Low-beta repetitive transcranial magnetic stimulation to human dorsolateral prefrontal cortex during object recognition memory sample presentation, at a task-related frequency observed in local field potentials in homologous macaque cortex, impairs subsequent recollection but not familiarity.

According to dual-process signal-detection (DPSD) theories, short- and long-term recognition memory draws upon both familiarity and recollection. It remains unclear how primate prefrontal cortex (PFC) contributes to these processes, but frequency-specific neuronal activities are considered to play a key role. In Experiment 1, nonhuman primate (NHP) local field potential (LFP) electrophysiological recordings in macaque left dorsolateral PFC (dlPFC) revealed performance-related differences in a low-beta frequency range during the sample presentation phase of a visual object recognition memory task. Experiment 2 employed a similar task in humans and targeted left dlPFC (and vertex as a control) with repetitive transcranial magnetic stimulation (rTMS) at 12.5 Hz during occasional sample presentations. This low-beta frequency rTMS to dlPFC decreased DPSD derived indices of recollection, but not familiarity, in subsequent memory tests of the targeted samples after short delays. The same number of rTMS pulses over the same total duration albeit at a random frequency had no effect on either recollection or familiarity. Neither stimulation protocols had any causal effect upon behaviour when targeted to the control site (vertex). In this study, our hypotheses for our human TMS study were derived from our observations in NHPs; this approach might inspire further translational research through investigation of homologous brain regions and tasks across species using similar neuroscientific methodologies to advance the neural mechanism of recognition memory in primates.

Distinct Roles for the Anterior Cingulate and Dorsolateral Prefrontal Cortices During Conflict Between Abstract Rules.

Distinct patterns of activity within the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (dlPFC) reported in neuroimaging studies during tasks involving conflict between competing responses have often been cited as evidence for their key contributions to conflict-monitoring and behavioral adaptation, respectively. However, supporting evidence from neuropsychological patients has been scarce and contradictory. We administered a well-studied analog of the Wisconsin Card Sorting Test, designed to elicit conflict between 2 abstract rules, to a cohort of 6 patients with damage to ACC or dlPFC. Patients who had sustained more significant damage to the ACC were not impaired either on a measure of "conflict cost" nor on measures of "conflict-induced behavioral adaptation." In contrast, damage to dlPFC did not affect the conflict cost measure but abolished the patients' ability to adapt their behavior following exposure to conflict, compared with controls. This pattern of results complements the findings from nonhuman primates with more circumscribed lesions to ACC or dlPFC on the same task and provides converging evidence that ACC is not necessary for performance when conflict is elicited between 2 abstract rules, whereas dlPFC plays a fundamental role in behavioral adaptation.

Transcranial magnetic stimulation to dorsolateral prefrontal cortex affects conflict-induced behavioural adaptation in a Wisconsin Card Sorting Test analogue.

A substantial body of literature has proposed a role for dorsolateral prefrontal cortex (dlPFC) in supporting behavioural adaptation during conflict tasks. The vast majority of the evidence in support of this interpretation comes from neuroimaging studies. However, in order to unequivocally ascribe such a role to dlPFC, it is important to determine whether or not it is essential for this mechanism, and this can only be achieved by lesioning the area or interfering with its activity. In this study, we investigated the effects of repeated Transcranial Magnetic Stimulation (rTMS) to dlPFC on performance on a conflict version of a Wisconsin Card Sorting Test analogue (used previously in circumscribed lesion studies in monkeys) in neurologically healthy human participants. Our results supported the view of dlPFC as a fundamental structure for optimal conflict-induced behavioural adaptation, as stimulation cancelled out the adaptation effect normally observed on control trials. We show that there is some indication of differential modulation of trial types by stimulation and we hypothesize that this might suggest a role for dlPFC in conflict-induced adaptation that is more specifically concerned with the maintenance of conflict-history information online across trials.

Differential contributions of dorsolateral and frontopolar cortices to working memory processes in the primate.

The ability to maintain and manipulate information across temporal delays is a fundamental requirement to bridge the gap between perception and action. In the case of higher-order behavior, the maintenance of rules and strategies is particularly helpful in bridging this gap. The prefrontal cortex (PFC) has long been considered critical for such processes, and research has focused on different subdivisions of PFC to gain an insight into their diverse contributions to these mechanisms. Substantial evidence indicates that dorsolateral PFC (dlPFC) is an important structure for maintaining information across delays, with cells actively firing across delays and lesions to this region causing deficits in tasks involving delayed responses and maintenance of rules online. Frontopolar cortex (FP), on the other hand, appears to show the opposite pattern of results, with cells not firing across delays and lesions to this region not affecting the same rule-based, delayed response tasks that are impaired following dlPFC lesions. The body of evidence therefore suggests that dlPFC and FP's contributions to working memory differ. In this article, we will provide a perspective on how these regions might implement distinct but complementary and interactive functions that contribute to more general temporally-extended processes and support flexible, dynamic behavior.

Essential functions of primate frontopolar cortex in cognition.

Brodmann's area 10 is one of the largest cytoarchitecturally defined regions in the human cerebral cortex, occupying the most anterior part of the prefrontal cortex [frontopolar cortex (FPC)], and is believed to sit atop a prefrontal hierarchy. The crucial contributions that the FPC makes to cognition are unknown. Rodents do not possess such [corrected] a FPC, but primates do, and we report here the behavioral effects of circumscribed FPC lesions in nonhuman primates. FPC lesions selectively impaired rapid one-trial learning about unfamiliar objects and unfamiliar objects-in-scenes, and also impaired rapid learning about novel abstract rules. Object recognition memory, shifting between established abstract behavioral rules, and the simultaneous application of two distinct rules were unaffected by the FPC lesion. The distinctive pattern of impaired and spared performance across these seven behavioral tasks reveals that the FPC mediates exploration and rapid learning about the relative value of novel behavioral options, and shows that the crucial contributions made by the FPC to cognition differ markedly from the contributions of other primate prefrontal regions.