Prof. Zhen Yuan’s group with the Center for Cognitive and Brain Sciences/Faculty of Health Sciences at the University of Macau, has achieved a series of significant advances in the field of behavioral addiction and decision making. They have systematically inspected the cognitive neural mechanism underlying behavioral addiction and decision-making. These pilot studies were published in several internationally renowned journals and their findings have received global attention in this field.

Behavioral addiction is a complex psychological and physiological phenomenon characterized by uncontrollable and compulsive repetitive behaviors, leading to a negative impact on an individual’s daily life. However, the cessation and treatment of addiction still face numerous challenges such as the high relapse rate. Therefore, gaining a deeper understanding of the cognitive neural mechanism associated with behavioral addiction including the detection of the changes in brain structure and functional networks, might pave a new avenue for the diagnosis and treatment of addiction.

Fig 1. Independent and conjunction analysis of rs-FC and GMV findings. A) Group difference in rs-FC between BA and HC groups. B) BA group showed reduced VBM results as compared to HC group. C) Analysis results based on the conjunction measure of rs-FC and VBM.

Prof. Yuan’s group discovered significant abnormalities in the large-scale brain networks of individuals with behavioral addiction. According to functional connectivity, they identified abnormal connections in networks related to inhibitory control, reward, and self-referential processes. These abnormal connections might contribute to impaired responses to inhibition, significant attribution, and reward-driven behaviors. Regarding brain structure changes, reduced volumes in the prefrontal cortex, anterior cingulate cortex, and gray matter of the frontal gyrus were detected for addicted individuals, demonstrating that these structural changes are associated with addiction-related cognitive and emotional regulation.

This work was published in the Journal of Behavioral Addiction’ (5 Year Impact Factor IF=8.9, JCR Q1), representing a significance advance in uncovering the neural mechanisms and offering a scientific basis for prevention and intervention of behavioral addiction.

In addition to behavioral addiction, Prof. Yuan’s team also inspected the cognitive process of decision-making. Decision-making is a crucial part of our daily lives, involving complex cognitive processes where individuals make choices based on rewards and risks. By studying decision-making behavior, we can not only uncover individual decision-making characteristics but also identify potential cognition changes in patients with certain diseases.

Fig 2. Schematic of the modified BART.

In particular, they discovered that chronic pain patients might exhibit more risk-taking behavior as compared to normal controls. Their study utilized a balloon analog risk task experiment to assess decision-making abilities. Their findings demonstrated that chronic pain patients tended to make more risk choices. Meanwhile, they might be more prone to generating unstable and impulsive actions when faced with decisions. Besides, Bayesian modeling revealed characteristics of weakened learning ability and increased randomness in decision-making processes among chronic pain patients. Their functional near-infrared spectroscopy imaging results demonstrated the chronic pain patients showed the changes in the function of prefrontal cortex (PFC) during decision-making. The abnormal PFC activity in patient groups might contribute more to their inclination towards risk decisions.

This work was published by the renowned neurophotonics journal Neurophotonics (Five-Year Impact Factor IF=5.3, JCR Q1) and was published online on May 18, 2023.

Fig 3. The activation patterns of PFC in BART. T-maps activation difference of PFC during BART between the chronic pain group and HCs。

Overall, this research sheds light on the challenges that chronic pain patients may encounter in decision-making, offering insights into their decision-making characteristics. Understanding these cognitive changes can contribute to the development of targeted interventions and support for individuals facing chronic pain.

The study was led by Prof. Zhen Yuan and PhD candidate Mr. Xinglin Zeng was the first author. This work was jointly supported by Macau Science and Technology Development Fund (FDCT 0048/2021/AGJ and FDCT 0020/2019/AMJ), Macao SAR Government Higher Education Fund (CP-UMAC-2020-01), and the University of Macau (MYRG 2020-00067-FHS and MYRG 2019-00082-FHS).

