Effective Connectivity Reveals Important Roles for Both the Hyperdirect (Fronto-Subthalamic) and the Indirect (Fronto-Striatal-Pallidal) Fronto-Basal Ganglia Pathways during Response Inhibition

Abstract

Fronto-basal ganglia pathways play a crucial role in voluntary action control, including the ability to inhibit motor responses. Response inhibition might be mediated via a fast hyperdirect pathway connecting the right inferior frontal gyrus (rIFG) and the presupplementary motor area (preSMA) with the subthalamic nucleus or, alternatively, via the indirect pathway between the cortex and caudate. To test the relative contribution of these two pathways to inhibitory action control, we applied an innovative quantification method for effective brain connectivity. Functional magnetic resonance imaging data were collected from 20 human participants performing a Simon interference task with an occasional stop signal. A single right-lateralized model involving both the hyperdirect and indirect pathways best explained the pattern of brain activation on stop trials. Notably, the overall connection strength of this combined model was highest on successfully inhibited trials. Inspection of the relationship between behavior and connection values revealed that fast inhibitors showed increased connectivity between rIFG and right caudate (rCaudate), whereas slow inhibitors were associated with increased connectivity between preSMA and rCaudate. In compliance, connection strengths from the rIFG and preSMA into the rCaudate were correlated negatively. If participants failed to stop, the magnitude of experienced interference (Simon effect), but not stopping latency, was predictive for the hyperdirect-indirect model connections. Together, the present results suggest that both the hyperdirect and indirect pathways act together to implement response inhibition, whereas the relationship between performance control and the fronto-basal ganglia connections points toward a top-down mechanism that underlies voluntary action control.

Deep Brain Stimulation of the Subthalamic Nucleus, but not Dopaminergic Medication, Improves Proactive Inhibitory Control of Movement Initiation in Parkinson's Disease

“…This view is consistent with the involvement of the slow indirect pathway/striatal loops and the fast hyperdirect pathway/STN loops in inhibitory control [8,34,[55][56][57]. It is reminiscent of 1) the cortico-striatal control account of how the brain gradually implements response thresholds by increasing activation from cortex to striatum in healthy participants [58]; 2) of the cortico-STN control account of how the brain relays fast reactive changes in the motor circuitry [59][60][61][62]; and 3) of the supplementary motor complex control account of how the brain switches from controlled to automatic sensorimotor processing [61].…”

Theta burst magnetic stimulation over the pre-supplementary motor area improves motor inhibition

“…Previous imaging evidence shows activation of the pre-SMA during performance of the go no-go [38,39], or stop signal tasks [3][4][5]7,9,21]. Greater pre-SMA activation has been associated with: (i) faster SSRTs [6], and (ii) stronger effective connectivity with the right caudate [40] and right IFG [37], related to gray matter densities [41]. Our results showing that continuous cTBS of the pre-SMA improves/speeds up motor inhibition is consistent with previous findings [6].…”

Clinical Motor and Cognitive Neurobehavioral Relationships in the Basal Ganglia

“…This has been hypothesized to be a result of decreased activity of the indirect or increased activation of the direct pathway [11,13,14]. Increased relative activity in the indirect pathway is associated with hypokinetic movement and behaviors [21][22][23]. The majority of input to the basal ganglia comes from a top down direction through the five loops from the frontal lobe [24] referenced above.…”