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Biomedical subjects

Charan Ranganath

Publications and source records attributed to Charan Ranganath.

At least 19 recordsLinked to original sources

Reinforcement learning signals predict future decisions.

Optimal behavior in a competitive world requires the flexibility to adapt decision strategies based on recent outcomes. In the present study, we tested the hypothesis that this flexibility emerges through a reinforcement learning process, in which reward prediction errors are used dynamically to adjust representations of decision options. We recorded event-related brain potentials (ERPs) while subjects played a strategic economic game against a computer opponent to evaluate how neural responses to outcomes related to subsequent decision-making. Analyses of ERP data focused on the feedback-related negativity (FRN), an outcome-locked potential thought to reflect a neural prediction error signal. Consistent with predictions of a computational reinforcement learning model, we found that the magnitude of ERPs after losing to the computer opponent predicted whether subjects would change decision behavior on the subsequent trial. Furthermore, FRNs to decision outcomes were disproportionately larger over the motor cortex contralateral to the response hand that was used to make the decision. These findings provide novel evidence that humans engage a reinforcement learning process to adjust representations of competing decision options.

Adult↗

Neural mechanisms of expert skills in visual working memory.

Expertise can increase working memory (WM) performance, but the cognitive and neural mechanisms of these improvements remain unclear. Here, we used functional magnetic resonance imaging to assess the degree to which expertise acquisition is supported by tuning of occipitotemporal object representations and tuning of prefrontal and parietal networks that may support domain-specific WM skills. We trained subjects to become experts in a novel category of complex visual objects and examined brain activity while they performed a WM task with objects from the expert category and from an untrained category. Visual expertise training resulted in improved recognition of expert, compared with untrained objects, and this effect was eliminated in a behavioral experiment by stimulus inversion. These behavioral changes were accompanied by increased recruitment of bilateral dorsolateral prefrontal, posterior parietal, and occipitotemporal cortices during WM encoding and maintenance. Across subjects, behavioral measures of expertise reliably predicted increased activation during maintenance of expert objects in all three regions. These neural expertise effects could not be attributed to differences in low-level stimulus characteristics between the two categories, familiarity with features of expert-domain objects, or familiarity with the WM task. These results are consistent with the idea that visual expertise improves WM performance through tuning of occipitotemporal object representations and through development of lateral prefrontal and posterior parietal networks that mediate the application of domain-specific mnemonic skills.

Brain Mapping↗

Dorsolateral prefrontal cortex promotes long-term memory formation through its role in working memory organization.

Results from neuroimaging studies have shown that the dorsolateral prefrontal cortex (DLPFC) implements processes critical for organizing items in working memory (WM). Based on its role in WM, we hypothesized that the DLPFC should contribute to long-term memory (LTM) formation by strengthening associations among items that are organized in WM. We conducted an event-related functional magnetic resonance imaging (fMRI) study to test this hypothesis by investigating prefrontal activity during performance of two different WM tasks: on "rehearse" trials, participants actively maintained triplets of words during a brief delay, whereas on "reorder" trials, participants actively organized each triplet during the delay. After scanning, subjects performed an LTM test on words presented during both WM conditions. Behavioral results showed that WM processing in the reorder condition enhanced LTM by strengthening inter-item associations. fMRI results showed that DLPFC activity specifically during reorder trials was predictive of subsequent LTM. In contrast, activity in the posterior ventrolateral prefrontal cortex was predictive of LTM for words studied on both reorder and rehearse trials. These results support the view that the DLPFC contributes to LTM formation through its role in organization of information in WM.

Adult↗

Intact recollection memory in high-performing older adults: ERP and behavioral evidence.

Numerous behavioral studies have suggested that normal aging has deleterious effects on episodic memory and that recollection is disproportionately impaired relative to familiarity-based recognition. However, there is a wide degree of variability in memory performance within the aging population and this generalization may not apply to all elderly adults. Here we investigated these issues by using event-related potentials (ERPs) to measure the effects of aging on the neural correlates of recollection and familiarity in older adults with recognition memory performance that was equivalent to (old-high) or lower than (old-low) that of young adults. Results showed that, behaviorally, old-high subjects exhibited intact recollection but reduced familiarity, whereas old-low subjects had impairments in both recollection and familiarity, relative to the young. Consistent with behavioral results, old-high subjects exhibited ERP correlates of recollection that were topographically similar to those observed in young subjects. However, unlike the young adults, old-high subjects did not demonstrate any neural correlates of familiarity-based recognition. In contrast to the old-high group, the old-low group exhibited neural correlates of recollection that were topographically distinct from those of the young. Our results suggest that the effects of aging on the underlying brain processes related to recollection and familiarity are dependent on individual memory performance and highlight the importance of examining performance variability in normal aging.

