Behavioral outcomes of late-onset or early-onset orbital frontal cortex (areas 11/13) lesions in rhesus monkeys

Abstract

The orbital frontal cortex (OFC) has been implicated in a number of psychiatric disorders, including depression, anxiety, phobia, and obsessive-compulsive disorder. Thus, a better understanding of its functions will likely provide critical information to understand the specific behavioral and cognitive processes affected in these human disorders. In recent years, a growing number of studies have provided evidence for anatomical and functional differentiation within the OFC. Here we discuss the effects of selective OFC (areas 11/13) lesions on social behavior, emotional regulation, and behavioral adaptation. Damage to these specific OFC subfields in adult monkeys resulted in profound changes in the flexible modulation of responses guided by reward value that could explain the poor fear regulation and disturbed social interactions observed in the same animals. A similar pattern of results was found when the OFC lesions were done in infancy. Thus, in monkeys, self-regulation abilities mediated by OFC areas 11/13 emerge from midinfancy through adolescence.

Figure 1

Representative cases: ventral view of the macaque brain showing (A) the borders of the orbital frontal subfields on a normal brain (left) and the labels of the orbital sulci (right), (B) the intended OFC (areas 11/13) lesions shown in grey, (C) the extent of OFC damage in a representative case with adult-onset aspiration lesions (case O-asp-6), and (D) the extent of OFC damage in a representative case with neonatal-onset aspiration lesions (case Neo-O-asp-5). Abbreviations: G: gustatory cortex; Ia: insular cortex (agranular); los: lateral orbital sulcus; mos: medial orbital sulcus; Pir: piriform cortex; PrCo: precentral opercular area. Cytoarchitectonic fields are as described previously.^,

Figure 2

Effects of OFC lesions on social interactions for adult animals with OFC lesions (Adult-OFC) and sham-operated controls (Adult-C). In A, personality attributes are listed along the outside of the radial plots, with the shaded area representing mean scores collected before surgery (pre) and the dashed lines representing scores measured after surgery (post). All ratings were on a five-point scale, ranging from not at all descriptive (score = 1) to very descriptive (score = 5). In B, frequency of “threat initiated” and “threat received” pre- and postsurgery (white bars and black bars, respectively) are given separately for subordinate and dominant animals of each group. ^*P < 0.05 and ^{* *}P < 0.01 for differences between pre- and postsurgery assessments.

Figure 3

The total frequency of tension-related behaviors (A), cage aggression (B), and freezing (C) during the no eye contact (NEC) or stare conditions of the human intruder paradigm for sham-operated controls (Adult-C) or animals with OFC lesions (Adult-OFC). Data are shown for both groups both before (pre) and after (post) surgery. ^*P < 0.05, difference between NEC and stare conditions in each testing phase.

Figure 4

Effects of neonatal OFC lesions on emotional reactivity toward the human intruder (A), reversal learning (B), and reinforcer devaluation (C). For each task, white bars represent animals with neonatal sham-operations (Neo-C), black bars represent animals with neonatal OFC lesions (Neo-OFC), bars with thin stripes represent animals with adult sham-operations (Adult-C), and bars with thick stripes represent animals with adult OFC lesions (Adult-OFC). ^*P < 0.05 indicates significant differences between the NEC and stare conditions in A, significant age differences for both groups in B, and significant differences from chance in C.