RDoC-based categorization of amygdala functions and its implications in autism

Abstract

Confusion endures as to the exact role of the amygdala in relation to autism. To help resolve this we turned to the NIMH's Research Domain Criteria (RDoC) which provides a classification schema that identifies different categories of behaviors that can turn pathologic in mental health disorders, e.g. autism. While RDoC incorporates all the known neurobiological substrates for each domain, this review will focus primarily on the amygdala. We first consider the amygdala from an anatomical, historical, and developmental perspective. Next, we examine the different domains and constructs of RDoC that the amygdala is involved in: Negative Valence Systems, Positive Valence Systems, Cognitive Systems, Social Processes, and Arousal and Regulatory Systems. Then the evidence for a dysfunctional amygdala in autism is presented with a focus on alterations in development, prenatal valproic acid exposure as a model for ASD, and changes in the oxytocin system therein. Finally, a synthesis of RDoC, the amygdala, and autism is offered, emphasizing the task of disambiguation and suggestions for future research.

Keywords: Amygdala; Autism; Oxytocin; Research domain criteria; Review; Valproic acid.

Figure 1:

The human amygdala, from Schumann 2011.

Figure 2:. Components, inputs, and outputs of the amygdala.

The BLA has bidirectional connections to sensory and cortical areas including the Insula, Fusiform gyrus, Prefrontal Cortex (PFC), Orbital Frontal Cortex (OFC), Anterior Cingulate Cortex (ACC), and Superior Temporal Sulcus (STS), as well as temporal memory areas including CA1 and 3 of the Hippocampus, and Entorhinal cortex. The BLA innervates the Ventral Striatum, including the Nucleus Accumbens core (NAcc) and shell (NAcs), and the Bed Nucleus of the Stria Terminalis (BNST) which is also connected with the CeA. Monoaminergic modulation of the BLA comes from the Dorsal Raphe, Ventral Tegmental Area (VTA), Substantia Nigra (SN), and Locus Coeruleus (LC). The CeA is connected to the Basal Forebrain including the Medial Septal Nucleus (mSN) and the Substantia Inominata (SI), which contains the Nucleus Basalis and together with the Ventral Pallidum (innervated by the BLA) provides cholinergic input to the BA. The CeA also connects to regions in the brainstem, midbrain, and pons, such as the Parabrachial nucleus (PBN), Caudal Pontine Reticular Nucleus (PnC), Periaqueductal Gray (PAG), and Nucleus of the Solitary Tract (NTS). The CeA projects to regions of the hypothalamus including the Dorsomedial Hypothalamic Nucleus (DMH), Posterior Paraventricular Thalamus (pPVT), Lateral Hypothalamus (LH), and Superchiasmatic Nucleus (SCN). Dashed line from Thalamus to CeA indicates a small number of direct projections there vs. substantial innervation of the LA.

Figure 3:

Developmental expansion of BLA dendritic arbors, from Ryan 2016.