Multi-modal MRI of hippocampal morphometry and connectivity after pediatric severe TBI

Abstract

This investigation explores memory performance using the California Verbal Learning Test in relation to morphometric and connectivity measures of the memory network in severe traumatic brain injury. Twenty-two adolescents with severe traumatic brain injury were recruited for multimodal MRI scanning 1-2 years post-injury at 13 participating sites. Analyses included hippocampal volume derived from anatomical T1-weighted imaging, fornix white matter microstructure from diffusion tensor imaging, and hippocampal resting-state functional magnetic resonance imaging connectivity as well as diffusion-based structural connectivity. A typically developing control cohort of forty-nine age-matched children also underwent scanning and neurocognitive assessment. Results showed hippocampus volume was decreased in traumatic brain injury with respect to controls. Further, hippocampal volume loss was associated with worse performance on memory and learning in traumatic brain injury subjects. Similarly, hippocampal fornix fractional anisotropy was reduced in traumatic brain injury with respect to controls, while decreased fractional anisotropy in the hippocampal fornix also was associated with worse performance on memory and learning in traumatic brain injury subjects. Additionally, reduced structural connectivity of left hippocampus to thalamus and calcarine sulcus was associated with memory and learning in traumatic brain injury subjects. Functional connectivity in the left hippocampal network was also associated with memory and learning in traumatic brain injury subjects. These regional findings from a multi-modal neuroimaging approach should not only be useful for gaining valuable insight into traumatic brain injury induced memory and learning disfunction, but may also be informative for monitoring injury progression, recovery, and for developing rehabilitation as well as therapy strategies.

Keywords: Connectivity; Fornix; Hippocampus; Memory; TBI.

Fig. 1

Functional and structural hippocampal networks in TD group. A,B: Network of brain regions with significant functional connectivity to the hippocampus. C: Left hippocampal structural connectome (6 of the same regions were found for the right hippocampus). Abbreviations: parahippocampal gyrus (PG, note, the FreeSurfer definition of PG includes also the entorhinal cortex), thalamus (Thal), the medial occipito-temporal and lingual sulcus (collateral sulcus, CS), amygdala (Amyg), temporal pole (TP), calcarine sulcus (CalcS), anterior transverse collateral sulcus (ATCS), lingual part of the medial occipito-temporal gyrus (lingual gyrus, LG)

Fig. 2

Hippocampus volume by group and memory performance score. A-B, group comparison of left and right hippocampus volume between TBI (yellow) and control cohort (gray), adjusted for age and sex; *p < 0.05. C-D, left and right hippocampus volume as a function of CVLT T-score for TBI (yellow) and control cohorts (gray), adjusted for age and sex

Fig. 3

Fornix FA by group and memory performance. A-B, group comparison of left and right fornix FA between TBI (yellow) and control cohort (gray), adjusted for age and sex; *p < 0.05. C-D, left and right fornix FA as a function of CVLT T-score for TBI (blue) and control cohorts (gray), adjusted for age and sex

Fig. 4

Hippocampal connectivity and CVLT. Top panel: Structural connectivity and memory performance. Fiber bundle capacity as a function of CVLT T-score for TBI (yellow) and control cohort (gray), adjusted for age and sex, for hippocampus with (A) thalamus and with (B) calcarine sulcus. Bottom panel: Association between hippocampus functional network connectivity and memory performance for left (C) and right (D) hippocampi. Spearman rank correlation between Hippocampal FC and CVLT T-score is shown for TBI (yellow) and control (gray) subjects