Indre V. Viskontas

Relational integration, inhibition, and analogical reasoning in older adults.

The difficulty of reasoning tasks depends on their relational complexity, which increases with the number of relations that must be considered simultaneously to make an inference, and on the number of irrelevant items that must be inhibited. The authors examined the ability of younger and older adults to integrate multiple relations and inhibit irrelevant stimuli. Young adults performed well at all but the highest level of relational complexity, whereas older adults performed poorly even at a medium level of relational complexity, especially when irrelevant information was presented. Simulations based on a neurocomputational model of analogical reasoning, Learning and Inference with Schemas and Analogies (LISA), suggest that the observed decline in reasoning performance may be explained by a decline in attention and inhibitory functions in older adults.

Symptoms of frontotemporal dementia provide insights into orbitofrontal cortex function and social behavior.

Abstract:  Recent investigations into the brain substrates of behavioral changes in frontotemporal dementia (FTD) demonstrate that the orbitofrontal cortex (OFC) plays a crucial role in normal social and emotional behavior. The initial symptoms of FTD reflect the early involvement of OFC as well as the disruption of an associated network involving the insula, striatum, and medial frontal lobes. As predicted by patients with other types of OFC lesions, FTD patients show impairments involving stimulus‐reward reversal learning, response inhibition, and ability to judge the appropriateness of their behavior in the social context. While the natural reward system remains intact in these patients, that is, patients will seek out directly rewarding stimuli, such as food and sex, with progressive OFC dysfunction they lose the ability to process complex stimulus‐reward contingencies. These abnormalities are apparent in their social interactions, which break down early in the disease. Also, deficits in emotion recognition and empathy have been directly linked to OFC atrophy in these patients. In contrast, some patients with early FTD show intact cognitive skills, including memory and executive functioning. Here, we review the behavioral and neuropsychological changes that accompany OFC atrophy in FTD and argue that phylogenetically new neurons found in this region, called von Economo neurons, are selectively vulnerable in FTD.

Distraction during relational reasoning: The role of prefrontal cortex in interference control

We compared the reasoning performance of patients with frontal-variant frontotemporal lobar degeneration (FTLD) with that of patients with temporal-variant FTLD and healthy controls. In a picture analogy task with a multiple-choice answer format, frontal-variant FTLD patients performed less accurately than temporal-variant FTLD patients, who in turn performed worse than healthy controls, when semantic and perceptual distractors were present among the answer choices. When the distractor answer choices were eliminated, frontal-variant patients showed relatively greater improvement in performance. Similar patient groups were tested with a relational-pattern reasoning task that included manipulations of one or two relations and both perceptual and semantic extraneous information. Frontal-variant patients showed performance deficits on all tasks relative to the other subject groups, especially when distracted. These results demonstrate that intact prefrontal cortex (PFC) is necessary for controlling interference from perceptual and semantic distractors in order to reason from relational structure.

Human medial temporal lobe neurons respond preferentially to personally relevant images

People with whom one is personally acquainted tend to elicit richer and more vivid memories than people with whom one does not have a personal connection. Recent findings from neurons in the human medial temporal lobe (MTL) have shown that individual cells respond selectively and invariantly to representations of famous people [Quian Quiroga R, Reddy L, Kreiman G, Koch C, Fried I (2005) Nature 435(7045):1102–1107]. Observing these cells, we wondered whether photographs of personally relevant individuals, such as family members, might be more likely to generate such responses. To address this issue, we recorded the activity of 2,330 neurons in the human MTL while patients viewed photographs of varying personal relevance: previously unknown faces and landscapes, familiar but not necessarily personally relevant faces and landscapes, and finally, photographs of the patients themselves, their families, and the experimenters. Our findings indicate that personally relevant photographs are indeed more likely to elicit selective responses in MTL neurons than photographs of individuals with whom the patients have had no personal contact. These findings further suggest that relevant stimuli are encoded by a larger proportion of neurons than less relevant stimuli, given that familiar or personally relevant items are linked to a larger variety of experiences and memories of these experiences.

Memory for famous people in patients with unilateral temporal lobe epilepsy and excisions

Memory for famous individuals was assessed by the use of a recognition test in which participants first made familiarity judgments, followed by forced-choice decisions to specific probes for identity. Patients with temporal lobe epilepsy (TLE) or excisions, 12 left hemisphere and 12 right hemisphere, and 18 control participants identified famous figures across 3 decades (1970s-1990s). Only patients with right TLE were impaired at familiarity judgments of faces; this deficit was evident only for the most recent decades. Both groups of patients, however, were impaired at naming famous faces and at providing semantic information about famous people. These findings suggest the integrity of temporal structures in both hemispheres is critical for retrieval of detailed semantic information about famous individuals.

The neural correlates of recollection: hippocampal activation declines as episodic memory fades.

