Figure 1.

Analysis of short-latency afferent inhibition (SAI) in our Parkinson’s Disease (PD) cohort and schematic representation of cholinergic sources in the human brain with their clinical correlates in PD. (A) Temporal evolution of SAI in our cohort of PD patients. The horizontal axis shows inter-stimulus interval (ISI) values (the time between the peripheral stimulation and cortical stimulation). ISIs were determined by adding 0, 2, 4, 6, and 8 ms to the latency of the N20 component. The vertical axis shows the percentage of test motor evoked potential (MEP) at each ISI. (B) Linear positive correlation between SAI at ISI N20+4 ms, Grand-Mean SAI and UPDRS III motor score in medicated patients. (C) Schematic representation of the three major sources of cholinergic projections in the brain and main clinical correlates in PD (red boxes). Basal forebrain neurons, including the nucleus basalis of Meynert (nbM), medial septal nucleus (MS) and diagonal band of Broca (DB) provide the cholinergic projections to the cerebral cortex and are responsible for cognitive impairment, gait impairment and psychosis. The pedunculopontine nucleus-laterodorsal tegmental complex [referred to as the pedunculopontine tegmental nucleus (PPN) and LDT], a brainstem center, provides cholinergic inputs primarily to the thalamus, but also has connections to the cerebellum, several brainstem nuclei, some striatal fibers, and the spinal cord. This system is mainly involved in walking disturbances, rem-sleep behavior disorders (RBDs) and psychosis. In addition, small populations of intrinsic cholinergic neurons are present in the hippocampus, striatum (cholinergic interneurons), parts of the reticular formation, and cerebellum. The cholinergic interneurons might be the main cause of motor symptoms in PD.