Neural mechanisms of emotional health in traumatic brain injury patients undergoing rTMS treatment

Abstract

Emotional dysregulation such as that seen in depression, are a long-term consequence of mild traumatic brain injury (TBI), that can be improved by using neuromodulation treatments such as repetitive transcranial magnetic stimulation (rTMS). Previous studies provide insights into the changes in functional connectivity related to general emotional health after the application of rTMS procedures in patients with TBI. However, these studies provide little understanding of the underlying neuronal mechanisms that drive the improvement of the emotional health in these patients. The current study focuses on inferring the effective (causal) connectivity changes and their association with emotional health, after rTMS treatment of cognitive problems in TBI patients (N = 32). Specifically, we used resting state functional magnetic resonance imaging (fMRI) together with spectral dynamic causal model (spDCM) to investigate changes in brain effective connectivity, before and after the application of high frequency (10 Hz) rTMS over left dorsolateral prefrontal cortex. We investigated the effective connectivity of the cortico-limbic network comprised of 11 regions of interest (ROIs) which are part of the default mode, salience, and executive control networks, known to be implicated in emotional processing. The results indicate that overall, among extrinsic connections, the strength of excitatory connections decreased while that of inhibitory connections increased after the neuromodulation. The cardinal region in the analysis was dorsal anterior cingulate cortex (dACC) which is considered to be the most influenced during emotional health disorders. Our findings implicate the altered connectivity of dACC with left anterior insula and medial prefrontal cortex, after the application of rTMS, as a potential neural mechanism underlying improvement of emotional health. Our investigation highlights the importance of these brain regions as treatment targets in emotional processing in TBI.

Fig. 1. Methods overview.

Flowchart depicting the pipeline of analysis methods.

Fig. 2. Effective connectivity changes after treatment with rTMS.

a The connectivity matrix representing the difference between pre-rTMS and post-rTMS connectivity in active group. The green gradient illustrates increase while purple gradient depicts decrease in connectivity. b The brain diagram of the connectivity difference between pre-rTMS and post-rTMS in active group. Nodes represent the brain regions, edges represent the effective connectivity, green and purple arrows show increase and decrease in connectivity while solid and dashed lines represent excitatory and inhibitory connections respectively. All the connection here are in units of Hertz (Hz), except the self-connections which are log-scaled. All the connections reported here survived the threshold of posterior probability >0.95 amounting to a strong evidence.

Fig. 3. Association between post-rTMS effective connectivity and emotional health.

a The association matrix between post-rTMS connectivity of active group and emotional health scores. The purple gradient indicates negative association while green gradient shows positive association. b The brain diagram of the association between post-rTMS effective connectivity of active group and emotional health. Green and Purple arrows illustrate the positive and negative association respectively. All the associations reported here survived the threshold of posterior probability >0.95 amounting to a strong evidence.