Deep brain stimulation of subthalamic nucleus modulates cortical auditory processing in advanced Parkinson's Disease.

Deep brain stimulation (DBS) has proven its clinical efficacy in Parkinson's disease (PD), but its exact mechanisms and cortical effects continue to be unclear. Subthalamic (STN) DBS acutely modifies auditory evoked responses, but its long-term effect on auditory cortical processing remains ambiguous. We studied with magnetoencephalography the effect of long-term STN DBS on auditory processing in patients with advanced PD. DBS resulted in significantly increased contra-ipsilateral auditory response latency difference at ~100 ms after stimulus onset compared with preoperative state. The effect is likely due to normalization of neuronal asynchrony in the auditory pathways. The present results indicate that STN DBS in advanced PD patients has long-lasting effects on cortical areas outside those confined to motor processing. Whole-head magnetoencephalography provides a feasible tool to study motor and non-motor neural networks in PD, and to track possible changes related to cortical reorganization or plasticity induced by DBS.

Validation of the Finnish Version of the Unified Dyskinesia Rating Scale.

INTRODUCTION: The Unified Dyskinesia Rating Scale (UDysRS) was developed to provide a comprehensive rating tool of dyskinesia in Parkinson's disease (PD). Because dyskinesia therapy trials involve multicenter studies, having a scale that is validated in multiple non-English languages is pivotal to international efforts to treat dyskinesia. The aim of the present study was to organize and perform an independent validation of the UDysRS Finnish version. METHODS: The UDysRS was translated into Finnish and then back-translated into English using 2 independent teams. Cognitive pretesting was conducted on the Finnish version and required modifications to the structure or wording of the translation. The final Finnish version was administered to 250 PD patients whose native language is Finnish. The data were analyzed to assess the confirmatory factor structure to the Spanish UDysRS (the reference standard). Secondary analyses included an exploratory factor analysis (EFA), independent of the reference standard. RESULTS: The comparative fit index (CFI), in comparison with the reference standard factor structure, was 0.963 for Finnish. In the EFA, where variability from sample to sample is expected, isolated item differences of factor structure were found between the Finnish and Reference Standard versions of the UDysRS. These subtle differences may relate to differences in sample composition or variations in disease status. CONCLUSION: The overall factor structure of the Finnish version was consistent with that of the reference standard, and it can be designated as the official version of the UDysRS for Finnish speaking populations.

Localization of Sensorimotor Cortex Using Navigated Transcranial Magnetic Stimulation and Magnetoencephalography.

The mapping of the sensorimotor cortex gives information about the cortical motor and sensory functions. Typical mapping methods are navigated transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG). The differences between these mapping methods are, however, not fully known. TMS center of gravities (CoGs), MEG somatosensory evoked fields (SEFs), corticomuscular coherence (CMC), and corticokinematic coherence (CKC) were mapped in ten healthy adults. TMS mapping was performed for first dorsal interosseous (FDI) and extensor carpi radialis (ECR) muscles. SEFs were induced by tactile stimulation of the index finger. CMC and CKC were determined as the coherence between MEG signals and the electromyography or accelerometer signals, respectively, during voluntary muscle activity. CMC was mapped during the activation of FDI and ECR muscles separately, whereas CKC was measured during the waving of the index finger at a rate of 3-4 Hz. The maximum CMC was found at beta frequency range, whereas maximum CKC was found at the movement frequency. The mean Euclidean distances between different localizations were within 20 mm. The smallest distance was found between TMS FDI and TMS ECR CoGs and longest between CMC FDI and CMC ECR sites. TMS-inferred localizations (CoGs) were less variable across participants than MEG-inferred localizations (CMC, CKC). On average, SEF locations were 8 mm lateral to the TMS CoGs (p < 0.01). No differences between hemispheres were found. Based on the results, TMS appears to be more viable than MEG in locating motor cortical areas.

Spontaneous sensorimotor cortical activity is suppressed by deep brain stimulation in patients with advanced Parkinson's disease.

Advanced Parkinson's disease (PD) is characterized by an excessive oscillatory beta band activity in the subthalamic nucleus (STN). Deep brain stimulation (DBS) of STN alleviates motor symptoms in PD and suppresses the STN beta band activity. The effect of DBS on cortical sensorimotor activity is more ambiguous; both increases and decreases of beta band activity have been reported. Non-invasive studies with simultaneous DBS are problematic due to DBS-induced artifacts. We recorded magnetoencephalography (MEG) from 16 advanced PD patients with and without STN DBS during rest and wrist extension. The strong magnetic artifacts related to stimulation were removed by temporal signal space separation. MEG oscillatory activity at 5-25 Hz was suppressed during DBS in a widespread frontoparietal region, including the sensorimotor cortex identified by the cortico-muscular coherence. The strength of suppression did not correlate with clinical improvement. Our results indicate that alpha and beta band oscillations are suppressed at the frontoparietal cortex by STN DBS in PD.

Cortico-muscular coherence parallels coherence of postural tremor and MEG during static muscle contraction.

