe characteristics of the visually evoked hemodynamic response (HDR) in groups of young and elderly adults. Checkerboard stimuli were presented for 500 ms either singly or in pairs separated by a 2-s intrapair interval while gradient-echo echoplanar fMRI images were acquired concurrently every 1 s. Activated voxels, identified by correlation with an empirically derived reference waveform, were found for both groups in cortex along the calcarine sulcus and in the fusiform gyrus, with the mean HDR latency in calcarine cortex peaking approximately 300 ms earlier than the HDR evoked in the fusiform gyrus. On average, younger subjects had twice as many activated voxels as older subjects. The mean HDR had a similar onset time, rate of rise, and peak amplitude in both groups. However, the HDRs of older subjects reached their peak earlier and were more variable across subjects. Despite having average HDR amplitudes similar to those of younger subjects, older subjects had higher noise levels in activated voxels, resulting in lower signal-to-noise ratios. Distribution analyses of voxel statistics (t value, peak amplitude, peak latency) revealed that older subjects had proportionally fewer small-effect-size voxels, due to their increased voxelwise noise. This finding was consistent with the smaller spatial extent of activation in older subjects. To investigate age differences in the refractory period of the visual HDR, the HDR evoked by the second stimulus of each pair was isolated by subtracting the HDR evoked by a single stimulus from the composite HDR evoked by a pair. Recovery measures were similar across the age groups.

Perceiving patterns in random series: dynamic processing of sequence in prefrontal cortex

We demonstrate that regions within human prefrontal cortex develop moment-to-moment models for patterns of events occurring in the sensory environment. Subjects viewed a random binary sequence of images, each presented singly and each requiring a different button press response. Patterns occurred by chance within the presented series of images. Using functional magnetic resonance imaging (fMRI), we identified activity evoked by viewing a stimulus that interrupted a pattern. Prefrontal activation was evoked by violations of both repeating and alternating patterns, and the amplitude of this activation increased with increasing pattern length. Violations of repeating patterns, but not of alternating patterns, activated the basal ganglia.

Precuneus Is a Functional Core of the Default-Mode Network

Efforts to understand the functional architecture of the brain have consistently identified multiple overlapping large-scale neural networks that are observable across multiple states. Despite the ubiquity of these networks, it remains unclear how regions within these large-scale neural networks interact to orchestrate behavior. Here, we collected functional magnetic resonance imaging data from 188 human subjects who engaged in three cognitive tasks and a resting-state scan. Using multiple tasks and a large sample allowed us to use split-sample validations to test for replication of results. We parceled the task-rest pairs into functional networks using a probabilistic spatial independent components analysis. We examined changes in connectivity between task and rest states using dual-regression analysis, which quantifies voxelwise connectivity estimates for each network of interest while controlling for the influence of signals arising from other networks and artifacts. Our analyses revealed systematic state-dependent functional connectivity in one brain region: the precuneus. Specifically, task performance led to increased connectivity (compared to rest) between the precuneus and the left frontoparietal network (lFPN), whereas rest increased connectivity between the precuneus and the default-mode network (DMN). The absolute magnitude of this effect was greater for DMN, suggesting a heightened specialization for resting-state cognition. All results replicated within the two independent samples. Our results indicate that the precuneus plays a core role not only in DMN, but also more broadly through its engagement under a variety of processing states.

Effects of Aging on the Neural Correlates of Successful Item and Source Memory Encoding

To investigate the neural basis of age-related source memory (SM) deficits, young and older adults were scanned with fMRI while encoding faces, scenes, and face-scene pairs. Successful encoding activity was identified by comparing encoding activity for subsequently remembered versus forgotten items or pairs. Age deficits in successful encoding activity in hippocampal and prefrontal regions were more pronounced for SM (pairs) as compared with item memory (faces and scenes). Age-related reductions were also found in regions specialized in processing faces (fusiform face area) and scenes (parahippocampal place area), but these reductions were similar for item and SM. Functional connectivity between the hippocampus and the rest of the brain was also affected by aging; whereas connections with posterior cortices were weaker in older adults, connections with anterior cortices, including prefrontal regions, were stronger in older adults. Taken together, the results provide a link between SM deficits in older adults and reduced recruitment of hippocampal and prefrontal regions during encoding. The functional connectivity findings are consistent with a posterior-anterior shift with aging previously reported in several cognitive domains and linked to functional compensation.

