Rhesus monkeys with damage to amygdala or orbitofrontal cortex perform well on novelty-based memory tasks.

The amygdala and orbitofrontal cortex (OFC) are interconnected regions that serve as key nodes in brain circuits supporting social and affective behaviors. An important question that has come into focus is whether these regions also play a fundamental role in responding to novelty. One possibility is that these regions are important for discriminating novel from familiar stimuli. An alternative possibility is that these regions contribute to affective responses to stimuli in novelty-based tasks. For example, the amygdala and OFC could contribute to assessing novel stimuli as being threatening or previously selected stimuli as having reward value. The present study tested rhesus macaque monkeys with damage to the amygdala or OFC, along with sham-operated control monkeys, across six variants of novelty-based memory tasks. The results showed that monkeys with damage to the amygdala or OFC performed better overall than control monkeys across the tasks. The results indicated that neither region was essential for discriminating novel from familiar stimuli. Instead, the findings suggested that the improved performance observed in novelty-based tasks following damage to these regions was more likely attributable to influences on affect. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Acoustic startle and prepulse inhibition deficits in adult monkeys with neonatal lesions of the hippocampus, amygdala and orbital frontal cortex.

Sensory-motor gating, the process of filtering sensory stimuli to modulate motor responses, is impaired in many psychiatric diseases but especially schizophrenia. Sensory-motor gating assessed with the prepulse inhibition paradigm (PPI) measures startle in response to preceding acoustic stimuli. PPI studies in rodents have consistently found that neonatal hippocampal lesions impair sensory-motor gating in adult animals, but its applicability to primates has yet to be tested. The study examined acoustic startle responses and PPI in adult rhesus monkeys with neonatal lesions of the hippocampus (Neo-Hibo), amygdala (Neo-Aibo), and orbital frontal cortex areas 11 and 13 (Neo-Oasp) and with sham-operations (Neo-C). All monkeys were initially habituated to the startle apparatus and assayed for acoustic startle response curves. Subsequently, PPI was measured with the prepulse occurring at 60, 120, 240, 480, 1000 and 5000 msec prior to the pulse onset. No significant group differences in baseline startle were found. Compared to Neo-C monkeys, Neo-Hibo monkeys showed normal startle curves as well as normal PPI at short prepulse delays but prepulse facilitation (PPF) at longer prepulse intervals. Neo-Aibo monkeys displayed enhanced startle responses with only minor changes in PPI, whereas Neo-Oasp monkeys had severe dampening of startle responses and impaired PPI at shorter prepulse intervals. These results support prior evidence from rodent literature of the involvement of each of these areas in the development of the complex cortico-limbic circuit modulating sensory-motor gating and may shade light on the specific neural structures associated with deficits in PPI reported in neuropsychiatric disorders, such as schizophrenia, autism spectrum disorders, and post-traumatic disorders.

Differential responses toward conditioned and unconditioned stimuli, but decreased hypothalamic-pituitary-adrenal axis responsiveness in neonatal hippocampal lesioned monkeys.

The hippocampus is important for long-term memory storage, but also plays a role in regulating the hypothalamic-pituitary-adrenal (HPA) axis and emotional behaviors. We previously reported that early hippocampal damage in monkeys result in increased anxious expression and blunted HPA responses to an acute stressor. Here, we further probe their responses toward aversive stimuli (conditioned and unconditioned) and evaluate HPA axis dysfunction. Responses toward social, innate, and learned aversive stimuli, fear potentiated acoustic startle, and pituitary-adrenal function were investigated in 13 adult rhesus monkeys with neonatal hippocampal lesions (Neo-Hibo=6) and controls (Neo-C=7). Neo-Hibo monkeys' responses depend on the type of unconditioned stimulus, with increased anxiety behaviors toward social and learned, but decreased reactivity toward innate stimuli. Neo-C and Neo-Hibo monkeys exhibited similar performance learning conditioned cues and safety signals. Neo-Hibo monkeys were less sensitive to HPA axis stimulation, potentially suggesting adrenal fatigue. Current findings suggest that the hippocampus plays a large role in regulating not only anxiety behaviors, but also the HPA-axis, a neural system crucial to regulate how we respond to the world around us. These data have important clinical significance considering that many developmental neuropsychiatric disorders exhibit altered hippocampal structure and function, emotional and HPA axis dysregulation.

Emotional responses in monkeys differ depending on the stimulus type, sex, and neonatal amygdala lesion status.

The amygdala plays an essential role in evaluating social information, threat detection, and learning fear associations. Yet, most of that knowledge comes from studies in adult humans and animals with a fully developed amygdala. Given the considerable protracted postnatal development of the amygdala, it is important to understand how early damage to this structure may impact the long-term development of behavior. The current study examined behavioral responses toward social, innate, or learned aversive stimuli among neonatal amygdala lesion (Neo-Aibo; males = 3, females = 3) or sham-operated control (Neo-C; males = 3, females = 4) rhesus macaques. Compared with controls, Neo-Aibo animals exhibited less emotional reactivity toward aversive objects, including faster retrieval of food reward, fewer fearful responses, and more manipulation of objects. This lower reactivity was only seen in response to social and innate aversive stimuli, whereas Neo-Aibo animals had similar responses to controls for learned aversive stimuli. The current study also detected sex differences in behavioral response to aversive stimuli, such that, as compared with males, females took longer to retrieve the food reward across all aversive stimuli types, but only expressed more hostility and more coo vocalizations during learned aversive trials. Early amygdala damage impacted the expression of some, but not all, sex differences. For example, neonatal amygdala damage eliminated the sex difference in object manipulation. These findings add important information that broaden our understanding of the role of the amygdala in the expression of sexually dimorphic behaviors, as well as its role in learning fear associations and threat detection. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Impaired safety signal learning may be a biomarker of PTSD.

A dysregulated fear response is one of the hallmark clinical presentations of patients suffering from posttraumatic stress disorder (PTSD). These patients show over-generalization of fear and in tandem an inability to inhibit fear responses in the presence of safety. Here, we summarize our recent findings using a conditional discrimination paradigm, which assesses safety signal processing (AX+/BX-) in combat and civilian PTSD populations. Overall, PTSD subjects demonstrate a lack of safety signal learning and an inability to modulate the fear responses with safety cues. We then review studies of the neurobiology of fear expression and inhibition in humans and non-humans, in order to provide a background for preliminary studies using reverse translation procedures in which the same AX+/BX- paradigm was used in rhesus macaques. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.