Controlling one’s world: identification of sub-regions of primate PFC underlying goal-directed behavior

Abstract

SummaryImpaired detection of causal relationships between actions and their outcomes can lead to maladaptive behavior. However, causal roles of specific prefrontal cortex (PFC) sub-regions and the caudate nucleus in mediating such relationships in primates are unclear. We inactivated and over-activated five PFC sub-regions, reversibly and pharmacologically: areas 24 (perigenual anterior cingulate cortex), 32 (medial PFC), 11 (anterior orbitofrontal cortex, OFC), 14 (rostral ventromedial PFC/medial OFC) and 14-25 (caudal ventromedial PFC), and the anteromedial caudate, to examine their role in expressing learned action-outcome contingencies using a contingency degradation paradigm in marmosets. Area 24 or caudate inactivation impaired the response to contingency change, while area 11 inactivation enhanced it, and inactivation of areas 14, 32 or 14-25 had no effect. Over-activation of areas 11 and 24 impaired this response. These findings demonstrate distinct roles of PFC sub-regions in goal-directed behavior and illuminate the candidate neurobehavioral substrates of psychiatric disorders including obsessive-compulsive disorder.

Neurobehavioral and neurochemical basis of compulsive behavior: A 7T magnetic resonance spectroscopy study in humans

“…There was also a relationship between the index of habitual responding and anterior cingulate Glu: GABA ratio in OCD patients alone. This is consistent with recent evidence of effects of pharmacologically stimulating activity of BA 24 (dorsal anterior cingulate) in the marmoset monkey with a Glu reuptake inhibitor, although we also saw de cits when a mixture of GABA agonists (muscimol and baclofen) were infused into this region (the only one of several other prefrontal areas examined to show these effects) 40 . Thus, there were differences, as well as similarities, in the neural substrates of habitual control between OCD patients and healthy volunteers.…”

“…Consequently, in this study we also included a behavioral measure of instrumental control over behavior, a modi ed contingency degradation test, which has previously been shown to be sensitive to de cits in OCD 38 , stimulant drug abusers 29 and in patients with frontal lesions 39 , as well as being related to scores on a subjective habit questionnaire 29 . Our habitual responding index was signi cantly related to Glu:GABA ratio in the SMA for the entire sample, consistent with a possible role for this premotor cortical region, in conjunction with the putamen to which it projects, as part of the so-called 'habit system', being broadly consistent with evidence from both human neuroimaging and animal studies 10,22,40 . However, a speci c role for the SMA, as distinct from other premotor regions in habitual control, has hitherto not been much researched (e.g., de Wit et al, 2012) 41,42 ; although a recent article 21 speci cally identi ed such a relationship for this region.…”

Prefrontal cortex and depression

“…7 Schematic of medial and orbital views of macaque and marmoset prefrontal and anterior cingulate cortex illustrating regions in which reductions or increases in activity induce behavioral deficits of relevance to symptoms of anhedonia, negative bias and despair/ helplessness in MDD. Relevant to anhedonia: Areas 47/12, 11/13, and 14 in macaques [115]; Areas 25 [61] and 14 [142] in marmosets; Negative bias in decision making: Area 32/24 border [39] and caudal OFC [202] in macaques; Areas 32 and 25 [41] and areas 47/12 and 11 [38] in marmosets; Action-outcome impairments: Areas 24 [206] and 32 [204] in marmosets; Attentional set-shifting: Area 47/12 in marmosets [207].…”

Cortical dopamine reduces the impact of motivational biases governing automated behaviour

“…Neurally, this integration could be implemented through interaction between the orbitofrontal cortex (OFC), processing Pavlovian values, and the rostral anterior cingulate cortex, processing instrumental action values. This idea is supported by a recent study in marmoset monkeys by Duan et al (2021) 65 showing that the rostral anterior cingulate cortex is necessary for detecting instrumental control of actions over outcomes, while the anterior orbitofrontal cortex (OFC) mediates Pavlovian influences on goal-directed behaviour. In line with this we have also recently shown that BOLD activity in the orbitofrontal / ventromedial prefrontal cortex predicts the degree of valence-induced invigoration 66 .…”