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.
Highlights
Working memory (WM) defines the psychological and neural processes responsible for keeping active a limited set of cognitive representations, and the executive capacity that acts upon those transiently stored representations
The results indicate that neonatal perirhinal cortex (PRh)-lesions slightly, but only transiently, impaired WM maintenance processes measured by the Session-Unique Delayed Nonmatching-to-Sample (SU-DNMS) task and impaired WM maintenance/monitoring processes measured by the Object Self-Ordered Task (OBJ-SO) task
The results suggest that neonatal PRh lesions may impact the ability to resolve proactive interference and/or inhibit perseverative responding rather than affecting working memory processes per se
Summary
Working memory (WM) defines the psychological and neural processes responsible for keeping active a limited set of cognitive representations, and the executive capacity that acts upon those transiently stored representations. Representations of objects, places, ideas, goals, or rules are maintained in WM and flexibly cooperate with process that monitor or manipulate the representations being kept “in mind.”. Evidence from human functional imaging (Ungerleider et al, 1998; D’Esposito et al, 1999; Owen et al, 1999; Petrides, 2000; Cannon et al, 2005), and lesion studies in monkeys (Mishkin et al, 1969; Passingham, 1975; Mishkin and Manning, 1978; Kowalska et al, 1991; Petrides, 1991, 1995), strongly support a distinction between the ventrolateral PFC (vlPFC) associated with maintenance processes and dorsolateral PFC (dlPFC) associated with monitoring/manipulation processes. More recent studies suggest that the prefrontal cortex is part of a broader network of interconnected brain areas involved in WM (see for review Constantinidis and Procyk, 2004). The dlPFC projects back to the posterior hippocampus (GoldmanRakic et al, 1984; Morris et al, 1999) providing a potential top-down mechanism regulating hippocampal-dependent WM processes
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