Adolescent↗

White matter changes compromise prefrontal cortex function in healthy elderly individuals.

Changes in memory function in elderly individuals are often attributed to dysfunction of the prefrontal cortex (PFC). One mechanism for this dysfunction may be disruption of white matter tracts that connect the PFC with its anatomical targets. Here, we tested the hypothesis that white matter degeneration is associated with reduced prefrontal activation. We used white matter hyperintensities (WMH), a magnetic resonance imaging (MRI) finding associated with cerebrovascular disease in elderly individuals, as a marker for white matter degeneration. Specifically, we used structural MRI to quantify the extent of WMH in a group of cognitively normal elderly individuals and tested whether these measures were predictive of the magnitude of prefrontal activity (fMRI) observed during performance of an episodic retrieval task and a verbal working memory task. We also examined the effects of WMH located in the dorsolateral frontal regions with the hypothesis that dorsal PFC WMH would be strongly associated with not only PFC function, but also with areas that are anatomically and functionally linked to the PFC in a task-dependent manner. Results showed that increases in both global and regional dorsal PFC WMH volume were associated with decreases in PFC activity. In addition, dorsal PFC WMH volume was associated with decreased activity in medial temporal and anterior cingulate regions during episodic retrieval and decreased activity in the posterior parietal and anterior cingulate cortex during working memory performance. These results suggest that disruption of white matter tracts, especially within the PFC, may be a mechanism for age-related changes in memory functioning.

Aged↗

Individual differences in extraversion and dopamine genetics predict neural reward responses.

Psychologists have linked the personality trait extraversion both to differences in reward sensitivity and to dopamine functioning, but little is known about how these differences are reflected in the functioning of the brain's dopaminergic neural reward system. Here, we show that individual differences in extraversion and the presence of the A1 allele on the dopamine D2 receptor gene predict activation magnitudes in the brain's reward system during a gambling task. In two functional MRI experiments, participants probabilistically received rewards either immediately following a behavioral response (Study 1) or after a 7.5 s anticipation period (Study 2). Although group activation maps revealed anticipation- and reward-related activations in the reward system, individual differences in extraversion and the presence of the D2 Taq1A allele predicted a significant amount of inter-subject variability in the magnitudes of reward-related, but not anticipation-related, activations. These results demonstrate a link between stable differences in personality, genetics, and brain functioning.

Alleles↗

Content-specific activation during associative long-term memory retrieval.

We tested whether visual stimulus material that is assumed to be processed in different cortical networks during perception (i.e., faces and spatial positions) is also topographically dissociable during long-term memory recall. With an extensive overlearning procedure, 12 participants learned paired associates of words and faces and words and spatial positions. Each word was combined with either one or two positions or one or two faces. fMRI was recorded several days later during a cued recall test, in which two words were presented and the participants had to decide whether these were linked to each other via a common mediator, i.e., a face or a position. This paradigm enforces retrieval from long-term memory without confounding recall with perceptual processes. A network of cortical areas was found to be differently activated during recall of positions and faces, including regions along the dorsal and ventral visual pathways, such as the parietal and precentral cortex for positions and the left prefrontal, temporal (including fusiform gyrus) and posterior cingulate cortex for faces. In a subset of these areas, the BOLD response was found to increase monotonically with the number of the to-be-re-activated associations. These results show that material-specific cortical networks are systematically activated during long-term memory retrieval that overlap with areas also activated by positions and faces during perceptual and working memory tasks.

Adult↗

Effects of unilateral prefrontal lesions on familiarity, recollection, and source memory.

Recognition memory can be supported by both the assessment of the familiarity of an item and by recollection of the context in which an item was encountered. Some have hypothesized that the prefrontal cortex (PFC) disproportionately contributes to recollection, whereas an alternative view is that the PFC contributes to both recollection and familiarity. Here, we examined the effects of prefrontal lesions on recollection and familiarity. Patients with unilateral PFC lesions and age-, gender-, and education-matched controls encoded pictures of meaningful objects that were presented briefly to the left or right visual field and subsequently performed recognition tests for centrally presented objects. Laterality effects within the PFC were also assessed in relation to recollection and familiarity processes. Patients with prefrontal lesions showed impaired familiarity-based recognition, and this deficit was specific for objects encoded by the lesioned hemisphere. In addition, recollection of the context in which each item was encountered was impaired independent of the visual field of presentation in patients with left prefrontal lesions. Recollection measured by subjective reports ("remember") was not impaired in either left or right frontal patients. These findings suggest that the PFC plays a critical role in recognition memory based on familiarity as well as recollection. Furthermore, these results suggest that left PFC regions are critical for source recollection.

Aged↗

Different mechanisms of episodic memory failure in mild cognitive impairment.

