Examining Hippocampal-Cerebellar Functional Connectivity across the Lifespan

2131 

Abstract Submission 

Kavishini Apasamy¹, Narender Ramnani¹, Carl Hodgetts²

¹Royal Holloway, University of London, Egham, United Kingdom, ²Royal Holloway University of London, London, United Kingdom

Kavishini Apasamy  
Royal Holloway, University of London
Egham, United Kingdom

Narender Ramnani  
Royal Holloway, University of London
Egham, United Kingdom

Carl Hodgetts  
Royal Holloway University of London
London, United Kingdom

Evidence from nonhuman species suggests that the hippocampus and cerebellum interact closely to support spatial cognition, with cerebellar disruption influencing hippocampal place cell coding and navigational behaviour (Rochefort et al., 2011). Neuroanatomical studies in nonhuman species suggest that these functional interactions may be mediated by direct (Heath and Harper, 1974) and indirect pathways, with the hippocampus receiving input from disparate parts of the cerebellar cortex, including lobule HVI, HVIIA (Crus I) and paraflocculus (Watson et al., 2019). However, the hippocampal-cerebellar connectivity remains poorly understood in humans. Given that hippocampal-connected areas of the cerebellum (lobule HVIIA and HVI) appear highly sensitive to ageing (Ramanoël et al., 2013), characterising this functional interaction has implications for understanding both the properties of an extended navigation system and its potential vulnerability to ageing and neurodegeneration.

Using CONN toolbox (Nieto-Castanon, 2022), we applied seed-based functional connectivity analyses to task-free fMRI data from 479 adults in the Cambridge Centre of Ageing and Neuroscience (CamCAN) dataset (330F, 323M, mean age= 54.3, SD= 18.6, range= 18-87) (Taylor et al., 2017). The hippocampal seed region-of-interest (ROI) was created using the Harvard-Oxford and Julich histological atlases and split into anterior and posterior subdivisions at the uncal apex. The cerebellum was interrogated using the SUIT Probabilistic Atlas (Diedrichsen et al., 2009). For seed-based analyses, fMRI time series of our hippocampal seeds (left, right, anterior, posterior) were used as regressors to examine Fisher-transformed correlation coefficients within the whole cerebellar cortex. Results were corrected for multiple comparisons in SPM12 (p<.05 FWE) and displayed on cerebellar flatmaps using SUIT.

We found strong functional connectivity between the hippocampus and widespread areas of the cerebellum, including the border of lobule HVI and HV, lobule HIX and lobule HVIIA. Contrasting the left and right hippocampus showed that they were preferentially connected with an area within contralateral lobule HVIIA (Fig 1a and 1b). Direct contrasts between the anterior and posterior hippocampus revealed that the anterior hippocampus displayed preferential connectivity with bilateral regions of lobule HVIIA (peak in right Crus II) (Fig 1c). In contrast, the posterior hippocampus showed stronger connectivity with lobule V (Fig 1d). Finally, we found strong age-related reductions in functional connectivity between the hippocampus and lobule HV and HVI. Similar patterns were observed for the anterior hippocampus, but the posterior hippocampus showed minimal age-related alterations in connectivity (Fig. 2).

These findings provide novel insights into the organisation of the hippocampal-cerebellar connectivity in humans. Aligning with nonhuman animal work, we show that the hippocampus functionally connects to widespread areas of the cerebellum, particularly lobule HVI and HVIIA (Crus I). Unlike prior anatomical work, however, we observed strong connectivity with lobule HVIIA (Crus II, rather than Crus I), as well as lobule HIX and HX. Functional connectivity differences between anterior and posterior hippocampus suggest that long-axis subdivisions based on neocortical connectivity are maintained in cerebellum. Ageing most strongly affected functional connectivity between the hippocampus and lobule HV and HVI, consistent with evidence showing age-related atrophy in lobule HVI (Ramanoël et al., 2013), which could be related to age-related behavioural deficits. Future studies are required to test novel hypotheses about the functional role of this interaction in humans, such as whether cerebellar circuits store and use forward models of hippocampal function to automate hippocampal processes, as seen in frontal lobe circuits (Ramnani, 2014).

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)

Space, Time and Number Coding

Aging ²

fMRI Connectivity and Network Modeling

Cortical Anatomy and Brain Mapping ¹

Aging

Cerebellum

Cognition

Degenerative Disease

FUNCTIONAL MRI

Other - Hippocampus