Nucleus basalis of Meynert neuronal activity in Parkinson's disease

Abstract

Objective: Neuronal loss within the cholinergic nucleus basalis of Meynert (nbM) correlates with cognitive decline in dementing disorders such as Alzheimer's disease and Parkinson's disease (PD). In nonhuman primates, the nbM firing pattern (5-40 Hz) has also been correlated with working memory and sustained attention. In this study, authors performed microelectrode recordings of the globus pallidus pars interna (GPi) and the nbM immediately prior to the implantation of bilateral deep brain stimulation (DBS) electrodes in PD patients to treat motor symptoms and cognitive impairment, respectively. Here, the authors evaluate the electrophysiological properties of the nbM in patients with PD.

Methods: Five patients (4 male, mean age 66 ± 4 years) with PD and mild cognitive impairment underwent bilateral GPi and nbM DBS lead implantation. Microelectrode recordings were performed through the GPi and nbM along a single trajectory. Firing rates and burst indices were characterized for each neuronal population with the patient at rest and performing a sustained-attention auditory oddball task. Action potential (AP) depolarization and repolarization widths were measured for each neuronal population at rest.

Results: In PD patients off medication, the authors identified neuronal discharge rates that were specific to each area populated by GPi cells (92.6 ± 46.1 Hz), border cells (34 ± 21 Hz), and nbM cells (13 ± 10 Hz). During the oddball task, firing rates of nbM cells decreased (2.9 ± 0.9 to 2.0 ± 1.1 Hz, p < 0.05). During baseline recordings, the burst index for nbM cells (1.7 ± 0.6) was significantly greater than those for GPi cells (1.2 ± 0.2, p < 0.05) and border cells (1.1 ± 0.1, p < 0.05). There was no significant difference in the nbM burst index during the oddball task relative to baseline (3.4 ± 1.7, p = 0.20). With the patient at rest, the width of the depolarization phase of APs did not differ among the GPi cells, border cells, and nbM cells (p = 0.60); however, during the repolarization phase, the nbM spikes were significantly longer than those for GPi high-frequency discharge cells (p < 0.05) but not the border cells (p = 0.20).

Conclusions: Neurons along the trajectory through the GPi and nbM have distinct firing patterns. The profile of nbM activity is similar to that observed in nonhuman primates and is altered during a cognitive task associated with cholinergic activation. These findings will serve to identify these targets intraoperatively and form the basis for further research to characterize the role of the nbM in cognition.

Keywords: AP = action potential; BK = big-conductance calcium-activated potassium; DBS = deep brain stimulation; EEG = electroencephalography; GABAergic = pertaining to or affecting the neurotransmitter gamma-aminobutyric acid; GPi = globus pallidus pars interna; HFD = high-frequency discharge; MCP = midcommissural point; PD = Parkinson’s disease; PD-MCI = mild cognitive impairment in PD; PDD = PD dementia; Parkinson’s disease; functional neurosurgery; microelectrode recording; nbM = nucleus basalis of Meynert; nucleus basalis of Meynert.