Bart Rypma

Age and Inhibition

Two experiments assess adult age differences in the extent of inhibition or negative priming generated in a selective-attention task. Younger adults consistently demonstrated negative priming effects; they were slower to name a letter on a current trial that had served as a distractor on the previous trial relative to one that had not occurred on the previous trial. Whether or not inhibition dissipated when the response to stimulus interval was lengthened from 500 ms in Experiment 1 to 1,200 ms in Experiment 2 depended upon whether young subjects were aware of the patterns across trial types. Older adults did not show inhibition at either interval. The age effects are interpreted within the Hasher-Zacks (1988) framework, which proposes inhibition as a central mechanism determining the contents of working memory and consequently influencing a wide array of cognitive functions.

Isolating the neural mechanisms of age-related changes in human working memory

Working memory (WM), the process by which information is coded into memory, actively maintained and subsequently retrieved, declines with age. To test the hypothesis that age-related changes in prefrontal cortex (PFC) may mediate this WM decline, we used functional MRI to investigate age differences in PFC activity during separate WM task components (encoding, maintenance, retrieval). We found greater PFC activity in younger than older adults only in dorsolateral PFC during memory retrieval. Fast younger subjects showed less dorsolateral PFC activation during retrieval than slow younger subjects, whereas older adults showed the opposite pattern. Thus age-related changes in dorsolateral PFC and not ventrolateral PFC account for WM decline with normal aging.

Neural correlates of cognitive efficiency

Since its inception, experimental psychology has sought to account for individual differences in human performance. Some neuroimaging research, involving complex behavioral paradigms, has suggested that faster-performing individuals show greater neural activity than slower performers. Other research has suggested that faster-performing individuals show less neural activity than slower performers. To examine the neural basis of individual performance differences, we had participants perform a simple speeded-processing task during fMRI scanning. In some prefrontal cortical (PFC) brain regions, faster performers showed less cortical activity than slower performers while in other PFC and parietal regions they showed greater activity. Regional-causality analysis indicated that PFC exerted more influence over other brain regions for slower than for faster individuals. These results suggest that a critical determinant of individual performance differences is the efficiency of interactions between brain regions and that slower individuals may require more prefrontal executive control than faster individuals to perform successfully.

Age differences in prefrontal cortical activity in working memory.

Working memory (WM) declines with advancing age. Brain imaging studies indicate that ventral prefrontal cortex (PFC) is active when information is retained in WM and that dorsal PFC is further activated for retention of large amounts of information. The authors examined the effect of aging on activation in specific PFC regions during WM performance. Six younger and 6 older adults performed a task in which, on each trial, they (a) encoded a 1- or 6-letter memory set, (b) maintained these letters over 5-s. and (c) determined whether or not a probe letter was part of the memory set. Comparisons of activation between the 1- and 6-letter conditions indicated age-equivalent ventral PFC activation. Younger adults showed greater dorsal PFC activation than older adults. Older adults showed greater rostral PFC activation than younger adults. Aging may affect dorsal PFC brain regions that are important for WM executive components.

Prefrontal modulation of working memory performance in brain injury and disease.

The inter‐related cognitive constructs of working memory (WM) and processing speed are fundamental components to general intellectual functioning in humans. Importantly, both WM and processing speed are highly susceptible to disruption in cases of brain injury, neurologic illness, and even in normal aging. A goal of this article is to summarize and critique the functional imaging studies of speeded working memory in neurologically impaired populations. This review focuses specifically on the role of the lateral prefrontal cortex in mediating WM performance and integrates the relevant WM literature in healthy adults with the current findings in the clinical literature. One important finding emerging from a summary of this literature is the dissociable contributions made by ventrolateral and dorsolateral prefrontal cortex (VLPFC and DLPFC) in guiding performance on tasks of WM. Throughout this review, it is shown that when cerebral resources are challenged, it is DLPFC, and often right DLPFC specifically, that plays a critical role in modulating WM functioning. In addition, this article will examine the relationship between task performance and brain activation across studies to clarify the role of increased DLPFC activity in clinical samples. Finally, explanations are offered for the observed increased DLPFC activation and the potentially unique role of right DLPFC in mediating WM performance during periods of cerebral challenge. Hum. Brain Mapp, 2006.

Neural and vascular variability and the fMRI-BOLD response in normal aging

Neural, vascular and structural variables contributing to the blood oxygen level-dependent (BOLD) signal response variability were investigated in younger and older humans. Twelve younger healthy human subjects (six male and six female; mean age: 24 years; range: 19-27 years) and 12 older healthy subjects (five male and seven female; mean age: 58 years; range: 55-71 years) with no history of head trauma and neurological disease were scanned. Functional magnetic resonance imaging measurements using the BOLD contrast were made when participants performed a motor, cognitive or a breath hold (BH) task. Activation volume and the BOLD response amplitude were estimated for the younger and older at both group and subject levels. Mean activation volume was reduced by 45%, 40% and 38% in the elderly group during the motor, cognitive and BH tasks, respectively, compared to the younger. Reduction in activation volume was substantially higher compared to the reduction in the gray matter volume of 14% in the older compared to the younger. A significantly larger variability in the intersubject BOLD signal change occurred during the motor task, compared to the cognitive task. BH-induced BOLD signal change between subjects was significantly less-variable in the motor task-activated areas in the younger compared to older whereas such a difference between age groups was not observed during the cognitive task. Hemodynamic scaling using the BH signal substantially reduced the BOLD signal variability during the motor task compared to the cognitive task. The results indicate that the origin of the BOLD signal variability between subjects was predominantly vascular during the motor task while being principally a consequence of neural variability during the cognitive task. Thus, in addition to gray matter differences, the type of task performed can have different vascular variability weighting that can influence age-related differences in brain functional response.

