Perirhinal Cortex Regions Research Articles

Assessing long-term neuroinflammatory responses to encephalopathy using MRI approaches in a rat endotoxemia model

Sepsis-associated encephalopathy (SAE) induces neuroinflammation, which is associated with cognitive impairment (CI). CI is also correlated with aging. We used contrast-enhanced magnetic resonance imaging (MRI), perfusion MRI, and MR spectroscopy to assess long-term alterations in BBB permeability, microvascularity, and metabolism, respectively, in a rat lipopolysaccharide-induced SAE model. Free radical-targeted molecular MRI was used to detect brain radical levels at 24h and 1week post-LPS injection. CE-MRI showed increased Gd-DTPA uptake in LPS rat brains at 24h in cerebral cortex, hippocampus, thalamus, and perirhinal cortex regions. Increased MRI signal intensities were observed in LPS rat brains in cerebral cortex, perirhinal cortex, and hippocampus regions 1week post-LPS. Long-term BBB dysfunction was detected in the cerebral cortex at 6weeks post-LPS. Increased relative cerebral blood flow (rCBF) in cortex and thalamus regions at 24h, decreased cortical and hippocampal rCBF at 6weeks, decreased cortical rCBF at 3 and 12weeks, and increased thalamus rCBF at 6weeks post-LPS, were detected. MRS indicated that LPS-exposed rat brains had decreased: NAA/Cho metabolite ratios at 1, 3, 6, and 12weeks; Cr/Cho at 1, 3, and 12weeks; and Myo-Ins/Cho at 1, 3, and 6weeks post-LPS. Free radical imaging detected increased radical levels in LPS rat brains at 24h and 1week post-LPS. LPS-exposed rats were compared to saline-treated controls. We clearly demonstrated BBB dysfunction, impaired vascularity, and decreased brain metabolites, as measures of long-term neuroinflammatory indicators, as well as increased free radicals in a LPS-induced rat SAE model.

Functional connectivity based parcellation of the human medial temporal lobe

Regional differences in large-scale connectivity have been proposed to underlie functional specialization along the anterior–posterior axis of the medial temporal lobe (MTL), including the hippocampus (HC) and the parahippocampal gyrus (PHG). However, it is unknown whether functional connectivity (FC) can be used reliably to parcellate the human MTL. The current study aimed to differentiate subregions of the HC and the PHG based on patterns of whole-brain intrinsic FC. FC maps were calculated for each slice along the longitudinal axis of the PHG and the HC. A hierarchical clustering algorithm was then applied to these data in order to group slices according to the similarity of their connectivity patterns. Surprisingly, three discrete clusters were identified in the PHG. Two clusters corresponded to the parahippocampal cortex (PHC) and the perirhinal cortex (PRC), and these regions showed preferential connectivity with previously described posterior-medial and anterior-temporal networks, respectively. The third cluster corresponded to an anterior PRC region previously described as area 36d, and this region exhibited preferential connectivity with auditory cortical areas and with a network involved in visceral processing. The three PHG clusters showed different profiles of activation during a memory-encoding task, demonstrating that the FC-based parcellation identified functionally dissociable sub-regions of the PHG. In the hippocampus, no sub-regions were identified via the parcellation procedure. These results indicate that connectivity-based methods can be used to parcellate functional regions within the MTL, and they suggest that studies of memory and high-level cognition need to differentiate between PHC, posterior PRC, and anterior PRC.

A Broader View of Perirhinal Function: From Recognition Memory to Fluency-Based Decisions

Although it is well established that the perirhinal cortex (PRC) makes an important contribution to recognition memory, the specific nature of this contribution remains uncertain. The finding that PRC activity is reduced for old compared with new items is typically attributed to the recovery of a long-term memory (LTM) signal. However, because old items are processed more easily or fluently than new items, reduced PRC activity could reflect increased fluency rather than LTM retrieval per se. We tested this hypothesis in humans using fMRI and a well-validated method to manipulate fluency: the masked priming paradigm. Some words during an old-new recognition test were preceded by conceptually related words (primes) that were subliminally presented (masked). The behavioral results replicated previous findings using this paradigm, whereby the fluency manipulation increased "oldness" responses to both old and new items. The fMRI analyses yielded two main sets of results. First, in the case of new items, which are independent from LTM retrieval, masked priming reduced PRC activity and predicted behavioral misattribution of fluency to oldness. Second, in the case of old items, the same PRC region showing fluency-related reductions for new items also contributed to "old" responding to old items. Individual differences in PRC attenuation also predicted oldness ratings to old items, and fluency modulated PRC connectivity with other brain regions associated with processing oldness signals, including visual cortex and right lateral prefrontal cortex. These results support a broader view in which the PRC serves a function more general than memory.

