Cerebellar Contribution to Context Processing in Extinction Learning and Recall

Abstract

Whereas acquisition of new associations is considered largely independent of the context, context dependency is a hallmark of extinction of the learned associations. The hippocampus and the prefrontal cortex are known to be involved in context processing during extinction learning and recall. Although the cerebellum has known functional and anatomic connections to the hippocampus and the prefrontal cortex, cerebellar contributions to context processing of extinction have rarely been studied. In the present study, we reanalyzed functional brain imaging data (fMRI) of previous work investigating context effects during extinction in a cognitive associative learning paradigm in 28 young and healthy subjects (Lissek et al. Neuroimage. 81:131-3, 2013). In that study, event-related fMRI analysis did not include the cerebellum. The 3 T fMRI dataset was reanalyzed using a spatial normalization method optimized for the cerebellum. Data of seven participants had to be excluded because the cerebellum had not been scanned in full. Cerebellar activation related to context change during extinction learning was most prominent in lobule Crus II bilaterally (p<0.01, t>2.53; partially corrected by predetermined cluster size). No significant cerebellar activations were observed related to context change during extinction retrieval. The posterolateral cerebellum appears to contribute to context-related processes during extinction learning, but not (or less) during extinction retrieval. The cerebellum may support context learning during extinction via its connections to the hippocampus. Alternatively, the cerebellum may support the shifting of attention to the context via its known connections to the dorsolateral prefrontal cortex. Because the ventromedial prefrontal cortex (vmPFC) is critically involved in context-related processes during extinction retrieval, and there are no known connections between the cerebellum and the vmPFC, the cerebellum may be less important during extinction recall.

Integrating Spatial Working Memory and Remote Memory: Interactions between the Medial Prefrontal Cortex and Hippocampus

“…Many other brain areas have been implicated in spatial processing including visual areas [29], parietal areas [30], auditory areas [31], the amygdala [32], the striatum [33], the mPFC [34], and even the cerebellum [35]. When analyzing neural networks involved in cognitive processes, some areas play specific roles and others may serve as more central processing nodes.…”

Beyond the classic extinction network: a wider, comparative view

“…Renewal effects, however, appeared to be impeded in patients with lesions of the more posterolateral cerebellar hemisphere which has connections with the prefrontal cortex and hippocampus (Bostan et al, 2013;Watson et al, 2019). Furthermore, we found activation of the posterolateral cerebellar hemisphere related to context change during extinction learning of cognitive associations in healthy participants in a 3T fMRI study (Chang et al, 2015). Our findings suggest that the cerebellum contributes to context-related effects of extinction.…”

A translational perspective on neural circuits of fear extinction: Current promises and challenges

“…This does not implicate that there are no neurons in other regions involved in the processes of interest. As another example, recent studies showed that the cerebellum contributes to fear extinction learning (Chang et al, 2015; Utz et al, 2015), an observation that was confirmed by a recent meta-analysis of extinction (Fullana et al, 2018). The cerebellum is however often ignored, or in many human neuroimaging research not even scanned.…”