Examination of processing speed deficits in multiple sclerosis using functional magnetic resonance imaging.

Although it is known that processing speed deficits are one of the primary cognitive impairments in multiple sclerosis (MS), the underlying neural mechanisms responsible for impaired processing speed remain undetermined. Using BOLD functional magnetic resonance imaging, the current study compared the brain activity of 16 individuals with MS to 17 healthy controls (HCs) during performance of a processing speed task, a modified version of the Symbol Digit Modalities Task. Although there were no differences in performance accuracy, the MS group was significantly slower than HCs. Although both groups showed similar activation involving the precentral gyrus and occipital cortex, the MS showed significantly less cerebral activity than HCs in bilateral frontal and parietal regions, similar to what has been reported in aging samples during speeded tasks. In the HC group, processing speed was mediated by frontal and parietal regions, as well as the cerebellum and thalamus. In the MS group, processing speed was mediated by insula, thalamus and anterior cingulate. It therefore appears that neural networks involved in processing speed differ between MS and HCs, and our findings are similar to what has been reported in aging, where damage to both white and gray matter is linked to processing speed impairments.

The effects of acute stress on human prefrontal working memory systems

We examined the relationship between acute stress and prefrontal-cortex (PFC) based working memory (WM) systems using behavioral (Experiment 1) and functional magnetic resonance imaging (fMRI; Experiment 2) paradigms. Subjects performed a delayed-response item-recognition task, with alternating blocks of high and low WM demand trials. During scanning, participants performed this task under three stress conditions: cold stress (induced by cold-water hand-immersion), a room temperature water control (induced by tepid-water hand-immersion), and no-water control (no hand-immersion). Performance was affected by WM demand, but not stress. Cold stress elicited greater salivary cortisol readings in behavioral subjects, and greater PFC signal change in fMRI subjects, than control conditions. These results suggest that, under stress, increases in PFC activity may be necessary to mediate cognitive processes that maintain behavioral organization.

A subsequent-memory effect in dorsolateral prefrontal cortex

The importance of brain regions for long-term memory encoding has been examined by comparison of encoding-related neural activity on trials in which successful recollection subsequently occurred to the encoding-related activity on trials in which successful recollection did not occur. We applied similar analyses to event-related functional magnetic resonance imaging (fMRI) data to explore the relative roles of dorsolateral and ventrolateral prefrontal cortex (PFC) regions during specific components of a working-memory (WM) maintenance task. The results of this study indicated that increases in dorsolateral PFC activity during encoding was related to subsequent retrieval-success. These results lend support to the hypothesis that ventrolateral PFC mediates a limited-capacity WM buffer that supports rehearsal maintenance functions while dorsolateral PFC mediates WM organization functions that accommodate the capacity limits of WM maintenance.

Increasing measurement accuracy of age-related BOLD signal change: Minimizing vascular contributions by resting-state-fluctuation-of-amplitude scaling

In this report we demonstrate a hemodynamic scaling method with resting‐state fluctuation of amplitude (RSFA) in healthy adult younger and older subject groups. We show that RSFA correlated with breath hold (BH) responses throughout the brain in groups of younger and older subjects which RSFA and BH performed comparably in accounting for age‐related hemodynamic coupling changes, and yielded more veridical estimates of age‐related differences in task‐related neural activity. BOLD data from younger and older adults performing motor and cognitive tasks were scaled using RSFA and BH related signal changes. Scaling with RSFA and BH reduced the skew of the BOLD response amplitude distribution in each subject and reduced mean BOLD amplitude and variability in both age groups. Statistically significant differences in intrasubject amplitude variation across regions of activated cortex, and intersubject amplitude variation in regions of activated cortex were observed between younger and older subject groups. Intra‐ and intersubject variability differences were mitigated after scaling. RSFA, though similar to BH in minimizing skew in the unscaled BOLD amplitude distribution, attenuated the neural activity‐related BOLD amplitude significantly less than BH. The amplitude and spatial extent of group activation were lower in the older than in the younger group before and after scaling. After accounting for vascular variability differences through scaling, age‐related decreases in activation volume were observed during the motor and cognitive tasks. The results suggest that RSFA‐scaled data yield age‐related neural activity differences during task performance with negligible effects from non‐neural (i.e., vascular) sources. Hum Brain Mapp, 2011.