Project Summary During motor preparation, millions of interconnected neurons work together to give rise to a ‘planned’ movement. We currently know little about the brain circuits and the communication between them in an intact nervous system during the preparation for shoulder or shoulder and hand combined movements. This gap in basic knowledge blocks the investigation of motor deficits in pathological conditions, such as hemiparetic stroke and Parkinson’s. A central movement plan is sent to targeted muscles via descending pathways. In humans, both corticospinal tracts (CSTs) that largely bypass the brainstem, and cortico-reticulospinal tracts (C-RSTs), via the brainstem, project to the upper extremity muscles. Although both proximal muscles and distal flexors receive projections from C-RSTs, distal extensors receive relatively less. Thus, the CSTs remain the primary resource for recruiting distal extensors. Therefore, we hypothesize that in able-bodied adults, distinct communication among various cortical areas, as quantified by cortical-cortical-connectivity (CCC), drives the CST and modulates the brainstem’s excitability to increase or decrease the reliance on the RSTs. This modulation is dependent on motor pathway connectivity (aim 1) and motor demands (aims 2 and 3). Forty able-bodied adults will be recruited to participate in the designed experiments in all three aims. In aim 1, participants will self-initiate hand opening (OPEN) or arm lifting (LIFT) task 5-6 s after a ‘ready’ sound (80dB); or move as quickly as possible after either a ‘go’ (80dB) or a ‘startling’ (115dB) sound that occurs 1.5-3 s after the ‘ready’ sound. We will quantify the default CCC for the self-initiated motor tasks, and the startle responses following a ‘startling’ sound compared to a ‘go’ sound. Because the startling sound activates the reticular formation and releases the prepared movements via RSTs, a short reaction time (< 120ms) will ensure the use of RSTs. Besides, because RSTs branch to multiple spinal segments, increased muscle co-activation patterns will reflect an increased brainstem activity during motor preparation. We expect to demonstrate that preparatory CCCs for OPEN and LIFT are different in healthy adults because shoulder abductors are more strongly innervated by RSTs, and finger extensors are primarily innervated by CSTs. In aims 2 and 3, participants will perform LIFT (aim 2) or hand opening while arm lifting (OPEN+LIFT, aim 3) against various shoulder abduction loads. We will demonstrate that CCCs will show motor demand- induced alterations that either increase or suppress the brainstem’s excitability. The proposed study will establish the default CCCs prior to OPEN, LIFT, or OPEN+LIFT tasks for the first time. We will also demonstrate the neuroanatomical connectivity- and task demand-dependent cortical modulation of the brainstem’s excitability in able-bodied adults. The proposed basic research fits the NINDS's focus for understanding an intact...