Cerebellar connections with limbic circuits: Anatomy and functional implications

Abstract

There is an emerging body of evidence suggesting that the cerebellum participates in limbic-related functions including emotion and affect. The underlying connectivity of the cerebellar cortex and nuclei with limbic-related brain areas and associative and paralimbic cortices suggests widespread cerebellar influence on behaviors including the experience and expression of emotion, sadness and grief, integrative hypothalamic visceral/sensory functions, pain perception, modulation, and intensity due to noxious stimuli, as well as other nonmotor behaviors. The key anatomical relationships are the fastigial nucleus projections to the ventral tegmental area (VTA), cerebellar interconnections with the septum, hippocampus and amygdala, direct cerebellar connections with hypothalamic circuits that integrate somatic-, visceral-, and limbic-related activity, and indirect connections with the nucleus accumbens (NAcc), a mesolimbic dopaminergic structure that predicts activity in a reward paradigm in limbic-related structures. Additionally, the cerebellum is interconnected with cingulate cortices that play a role in motivation and emotional drive, and with associative and paralimbic regions of prefrontal, posterior parietal, superior temporal polymodal, and parahippocampal regions heavily implicated in high order processing important for the integration of cognition and emotion. These connections between cortical and subcortical areas of the limbic system with the cerebellum (vermis and fastigial nucleus in particular) are the likely anatomical underpinning of the demonstrated cerebellar influence on limbic-related behaviors in the clinical setting and in earlier behavioral and physiological studies. These cerebellar connections with cerebral limbic areas are also implicated in neurodevelopmental disorders such as autism which demonstrate neuropathology and aberrant neurochemistry in the cerebellar cortex and nuclei. Defining the vermis and fastigial nuclei as the probable location of the limbic cerebellum has relevance for future studies of cerebrocerebellar interconnections and functional coupling, and for therapeutic strategies that attempt to enhance cerebellar modulation of limbic-related structures in order to treat neuropsychiatric disorders.