The Perirhinal Cortex and Recognition Memory Interference

There has recently been an increase in interest in the effects of visual interference on memory processing, with the aim of elucidating the role of the perirhinal cortex (PRC) in recognition memory. One view argues that the PRC processes highly complex conjunctions of object features, and recent evidence from rodents suggests that these representations may be vital for buffering against the effects of pre-retrieval interference on object recognition memory. To investigate whether PRC-dependent object representations play a similar role in humans, we used functional magnetic resonance imaging to scan neurologically healthy participants while they performed a novel interference-match-to-sample task. This paradigm was specifically designed to concurrently assess the impact of object versus spatial interference, on recognition memory for objects or scenes, while keeping constant the amount of object and scene information presented across all trials. Activity at retrieval was examined, within an anatomically defined PRC region of interest, according to the demand for object or scene memory, following a period of object compared with spatial interference. Critically, we found greater PRC activity for object memory following object interference, compared with object memory following scene interference, and no difference between object and scene interference for scene recognition. These data demonstrate a role for the human PRC during object recognition memory, following a period of object, but not scene interference, and emphasize the importance of representational content to mnemonic processing.

Binary Willshaw learning yields high synaptic capacity for long-term familiarity memory

In this study, we investigate from a computational perspective the efficiency of the Willshaw synaptic update rule in the context of familiarity discrimination, a binary-answer, memory-related task that has been linked through psychophysical experiments with modified neural activity patterns in the prefrontal and perirhinal cortex regions. Our motivation for recovering this well-known learning prescription is two-fold: first, the switch-like nature of the induced synaptic bonds, as there is evidence that biological synaptic transitions might occur in a discrete stepwise fashion. Second, the possibility that in the mammalian brain, unused, silent synapses might be pruned in the long-term. Besides the usual pattern and network capacities, we calculate the synaptic capacity of the model, a recently proposed measure where only the functional subset of synapses is taken into account. We find that in terms of network capacity, Willshaw learning is strongly affected by the pattern coding rates, which have to be kept fixed and very low at any time to achieve a non-zero capacity in the large network limit. The information carried per functional synapse, however, diverges and is comparable to that of the pattern association case, even for more realistic moderately low activity levels that are a function of network size.

The Medial Temporal Lobe Supports Conceptual Implicit Memory

The medial temporal lobe (MTL) is generally thought to be critical for explicit, but not implicit, memory. Here, we demonstrate that the perirhinal cortex (PRc), within the MTL, plays a role in conceptually-driven implicit memory. Amnesic patients with MTL lesions that converged on the left PRc exhibited deficits on two conceptual implicit tasks (i.e., exemplar generation and semantic decision). A separate functional magnetic resonance imaging (fMRI) study in healthy subjects indicated that PRc activation during encoding of words was predictive of subsequent exemplar generation. Moreover, across subjects, the magnitude of the fMRI and behavioral conceptual priming effects were directly related. Additionally, the PRc region implicated in the fMRI study was the same region of maximal lesion overlap in the patients with impaired conceptual priming. These patient and imaging results converge to suggest that the PRc plays a critical role in conceptual implicit memory, and possibly conceptual processing in general.

P3-081 Development of automated identification of cortical regions on MRI scans in AD patients

Regional differences in large-scale connectivity have been proposed to underlie functional specialization along the anterior–posterior axis of the medial temporal lobe (MTL), including the hippocampus (HC) and the parahippocampal gyrus (PHG). However, it is unknown whether functional connectivity (FC) can be used reliably to parcellate the human MTL. The current study aimed to differentiate subregions of the HC and the PHG based on patterns of whole-brain intrinsic FC. FC maps were calculated for each slice along the longitudinal axis of the PHG and the HC. A hierarchical clustering algorithm was then applied to these data in order to group slices according to the similarity of their connectivity patterns. Surprisingly, three discrete clusters were identified in the PHG. Two clusters corresponded to the parahippocampal cortex (PHC) and the perirhinal cortex (PRC), and these regions showed preferential connectivity with previously described posterior-medial and anterior-temporal networks, respectively. The third cluster corresponded to an anterior PRC region previously described as area 36d, and this region exhibited preferential connectivity with auditory cortical areas and with a network involved in visceral processing. The three PHG clusters showed different profiles of activation during a memory-encoding task, demonstrating that the FC-based parcellation identified functionally dissociable sub-regions of the PHG. In the hippocampus, no sub-regions were identified via the parcellation procedure. These results indicate that connectivity-based methods can be used to parcellate functional regions within the MTL, and they suggest that studies of memory and high-level cognition need to differentiate between PHC, posterior PRC, and anterior PRC.

