How does ventrolateral prefrontal cortex (VLPFC) control mnemonic processing? Alternative models propose that VLPFC guides top-down (controlled) retrieval of knowledge from long-term stores or selects goal-relevant products of retrieval from among competitors. A paucity of evidence supports a retrieval/selection distinction, raising the possibility that these models reduce to a common mechanism. Here, four manipulations varied semantic control demands during fMRI: judgment specificity, cue-target-associative strength, competitor dominance, and number of competitors. Factor analysis revealed evidence for a metafactor that accounted for common behavioral variance across manipulations and for functional variance in left mid-VLPFC. These data support a generalized control process that selects relevant knowledge from among competitors. By contrast, left anterior VLPFC and middle temporal cortex were sensitive to cue-target-associative strength, but not competition, consistent with a control process that retrieves knowledge stored in lateral temporal cortex. Distinct PFC mechanisms mediate top-down retrieval and postretrieval selection.

ABSTRACT:Medial temporal lobe (MTL) structures often respond to stimulus repetition with a reduction in neural activity. Such novelty/ familiarity responses reflect the mnemonic consequences of initial stimulus encounter, although the aspects of initial processing that lead to novelty/familiarity responses remain unspecified. The current functional magnetic resonance imaging (fMRI) experiment examined the sensitivity of MTL to changes in the semantic representations/processes engaged across stimulus repetitions. During initial study blocks, words were visually presented, and participants made size, shape, or composition judgments about the named referents. During repeated study blocks, the initial words were visually re-presented along with novel words, and participants made size judgments for all items. Behaviorally, responses were faster to repeated words in which the same task was performed at initial and repeated exposure (i.e., size3size) relative to repeated words in which the tasks differed (i.e., composition3size and shape3size). fMRI measures revealed activation reductions in left parahippocampal cortex following same-task and different-task repetition; numerically, the effect was larger in the same-task condition. Accordingly, left parahippocampal cortex demonstrates sensitivity to perceptual novelty/familiarity, and it remains unclear whether this region also is sensitive to novelty/familiarity in the conceptual domain. In left perirhinal cortex, a novelty/familiarity effect was observed in the same-task condition but not in the differenttask condition, thus revealing sensitivity to the degree of semantic overlap across exposures but insensitivity to perceptual repetition of the visual word form. Perirhinal sensitivity to semantic repetition and insensitivity to perceptual repetition suggests that human perirhinal cortex receives conceptual inputs, with perirhinal contributions to declarative memory perhaps partially stemming from its role in processing semantic aspects of experiences.

The cortical pathology in Alzheimer's disease (AD) should lead to the loss of effective interaction between distinct neocortical areas. This study compared 2 conditions within a single sensory integration task that differed in the demands placed on effective cross-cortical interaction. AD patients were impaired in their ability to bind distinct visual features of a stimulus when this binding placed greater demands on cross-cortical interaction (i.e., motion and color) but were not impaired when this binding placed lesser demands on such interaction (i.e., motion and luminance). In contrast, neurologically intact individuals and patients with Huntington's disease were able to effectively bind features under both conditions. These results provide psychophysical support for the presence of functional disconnectivity in AD and demonstrate the utility of AD for investigating the neurocognitive substrates of sensory integration.

A major difference between humans and other animals is our capacity to maintain information in working memory (WM) while performing secondary tasks, which enables sustained, complex cognition. A common assumption is that the lateral prefrontal cortex (PFC) is critical for WM performance in the presence of distracters, but direct evidence is scarce. We assessed the relationship between fMRI activity and WM performance within-subjects, with performance matched across Distracter and No-distracter conditions. Activity in ventrolateral PFC during WM encoding and maintenance positively predicted performance in both conditions, whereas activity in the pre-supplementary motor area (pre-SMA) predicted performance only under distraction. Other parts of dorsolateral and ventrolateral PFC predicted performance only in the No-distracter condition. These findings challenge a lateral PFC-centered view of distracter-resistance, and suggest that the lateral PFC supports a type of WM representation that is efficient for dealing with task-irrelevant input but is nonetheless easily disrupted by dual-task demands.