Impaired perceptual integration and memory for unitized representations are associated with perirhinal cortex atrophy in Alzheimer's disease

Abstract

Unitization, the capacity to encode associations as one integrated entity, can enhance associative memory in populations with an associative memory deficit by promoting familiarity-based associative recognition. Patients with Alzheimer's Disease (AD) are typically impaired in associative memory compared with healthy controls, but do not benefit from unitization strategies. Using fragmented pictures of objects, this study aimed at assessing which of the cognitive processes that compose unitization is actually affected in AD: the retrieval of unitized representations itself, or some earlier stages of processing, such as the integration process at a perceptual or conceptual stage of representation. We also intended to relate patients' object unitization capacity to the integrity of their perirhinal cortex (PrC), as the PrC is thought to underlie unitization and is also one of the first affected regions in AD. We evaluated perceptual integration capacity and subsequent memory for those items that have supposedly been unitized in 23 mild AD patients and 20 controls. We systematically manipulated the level of perceptual integration during encoding by presenting object pictures that were either left intact, separated into two fragments, or separated into four fragments. Subjects were instructed to unitize the fragments into a single representation. Success of integration was assessed by a question requiring the identification of the object. Participants also underwent a structural MRI exam, and measures of PrC, posterior cingulate cortex volume and thickness, and hippocampal volume, were extracted. The results showed that patients' perceptual integration performance decreased with the increased fragmentation level, and that their memory for unitized representations was impaired whatever the demands in terms of perceptual integration at encoding. Both perceptual integration and memory for unitized representations were related to the integrity of the PrC, and memory for unitized representations was also related to a lesser extent to the volume of the hippocampus. We argue that, globally, Tthis supports representational theories of memory that hold that the role of the PrC is not only perceptual nor only mnemonic but instead underlies complex object representation.

Building memories on prior knowledge: behavioral and fMRI evidence of impairment in early Alzheimer’s Disease

“…Knowledge about unique entities like faces has been shown to be impaired early in AD due to tau pathology in subhippocampal structures (entorhinal and perirhinal cortices) (Braak and Braak, 1995), thus disrupting semantic retrieval (Didic et al, 2011). This interpretation is also consistent with the finding that the advantage of unitization for alleviating the associative memory deficit is absent in early AD patients (D'Angelo et al, 2016), in relation to perirhinal cortex atrophy (Delhaye et al, 2018(Delhaye et al, , 2019.…”

Distinct disease‐sensitive GABAergic neurons in the perirhinal cortex of Alzheimer's mice and patients

“…SOM interneurons are low-threshold spiking cells that generally target the more distal dendrites of pyramidal cells, which receive excitatory input (31,65,81) thus likely regulating the dendritic integration of the excitatory synaptic inputs (16). Recently, SOM neurons have been identified as regulators of beta/low gamma (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) Hz) oscillations in the neocortex (83), thus a loss of these interneurons could reduce the activity in this frequency range affecting overlying processes. In this sense, the participation of SOM cells in synaptic plasticity and memory processes has been widely documented (49,87), and it has been suggested that a downregulation of somatostatin, and in consequence the levels of the Abeta-cleaving enzyme neprilysin, is a main risk factor for the development of AD (30).…”

“…This is a subregion of the parahippocampal gyrus composed of two subdivisions, Brodmann areas 35 and 36, also known as transentorhinal cortex and ectorhinal cortex, respectively, and represents an important component of the medial temporal memory system, linking sensory association cortices with the hippocampal formation . This cortical region plays an essential role in higher cognitive functions including episodic memory (recollection), semantic memory (familiarity) and visual perceptual processing systems , indeed, lesions of the perirhinal cortex lead to recognition memory impairment . Despite its relevance in memory processes, and the fact that the area 35 of the perirhinal cortex is the first cortical region to be affected by neurofibrillary pathology in AD patients (Braak I stage) the perirhinal cortex has been, however, surprisingly understudied at the neuropathological level in AD patients or animal models, and no studies have been performed so far to determine the AD‐associated GABAergic neuronal vulnerability in this cortical region.…”

Associative memory for conceptually unitized word pairs in mild cognitive impairment is related to the volume of the perirhinal cortex

“…Further, in this study, as in most previous studies, the source of this impairment remains uncertain, whether it is in the creation of a unitized and integrated representation at the encoding stage or in the subsequent recognition stage. Only one study previously suggested that both the capacity to form a complex and integrated representation at an initial processing stage and the recognition of unitized associations were impaired in AD, but this was for perceptual unitization (Delhaye et al, 2019). Here, one possible explanation could be that some conceptual impairments, or subtle difficulties with semantic memory in MCI patients (Joubert et al, 2008), as suggested by their impaired conceptual fluency scores in this study, could have led patients to some difficulty properly combining the concepts in the high-unitization condition.…”

“…Indeed, in AD, the few existing studies on this topic have failed to find any benefit from unitization to mitigate patients' associative memory deficit (Bastin et al, 2014). It is possible that the substantial NFT pathology in PrC prevents AD patients from efficiently recruiting the PrC to effectively perform unitization by hampering the formation of a complex integrated representation (Delhaye, Bahri, Salmon, & Bastin, 2019).…”