Corticokinematic coherence (CKC), i.e., coherence calculated between MEG and an accelerometer signal, recording movement kinematics, can be used for functional mapping of the sensorimotor cortex. Cortical sources of CKC, induced by both voluntary and passive movements, localize at the proximity of sensorimotor cortex. We tested the CKC during a static muscle contraction to compare it with simultaneously measured cortico-muscular coherence (CMC) estimated between MEG and surface EMG to study the role of postural tremor in CMC in ten healthy volunteers. CKC was detectable also during this static task. CKC and CMC spectra had similar power distributions, and sources of CMC and CKC colocalized at the cortex in close proximity of the central sulcus. During the static hold task, the accelerometer signal originates from the postural tremor. The similarities between CMC and CKC indicate that postural tremor is related to CMC in healthy subjects.

Cortico-muscular coherence in advanced Parkinson's disease with deep brain stimulation.

OBJECTIVE: Cortico-muscular coherence (CMC) is thought to reflect the interplay between cortex and muscle in motor coordination. In Parkinson's disease (PD) patients, levodopa has been shown to enhance CMC. This study examined whether subthalamic nucleus (STN) deep brain stimulation (DBS) affects the CMC in advanced PD. METHODS: Magnetoencephalography (MEG) and electromyography (EMG) measurements were done simultaneously both with DBS on and off to determine the CMC during wrist extension. The spatiotemporal signal space separation (tSSS) was used for artifact suppression. RESULTS: CMC peaks between 13 and 25 Hz were found in 15 out of 19 patients. The effect of DBS on CMC was variable. Moreover, the correlation between CMC and motor performance was inconsistent; stronger CMC did not necessarily indicate better function albeit tremor and rigidity may diminish the CMC. Patients having CMC between 13 and 25 Hz had the best motor scores at the group level. CONCLUSIONS: DBS modifies the CMC in advanced PD with large interindividual variability. SIGNIFICANCE: DBS does not systematically modify CMC amplitude in advanced PD. The results suggest that some components of the CMC may be related to the therapeutic effects of DBS.

Somatomotor mu rhythm amplitude correlates with rigidity during deep brain stimulation in Parkinsonian patients.

OBJECTIVE: Parkinsonian patients have abnormal oscillatory activity within the basal ganglia-thalamocortical circuitry. Particularly, excessive beta band oscillations are thought to be associated with akinesia. We studied whether cortical spontaneous activity is modified by deep brain stimulation (DBS) in advanced Parkinson's disease and if the modifications are related to the clinical symptoms. METHODS: We studied the effects of bilateral electrical stimulation of subthalamic nucleus (STN) on cortical spontaneous activity by magnetoencephalography (MEG) in 11 Parkinsonian patients. The artifacts produced by DBS were suppressed by tSSS algorithm. RESULTS: During DBS, UPDRS (Unified Parkinson's Disease Rating Scale) rigidity scores correlated with 6-10 Hz and 12-20 Hz somatomotor source strengths when eyes were open. When DBS was off UPDRS action tremor scores correlated with pericentral 6-10 Hz and 21-30 Hz and occipital alpha source strengths when eyes open. Occipital alpha strength decreased during DBS when eyes closed. The peak frequency of occipital alpha rhythm correlated negatively with total UPDRS motor scores and with rigidity subscores, when eyes closed. CONCLUSION: STN DBS modulates brain oscillations both in alpha and beta bands and these oscillations reflect the clinical condition during DBS. SIGNIFICANCE: MEG combined with an appropriate artifact rejection method enables studies of DBS effects in Parkinson's disease and presumably also in the other emerging DBS indications.

Effects of DBS on auditory and somatosensory processing in Parkinson's disease.

Motor symptoms of Parkinson's disease (PD) can be relieved by deep brain stimulation (DBS). The mechanism of action of DBS is largely unclear. Magnetoencephalography (MEG) studies on DBS patients have been unfeasible because of strong magnetic artifacts. An artifact suppression method known as spatiotemporal signal space separation (tSSS) has mainly overcome these difficulties. We wanted to clarify whether tSSS enables noninvasive measurement of the modulation of cortical activity caused by DBS. We have studied auditory and somatosensory-evoked fields (AEFs and SEFs) of advanced PD patients with bilateral subthalamic nucleus (STN) DBS using MEG. AEFs were elicited by 1-kHz tones and SEFs by electrical pulses to the median nerve with DBS on and off. Data could be successfully acquired and analyzed from 12 out of 16 measured patients. The motor symptoms were significantly relieved by DBS, which clearly enhanced the ipsilateral auditory N100m responses in the right hemisphere. Contralateral N100m responses and somatosensory P60m responses also had a tendency to increase when bilateral DBS was on. MEG with tSSS offers a novel and powerful tool to investigate DBS modulation of the evoked cortical activity in PD with high temporal and spatial resolution. The results suggest that STN-DBS modulates auditory processing in advanced PD. Hum Brain Mapp, 2011. © 2010 Wiley-Liss, Inc.