Brain tissue properties differentiate between motor and limbic basal ganglia circuits

Abstract

Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high-resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of changes in the established covariance pattern aiming at accurate diagnosis of basal ganglia disorders and prediction of treatment outcome.

Keywords: MT; R2*; diffusion-weighted imaging; multiparameter mapping; voxel-based quantification.

Figure 1

Representation of averaged (n = 13) subthalamic nucleus—STN, probabilistic connectivity gradients for motor, associative, and limbic cortical areas. Hot colors represent high connectivity probability, and cold colors represent low probability. Axial (left panel), coronal (middle panel), and sagittal view (right panel) of connectivity to limbic (top row), associative (middle row), and motor (bottom row) cortical areas. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 2

Covariance of multiparameter maps between motor and limbic/associative STN subregions and corresponding areas in basal ganglia. Statistical parametric maps of significant magnetization transfer (MT) saturation, longitudinal relaxation rate R1 (1/T1), and effective transversal relaxation rate (R2*) covariance with limbic/associative (yellow) and motor STN (blue) are superimposed on averaged MT saturation maps of all study participants. Results are presented after P < 0.05 family‐wise error correction for multiple comparisons. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 3

Panel right: Representation of tissue property covariance results within the striatum (putamen and caudate nucleus). Statistical parametric maps of tissue property covariance between striatum and limbic/associative (yellow) or motor (blue) STN. Magnetization transfer (MT) saturation maps best captures limbic/associative covariance (yellow), while effective transverse relaxation rate, R2*, is more relevant for motor covariance (blue). Panel left: Corresponding slices from tracing studies in non‐human primates (from Haber, 2010, with permission). OFC, orbitofrontal cortex; DPFC, dorsolateral prefrontal cortex; vmPFC, ventromedial prefrontal cortex. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]