The function of mPFC-NAc circuit in decision impulsivity- a study based on an animal model

Abstract: Insufficient behavior control in patients with attention deficit / hyperactivity disorder (ADHD) is closely related to decision impulsivity, which is regulated by medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). mPFC and NAc is involved in the regulation of decision-making process and impulsivity, and the structure and function of mPFC and NAc are abnormal in ADHD. The relationship between the functional coupling of mPFC-NAc circuit and abnormal decision impulsivity in ADHD is still under debate, abnormality of this circuit may provide explanations to the neural mechanism underlying ADHD.       Wistar (WIS) rats and ADHD rats (SHR, spontaneously hypertensive rat) were used as subjects of this study. We recorded the local field potential (LFP) of mPFC and NAc using multi-channel electrophysiology during a delay discounting task (DDT). We further analyzed the coherence difference of Theta (4~12Hz) oscillation in expectation period (0~3s) and compared this measure between the two groups.     Results: (1) SHR rats had higher decision impulsivity level than WIS group. Power spectral density between 7~9Hz of LFP in mPFC and NAc increased in both groups. (2) When choosing large/delayed rewards, coherence of mPFC-NAc activity increased compared to small/immediate rewards in WIS group. This indicates the mPFC-NAc circuit involves in decision impulsivity. (3) When choosing large/delayed rewards, mPFC-NAc activity in SHR group showed lower coherence than WIS group, indicating SHR rats have weaker mPFC-NAc functional connections. (4) Coherence of mPFC-NAc activity is higher during initial choice behavioral than continuous choice behavior. It indicated that stronger mPFC-NAc functional connections are required during controlled information processing which is dominant in initial choice behavioral, while automatic processing is dominant in continuous choice behavior. Coherence of mPFC-NAc activity is higher in WIS group than WIS group when choosing large/immediate rewards. It indicated that the decision impulsivity deficits in SHR rats results from mPFC-NAc weak functional connections. (5) Coherence of mPFC-NAc activity is higher in shift trials than continuous trials. Plus, WIS group showed an overall higher coherence than SHR group. This indicated that mPFC-NAc circuit heavily involves in controlled information processing, and SHR group has deficiency of this process. (6) Regression analysis showed that coherence difference of mPFC-NAc activity in prediction period has positive correlation with delayed large reward selection rate in WIS group, that is, the more coherence of mPFC-NAc Theta activity increased during prediction period, the less decision impulsivity WIS rats behaved during choice period. However, the coherence difference cannot predict decision impulsivity in SHR group.     Conclusion: mPFC-NAc heavily involves in decision impulsivity. Increase of coherence of mPFC-NAc theta oscillation in prediction period can predict impulsivity level. Decision impulsivity in ADHD as a consequence of the dysfunction, is caused by a weak mPFC-NAc functional connection.