Supplementary Motor Area Activity Differs in Parkinson’s Disease with and without Freezing of Gait

Figure 2

Modeling the neuronal processes potentially affecting cortical activity captured by the CZ electrode. Normal function is shown in blue arrows. The SMA starts the cueing for self-initiated actions, such as volitional walking, standing from a chair, or turning. This signal travels via the supraspinal locomotor network towards the mesencephalic locomotor region (MLR) through the hyperdirect pathway that connects the SMA and the subthalamic nucleus (STN). The STN acts as an intermediary between SMA and the MLR, and it is responsible for gating the SMA feedforward and cerebellar feedback from activating or inhibiting the MLR. The MLR then triggers the pontomedullary reticular formation (PMRF), which drives the central pattern generators (CPG) to produce the control patterns for locomotion [13]. This control loop is facilitated by dopamine; without it, an intention does not successfully convey movement. Disrupted function is shown in red arrows. It has been recently proposed that in PD, FoG may be caused by disrupted basal ganglia (BG)-SMA cues due to episodic crosstalk from the motor, cognitive, and limbic areas. This event-triggered crosstalk leads to gait initiation lock or FoG [14]. It is also plausible that impaired connectivity between the cortico-BG circuits and the cerebellum contribute to the appearance of FoG in PD [15] potentially reflecting neuronal activity deficits also in the cerebellum [16], which was implicated with complex gait conditions [17]. BG: basal ganglia, CPGs: central pattern generators, MLR: mesencephalic locomotor network, PMRF: pontomedullary reticular formation, SMA: supplementary motor area, SN: substantia nigra, STN: subthalamic nucleus, TH: thalamus, and VTA: ventral tegmental area.