Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus.

Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory-motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing.

Subthalamic deep brain stimulation improves auditory sensory gating deficit in Parkinson's disease.

OBJECTIVE: While motor effects of dopaminergic medication and subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients are well explored, their effects on sensory processing are less well understood. Here, we studied the impact of levodopa and STN-DBS on auditory processing. METHODS: Rhythmic auditory stimulation (RAS) was presented at frequencies between 1 and 6Hz in a passive listening paradigm. High-density EEG-recordings were obtained before (levodopa ON/OFF) and 5months following STN-surgery (ON/OFF STN-DBS). We compared auditory evoked potentials (AEPs) elicited by RAS in 12 PD patients to those in age-matched controls. Tempo-dependent amplitude suppression of the auditory P1/N1-complex was used as an indicator of auditory gating. RESULTS: Parkinsonian patients showed significantly larger AEP-amplitudes (P1, N1) and longer AEP-latencies (N1) compared to controls. Neither interruption of dopaminergic medication nor of STN-DBS had an immediate effect on these AEPs. However, chronic STN-DBS had a significant effect on abnormal auditory gating characteristics of parkinsonian patients and restored a physiological P1/N1-amplitude attenuation profile in response to RAS with increasing stimulus rates. CONCLUSIONS: This differential treatment effect suggests a divergent mode of action of levodopa and STN-DBS on auditory processing. SIGNIFICANCE: STN-DBS may improve early attentive filtering processes of redundant auditory stimuli, possibly at the level of the frontal cortex.

Reversible, irreversible and effective transverse relaxation rates in normal aging brain at 3T.

Quantitative transverse relaxation rates in normal aging brain are essential to investigate pathologies associated with iron accumulation and tissue degeneration. Since absolute values depend on imaging methods and magnetic field strengths, continuous evaluation of specific reference values remains requisite. Multi-echo turbo spin echo and multi-echo gradient recalled echo imaging sequences were applied to 66 healthy subjects (18-84years) at 3T to quantify the irreversible (R2), effective (R2*) and reversible (R2'=R2*-R2) transverse relaxation rates. Representative regions-of-interest (ROIs) were determined automatically in gray matter (GM) and white matter (WM) on T1-weighted scans. Phantom experiments of different sized iron-oxide particles were conducted to explore the correlation of R2' related to R2 for the evaluation of the size of iron deposits. R2 decreased with age for the majority of ROIs, but increased for putamen, head of caudate nucleus and nucleus accumbens. R2* and R2' increased with age in deep GM structures except for the thalamus. R2* and R2' showed a distinct dependency on fiber orientation in exemplary WM regions. R2', R2 and R2* were strongly linear proportional to age-related iron content in deep GM with slopes of 0.88, 0.18 and 1.08 in [1/s/mg Fe per 100g wet tissue] and intercepts of 1.69, 9.25 and 10.69 in [1/s], respectively. Linear and non-linear curve fitting of R2' vs. R2 in phantoms revealed increased slopes with increasing particle size. In vivo, averaged R2' vs. R2 data points of patients with Parkinson's disease and progressive supranuclear palsy were above the fitted curves of healthy subjects suggesting larger sized iron deposits in these neurodegenerative diseases. Decreased R2 with age may reflect physiological tissue degeneration, whereas increased R2* and R2' with age most likely denote physiological iron accumulation. The low intercept of R2' vs. iron content suggests a nearly sole sensitivity of R2' to iron in deep GM, potentially allowing a more specific estimation of the iron content than R2 or R2*. Since R2* and R2' depend on the fiber orientation, their feasibility to estimate iron content in WM is challenging. The analysis of R2' related to R2 may provide valuable information about the size of iron deposits.

Automated volumes-of-interest identification for classical and atypical Parkinsonian syndrome differentiation using T2' MR imaging.

OBJECTIVES: In clinical routine, patients with classical Parkinsonian syndromes (CPS) need to be differentiated from those with atypical Parkinsonian syndromes (APS), particularly with respect to prognosis and treatment decision. To date, this diagnosis is mainly based on clinical criteria, leading to failure rates up to 25%, motivating the development of image-based decision support systems. Magnetic resonance imaging (MRI) and in particular T2´ image sequences have been suggested as a potential marker for differential diagnosis. The aim of this study was to investigate whether automatically identified T2´ volumes-of-interest (VOIs) can be used for an automatic differentiation of CPS and APS patients. MATERIAL AND METHODS: 74 MRI datasets were available for this hypothesis generating trial, including image sequences from 24 healthy subjects, 33 CPS and 17 APS patients. First, a problem-specific reference atlas was generated using the healthy control datasets. Next, patients' datasets were registered to the atlas. Voxel-wise t-tests, reflecting significance levels of T2´ value differences between CPS and APS patients, were then applied for calculation of a p-map. Finally, the calculated p-map was thresholded and a connected component analysis was performed for final VOI detection. In parallel, manually defined VOIs were determined in grey and white matter for comparison. RESULTS: Three VOIs in parts of the basal ganglia and the left occipital lobe were automatically identified by the presented method. There was a trend for higher area under the curve on multivariable receiver operating characteristic curves for automatically determined VOIs over manually defined VOIs (0.939 vs. 0.818, p = 0.0572). CONCLUSION: The diagnostic role of automatically defined VOIs in differentiation of CPS and APS patients based on T2´ image sequences should be further investigated.

How does attention attenuate target-distractor interference in vision?. Evidence from magnetoencephalographic recordings.

This study used magnetoencephalographic and electroencephalographic recordings to investigate the neural mechanisms that underlie the attentional resolution of ambiguous feature coding in visual search. We addressed this issue by comparing neural activity related to target discrimination under conditions of more versus less feature overlap between the target and distractor items. The results show that increasing feature overlap leads to a focal enhancement of neural activity in ventral occipito-temporal areas, consistent with the larger need to attenuate distractor interference. Furthermore, the results suggest that distractor attenuation proceeds as a stepwise operation, with different spatial locations containing interfering features being suppressed successively. These findings support theories of visual search that emphasize location-based attentional selection as a key mechanism in resolving ambiguous feature coding in vision.