Functional gradients of striatum and its linkage with frontal cortical function in cocaine addiction

491 

Abstract Submission 

Ran Zhang¹, Feng Zhou¹, Ting Xu², Debo Dong¹, Yawei Qi¹, Qinghua He¹

¹Southwest University, Chongqing, China, ²University of Electronic Science and Technology of China, Chengdu, Sichuan, China

Ran Zhang  
Southwest University
Chongqing, China

Feng Zhou  
Southwest University
Chongqing, China

Ting Xu  
University of Electronic Science and Technology of China
Chengdu, Sichuan, China

Debo Dong  
Southwest University
Chongqing, China

Yawei Qi  
Southwest University
Chongqing, China

Qinghua He  
Southwest University
Chongqing, China

Dysregulated striatal function and executive control deficits are typically characterized in the development and perpetuation of cocaine addiction, as evidenced by animal models and human neuroimaging studies. Recently, connectome gradient-based approaches have emerged as a promising alternative to traditional parcellation-based methods for indicating continuous variations in neural organization across cortical and subcortical systems. These approaches pose huge potential in offering a novel perspective on elucidating dysfunction of striatum in cocaine addiction. Here we systematically examined the abnormalities of intra-striatal and striatal-cerebral cortex functional connectome gradient in cocaine users and revealed the effect of repetitive transcranial magnetic stimulation (rTMS) on striatal function, to facilitate the understanding about functional connectome hierarchy of striatum in cocaine addiction and treatment targets.

In the present study, we investigated cocaine use disorder (CUD)-related alterations in the intra-striatal and striatal-cerebral cortex functional gradient using resting-state functional magnetic resonance imaging (MRI) data from 85 participants (41 patients and 44 healthy controls (HC)). To validate our findings, we included two groups of patients with cocaine addiction, who were randomly assigned to receive either active or sham rTMS treatment over the left dorsolateral prefrontal cortex (dlPFC) and underwent pre- and post-treatment assessments. Based on the observed gradient changes, we used the left caudate cluster as seed to compute Pearson' correlation coefficient between each voxel in the cerebral cortex, and then compared these functional connectivity (FC) patterns between different groups to clarify the FC associated with principle gradient alterations.

Consistent with previous studies, our findings confirmed the presence of the primary intra-striatal gradient that delineates fundamental anatomical subdivisions. This gradient follows a gradual axis extending from the caudate to the nucleus accumbens and ultimately to the caudal putamen. Compared to the HC group, CUD group exhibited increased abnormal gradient values mostly in the left caudate (x/y/z: -8/6/14, T = 4.86, pfwe-voxel < 0.05), with the same findings observed in their striatal-cortical functional gradient maps. To further validate our findings, we conducted the same functional gradient analysis in an independent longitudinal MRI study that examined the effectiveness of rTMS over the dlPFC for CUD. Results demonstrated a significant group × time interaction effect (F(1,42) = 4.75, p = 0.03, partial η2=0.10). Post-hoc tests revealed that active rTMS led to significantly lower gradient values in the left dorsal caudate relative to sham stimulation (t42 = -1.88, p = 0.07). Given that patients receiving active rTMS had an alteration in abnormal gradient values, the left dorsal caudate-based FC analysis was conducted to show whether the gradient variations are associated with FC. Results showed that both the CUD group and the active treatment group exhibited alternative FC to several prefrontal regions (e.g., dlPFC), in comparison to the control groups.

Our study characterized the functional gradient of striatal function in patients with CUD and revealed the aberrant gradient values specifically in the left dorsal striatum. In addition, we identified that rTMS treatment may have a beneficial effect on the neural activity within the dorsal stratum. These findings suggest that alterations in striatal organization could serve as a neurobiological trait marker across cocaine addiction and may further enhance the progress of developing new potential therapeutics.

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

fMRI Connectivity and Network Modeling ²

Addictions

FUNCTIONAL MRI

Sub-Cortical

Transcranial Magnetic Stimulation (TMS)