Divergent pallidal pathways underlying distinct Parkinsonian behavioral deficits

The basal ganglia are a group of subcortical nuclei that regulates motor and cognitive functions1,2. Recent identification of neuronal heterogeneity in the basal ganglia suggests that functionally distinct neural circuits defined by their efferent projections exist even within the same nuclei3-5. This distinction may account for a multitude of symptoms associated with basal ganglia disorders such as Parkinson’s disease (PD)6,7. However, our incomplete understanding of the basal ganglia functional organization has hindered further investigation of individual circuits that may underlie different behavioral symptoms in disease states. Here we functionally define two distinct classes of parvalbumin-expressing neurons in the mouse external globus pallidus (GPe-PV) embedded within discrete neural pathways and establish their contributions to different Parkinsonian behavioral deficits. We find that GPe-PV neurons projecting to the substantia nigra pars reticulata (SNr) or parafascicular thalamus (PF) undergo different electrophysiological adaptations in response to dopamine depletion. Furthermore, counteracting these adaptations in each population can selectively alleviate movement deficits or behavioral inflexibility in a Parkinsonian mouse model. Our findings provide a novel framework to understand the circuit basis of separate behavioral symptoms in Parkinsonian state which could provide better strategies for the treatment of PD.

Clinical and neurophysiological aspects of fatigue

While fatigue and excessive daytime sleepiness may coexist in many medical, neurological, and primary sleep disorders, they are distinct clinical symptoms that have different etiologies and treatment strategies. Making the distinction between fatigue and sleepiness is crucial to the management of a variety of conditions. This chapter provides an overview of fatigue from the perspective of the general practitioner, neurologist, and sleep specialist, and summarizes recent research developments in the field, including neuroimaging in fatigue. Emphasis is placed on the evaluation of fatigue in patients with a variety of neurological conditions (including multiple sclerosis, basal ganglia disorders, and post-polio fatigue), medical disorders, and sleep disorders, as well as on chronic fatigue syndrome.

Basal Ganglia

The core function of the basal ganglia is action selection, the process of choosing between mutually exclusive actions. Under baseline or default conditions, the basal ganglia suppress movement and prevent more than one movement from occurring simultaneously. The importance of chunking and operational learning is explored through exemplary typing tasks. Pathways through the basal ganglia employ the same input and output ports. Inputs far outnumber outputs from the basal ganglia. Subcortical loops through the basal ganglia are more effective than are cortical loops. The functions of the hyperdirect, direct and indirect pathways to motor control in the skeletomotor loop are detailed. Hemiballismus, Parkinson’s disease, and Huntington’s disease are key basal ganglia disorders. The use of deep brain stimulation (DBS) of the subthalamic nucleus as a treatment for Parkinson’s disease is discussed. Finally, additional basal ganglia loops such as the oculomotor loop are introduced.