The present study examined the interactions between the human PPNR and the cortices during both arm and leg movements. We found that voluntary movements changed PPNR activities and functional interactions between the cortices and the PPNR. In addition, dopaminergic medications modulated PPNR activities and their interactions with the cortices during planning and execution of voluntary movements.
The PPNR MRP onset latencies of approximately −2 seconds in the ON state were similar to MRP onset latencies recorded from the STN in the ON state and the ventral thalamus (VT) (approximately −2.1 seconds).21,22
We found phase reversals between adjacent PPNR contact pairs (), suggesting that PPNR MRP represents focal activities instead of far field potentials. The findings of MRP in the STN, the VT, and the PPNR are consistent with the hypothesis that subcortical nuclei may contribute to the cortical MRP23
and the PPNR is part of the subcortical circuits involved in movement preparation.
Frequency analysis revealed modulations of PPNR theta and beta frequencies that were similar with upper or lower limb movements and between the ipsilateral and contralateral sides. The strength of coherence between EEG and PPNR LFP was approximately 0.1, similar to previous studies of coherences between EEG and STN or GPi LFP.24,25
Because PPNR coherence with the cortex was found only in the ON state, dopaminergic medications promoted the interactions between the cortex and the PPNR in patients with PD. This is consistent with findings that dopaminergic medications restore the deficient activation of SMA and related motor circuits in PD.26,27
We found that PPNR theta ERD during movement preparation and execution was more prominent in the ON state than in the OFF state (), suggesting that dopaminergic medications promoted suppression of theta rhythm during voluntary movements. Coherences between the PPNR and the sensorimotor regions in the theta band were stronger between the ipsilateral than the contralateral sensorimotor region (), consistent with a diffusion tractography study showing strong connections between the human PPNR and the ipsilateral sensorimotor cortex.4
The ipsilateral sensorimotor region led the PPNR in the premovement period (figure e-2A) but lagged the PPNR in the movement execution period (figure e-2B), suggesting that the ipsilateral sensorimotor cortex may drive the PPNR during movement preparation and receive sensory feedback through the PPNR during movement execution. Animal studies supported the idea that the PPNR is involved with sensory feedback, especially the selection of relevant sensory information for motor programming and execution.3
Theta band coherences were observed between the ipsilateral sensorimotor cortex and the VT in both humans and animals28,29
and the brainstem trigeminal sensory nucleus in rats.29
These theta coherences were thought to link different neuronal populations for the continuous monitoring of sensory information in the environment.28,29
The human PPNR theta band may be part of cortical brainstem thalamocortical system that monitors continuous stream of sensory information.
Beta oscillation is a prominent feature of human parkinsonism.30,31
Excessive beta oscillations in the BG30,32–34
and in the cortices may lead to abnormal cortical motor output responsible for parkinsonian motor symptoms.32,35
Levodopa as well as voluntary movements decreased beta oscillations in the STN and GPi.32,36,37
STN or GPi high-frequency DBS (>100 Hz) as well as dopaminergic medications may disrupt the abnormal beta synchronization in the basal ganglia, resulting in improvement of motor symptoms.35
Premovement beta oscillation in the PPNR decreased in the OFF state but increased in the ON state (). Premovement beta ERS has not been observed in the BG or the cortex, suggesting that beta oscillation may have different functional significances in the BG (STN and GPi) and the PPNR. There was stronger activation of PPNR beta frequency before ankle movements than before wrist movements (), and PPNR beta coherence with the cortices was also more robust before ankle movements than before wrist movements (). This may indicate that the PPNR is more involved with lower than with upper extremity movements, consistent with studies showing that PPNR DBS normalized lower limb spinal reflexes38
and improved falls in patients with advanced PD.15
The occurrence of beta coherence between the cortices and PPNR before movement onset is opposite to the findings in the VT in tremor patients, where there was beta band coherence between the midline EEG and VT in the resting period, but it was reduced approximately 1 second before movement onset. Also, beta coherence between the midline EEG and STN decreased rather than increased just before movement onset in patients with PD.39,40
These differences in beta coherence may indicate that SMA modulates the PPNR, the VT, and the BG during movement preparation through distinct pathways.
Beta coherence between the midline prefrontal region and the PPNR was only found in the ON state (), suggesting that dopaminergic medications may facilitate cortical excitatory drive from the SMA to the PPNR (figure e-2C), consistent with findings in human neuroimaging studies regarding the facilitatory effects of dopaminergic medications and PPNR DBS on the SMA-related motor circuits.5,26,27
The premovement beta excitatory drive from the SMA to the PPNR may be involved with formulation of motor program for movement executions. Thus, the beta rhythm in the human PPNR may be prokinetic rather than antikinetic. This may explain the general findings that PPNR DBS at lower frequencies was more effective than at high frequencies (>100 Hz) for the alleviation of motor symptoms in patients with PD.7,15,16
PPNR DBS at beta frequency (approximately 30 Hz) was reported to alleviate rigidity and gait dysfunctions, whereas PPNR DBS at gamma frequencies (50 to 70 Hz) was found to decrease falls.15
The PPNR beta band coherence was present just before movements (), coincident in time with the beta ERS () and the brief attenuation of PPNR theta band coherence (). The different findings for PPNR theta and beta rhythms suggest that they may have different functions associated with 2 different PPNR cortical circuits. The sensory circuits may act through theta oscillations between the PPNR and the sensorimotor cortices, which are active continuously and switch off before movement execution. The motor circuit is then activated and may act through the PPNR beta oscillations driven through the SMA for mediating motor-related function. See appendix e-1 for discussion of the limitations of the study.
Activities of the PPNR change during movement preparation and execution in patients with PD. PPNR theta and beta oscillatory activities are modulated by voluntary movements and dopaminergic medications. Dopaminergic medications promote interactions between the cortices and the PPNR. Compared with oscillations in the BG, the human PPNR oscillations may be modulated differently by voluntary movements and dopaminergic medications and may have different functional significances.