Non-invasive mapping of connections of the human hippocampus using diffusion imaging

Introduction: There is only little evidence from in-vivo studies on how the human hippocampus is connected to other brain areas – most information is based on post-mortem or animal tracing studies. Here we identified and evaluated specific connections between the human hippocampus and 18 ipsi- and contralateral cortical and subcortical targets.

Methods and subjects: We applied a probabilistic tractography algorithm to diffusion weighted imaging data obtained from up to now 22 healthy subjects (12 male, mean age 36.18yrs, SD 12.46yrs). Seeds were the left and right hippocampus, defined by a combination of automatic and manual volumetry, and 18 targets taken from the AAL template. Diffusion weighted images were obtained using a 3T MRI scanner (Siemens Trio, Erlangen) with 60 gradient directions and three repetitions to improve signal-to-noise-ratio (scan parameters: TR 1200ms, TE 100, 72 axial slices, voxel size 1.7×1.7mm, matrix size 128×128, b-value 1000s/mm2). FMRIB Diffusion Toolkit (FDT, part of FSL, Ver. 4.1.1, FMRIB, Oxford) was used for both preprocessing and statistical analysis of DWI data. This approach allows the quantification of connectivity between different structures.

Results: The three main targets of hippocampal connectivity that were consistent throughout all 22 subjects were: the ipsilateral amygdala connected to the anterior part of the hippocampus, the ipsilateral striatum to more medial and the ipsilateral posterior cingulate/retrosplenial cortex to the more posterior parts of the hippocampus.

Conclusions: The hippocampus is a highly associative structure and essential for memory and other cognitive processes and therefore white matter connections to mesolimbic structures are well expected. Especially amygdalo-hippocampal pathways are involved in the influence of emotional stimuli on memory and connections with the striatum are known to be involved in memory-reward interactions. These results may shed further light on hippocampal connectivity in health and especially in diseases which are thought to involve the medial temporal lobe, as schizophrenia or medial temporal lobe epilepsy.

Comparison of connectivity-based segmentation of the left and right hippocampus in three different subjects.

This study was supported in part by the DFG research cluster TR3 “Mesial temporal lobe epilepsies“.