Memories for certain events tend to linger in rich, vivid detail, and retrieval of these memories includes a sense of re‐experiencing the details of the event. Most events, however, are not retained in any detailed way for more than a few days. According to one theory, the hippocampus plays a specific role in supporting episodic retrieval, that is, the re‐experiencing of an event as part of ones personal past. This theory predicts that as episodic memories fade over time and are reduced to feelings of familiarity, activity in the hippocampus should no longer be associated with retrieval. We used high‐resolution functional imaging to explore neural activity in medial temporal lobe subregions while participants performed a recognition task at both a short (10‐min) and long (1‐week) study‐test delay. For each recognized item, subjects made “Remember/Know” judgments, allowing us to distinguish between items that were consistently episodic across the two tests and items that were initially episodic, but later became merely familiar. Our results demonstrate that activity in the subiculum is specifically associated with episodic recollection. Overall, recollected items were associated with higher activity in the subiculum than other items. For transiently recollected items, there was a decrease in subicular activity across the 1‐week delay as memory faded from recollection to familiarity, whereas consistently recollected items were associated with enhanced subicular activity at both delays. These results provide evidence of a link between subicular activation and recollective experience.

Neural activity in the hippocampus and perirhinal cortex during encoding is associated with the durability of episodic memory

Studies examining medial temporal lobe (MTL) involvement in memory formation typically assess memory performance after a single, short delay. Thus, the relationship between MTL encoding activity and memory durability over time remains poorly characterized. To explore this relationship, we scanned participants using high-resolution functional imaging of the MTL as they encoded object pairs; using the remember/know paradigm, we then assessed memory performance for studied items both 10 min and 1 week later. Encoding trials were classified as either subsequently recollected across both delays, transiently recollected (i.e., recollected at 10 min but not after 1 week), consistently familiar, or consistently forgotten. Activity in perirhinal cortex (PRC) and a hippocampal subfield comprising the dentate gyrus and CA fields 2 and 3 reflected successful encoding only when items were recollected consistently across both delays. Furthermore, in PRC, encoding activity for items that later were consistently recollected was significantly greater than that for transiently recollected and consistently familiar items. Parahippocampal cortex, in contrast, showed a subsequent memory effect during encoding of items that were recollected after 10 min, regardless of whether they also were recollected after 1 week. These data suggest that MTL subfields contribute uniquely to the formation of memories that endure over time, and highlight a role for PRC in supporting subsequent durable episodic recollection.

Ensembles of human MTL neurons “jump back in time” in response to a repeated stimulus

Episodic memory, which depends critically on the integrity of the medial temporal lobe (MTL), has been described as “mental time travel” in which the rememberer “jumps back in time.” The neural mechanism underlying this ability remains elusive. Mathematical and computational models of performance in episodic memory tasks provide a specific hypothesis regarding the computation that supports such a jump back in time. The models suggest that a representation of temporal context, a representation that changes gradually over macroscopic periods of time, is the cue for episodic recall. According to these models, a jump back in time corresponds to a stimulus recovering a prior state of temporal context. In vivo single‐neuron recordings were taken from the human MTL while epilepsy patients distinguished novel from repeated images in a continuous recognition memory task. The firing pattern of the ensemble of MTL neurons showed robust temporal autocorrelation over macroscopic periods of time during performance of the memory task. The gradually‐changing part of the ensemble state was causally affected by the visual stimulus being presented. Critically, repetition of a stimulus caused the ensemble to elicit a pattern of activity that resembled the pattern of activity present before the initial presentation of the stimulus. These findings confirm a direct prediction of this class of temporal context models and may be a signature of the mechanism that underlies the experience of episodic memory as mental time travel.

Relational integration in older adults

Reasoning requires making inferences based on information gleaned from a set of relations. The relational complexity of a problem increases with the number of relations that must be considered simultaneously to make a correct inference. Previous work (Viskontas, Morrison, Holyoak, Hummel, & Knowlton, 2004) has shown that older adults have difficulty integrating multiple relations during analogical reasoning, especially when required to inhibit irrelevant information. We report two experiments that examined the ability to integrate multiple relations in younger, middle-aged, and older adults performing two other reasoning tasks. These tasks systematically varied relational complexity, and required either inductive reasoning (a version of the Ravens Matrices Task) or transitive inference. Our results show that as people age they have increasing difficulty in solving problems that require them to integrate multiple relations. This difficulty may stem from a decrease in working memory capacity.

Anti-Saccade Performance Predicts Executive Function and Brain Structure in Normal Elders

ObjectiveTo assess the neuropsychological and anatomical correlates of anti-saccade (AS) task performance in normal elders. BackgroundThe AS task correlates with neuropsychological measures of executive function and frontal lobe volume in neurological diseases, but has not been studied in a well-characterized normal elderly population. Because executive dysfunction can indicate an increased risk for cognitive decline in cognitively normal elders, we hypothesized that AS performance might be a sensitive test of age-related processes that impair cognition. MethodThe percentage of correct AS responses was evaluated in 48 normal elderly subjects and associated with neuropsychological test performance using linear regression analysis and gray matter volume measured on magnetic resonance imaging scans using voxel-based morphometry. ResultsThe percentage of correct AS responses was associated with measures of executive function, including modified trails, design fluency, Stroop inhibition, abstraction, and backward digit span, and correlated with gray matter volume in 2 brain regions involved in inhibitory control: the left inferior frontal junction and the right supplementary eye field. The association of AS correct responses with neuropsychological measures of executive function was strongest in individuals with fewer years of education. ConclusionsThe AS task is sensitive to executive dysfunction and frontal lobe structural alterations in normal elders.