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.

Impaired Cognitive Flexibility After Neonatal Perirhinal Lesions in Rhesus Macaques

“…Figure 1 shows pre-surgical and post-surgical MR images of a representative case (Neo-PRh-6). Images from additional cases have been previously published (Zeamer et al, 2015; Weiss and Bachevalier, 2016; Weiss et al, 2016, 2017; Ahlgrim et al, 2017).…”

“…Arrows point to the rhinal sulcus (left column) and to areas of hypersignal (right column). See Zeamer et al (2015), Weiss and Bachevalier (2016), Weiss et al (2016, 2017), and Ahlgrim et al (2017) for illustration of lesion extent for additional Neo-PRh cases.…”

“…A recent study reported that adult monkeys with neonatal lesions of the perirhinal cortex (Neo-PRh) had working memory (WM) impairments that were characterized by a tendency to make perseverative errors on tasks that generated proactive interference (Weiss et al, 2016). However, the same Neo-PRh animals were unimpaired when tested with a WM task that was devoid of interference (Weiss et al, 2016). Taken together, these data suggested that the Neo-PRh lesions may have resulted in difficulty resolving proactive interference, rather than a deficit in WM per se .…”

“…Previous research indicated that monkeys with neonatal perirhinal lesions (Neo-PRh) were impaired on working memory (WM) tasks that generated proactive interference, but performed normally on WM tasks devoid of interference (Weiss et al, 2016). This finding suggested that the early lesions disrupted cognitive processes important for resolving proactive interference, such as behavioral inhibition and cognitive flexibility.…”

Off to a Good Start: The Early Development of the Neural Substrates Underlying Visual Working Memory

“…In addition to hippocampal lesions, Weiss et al ( 2016 ) found that neonatal lesions to another area of MTL, the perirhinal cortex, impacted VWM performance on tasks believed to rely on the vlPFC. In their study, macaques with neonatal lesions of perirhinal cortex (Neo-PRh) were impaired on a DNMS task at short delays, as well as an Obj-SO task; both repeated stimuli across trials, and thus required trial-to-trial updating of information in VWM.…”