Mild cognitive impairment (MCI), defined as episodic memory impairment beyond what is expected in normal aging, is often associated with hippocampal atrophy (HA) and may represent incipient Alzheimer's disease. However, recent studies suggest that MCI is very heterogeneous and multiple etiologies likely exist. One possibility is small vessel cerebrovascular disease (CVD). Specifically, we hypothesized that white matter hyperintensities (WMH), an MRI marker for CVD, would lead to impairments in executive control processes critical for working memory that may, in turn, result in episodic memory impairment. To test this hypothesis, we examined a group of subjects clinically diagnosed with MCI and used MRI to further subcategorize individuals as either MCI with severe white matter hyperintensities (MCI-WMH) or MCI with severe hippocampal atrophy (MCI-HA). MCI-WMH, MCI-HA, and matched control subjects each performed a battery of working memory and episodic memory tasks. Results showed that MCI-HA and MCI-WMH were equally impaired on the episodic memory task relative to controls, but MCI-WMH were additionally impaired on tests tapping verbal and spatial working memory abilities and attentional control processes. These results suggest that CVD and hippocampal dysfunction are associated with distinct neuropsychological profiles. Although both syndromes are associated with episodic memory deficits, CVD is additionally associated with working memory and executive control deficits.

Aged↗

Lag-sensitive repetition suppression effects in the anterior parahippocampal gyrus.

Single-unit recording studies of monkeys have shown that neurons in perirhinal and entorhinal cortex exhibit activity reductions following stimulus repetition, and some have suggested that these "repetition suppression" effects may represent neural signals that support recognition memory. Critically, repetition suppression effects are most pronounced at short intervals between stimulus repetitions. Here, we used event-related functional magnetic resonance imaging (fMRI) to identify repetition suppression effects in the human medial temporal lobe and determine whether these effects are sensitive to the length of the interval between repetitions. Twenty-one participants were scanned while performing a continuous recognition memory task in which the interval between item repetitions was parametrically varied from 2 to 32 intervening items. We found evidence of repetition suppression in the anterior parahippocampal gyrus, but only when the repetition interval was relatively short. Moreover, bilateral hippocampal regions showed lag-sensitive repetition effects. Our results demonstrate that activity in the human medial temporal cortex, like that of monkeys, exhibits repetition suppression effects that are sensitive to the length of the interval between repetitions.

Adolescent↗

Functional connectivity with the hippocampus during successful memory formation.

Although it is well established that the hippocampus is critical for episodic memory, little is known about how the hippocampus interacts with cortical regions during successful memory formation. Here, we used event-related functional magnetic resonance imaging (fMRI) to identify areas that exhibited differential functional connectivity with the hippocampus during processing of novel objects that were subsequently remembered or forgotten on a postscan test. Functional connectivity with the hippocampus was enhanced during successful, as compared with unsuccessful, memory formation, in a distributed network of limbic cortical areas-including perirhinal, orbitofrontal, and retrosplenial/posterior cingulate cortex-that are anatomically connected with the hippocampal formation. Increased connectivity was also observed in lateral temporal, medial parietal, and medial occipital cortex. These findings demonstrate that successful memory formation is associated with transient increases in cortico-hippocampal interaction.

Adult↗

Directing the mind's eye: prefrontal, inferior and medial temporal mechanisms for visual working memory.

Human and nonhuman primates have a remarkable ability to recall, maintain and manipulate visual images in the absence of external sensory stimulation. Evidence from lesion, single-unit neurophysiological and neuroimaging studies shows that these visual working memory processes are consistently associated with sustained activity in object-selective inferior temporal neurons. Furthermore, results from these studies suggest that mnemonic activity in the inferior temporal cortex is, in turn, supported by top-down inputs from multimodal regions in prefrontal and medial temporal cortex, and under some circumstances, from the hippocampus.

Animals↗

Doubts about double dissociations between short- and long-term memory.

Historically, psychologists and neuroscientists have distinguished between processes supporting memory for events across retention delays of several seconds (short-term memory, STM), and those supporting memory for events across longer retention delays of minutes or more (long-term memory, LTM). Dissociations reported in some neuropsychological studies have contributed to a popular view that there must be neurally distinct memory stores that differentially support STM and LTM. In this article, we review evidence from recent studies regarding dissociations between STM and LTM. We suggest that the evidence reveals problems with claims of selective STM or LTM impairments, which in turn questions whether theories of memory need to propose neurally distinct stores for short- and long-term retention. We consider alternative ways to explain the neural mechanisms of memory across different retention intervals.

Animals↗

Working memory maintenance contributes to long-term memory formation: neural and behavioral evidence.

