The nucleus accumbens (NAc), an integral part of basal forebrain, has become an important target of deep brain stimulation for some neuropsychiatric disorders when refractory to medical treatment. Within the nucleus there is a clear distinction between the shell and core subregions, defined by distinct cytoarchitectonics and connectivity patterns1. Growing evidence supported that the NAc has been involved in epileptogenesis, especially its shell portion2, 3. Previous studies performed NAc stimulation in patients with intractable partial epilepsy, which provided initial evidence for its safety and feasibility2. However little is known about the exact parcellation within the NAc in individuals, and structural alterations of NAc subdivisions in TLE patients remains unclear. The purpose of our study was to parcel nucleus accumbens into core and shell portions using DTI probabilistic tractography in individual mTLE patients for guiding NAc shell stereotactic target localization and investigate the structural alteration of each NAc subdivision in mTLE patients.

Subjects and data acquisition: MR imaging was conducted on 40 mTLE patients (17 left TLE patients, aged 26.9±12.1y; and 23 right TLE patients, aged 26.4±8.4y) and 25 age-matched controls (age 27.6±13.2y) using a 3.0T MR scanner (Philips Achieva TX) with 8-channel head coil. The DTI acquisition was planned along the AC/PC line using a SE-EPI sequence with TR=9737 ms, TE=88 ms, b=1000 s/mm2, gradient directions=32, FOV= 224 × 224 mm, 112 × 112 matrix, isotropic 2 mm resolution, 70 axial slices with no interslice gap. For anatomical segmentation a 3D T1-weighted scan with was also performed.

Data analysis: The DTI connectivity-based parcellation was performed using procedures described in a previous report4. For each subject, T1-weighted scans were processed using FIRST (fMRIB Integrated Registration and Segmentation Tool) to localize the NAc. We transformed the NAc seed mask to the individual DTI space. Whole-brain probabilistic tractography was performed using the PROBTRACKX to estimate the connections between each NAc seed voxel and any target voxel in the whole brain. The connectivity matrixbetween NAc seed voxels and target voxels was derived, and used to generate a symmetric cross-correlation matrix .The cross-correlation matrix was fed into a k-means clustering algorithm to group together the seed voxels that share a similar connection profiles with the rest of the brain. The automated classification using k-means clustering produced individual parcellation of the NAc into 2 subdivisions. Putative core and shell portions were identified by the location and shape as described in previous anatomical researches5. Then we measured diffusion parameters of each NAc subdivison for statistics.

Statistical analysis: Using the independent-samples t-test, the diffusion parameters included FA, MD, parallel (λ||) and perpendicular diffusivity(λ⊥) in left and right mTLE groups were respectively compared with those in control group for each NAc subdivision

In each subject, we observed an approximate medial–lateral parcellation, dividing the NAc into two parts. The location and shape of the two portions approximately matched cytoarchitecturally identified NAc core and shell in postmortem human tissue4. Based on this correspondence, we identified the medial–caudal portion as putative shell (pshell) and the lateral–rostral portion as putative core (pcore) of NAc. Individual parcellation illustration for one subject is shown in Figure 1. The result of t-tests of diffusion parameters are shown in Table 1. Compared to control group, left mTLE group showed significantly decreased FA while elevated MD, parallel (λ||) and perpendicular diffusivities (λ⊥) in the left pshell portion, as well as increased perpendicular diffusivity (λ⊥) in the right pshell portion, but did not show significant differences in the pcore portion. The right mTLE group exhibited decreased FA and increased perpendicular diffusivity (λ⊥) in the left pshell portion, as well as an elevated L3 value in the right pshell. The right pcore of NAc in right mTLE group also appeared decreased FA, yet the left pcore portion did not yield any significant differences.This is the first study to parcel nucleus accumbens into core and shell portions using DTI probabilistic tractography among individual mTLE patients. The exact stereotactic anatomy of the core and shell portion of NAc would help neurosurgeons to perform the NAc shell deep brain stimulation (DBS) in suppressing seizure propagation. Our results revealed that both left and right mTLE patients exhibited decreased FA as well as increased MD and parallel and perpendicular diffusivities in shell portion of bilateral NAc, while absence of significant alterations in the core, which may reflect neuronal degeneration and damage mainly in shell portions caused by seizure, and suggest a possible role of the NAc shell in epileptogenesis.