Allyson Rosen

Dissociable contributions of prefrontal and parietal cortices to response selection.

The ability to select between possible responses to a given situation is central to human cognition. The goal of this study was to distinguish between brain areas representing candidate responses and areas selecting between competing response alternatives. Event-related fMRI data were acquired while 10 healthy adults performed a task used to examine response competition: the Eriksen flanker task. Left parietal cortex was activated by either of two manipulations that increased the need to maintain a representation of possible responses. In contrast, lateral prefrontal and rostral anterior cingulate cortices were specifically engaged by the need to select among competing response alternatives. These findings support the idea that parietal cortex is involved in activating possible responses on the basis of learned stimulus-response associations, and that prefrontal cortex is recruited when there is a need to select between competing responses.

Neural Basis of Endogenous and Exogenous Spatial Orienting: A Functional MRI Study

Whole-brain functional magnetic resonance imaging (MRI) was used to examine the neural substrates of internally (endogenous) and externally (exogenous) induced covert shifts of attention. Thirteen normal subjects performed three orienting conditions: endogenous (location of peripheral target predicted by a central arrow 80 of the time), exogenous (peripheral target preceded by a noninformative peripheral cue), and control (peripheral target preceded by noninformative central cue). Behavioral results indicated faster reaction times (RTs) for valid than for invalid trials for the endogenous condition but slower RTs for valid than for invalid trials for the exogenous condition (inhibition of return). The spatial extent and intensity of activation was greatest for the endogenous condition, consistent with the hypothesis that endogenous orienting is more effortful (less automatic) than exogenous orienting. Overall, we did not observe distinctly separable neural systems associated with the endogenous and exogenous orienting conditions. Both exogenous and endogenous orienting, but not the control condition, activated bilateral parietal and dorsal premotor regions, including the frontal eye fields. These results suggest a specific role for these regions in preparatory responding to peripheral stimuli. The right dorsolateral prefrontal cortex (BA 46) was activated selectively by the endogenous condition. This finding suggests that voluntary, but not reflexive, shifts of attention engage working memory systems.

Variable effects of aging on frontal lobe contributions to memory.

Declarative memory declines with age, but there is profound variation in the severity of this decline. Healthy elderly adults with high or low memory scores and young adults viewed words under semantic or non-semantic encoding conditions while undergoing fMRI. Young adults had superior memory for the words, and elderly adults with high memory scores had better memory for the words than those with low memory scores. The elderly with high scores had left lateral and medial prefrontal activations for semantic encoding equal to the young, and greater right prefrontal activation than the young. The elderly with low scores had reduced activations in all three regions relative to the elderly with high memory scores. Thus, successful aging was characterized by preserved left prefrontal and enhanced right prefrontal activation that may have provided compensatory encoding resources.

Practice-related functional activation changes in a working memory task.

The effects of practice on the functional anatomy of a visuospatial working memory (VSWM) task were studied using functional Magnetic Resonance Imaging (fMRI). Functional imaging was conducted as subjects completed a moderate (Experiment 1) or extensive (Experiment 2) amount of practice on a delayed‐match‐to‐sample task. While improvement in task performance was seen with practice, the tasks dependence upon VSWM did not change. Activations in frontal (inferior, middle, and precentral gyri and superior frontal sulcus), parietal (intra‐parietal sulcus, inferior parietal lobule, and precuneus) and cingulate (anterior and posterior) regions were observed as were bilateral insular and occipital activations. With the exception of the posterior cingulate, practice produced activation decreases in these regions, thus providing little evidence for a re‐organization of the functional neuroanatomy. Fewer regions passing statistical criteria were observed at the end of practice relative to early in practice. Regions that were lost were mostly posterior (occipital and precuneus) but also included the left middle frontal gyrus, left precentral gyrus, and right insula suggesting that a more precise VSWM functional map can be observed once processes specific to encountering a novel task are removed. Little further activation changes were observed after extensive practice. These results suggest, minimally, that practice effects should be considered so as to avoid incorrectly attributing functional activation to a cognitive process of interest. Further, these data show that the dynamics of functional change can be tracked while a task is being learned and as an important cognitive process becomes more skilled. Microsc. Res. Tech. 51:54–63, 2000.

Functional MRI evidence for subcortical participation in conceptual reasoning skills

LESIONS involving the dorsolateral prefrontal lobes may produce deficits on conceptual reasoning (CR) tasks in humans. Such deficits can also occur with subcortical lesions involving the basal ganglia, thalamus, or cerebellum, suggesting a common, yet widespread, neural network supporting this executive function. Here we report the results of a whole brain functional magnetic resonance imaging (fMRI) experiment in healthy volunteers while performing a CR task. Compared to a sensorimotor control condition, the CR task resulted in discrete subcortical activation sites primarily involving the right basal ganglia, right thalamus and left lateral cerebellum. Cortical activation was present in multiple systems, including the dorsolateral prefrontal and inferior frontal/insular areas; posterior parietal, superior extrastriate, and premotor areas; inferior extrastriate and middle temporal regions; and midline pre-supplementary motor and anterior cingulate regions. Our findings provide strong evidence that CR is mediated by interacting neural systems involving the cerebral cortex, basal ganglia, thalamus, and cerebellum.

