Neonatal Perirhinal Lesions in Rhesus Macaques Alter Performance on Working Memory Tasks with High Proactive Interference

Abstract

The lateral prefrontal cortex is known for its contribution to working memory (WM) processes in both humans and animals. Yet, recent studies indicate that the prefrontal cortex is part of a broader network of interconnected brain areas involved in WM. Within the medial temporal lobe (MTL) structures, the perirhinal cortex, which has extensive direct interactions with the lateral and orbital prefrontal cortex, is required to form active/flexible representations of familiar objects. However, its participation in WM processes has not be fully explored. The goal of this study was to assess the effects of neonatal perirhinal lesions on maintenance and monitoring WM processes. As adults, animals with neonatal perirhinal lesions and their matched controls were tested in three object-based (non-spatial) WM tasks that tapped different WM processing domains, e.g., maintenance only (Session-unique Delayed-nonmatching-to Sample, SU-DNMS), and maintenance and monitoring (Object-Self-Order, OBJ-SO; Serial Order Memory Task, SOMT). Neonatal perirhinal lesions transiently impaired the acquisition of SU-DNMS at a short (5 s) delay, but not when re-tested with a longer delay (30 s). The same neonatal lesions severely impacted acquisition of OBJ-SO task, and the impairment was characterized by a sharp increase in perseverative errors. By contrast, neonatal perirhinal lesion spared the ability to monitor the temporal order of items in WM as measured by the SOMT. Contrary to the SU-DNMS and OBJ-SO, which re-use the same stimuli across trials and thus produce proactive interference, the SOMT uses novel objects on each trial and is devoid of interference. Therefore, the impairment of monkeys with neonatal perirhinal lesions on SU-DNMS and OBJ-SO tasks is likely to be caused by an inability to solve working memory tasks with high proactive interference. The sparing of performance on the SOMT demonstrates that neonatal perirhinal lesions do not alter working memory processes per se but rather impact processes modulating impulse control and/or behavioral flexibility.

Keywords: excitotoxic lesion; perseveration; proactive interference; self-ordered task; serial order memory.

Figure 1

Coronal MRI from a representative case (Neo-PRh-4). Pre-surgical structural T1-weighted images at three rostro-caudal levels through the perirhinal cortex (left column). Post-surgical FLAIR images (right column) at the same rostro-caudal levels show hypersignals (whiter areas) that are indicative of edema and cell damage. Arrows point to the rhinal sulcus on the left and to hypersignals on the right.

Figure 2

Session-Unique DNMS performance. Average number (±SEM) of errors to reach criterion on Session-Unique DNMS at delays of 5 and 30 s for animals with neonatal perirhinal lesions (filled bars) and controls (open bars). ^*p < 0.05.

Figure 3

Object self-ordered task performance. Average number (±SEM) of primary errors (A) and perseverative errors (B) to criterion on the object self-ordered task (Obj-SO) at delays of 5 and 30 s for animals with neonatal perirhinal lesions (filled bars) and controls (open bars). ^*p < 0.05.