Study finds alterations in brain connectivity among young adult cannabis users

Globally, cannabis use has increased in recent years. According to the World Health Organization (WHO), about 147 million people, or 2.5% of the world population, consume cannabis. The neurobiological mechanisms of cannabis are yet to be identified, particularly in youth. Cannabis dependence has been associated with a wide range of neurocognitive deficits, such as risky behaviors, impaired episodic memory, and weak performance in tasks that require cognitive function.

Study: Altered brain structural and functional connectivity in cannabis users. Image Credit: Lightspring / Shutterstock

Background

Network analyses and morphometry are two methods commonly used to analyze how cannabis affects brain structure and function. Morphometry analysis provides insights into the changes in the thickness or volume of brain tissues. Although prior research did not find any morphological alterations in the brain of individuals under high cannabis use, recent evidence contradicts this finding. Recent studies have indicated that cannabis use induces parahippocampal, hippocampal, and lateral atrophy. 

Changes in brain structure and function might not occur solely due to local changes in brain morphology but also to alterations in interactions between brain regions. As a result, many studies developed brain modeling as a network to understand the factors responsible for the changes in brain function and structural connectivity due to chronic cannabis use. 

The majority of the large-scale brain network studies have presented heterogeneous findings on how cannabis use affects the brain’s structural and functional connectivity. One previous study evaluated the effect of prolonged cannabis use on axonal connectivity and found compromised structural connectivity in the splenium of the corpus callosum, commissural fibers, and fornix. An increased structural fractional anisotropy was observed in regular cannabis users.

Analysis of resting-state functional connectivity in cannabis users revealed an enhanced local functional connectivity in the midbrain, ventral striatum, brainstem, and lateral thalamus. A seed-based connectivity analysis revealed no significant differences in whole-brain functional connectivity between healthy controls and cannabis users. A graph theoretical analysis also indicated no difference in regional and global properties of resting-state functional networks between non-cannabis and cannabis users.

Densely-connected hubs, known as “rich clubs,” have been identified in brain networks. These play a crucial role in information integration across structural and functional brain networks. However, not many studies have analyzed the alternations in functional and structural connectivity of brain networks in cannabis users.

About the Study

A recent Scientific Reports study has investigated the alterations in brain functional and structural connectivity in cannabis users and compared the results with healthy controls. The changes in the rich club organization in cannabis users were also studied using graph theoretical metrics.

Participants were included in the Human Connectome Project (HCP) dataset, 72 of whom were cannabis users. In addition, 73 healthy individuals were recruited for the control group. Diffusion-weighted images (DWI) and resting-state functional magnetic resonance images (rs-fMRI) were analyzed in this study.

Study Findings

The graphical measures revealed no significant difference in global network measures for either structural or functional networks between cannabis users and healthy controls. However, a considerable difference was observed in the clustering coefficient and nodal degree for functional and structural networks between the two groups.

Compared to control, the structural networks in cannabis users exhibited lower degree centrality within the left frontal opercular, inferior parietal cortex, posterior opercular cortex, and in right lateral temporal, visual areas, and posterior cingulate. Compared to the control, an increased structural degree in a few nodes in the left parieto-occipital regions, including V3CD was observed in cannabis users. In the context of functional networks, a significant decrease in the left frontal operculum was observed in cannabis users.

Processing pipeline for brain structural and functional Network Analysis. A structural connectome was constructed for each individual using fiber tractography and a parcellation scheme. A functional connectome was also constructed for each individual by calculating the pairwise Pearson’s correlation coefficient of the average time courses of 379 regions. A graph-theoretical analysis was then performed to investigate the topological properties and rich-club organization of the structural and functional brain networks in both healthy controls and cannabis users.

A higher clustering coefficient was observed, which indicated elevated local segregation within the frontoparietal regions that include inferior frontal cortices, frontal opercular, and the premotor cortex structural networks. In addition, some regions in the posterior areas, such as the ventral stream visual cortex and V3CD, exhibited lower coefficients in cannabis users.

In cannabis users, the functional networks were characterized by elevated clustering coefficients in the ventral stream visual cortex, left inferior frontal cortex FST, and area TG dorsal. A lower local functional segregation was observed within the right hemisphere in the dorsolateral prefrontal cortex, Diencephalon ventral area, and para hippocampal region in cannabis users, compared to the control group.

The current study observed that the structurally rich club nodes were primarily present in the left bilateral frontal, temporal, and centro-occipital areas, along with deep brain structures for cannabis users and non-users. Interestingly, compared to the control group, the structural networks in cannabis users exhibited a higher and lower number of rich-club nodes within the superior and inferior temporal gyri, respectively. The functional rich-club nodes were mostly distributed within parietal and posterior areas for both groups. 

Conclusions

The current study investigated the alterations in the brain structural and functional connectivity in cannabis users based on a graph-theoretic analysis. The brain network of both groups exhibited small-world properties. Regional effects on network segregation and integration measures were observed, which were more prominent in the insular, frontal opercular, and lateral/medial temporal cortices. Nevertheless, no change in the global properties of the brain network was observed. The rich-club analysis revealed no significant difference between the two groups. In the future, time-varying changes in resting state functional connectivity patterns in cannabis users must be studied.