Accumbofrontal tract integrity is related to early life adversity and feedback learning

Abuse, neglect, exposure to violence, and other forms of early life adversity (ELA) are incredibly common and significantly impact physical and mental development. While important progress has been made in understanding the impacts of ELA on behavior and the brain, the preponderance of past work has primarily centered on threat processing and vigilance while ignoring other potentially critical neurobehavioral processes, such as reward-responsiveness and learning. To advance our understanding of potential mechanisms linking ELA and poor mental health, we center in on structural connectivity of the corticostriatal circuit, specifically accumbofrontal white matter tracts. Here, in a sample of 77 youth (Mean age = 181 months), we leveraged rigorous measures of ELA, strong diffusion neuroimaging methodology, and computational modeling of reward learning. Linking these different forms of data, we hypothesized that higher ELA would be related to lower quantitative anisotropy in accumbofrontal white matter. Furthermore, we predicted that lower accumbofrontal quantitative anisotropy would be related to differences in reward learning. Our primary predictions were confirmed, but similar patterns were not seen in control white matter tracts outside of the corticostriatal circuit. Examined collectively, our work is one of the first projects to connect ELA to neural and behavioral alterations in reward-learning, a critical potential mechanism linking adversity to later developmental challenges. This could potentially provide windows of opportunity to address the effects of ELA through interventions and preventative programming.

AMPAkines potentiate the corticostriatal pathway to reduce acute and chronic pain

The corticostriatal circuit plays an important role in the regulation of reward- and aversion-types of behaviors. Specifically, the projection from the prelimbic cortex (PL) to the nucleus accumbens (NAc) has been shown to regulate sensory and affective aspects of pain in a number of rodent models. Previous studies have shown that enhancement of glutamate signaling through the NAc by AMPAkines, a class of agents that specifically potentiate the function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, reduces acute and persistent pain. However, it is not known whether postsynaptic potentiation of the NAc with these agents can achieve the full anti-nociceptive effects of PL activation. Here we compared the impact of AMPAkine treatment in the NAc with optogenetic activation of the PL on pain behaviors in rats. We found that not only does AMPAkine treatment partially reconstitute the PL inhibition of sensory withdrawals, it fully occludes the effect of the PL on reducing the aversive component of pain. These results indicate that the NAc is likely one of the key targets for the PL, especially in the regulation of pain aversion. Furthermore, our results lend support for neuromodulation or pharmacological activation of the corticostriatal circuit as an important analgesic approach.

Corticostriatal White Matter Integrity and Dopamine D1 Receptor Availability Predict Age Differences in Prefrontal Value Signaling during Reward Learning

Probabilistic reward learning reflects the ability to adapt choices based on probabilistic feedback. The dopaminergically innervated corticostriatal circuit in the brain plays an important role in supporting successful probabilistic reward learning. Several components of the corticostriatal circuit deteriorate with age, as it does probabilistic reward learning. We showed previously that D1 receptor availability in NAcc predicts the strength of anticipatory value signaling in vmPFC, a neural correlate of probabilistic learning that is attenuated in older participants and predicts probabilistic reward learning performance. We investigated how white matter integrity in the pathway between nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC) relates to the strength of anticipatory value signaling in vmPFC in younger and older participants. We found that in a sample of 22 old and 23 young participants, fractional anisotropy in the pathway between NAcc and vmPFC predicted the strength of value signaling in vmPFC independently from D1 receptor availability in NAcc. These findings provide tentative evidence that integrity in the dopaminergic and white matter pathways of corticostriatal circuitry supports the expression of value signaling in vmPFC which supports reward learning, however, the limited sample size calls for independent replication. These and future findings could add to the improved understanding of how corticostriatal integrity contributes to reward learning ability.

It’s a Storm, It’s a Gale: Epilepsy Initiation From the Corticostriatal Circuit

[Box: see text]