P3-079 Characterization of neurodegenerative disease radioligands by tissue microarray analysis

Regional differences in large-scale connectivity have been proposed to underlie functional specialization along the anterior–posterior axis of the medial temporal lobe (MTL), including the hippocampus (HC) and the parahippocampal gyrus (PHG). However, it is unknown whether functional connectivity (FC) can be used reliably to parcellate the human MTL. The current study aimed to differentiate subregions of the HC and the PHG based on patterns of whole-brain intrinsic FC. FC maps were calculated for each slice along the longitudinal axis of the PHG and the HC. A hierarchical clustering algorithm was then applied to these data in order to group slices according to the similarity of their connectivity patterns. Surprisingly, three discrete clusters were identified in the PHG. Two clusters corresponded to the parahippocampal cortex (PHC) and the perirhinal cortex (PRC), and these regions showed preferential connectivity with previously described posterior-medial and anterior-temporal networks, respectively. The third cluster corresponded to an anterior PRC region previously described as area 36d, and this region exhibited preferential connectivity with auditory cortical areas and with a network involved in visceral processing. The three PHG clusters showed different profiles of activation during a memory-encoding task, demonstrating that the FC-based parcellation identified functionally dissociable sub-regions of the PHG. In the hippocampus, no sub-regions were identified via the parcellation procedure. These results indicate that connectivity-based methods can be used to parcellate functional regions within the MTL, and they suggest that studies of memory and high-level cognition need to differentiate between PHC, posterior PRC, and anterior PRC.

Perceptual and semantic contributions to episodic memory: evidence from semantic dementia and Alzheimer's disease

Previous group studies involving patients with semantic dementia, who have impaired semantic memory associated with temporal lobe atrophy, have documented the preservation of pictorial recognition memory, in contrast to patients with early Alzheimer's disease, who characteristically exhibit amnesia. The present study replicated this general pattern, although four of the semantic dementia patients with the most severe semantic deficit additionally had impaired recognition memory. Three factors that might contribute to this pattern of memory performance were examined: atrophic damage to medial temporal lobe regions, degradation of semantic representations, and disruption to visuoperceptual processes. Assessment of MRI scans revealed that atrophy affecting the perirhinal cortex region accurately predicted the recognition memory deficit seen at advanced stages of semantic dementia, but there was no evidence that it could be attributed directly either to degraded semantic knowledge or disrupted perceptual processing. In Alzheimer's disease, evidence suggested that visuoperceptual impairment might be involved in the poor recognition memory typically seen in the disorder. These results have implications for the differential diagnosis of semantic dementia and Alzheimer's disease and for cognitive and neural theories of human long-term memory.

The effects of neurotoxic lesions of the perirhinal cortex combined to fornix transection on object recognition memory in the rat

The effects of lesions centred in the perirhinal cortex region (Prh) or in both the perirhinal cortex region and the fornix (Prh+Fx) were assessed in two different working memory tasks, one spatial the other nonspatial. For the spatial task the rats were tested in an eight arm radial maze, using a standard procedure in which they were rewarded for avoiding previously visited arms. The Prh+Fx, but not the Prh, rats produced significantly more errors (re-entries) and these started significantly earlier in each session when compared with a surgical control group. The nonspatial task was a test of spontaneous object recognition in which rats were tested on their ability to discriminate between a familiar and a novel object. For the initial tests the Prh group failed to discriminate between the objects, but the Prh+Fx group showed a clear preference for the novel object. Observation of the test showed, however, that the Prh+Fx group were spending a greater length of time initially exploring the sample (familiar) object. When the amount of exposure to the sample object was limited to either 20 or 40 s (i.e. was the same for all three groups), the Prh+Fx group now failed to discriminate between the two objects. This change was especially evident for shorter sample duration (20 s). The Prh group did, however, show an amelioration of their deficit with this further testing. The present results support previous dissociation between spatial and nonspatial working memory, and indicate that there may be some recovery of function following perirhinal cortical damage.