PURPOSE: Technical advances in functional tendon and nerve transfers, most recently in the lower extremity, have improved patient outcomes following limb salvage. However, rigorous research defining and comparing clinical outcomes for the multiple available surgical options remains lacking. In the absence of such data to guide surgical decision making, we aim to gain a better understanding of the neuromuscular organization of gait (i.e. muscle synergies) to glean insights into donor-recipient pairings for functional lower extremity reconstruction aiming to restore walking. METHODS: A MEDLINE search (2000-2020) was performed using terms such as ‘motor module’, ‘synergy’, and ‘walking’. Studies with extractable data on muscle synergies in healthy human subjects during a walking gait were included. RESULTS: Thirty-eight studies were included, incorporating data from 416 participants. Muscle activity was measured using surface EMG in all but two studies. Muscle synergies were extracted using several computational techniques, including non-negative matrix factorization, principal component analysis, torque decomposition, and factor analysis. Each study identified between three and seven muscle synergies, with an average of 4.5 +/- 0.9. 82% of studies reported four or five synergies. The synergies observed across studies could be reclassified into four temporally-independent synergies. Synergy A was active at weight acceptance and included vastus lateralis (reported in 63% of studies), rectus femoris (63%), gluteus medius (58%), vastus medialis (53%), and gluteus maximus (39%). Synergy B, active during late stance, included soleus (87%), medial (79%) and lateral (53%) heads of the gastrocnemius, and peroneus (37%). Synergy C, active at early swing, included tibialis anterior (84%), rectus femoris (41%), erector spinae (32%), and adductors (27%). Synergy D, active at late swing, included biceps femoris (86%), semitendinosus (65%), semimembranosus (24%), and tibialis anterior (22%). CONCLUSIONS: This is the first study to systematically review the neuromuscular organization of gait and apply these findings to surgical decision making. In cases of quadriceps weakness, obturator to femoral nerve transfers have been described with favorable reliability in outcomes.1,2 The obturator nerve plays an important role in hip stabilization and thus fires synergistically in early stance with the quadriceps during synergy A. In deficiencies of plantar flexion, the ankle cannot stabilize against natural dorsiflexion in late stance. The peroneus, providing ankle stability and firing synergistically with plantar flexors in synergy B, may serve as a donor nerve/tendon to reconstruct injuries of the superficial posterior compartment. Even in the absence of obvious synergies, built-in redundancy in lower extremity function provides several expendable donors that may restore range of motion and stability; these data inform which pairings are least antagonistic and most likely to be successful. For example, while transfers of the tibialis posterior,3 FDL/FHL,4 and gastrocenemius5 have been described in cases of foot drop, we prefer simultaneous nerve/tendon transfer of the lateral gastrocnemius because it is expendable, leaving the medial head and soleus intact, and less antagonistic than other transfers, allowing the tendon to more naturally and effectively dorsiflex. Surgical plans aiming to restore the four basic synergies identified herein could allow for restoration of independent gait following significant lower extremity injury. REFERENCES: 1. Dubois E, Popescu IA, Sturbois Nachef N, Teboul F, Goubier JN. Repair of the femoral nerve by two motor branches of the obturator nerve: A case report. Microsurgery. Mar 2020;40(3):387-390. doi:10.1002/micr.30527 2. Rastrelli M, Tocco-Tussardi I, Tropea S, Rossi CR, Rizzato S, Vindigni V. Transfer of the anterior branch of the obturator nerve for femoral nerve reconstruction and preservation of motor function: A case report. Int J Surg Case Rep. 2018;51:58-61. doi:10.1016/j.ijscr.2018.08.004 3. Agarwal P, Gupta M, Kukrele R, Sharma D. Tibialis posterior (TP) tendon transfer for foot drop: A single center experience. J Clin Orthop Trauma. May-Jun 2020;11(3):457-461. doi:10.1016/j.jcot.2020.03.007 4. Movahedi Yeganeh M. Triple Tendon Transfer for Correction of Foot Deformity in Common Peroneal Nerve Palsy. Foot Ankle Int. Jun 2016;37(6):665-9. doi:10.1177/1071100716629779 5. Leclere FM, Badur N, Mathys L, Vogelin E. Neurotized lateral gastrocnemius muscle transfer for persistent traumatic peroneal nerve palsy: Surgical technique. Neurochirurgie. Aug 2015;61(4):292-7. doi:10.1016/j.neuchi.2014.08.001