Abstinence-induced changes in self-report craving correlate with event-related FMRI responses to smoking cues.

Drug cues have been shown to activate brain regions involved in attention, motivation, and reward in addicted users. However, as studies have typically measured responses in only one state (ie drug abstinence), it is unclear whether observed activations represent amplification by abstinence or stable responses. Thus, the present study was designed to evaluate the stability of event-related responses to visual drug cues in dependent smokers (n=13) using event-related functional magnetic resonance imaging measures. Imaging was conducted following smoking as usual and following overnight abstinence, and self-reported craving measures were obtained before, during, and after scanning. Analysis of hemodynamic response (HDR) amplitudes in each of 13 regions of interest revealed larger responses to smoking compared to control cues in ventral anterior cingulate gyrus (vACG) and superior frontal gyrus. Responses to smoking cues in these and all other regions revealed no effects of abstinence/satiety, thus supporting the notion that cue-elicited brain responses are relatively stable. However, while the abstinence manipulation did not alter group-level responses to smoking cues, at the individual level, abstinence-induced changes in craving (abstinence minus satiety) were positively correlated with changes in HDR amplitude to smoking cues in frontal regions including left inferior frontal gyrus, left vACG, and bilateral middle frontal gyrus. These results suggest that brain responses to smoking cues, while relatively stable at the group level following short-term abstinence, may be modulated by individual differences in craving in response to abstinence—particularly in regions subserving attention and motivation.

Distinct Value Signals in Anterior and Posterior Ventromedial Prefrontal Cortex

The core feature of an economic exchange is a decision to trade one good for another, based on a comparison of relative value. Economists have long recognized, however, that the value an individual ascribes to a good during decision making (i.e., their relative willingness to trade for that good) does not always map onto the reward they actually experience. Here, we show that experienced value and decision value are represented in distinct regions of ventromedial prefrontal cortex (VMPFC) during the passive consumption of rewards. Participants viewed two categories of rewards—images of faces that varied in their attractiveness and monetary gains and losses—while being scanned using functional magnetic resonance imaging. An independent market task, in which participants exchanged some of the money that they had earned for brief views of attractive faces, determined the relative decision value associated with each category. We found that activation of anterior VMPFC increased with increasing experienced value, but not decision value, for both reward categories. In contrast, activation of posterior VMPFC predicted each individuals relative decision value for face and monetary stimuli. These results indicate not only that experienced value and decision value are represented in distinct regions of VMPFC, but also that decision value signals are evident even in the absence of an overt choice task. We conclude that decisions are made by comparing neural representations of the value of different goods encoded in posterior VMPFC in a common, relative currency.

Cerebral white matter integrity mediates adult age differences in cognitive performance

Previous research has established that age-related decline occurs in measures of cerebral white matter integrity, but the role of this decline in age-related cognitive changes is not clear. To conclude that white matter integrity has a mediating (causal) contribution, it is necessary to demonstrate that statistical control of the white matter–cognition relation reduces the magnitude of age–cognition relation. In this research, we tested the mediating role of white matter integrity, in the context of a task-switching paradigm involving word categorization. Participants were 20 healthy, community-dwelling older adults (60–85 years), and 20 younger adults (18–27 years). From diffusion tensor imaging tractography, we obtained fractional anisotropy (FA) as an index of white matter integrity in the genu and splenium of the corpus callosum and the superior longitudinal fasciculus (SLF). Mean FA values exhibited age-related decline consistent with a decrease in white matter integrity. From a model of reaction time distributions, we obtained independent estimates of the decisional and nondecisional (perceptual–motor) components of task performance. Age-related decline was evident in both components. Critically, age differences in task performance were mediated by FA in two regions: the central portion of the genu, and splenium–parietal fibers in the right hemisphere. This relation held only for the decisional component and was not evident in the nondecisional component. This result is the first demonstration that the integrity of specific white matter tracts is a mediator of age-related changes in cognitive performance.