Paper Information:

Zeng, X., Han, X., Gao, F., Sun, Y., Yuan, Z. (2023). Abnormal structural alterations and disrupted functional connectivity in behavioral addiction: a multi-modality meta-analysis of VBM and fMRI studies. Journal of Behavioral Addictions, Accepted & In press.

Zeng, X., Tang, W., Gao, F., Tang, Z., Zhang, Z., Zhang, J., Du, M., Chen, Z., Chen, X., & Yuan, Z. (2023). Behavioral modeling and neuroimaging of impaired risky decision making in patients with chronic musculoskeletal pain. Neurophotonics, 10(2), 020901.

Further, Prof. Yuan Zhen’s research team has made significant progress in the construction of a human-to-monkey cross-species brain atlas to study addition and decision making. Their team used neuroimaging data from two populations to detect connectivity patterns that can achieve hierarchical parcellation of human-to-monkey brain subregions at a macroscopic level based on the differences within species and the similarities between homologous brain regions across species. Their team has designed two cross-species brain atlas construction schemes based on structural and functional neuroimaging modalities, and reliable partitioning analysis has been performed in key brain regions involved in addiction and decision-making, such as the substantia nigra and striatum. The relevant research work have been published in the international academic journals of Cerebral Cortex and Human Brain Mapping.

Brain atlases serve as a ‘navigation’ tool for the investigation of cognition and brain disorders. Traditional brain atlases are customized for single-species studies, where the mapping process considers only the differences in connectivity patterns between brain regions without any constraints of homology. This leads to a lack of well-established homologous mapping relationships between partitions obtained separately from multiple species, and even significant deviations. Applying traditional brain atlases to cross-species studies will inevitably introduce certain biases in the conclusions. On the other hand, the newly constructed brain atlas is specifically designed for cross-species research. The mapping process filters out species-specific details, resulting in reduced accuracy and precision of the atlas. By contrast, the knowledge generated based on this atlas exhibits significantly improved transferability.

Fig 4. Drawing of traditional single-species brain atlas and novel cross-species brain atlas. Schematic illustration of a demonstration of the second cross-species mapping scheme on the substantia nigra. Structural connectivity pattern based on striatum-sigma-striatum/thalamus (A), division of substantia nigra in a single species (B), cross-species division of human-macaque substantia nigra and corresponding two pairs of homologous subs District (C&D).

The striatum and substantia nigra are important subcortical nodes in the basal ganglia circuit. With the new approach, their team has redefined the striatum in the human-to-monkey brain as six pairs of homologous subregions, particularly a central region called the ventral striatum that processes reward and aversion information. Its functional abnormalities are strongly related to the onset and development of addiction. In particular, based on the striatum-substantia nigra-striatum loop connections, the team has mapped the substantia nigra in the human-to-monkey brain as two pairs of homologous subregions, highlighting their distinct connectivity patterns and functional implications. The research team has demonstrated the reliability of these partitions from multiple perspectives and pointed out that researchers can achieve reliable localization and subsequent investigations of addiction, decision-making, and related topics at a multi-species level based on these newly defined homologous subregions rather than using the traditional mapping methods.

The study was led by Prof. Zhen Yuan and postdoc fellow Dr. Xiaoluan Xia was the first author. This work was jointly supported by Macau Science and Technology Development Fund (FDCT 0048/2021/AGJ and FDCT 0020/2019/AMJ), Macao SAR Government Higher Education Fund (CP-UMAC-2020-01), and the University of Macau (MYRG 2020-00067-FHS and MYRG 2019-00082-FHS).

Paper Information:

Xia, X., Zeng, X., Gao, F., Yuan, Z. (2023). Mapping cross-species connectome atlas of human and macaque striatum. Cerebral Cortex. (5-years IF: 4.6)

Xia, X., Zeng, X., Gao, F., Hua, L., Huang, S., Yuan, Z. (2023) Striatonigrostriatal connectivity-based cross-species parcellation of human and macaque substantia nigra. Human Brain Mapping (IF: 5.4). 2023;1–15.