The Cerebral Network of Parkinson's Tremor: An Effective Connectivity fMRI Study

Abstract

Parkinson's resting tremor has been linked to pathophysiological changes both in the basal ganglia and in a cerebello-thalamo-cortical motor loop, but the role of those circuits in initiating and maintaining tremor remains unclear. Here, we test whether and how the cerebello-thalamo-cortical loop is driven into a tremor-related state by virtue of its connectivity with the basal ganglia. An internal replication design on two independent cohorts of tremor-dominant Parkinson patients sampled brain activity and tremor with concurrent EMG-fMRI. Using dynamic causal modeling, we tested: (1) whether activity at the onset of tremor episodes drives tremulous network activity through the basal ganglia or the cerebello-thalamo-cortical loop and (2) whether the basal ganglia influence the cerebellothalamo-cortical loop through connectivity with the cerebellum or motor cortex. We compared five physiologically plausible circuits, model families in which transient activity at the onset of tremor episodes (assessed using EMG) drove network activity through the internal globus pallidus (GPi), external globus pallidus, motor cortex, thalamus, or cerebellum. In each family, we compared two models in which the basal ganglia and cerebello-thalamo-cortical loop were connected through the cerebellum or motor cortex. In both cohorts, cerebral activity associated with changes in tremor amplitude (using peripheral EMG measures as a proxy for tremor-related neuronal activity) drove network activity through the GPi, which effectively influenced the cerebello-thalamo-cortical loop through the motor cortex. We conclude that cerebral activity related to Parkinson's tremor first arises in the GPi and is then propagated to the cerebellothalamo-cortical circuit.

The vicious circle of hypometabolism in neurodegenerative diseases: Ways and mechanisms of metabolic correction

“…In PD, epilepsy is considered as an uncommon comorbidity in a few available studies (Vercueil, 2006), but also see: Son et al (2016). However, Parkinson's resting tremor is definitely induced by paroxysmal synchronous activity of the cerebello-thalamocortical network (Hallett, 2014;Singh et al, 2016), is likely initiated in motor cortex (Dirkx et al, 2016) and represents a harmful example of rhythmic collective dynamics of large brain cell networks resembling the epileptic ones (Velazquez et al, 2015).…”

Structural connectivity differences in motor network between tremor-dominant and nontremor Parkinson's disease

“…Functional magnetic resonance imaging (fMRI) studies clearly demonstrated that the activation at the level of the prefrontal cortex and the globus pallidus was reduced in patients with NT-PD compared to those with TD-PD and controls [Prodoehl et al, 2013]. On the other hand, in TD-PD patients, cerebral activity related to tremor first arised in the internal globus pallidus and was then propagated to the cerebello-thalamo-cortical loop, the "dimmer-switch hypothesis" [Dirkx et al, 2016;Helmich et al, 2011Helmich et al, , 2012.…”

Reorganization of cerebro‐cerebellar circuit in patients with left hemispheric gliomas involving language network: A combined structural and resting‐state functional MRI study

“…In contrast to the limited number of investigations addressing the role of cerebro-cerebellar circuit in language network reorganization following supratentorial lesion (Lidzba, Wilke, Staudt, Krageloh-Mann, & Grodd, 2008), similar studies have been extensively performed in the investigation of various higher-order cognitive functions in healthy subjects, and patients with neurodegenerative, neurodevelopmental, neurological, and psychiatric diseases (Buckner, 2013;Buckner, Krienen, Castellanos, Diaz, & Yeo, 2011;Dirkx et al, 2016;Guo et al, 2016;Kim et al, 2014;Marien et al, 2014Marien et al, , 2009O'Callaghan et al, 2016;Schmahmann and Sherman, 1998). In healthy subjects, task-fMRI research on the functional topography of human cerebellum revealed that the activation areas for language were mainly located in lobule VI and Crus I with a prominently rightlateralizing pattern, which reflected crossed organizational arrangement of cerebro-cerebellar circuit (Stoodley and Schmahmann, 2009;Stoodley, Valera, & Schmahmann, 2012).…”