Abstract
Neural circuits controlling fast movements are inherently unsteady as a result of their reciprocal innervation. This instability is enhanced by increased membrane excitability. Recent studies indicate that the loss of external inhibition is an important factor in the pathogenesis of several tremor disorders such as essential tremor, cerebellar kinetic tremor or parkinsonian tremor. Shaikh and colleagues propose a new conceptual scheme to analyze tremor disorders. Oscillations are simulated by changing the intrinsic membrane properties of burst neurons. The authors use a model neuron of Hodgkin-Huxley type with added hyperpolarization activated cation current (Ih), low threshold calcium current (It), and GABA/glycine mediated chloride currents. Post-inhibitory rebound is taken into account. The model includes a reciprocally innervated circuit of neurons projecting to pairs of agonist and antagonist muscles. A set of four burst neurons has been simulated: inhibitory agonist, inhibitory antagonist, excitatory agonist, and excitatory antagonist. The model fits well with the known anatomical organization of neural circuits for limb movements in premotor/motor areas, and, interestingly, this model does not require any structural modification in the anatomical organization or connectivity of the constituent neurons. The authors simulate essential tremor when Ih is increased. Membrane excitability is augmented by up-regulating Ih and It. A high level of congruence with the recordings made in patients exhibiting essential tremor is reached. These simulations support the hypothesis that increased membrane excitability in potentially unsteady circuits generate oscillations mimicking tremor disorders encountered in daily practice. This new approach opens new perspectives for both the understanding and the treatment of neurological tremor. It provides the rationale for decreasing membrane excitability by acting on a normal ion channel in a context of impaired external inhibition.
Highlights
Tremor is defined as a rapid oscillation of a body part [1]
Tremor is one of the most common movement disorders encountered in clinical practice and is associated with a neurological disease in most cases [2]
Tremor is distinct from other movement disorders, such as dystonia, chorea, athetosis, tics or myoclonus, even though several movement disorders may co-exist
Summary
Tremor is defined as a rapid oscillation of a body part [1]. Tremor is one of the most common movement disorders encountered in clinical practice and is associated with a neurological disease in most cases [2]. Spindles inhibit motor neurons to antagonist muscles through Ia inhibitory interneurons. Clinical scores of disability Clinical characterization of tremor Evaluation of tremor in 2 dimensions Assessment of muscle discharges and motor units Position/displacement Rotational motion Acceleration signal Changes in magnetic field Position in 3 dimensions Force Displacement/rotation Interactions torques Simulation of neural circuits tion of the distribution of power.
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