Modeling the prevalence and incidence of Alzheimer's disease and mild cognitive impairment

A number of systems have been proposed for classifying older adults who suffer from cognitive impairment or decline but do not yet meet criteria for Alzheimers disease (AD). The classification, Mild Cognitive Impairment (MCI), has attracted much attention. It uses relatively specific diagnostic criteria and individuals who meet these criteria appear to be at substantial risk for the development of AD. However, little data is available to define the prevalence of MCI in any age group. We propose a simple mathematical model for the progression of patients from Non-Affected (NA) to MCI to AD. This first-order Markov model defines the likely prevalence of MCI at specific ages. Primary assumptions of the model include an AD prevalence of 1% at age 60 increasing to 25% at age 85 and a conversion rate from MCI to AD of 10% constant across all ages considered. We used the best available information for our model and found (1) that the MCI prevalence increased from 1% at age 60 to 42% at age 85 and (2) that the conversion rate from NA to MCI increased from 1% per year at age 60 to 11% at age 85. In conclusion, this model allows estimation of prevalence of MCI and conversion from NA to MCI based upon known prevalences of AD, conversion rates of MCI to AD, and death rates. Due to its substantial prevalence, MCI may be an important target for screening and possible intervention.

Mapping of semantic, phonological, and orthographic verbal working memory in normal adults with functional magnetic resonance imaging

Twelve neurologically normal participants (4 men and 8 women) performed semantic, phonological, and orthographic working memory tasks and a control task during functional magnetic resonance imaging. Divergent regions of the posterior left hemisphere used for decoding and storage of information emerged in each working memory versus control task comparison. These regions were consistent with previous literature on processing mechanisms for semantic, phonological, and orthographic information. Further, working memory versus control task differences extended into the left frontal lobe, including premotor cortex, and even into subcortical structures. Findings were consistent with R. C. Martin and C. Romanis (1994) contention that different forms of verbal working memory exist and further suggest that a reconceptualization of premotor cortex functions is needed.

Cognitive Training Changes Hippocampal Function in Mild Cognitive Impairment: A Pilot Study

A randomized pilot experiment examined the neural substrates of response to cognitive training in participants with mild cognitive impairment (MCI). Participants performed exercises previously demonstrated to improve verbal memory and an active control group performed other computer activities. An auditory-verbal fMRI task was conducted before and after the two-month training program. Verbal memory scores improved significantly and left hippocampal activation increased significantly in the experimental group (gains in 5 of 6 participants) relative to the control group (reductions in all 6 participants). Results suggest that the hippocampus in MCI may retain sufficient neuroplasticity to benefit from cognitive training.

Decreased prefrontal, anterior cingulate, insula, and ventral striatal metabolism in medication-free depressed outpatients with bipolar disorder

This study explored whether cerebral metabolic changes seen in treatment resistant and rapid cycling bipolar depression inpatients are also found in an outpatient sample not specifically selected for treatment resistance or rapid cycling. We assessed 15 depressed outpatients with bipolar disorder (six type I and nine type II) who were medication-free for at least 2 weeks and were not predominantly rapid cycling. The average 28-item Hamilton Depression Scale (HAM-D) total score was 33.9. The healthy control group comprised 19 age-matched subjects. All participants received a resting quantitative 18F-fluoro-deoxyglucose positron emission tomography scan. Data analyses were performed with Statistical Parametric Mapping (SPM5). Analyses revealed that depressed patients exhibited similar global metabolism, but decreased absolute regional metabolism in the left much more than right dorsolateral prefrontal cortex, bilateral (left greater than right) insula, bilateral subgenual prefrontal cortex, anterior cingulate, medial prefrontal cortex, ventral striatum, and right precuneus. No region exhibited absolute hypermetabolism. Moreover, HAM-D scores inversely correlated with absolute global metabolism and regional metabolism in the bilateral medial prefrontal gyrus, postcentral gyrus, and middle temporal gyrus. Analysis of relative cerebral metabolism yielded a similar, but less robust pattern of findings. Our findings confirm prefrontal and anterior paralimbic metabolic decreases in cerebral metabolism outside of inpatients specifically selected for treatment resistant and rapid cycling bipolar disorder. Prefrontal metabolic rates were inversely related to severity of depression. There was no evidence of regional hypermetabolism, perhaps because this phenomenon is less robust or more variable than prefrontal hypometabolism.

Differential Associations Between Entorhinal and Hippocampal Volumes and Memory Performance in Older Adults.

Magnetic resonance imaging-derived entorhinal and hippocampal volumes were measured in 14 nondemented, community-dwelling older adults. Participants were selected so that memory scores from 2 years prior to scanning varied widely but were not deficient relative to age-appropriate norms. A median split of these memory scores defined high-memory and low-memory groups. Verbal memory scores at the time of imaging were lower, and entorhinal and hippocampal volumes were smaller, in the low-memory group than in the high-memory group. Left entorhinal cortex volume showed the strongest correlation (r= .79) with immediate recall of word lists. Left hippocampal volume showed the strongest correlation (r= .57) with delayed paragraph recall. These results suggest that entorhinal and hippocampal volumes are related to individual differences in dissociable kinds of memory performance among healthy older adults.