**1. Introduction**

Traumatic brain injury (TBI) is the leading cause of death and disability in individuals below age 45, which typically caused by motor vehicle crashes, falls, contact sports, or

**Citation:** Xue, Q.; Wang, L.; Zhao, Y.; Tong, W.; Wang, J.; Li, G.; Cheng, W.; Gao, L.; Dong, Y. Cortical and Subcortical Alterations and Clinical Correlates after Traumatic Brain Injury. *J. Clin. Med.* **2022**, *11*, 4421. https://doi.org/10.3390/ jcm11154421

Academic Editor: Elliott J. Mufson

Received: 23 May 2022 Accepted: 5 July 2022 Published: 29 July 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

assaults. TBI often results in persistent cognitive impairment and psychiatric symptoms, including memory deficit, anxiety, and depression, which exert a negative impact on quality of life and rehabilitation process [1–3]. Due to the significant heterogeneity in the clinical presentation and neuropathological across TBI patients, it is challenging to predict the risk of comorbid psychiatric disorders and cognitive impairment [4]. Previous studies found that TBI severity is not correlated with neuropsychiatric outcome [5,6]. Meanwhile, previous findings for the correlation between lesion location and cognitive function and psychiatric complaints were inconsistent [7].

Although TBI is heterogeneous in the cause and intensity of impact, it still exhibits a featured pattern of anatomical injuries. The impact typically results in contusions involving the basal and polar regions of the frontal and temporal lobes [8,9]. Besides focal brain injuries, diffuse axonal injuries (DAI) occur after TBI, which frequently affect the frontal and temporal WM, corpus callosum, and brainstem [10]. Traditionally, cognitive deficits and psychiatric disorders following TBI are considered to be associated with prefrontal and medial temporal lobe lesions, however the location and extent of these contusions often cannot fully explain the patient s impairments [11–14]. During the acute and subacute stages of TBI, secondary damages including inflammation, apoptosis, excitotoxicity, and prolonged hypo-perfusion result in progressive and widespread white matter (WM) atrophy and gray matter (GM) volume loss across large areas of the brain spanning most of the cortex and subcortical areas over time [14–16]. These abnormalities in the parietal and occipital lobes and subcortical regions including basal ganglions and thalamus are closely related to post-traumatic cognitive functions and psychiatric symptoms [14,17,18]. Due to the heterogeneity inherent to study design and various pipelines of data pre-processing, parcellation, and analysis among the previous studies, the topographical distribution of morphometric changes and their clinical associations related to post-traumatic psychiatric symptoms and memory function remains inconsistent.

In the present study, we assessed the cortical and subcortical GM and WM damage and its relation to post-traumatic neuropsychological measurements of anxiety and depressive symptoms and memory function. We then investigated the relationships between disruption of WM microstructure and the decrease in GM volume. We aimed to obtain a comprehensive understanding of the relationship between the structural alterations and psychiatric symptoms and memory following TBI and determine the brain regions correlated with clinical measurements.
