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). In ADHD patients, the mPFC and NAc show abnormality both structurally and functionally, indicating that these two brain regions are involved in regulation of decision-making, especially impulsivity. Although extensive anatomical connections between mPFC and NAc have been found, the role of mPFC-NAc circuit in decision impulsivity remains to be investigated.

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 (4~12 Hz) oscillation in expectation period (0~3s) and compared this measure between the two groups.

The results showed that: (1) In the DDT task, when the delay time was 10s, SHR rats had higher decision impulsivity level than WIS group (F(1, 14) = 25.08, p < 0.001, η²_p = 0.64). Power spectral density between 6~12 Hz 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 (F(1, 104) = 252.90, p < 0.001, η²_p = 0.71). This indicates that the mPFC-NAc circuit mediates decision impulsivity. (3) When choosing large/delayed rewards, mPFC-NAc activity in SHR group showed lower coherence than WIS group (F(1, 104) = 119.57, p < 0.001, η²_p = 0.53), indicating SHR rats have weaker mPFC-NAc functional connections (see Figure 1A, Figure 1B).

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 (dominant in initial choice behavioral), rather than automatic information processing (dominant in continuous choice behavior). Coherence of mPFC-NAc activity is higher in WIS group than SHR group when choosing large/immediate rewards (initial trials: F(1, 108) = 105.86, p < 0.001, η²_p = 0.50; continuous trials: F(1, 108) = 6.38, p = 0.013, η²_p = 0.06, see Figure 2A, Figure 2B). It indicated that the decision impulsivity deficits in SHR rats results from mPFC-NAc weak functional connections.

Coherence of mPFC-NAc activity is higher in shift trials than continuous trials. Plus, WIS group showed an overall higher coherence than SHR group (continuous trials: F(1, 110) = 45.67, p < 0.001, η²_p = 0.29; shift trials: F(1, 110) = 154.07, p < 0.001, η²_p = 0.58, see Figure 3A, Figure 3B). This indicated that mPFC-NAc circuit heavily involves in controlled information processing, and SHR group has deficiency of this process.

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 (r = 0.65; F(1, 22) = 15.46, p < 0.001, R² = 0.42, see Figure 4A), 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 (r = 0.33; F(1, 27) = 3.12, p = 0.089, R² = 0.11, see Figure 4B).

This study showed that mPFC-NAc heavily involves in decision impulsivity. Increase of coherence of mPFC-NAc theta oscillation in prediction period can predict impulsivity level. The study revealed that weak mPFC-NAc functional connections mediate decision impulsivity in ADHD and brought new perspectives in the treatment of ADHD.

Key words: attention deficit/hyperactivity disorder, decision impulsivity, mPFC, NAc, neural network oscillation