The anterior temporal lobes are critically involved in acquiring new conceptual knowledge:evidence for impaired feature integration in semantic dementia

AbstractRecent evidence from multiple neuroscience techniques indicates that regions within the anterior temporal lobes (ATLs) are a critical node in the neural network for representing conceptual knowledge, yet their function remains elusive. The hub-and-spoke model holds that ATL regions act as a transmodal conceptual hub, distilling the various sensory-motor features of objects and words into integrated, coherent conceptual representations. Single-cell recordings in monkeys suggest that the ATLs are critically involved in visual associative learning; however, investigations of this region in humans have focused on existing knowledge rather than learning. We studied acquisition of new concepts in semantic dementia patients, who have cortical damage centred on the ventrolateral aspects of the ATLs. Patients learned to assign abstract visual stimuli to two categories. The categories conformed to a family resemblance structure in which no individual stimulus features were fully diagnostic; thus the task required participants to form representations that integrate multiple features into a single concept. Patients were unable to do this, instead responding only on the basis of individual features. The study reveals that integrating disparate sources of information into novel coherent concepts is a critical computational function of the ATLs. This explains the central role of this region in conceptual representation and the catastrophic breakdown of concepts in semantic dementia

Stimulus familiarity modulates functional connectivity of the perirhinal cortex and anterior hippocampus during visual discrimination of faces and objects

Recent research suggests that the medial temporal lobe (MTL) is involved in perception as well as in declarative memory. Amnesic patients with focal MTL lesions and semantic dementia patients showed perceptual deficits when discriminating faces and objects. Interestingly, these two patient groups showed different profiles of impairment for familiar and unfamiliar stimuli. For MTL amnesics, the use of familiar relative to unfamiliar stimuli improved discrimination performance. By contrast, patients with semantic dementia—a neurodegenerative condition associated with anterolateral temporal lobe damage—showed no such facilitation from familiar stimuli. Given that the two patient groups had highly overlapping patterns of damage to the perirhinal cortex, hippocampus, and temporal pole, the neuroanatomical substrates underlying their performance discrepancy were unclear. Here, we addressed this question with a multivariate reanalysis of the data presented by Barense et al. (2011), using functional connectivity to examine how stimulus familiarity affected the broader networks with which the perirhinal cortex, hippocampus, and temporal poles interact. In this study, healthy participants were scanned while they performed an odd-one-out perceptual task involving familiar and novel faces or objects. Seed-based analyses revealed that functional connectivity of the right perirhinal cortex and right anterior hippocampus was modulated by the degree of stimulus familiarity. For familiar relative to unfamiliar faces and objects, both right perirhinal cortex and right anterior hippocampus showed enhanced functional correlations with anterior/lateral temporal cortex, temporal pole, and medial/lateral parietal cortex. These findings suggest that in order to benefit from stimulus familiarity, it is necessary to engage not only the perirhinal cortex and hippocampus, but also a network of regions known to represent semantic information

Influence of Conceptual Knowledge on Visual Object Discrimination: Insights from Semantic Dementia and MTL Amnesia

Recent evidence suggests that the perirhinal cortex is involved in perception of complex objects with ambiguous features. Anterior regions of the temporal lobes, including the perirhinal cortex as well as lateral cortex, are also thought to play a critical role in semantic memory. To understand how semantic factors might contribute to perceptual discrimination of complex objects, we studied visual object discrimination in patients with semantic dementia (SD)—a neurodegenerative condition characterized by progressive deterioration of semantic knowledge and atrophy to anterior temporal lobes (including perirhinal cortex). In 3 experiments, we assessed discrimination of meaningful (e.g., familiar real-world objects) and novel (e.g., blobs) objects with varying feature ambiguity levels. In a fourth experiment, we compared SD patients with amnesic patients with nonprogressive medial temporal lobe (MTL) lesions and less impaired semantic memory. Across studies, patients with perirhinal damage were impaired at discriminating objects with a high, but not low, degree of feature ambiguity, consistent with previous work indicating a perceptual role for this structure. Stimulus meaningfulness, however, differentially influenced performance in SD patients compared with MTL amnesics, suggesting that perceptual representations of complex objects (dependent upon perirhinal cortex) interact with higherorder abstract conceptual representations, even for tasks with no overt semantic component.Medical Research Council, a Peterhouse Research Fellowship (to M.D.B.), a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (to M.D.B.), and the Wales Institute of Cognitive Neuroscience (to K.S.G.

Functional specialization in the human medial temporal lobe.

Investigations of memory in rats and nonhuman primates have demonstrated functional specialization within the medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampal formation and underlying entorhinal, perirhinal, and parahippocampal cortices. Most studies in humans, however, especially in patients with brain damage, suggest that the human MTL is a unitary memory system supporting all types of declarative memory, our conscious memory for facts and events. To resolve this discrepancy, amnesic patients with either selective hippocampal damage or more extensive MTL damage were tested on variations of an object discrimination task adapted from the nonhuman primate literature. Although both groups were equally impaired on standard recall-based memory tasks, they exhibited different profiles of performance on the object discrimination test, arguing against a unitary view of MTL function. Cases with selective hippocampal damage performed normally, whereas individuals with broader MTL lesions were impaired. Furthermore, deficits in this latter group were related not to the number of discriminations to be learned and remembered, but to the degree of "feature ambiguity," a property of visual discriminations that can emerge when features are part of both rewarded and unrewarded stimuli. These findings resolve contradictions between published studies in humans and animals and introduce a new way of characterizing the impairments that arise after damage to the MTL

The perirhinal cortex modulates V2 activity in response to the agreement between part familiarity and configuration familiarity

Research has demonstrated that the perirhinal cortex (PRC) represents complex object-level feature configurations, and participates in familiarity versus novelty discrimination. Barense et al. [(in press) Cerebral Cortex, 22:11, doi:10.1093/cercor/bhr347] postulated that, in addition, the PRC modulates part familiarity responses in lower-level visual areas. We used fMRI to measure activation in the PRC and V2 in response to silhouettes presented peripherally while participants maintained central fixation and performed an object recognition task. There were three types of silhouettes: Familiar Configurations portrayed real-world objects; Part-Rearranged Novel Configurations created by spatially rearranging the parts of the familiar configurations; and Control Novel Configurations in which both the configuration and the ensemble of parts comprising it were novel. For right visual field (RVF) presentation, BOLD responses revealed a significant linear trend in bilateral BA 35 of the PRC (highest activation for Familiar Configurations, lowest for Part-Rearranged Novel Configurations, with Control Novel Configurations in between). For left visual field (LVF) presentation, a significant linear trend was found in a different area (bilateral BA 38, temporal pole) in the opposite direction (Part-Rearranged Novel Configurations highest, Familiar Configurations lowest). These data confirm that the PRC is sensitive to the agreement in familiarity between the configuration level and the part level. As predicted, V2 activation mimicked that of the PRC: for RVF presentation, activity in V2 was significantly higher in the left hemisphere for Familiar Configurations than for Part-Rearranged Novel Configurations, and for LVF presentation, the opposite effect was found in right hemisphere V2. We attribute these patterns in V2 to feedback from the PRC because receptive fields in V2 encompass parts but not configurations. These results reveal two new aspects of PRC function: (1) it is sensitive to the congruency between the familiarity of object configurations and the parts comprising those configurations and (2) it likely modulates familiarity responses in visual area V2.Grant sponsor: NSF; Grant number: BCS 0960529 (to M.A.P.); Grant CIHR; Grant number: MOP-115148 (to M.D.B.); Grant sponsor: McKnight Brain Research Foundation Grant sponsor: NSERC Discovery Grant (to M.D.B.