Revealed: Anterior prefrontal-putamen circuit critical to response inhibition in humans

The prefrontal-subthalamic neural circuit of the human brain is responsible for shutting down inappropriate responses. The striatum in the brain is the main pathway for direct or excitatory and indirect or inhibitory signals, and this indirect pathway is thought to serve as an alternative arresting mechanism in humans. However, we do not have a clear understanding of how arrest is mediated by the prefrontal-striate indirect pathway.

Now, a group of researchers, led by Dr. Takahiro Osada of Juntendo University School of Medicine, explains the mechanism of the prefrontal-striatal indirect pathway. The researchers published their findings in Cell reports. “We have discovered a new neural network in the brain that is involved in inhibiting inappropriate responses. This work will shed light on disordered processes limiting movement after injury and may even be relevant for the management of neuropsychiatric disorders,” says Dr. Osada, stressing the importance of the study.

Researchers have leveraged low-intensity transcranial ultrasound stimulation (TUS) to probe arrest responses in the basal ganglia region of the human brain. Although neuroimaging studies have previously detected activation in the striatum during response inhibition studies, specific regions within this area could not be identified. TUS is advantageous because the technology allows non-invasive stimulation of deep brain structures with high spatial precision down to a few millimeters.

The team first used functional magnetic resonance imaging (fMRI) to visualize regions of the basal ganglia that were activated during this response inhibition. After that, responses within the basal ganglia were stimulated with TUS to examine the disruption of response inhibition performance. The researchers then used diffusion MRI analysis to see if the cerebrocortical region of the brain could function as a counterpart to the striatum. Finally, the team used TUS to understand how critical the cortical counterpart was during response inhibition.

The fMRI results confirmed that there was activity in the right anterior putamen during response inhibition. Importantly, TUS directed to both the anterior putamen and subthalamic nucleus regions resulted in significantly impaired arrest performance in test subjects. “We were also able to identify a strong link between the anterior putamen and the right anterior inferior frontal cortex (IFC). When we directed the TUS to the right anterior IFC, arresting performance was again significantly impaired,” explains Dr. Osada.

The group is confident that the findings will help further research exploring the neural mechanisms of response inhibition, given that they have identified the role of the anterior IFC-anterior putamen circuit – a new cortico-basal network – in the inhibition of inappropriate responses. This is promising because it opens the door not only to examining individual regions of the brain, but also to performing experiments at the level of the brain as a whole.

But what are the wider implications for the team’s findings? Dr. Osada concludes: “I strongly believe that this research can help us develop better artificial intelligence as we gain insight into brain function using tools such as TUS and fMRI. Dysfunction of the cortico-basal ganglia network is linked to neuropsychiatric disorders and much remains to be discovered using our methodology in terms of the pathophysiological mechanisms behind these conditions.”

Provided by Juntendo University Research Promotion Center