Theories of human memory have led to conflicting views regarding the relationship between working memory (WM) maintenance and episodic long-term memory (LTM) formation. Here, we tested the prediction that WM maintenance operates in two stages, and that processing during the initial stage of WM maintenance promotes successful LTM formation. Results from a functional magnetic resonance imaging study showed that activity in the dorsolateral prefrontal cortex and hippocampus during the initial stage of WM maintenance was predictive of subsequent LTM performance. In a behavioral experiment, we demonstrated that interfering with processing during the initial stage of WM maintenance impaired LTM formation. These results demonstrate that processing during the initial stage of WM maintenance directly contributes to successful LTM formation, and that this effect is mediated by a network that includes the dorsolateral prefrontal cortex and the hippocampus.

Adult↗

Inferior temporal, prefrontal, and hippocampal contributions to visual working memory maintenance and associative memory retrieval.

Higher order cognition depends on the ability to recall information from memory and hold it in mind to guide future behavior. To specify the neural mechanisms underlying these processes, we used event-related functional magnetic resonance imaging to compare brain activity during the performance of a visual associative memory task and a visual working memory task. Activity within category-selective subregions of inferior temporal cortex reflected the type of information that was actively maintained during both the associative memory and working memory tasks. In addition, activity in the anterior prefrontal cortex and hippocampus was specifically enhanced during associative memory retrieval. These data are consistent with the view that the active maintenance of visual information is supported by activation of object representations in inferior temporal cortex, but that goal-directed associative memory retrieval additionally depends on top-down signals from the anterior prefrontal cortex and medial temporal lobes.

Adolescent↗

Dissociable neural correlates for familiarity and recollection during the encoding and retrieval of pictures.

Results from behavioral studies have supported the idea that recognition memory can be supported by at least two different processes, recollection and familiarity. However, it remains unclear whether these two forms of memory reflect neurally distinct processes. Furthermore, it is unclear whether recollection and familiarity can be best conceived as differing primarily in terms of retrieval processing, or whether they additionally differ at encoding. To address these issues, we used event-related brain potentials (ERPs) to monitor neural correlates of familiarity and recollection at both encoding and retrieval. Participants studied pictures of objects in two types of study blocks and subsequently made remember-know and source memory judgments during retrieval. Results showed that, during encoding, neural correlates of subsequent familiarity and recollection onsetted in parallel, but exhibited differences in scalp topography and time course. Subsequent familiarity-based recognition was associated with a left-lateralized enhanced positivity and observed at anterior scalp sites from 300 to 450 ms, whereas subsequent recollection was associated with a topographically distinct right-lateralized positivity at anterior scalp sites from 300 to 450 ms and bilateral activity from 450 to 600 ms. During retrieval, neural correlates of familiarity emerged earlier than correlates of recollection. Familiarity was associated with an enhanced positivity at frontopolar scalp sites from 150 to 450 ms, whereas recollection was associated with positive ERP modulations over bilateral frontal (300-600 ms) and parietal (450-800 ms) sites. These results demonstrate that familiarity and recollection reflect the outcome of neurally distinct memory processes at both encoding and retrieval.

Adolescent↗

Category-specific modulation of inferior temporal activity during working memory encoding and maintenance.

Findings from neurophysiology have supported the view that visual working memory (WM) relies on modulation of activity in object-selective populations of neurons in inferior temporal cortex. Here, using event-related functional magnetic resonance imaging, we investigated whether similar mechanisms support human visual working memory encoding and maintenance processes. We identified regions in inferior temporal cortex that exhibited category-specific responses during perception of faces (fusiform face area [FFA]) or scenes (parahippocampal place area [PPA]) and investigated whether activity in these regions would be modulated by demands to actively encode and maintain faces and scenes. Results showed that independent of perceptual stimulation, the FFA and PPA exhibited greater encoding- and maintenance-related activity when their favored stimulus was relevant to the recognition task. In contrast, maintenance-related activity in the dorsolateral prefrontal cortex (PFC) was modulated by memory load, regardless of the type of information that was task relevant. These results are consistent with the view that visual working memory encoding and maintenance processes are implemented through modulation of inferior temporal activity by prefrontal cortex.

Adult↗

Dissociable correlates of recollection and familiarity within the medial temporal lobes.

Regions in the medial temporal lobes (MTL) have long been implicated in the formation of new memories for events, however, it is unclear whether different MTL subregions support different memory processes. Here, we used event-related functional magnetic resonance imaging (fMRI) to examine the degree to which two recognition memory processes-recollection and familiarity-were supported by different MTL subregions. Results showed that encoding activity in the rhinal cortex selectively predicted familiarity-based recognition, whereas, activity in the hippocampus and posterior parahippocampal cortex selectively predicted recollection. Collectively, these results support the view that different subregions within the MTL memory system implement unique encoding processes that differentially support familiarity and recollection.

Adolescent↗