Thalamocortical connectivity in healthy children: asymmetries and robust developmental changes between ages 8 and 17 years

Abstract

Background and purpose: Thalamocortical connections play a crucial role in complex cognitive functioning, and several neuropsychiatric disorders may involve aberrant thalamocortical circuitry. Here, we quantified the cortical pattern and age-related changes of thalamocortical connections by using probabilistic tractography in children and adolescents. We hypothesized that detectable asymmetry (left>right) exists in thalamocortical fiber connections and the connectivity increases with age during maturation.

Materials and methods: Diffusion tensor imaging was acquired in 15 normally developing children (age range, 8.3-17.3 years; 11 males), and fiber tracking was initiated from the thalami. The cortical distribution of ipsilateral thalamocortical fibers was quantified by using a landmark-constrained conformal mapping technique. Furthermore, hemispheric asymmetries and potential age-related changes in regional thalamocortical connections were assessed.

Results: The left thalamus had significantly higher overall cortical connectivity than the right thalamus (P < .001). Left prefrontal cortical areas showed significantly higher thalamic connectivity compared with homotopic regions of the right hemisphere (P < .001), regardless of the applied parameters. There was an increase of overall thalamocortical connectivity with age, with the most pronounced age-related increases in bilateral prefrontal areas (P < .002). However, thalamic connectivity of some other cortical regions (right sensorimotor, left inferior temporal) showed a decrease with age.

Conclusions: Our results indicate a region-specific left>right asymmetry and robust developmental changes in thalamocortical (particularly thalamo-prefrontal) connectivity during late childhood and adolescence. These data further add to our knowledge about structural lateralizations and their development in the maturing brain.

Fig 1.

Images showing the seed and target definition for fiber tracking. A, Regions of interest were drawn on 7 consecutive planes of each subject's FA images to outline the thalamus. These representative images of 1 subject show the 3D seed region of the left thalamus loaded in the native FSPGR space. B, Representative image of the target layer (white color) in one of the subjects. The target mask contained the layer between the cortical surface and the 2-mm shrunken white matter mask. FTEs were obtained by extending the surface elements 30 mm deeper into the brain to select the underlying portion of the target mask. C, Superior, lateral, and inferior views of the ICBM152 template brain surface with the 8 cortical target regions on each side encompassing sets of surface elements. The cortical regions were defined by using main sulci as references. Those surface elements that extended a landmark sulcus were assigned to the region to which their largest part belonged. Importantly, the territory outlined with magenta (on the inferior surface) was not analyzed.

Fig 2.

Average thalamocortical connectivity map of the 15 subjects visualized on the 3D brain surface of the ICBM152 template brain. The thalamocortical connectivity scores of each homotopic surface element were averaged among the 15 subjects, and the surface elements of the template brain were color-coded based on these average values. Notably, only the ipsilateral thalamic connections of each hemisphere are shown. It can be appreciated that the bilateral sensorimotor cortical areas have the strongest thalamic connectivity and that certain cortical regions (eg, prefrontal, inferior temporal) show profound hemispheric asymmetries.

Fig 3.

Bar graph showing the thalamocortical connectivity scores (mean ± SE) for the cortex (sum of the analyzed 8 regions) and each individual cortical region. Significant (P < .01) and reproducible (parameter-independent) left>right hemispheric asymmetries are indicated with asterisk.

Fig 4.

Scatterplot showing a significant positive correlation between age and thalamic connectivity scores of the left and right prefrontal cortex (P = .001 and P = .002, respectively).