Resting state connectivity of the human habenula at ultra-high field

Abstract

The habenula, a portion of the epithalamus, is implicated in the pathophysiology of depression, anxiety and addiction disorders. Its small size and connection to other small regions prevent standard human imaging from delineating its structure and connectivity with confidence. Resting state functional connectivity is an established method for mapping connections across the brain from a seed region of interest. The present study takes advantage of 7T fMRI to map, for the first time, the habenula resting state network with very high spatial resolution in 32 healthy human participants. Results show novel functional connections in humans, including functional connectivity with the septum and bed nucleus of the stria terminalis (BNST). Results also show many habenula connections previously described only in animal research, such as with the nucleus basalis of Meynert, dorsal raphe, ventral tegmental area (VTA), and periaqueductal grey (PAG). Connectivity with caudate, thalamus and cortical regions such as the anterior cingulate, retrosplenial cortex and auditory cortex are also reported. This work, which demonstrates the power of ultra-high field for mapping human functional connections, is a valuable step toward elucidating subcortical and cortical regions of the habenula network.

Trial registration: ClinicalTrials.gov NCT00047853.

Keywords: 7T; Anxiety; Depression; Seed-based functional connectivity.

Figure 1

Whole brain (within field of view) results in axial slices, overlaid on averaged group anatomy that had been nonlinearly normalized to an MNI template. p<0.0000001. Left is left. The same thresholding and color scale are used for Figures 2 and 3. Note that the large epi/thalamus cluster does not include the lateral geniculate nucleus, medial geniculate nucleus, lateral pulvinar and anterior lateral nuclei.

Figure 2

A–F: Habenula functional connectivity with subcortical regions, magnified views. Overlaid on MNI2009a template.

Figure 3

A–C: Habenula functional connectivity with cortical regions. Arrows (left to right) point to A: supragenual anterior cingulate cortex (ACC), dorsal ACC and posterior ACC. B: retrosplenial cortex. C: left primary auditory cortex and posterior insula.