Single to Two Cluster State Transition of Primary Motor Cortex 4-posterior (MI-4p) Activities in Humans

The human primary motor cortex has dual representation of the digits, namely, area 4 anterior (MI-4a) and area 4 posterior (MI-4p). We have previously demonstrated that activation of these two functional subunits can be identified independently by functional magnetic resonance imaging (fMRI) using independent component-cross correlation-sequential epoch (ICS) analysis. Subsequent studies in patients with hemiparesis due to subcortical lesions and monoparesis due to peripheral nerve injury demonstrated that MI-4p represents the initiation area of activation, whereas MI-4a is the secondarily activated motor cortex requiring a “long-loop” feedback input from secondary motor systems, likely the cerebellum. A dynamic model of hand motion based on the limit cycle oscillator predicts that the specific pattern of entrainment of neural firing may occur by applying appropriate periodic stimuli. Under normal conditions, such entrainment introduces a single phase-cluster. Under pathological conditions where entrainment stimuli have insufficient strength, the phase cluster splits into two clusters. Observable physiological phenomena of this shift from single cluster to two clusters are: doubling of firing rate of output neurons; or decay in group firing density of the system due to dampening of odd harmonics components. While the former is not testable in humans, the latter can be tested by appropriately designed fMRI experiments, the quantitative index of which is believed to reflect group behavior of neurons functionally localized, e.g., firing density in the dynamic theory. Accordingly, we performed dynamic analysis of MI-4p activation in normal volunteers and paretic patients. The results clearly indicated that MI-4p exhibits a transition from a single to a two phase-cluster state which coincided with loss of MI-4a activation. The study demonstrated that motor dysfunction (hemiparesis) in patients with a subcortical infarct is not simply due to afferent fiber disruption. Maintaining proper afferent signals from MI-4p requires proper functionality of MI-4a and, hence, appropriate feedback signals from the secondary motor system.