Subthalamic oscillatory activity during normal and impaired speech.

OBJECTIVE: We studied the relationship between oscillatory activity in the subthalamic nucleus (STN) and speech production in order to better understand the functional role of the STN. METHODS: We simultaneously recorded subthalamic local field potentials and audio recordings from 5 patients with Parkinson's disease while they performed verbal fluency tasks. We then analyzed the oscillatory signals present in the subthalamic nucleus during these tasks. RESULTS: We report that normal speech leads to a suppression of subthalamic alpha and beta power. Contrarily, a patient with motor blocks during speech initiation showed a low beta power increase. We also report an increase in error rates in the phonemic non-alternating verbal fluency task during deep brain stimulation (DBS). CONCLUSIONS: We confirm previous findings that intact speech leads to desynchronization in the beta range in the STN. The speech related narrowband beta power increase in a patient with speech problems suggests that exaggerated synchronization in this frequency band is associated with motor blocks during speech initiation. The increased number of errors in verbal fluency tasks during DBS might be caused by an impairment of the response inhibition network caused by stimulation of the STN. SIGNIFICANCE: We suggest that the inability to attenuate beta activity during motor processes is associated with motor freezing across motor behaviours such as speech and gait, as previously shown for freezing of gait.

Peaks in the beta band of the human subthalamic nucleus: a case for low beta and high beta activity.

OBJECTIVE: Peaks in the beta band of local field potentials (LFPs) may serve as a biological feedback signal for closed-loop deep brain stimulation (DBS) in Parkinson's disease (PD). However, the specific frequency of such peaks and their response to DBS and to different types of movement remains uncertain. In the present study, the authors examined the abundance of discernible peaks in the beta band and the effect of different types of movement and DBS on these peaks. METHODS: Subthalamic nucleus LFPs were analyzed from 38 patients with PD in a frequency range between 10 and 35 Hz, as well as the impact of movement (gait, hand movements) and electrical stimulation on these peaks. The position of the electrode segments from which LFPs were recorded was computed. RESULTS: The authors found a bimodal distribution of peaks in the beta band with discernible high- (27 Hz) and low-frequency (15 Hz) peaks. Movement of either hand had no significant effect on these peaks, whereas walking significantly reduced high-frequency beta peaks but not the peaks in the low beta band. Stimulation caused an amplitude-dependent suppression of both peaks. CONCLUSIONS: DBS suppresses LFP beta peaks of different frequencies, whereas beta suppression caused by movement is dependent on the type of movement and frequency of the peak. These results will support the investigation of distinct LFP spectra for the application of closed-loop DBS.

Deep Brain Stimulation Programming for Movement Disorders: Current Concepts and Evidence-Based Strategies.

Deep brain stimulation (DBS) has become the treatment of choice for advanced stages of Parkinson's disease, medically intractable essential tremor, and complicated segmental and generalized dystonia. In addition to accurate electrode placement in the target area, effective programming of DBS devices is considered the most important factor for the individual outcome after DBS. Programming of the implanted pulse generator (IPG) is the only modifiable factor once DBS leads have been implanted and it becomes even more relevant in cases in which the electrodes are located at the border of the intended target structure and when side effects become challenging. At present, adjusting stimulation parameters depends to a large extent on personal experience. Based on a comprehensive literature search, we here summarize previous studies that examined the significance of distinct stimulation strategies for ameliorating disease signs and symptoms. We assess the effect of adjusting the stimulus amplitude (A), frequency (f), and pulse width (pw) on clinical symptoms and examine more recent techniques for modulating neuronal elements by electrical stimulation, such as interleaving (Medtronic®) or directional current steering (Boston Scientific®, Abbott®). We thus provide an evidence-based strategy for achieving the best clinical effect with different disorders and avoiding adverse effects in DBS of the subthalamic nucleus (STN), the ventro-intermedius nucleus (VIM), and the globus pallidus internus (GPi).

Deep Brain Stimulation Programming 2.0: Future Perspectives for Target Identification and Adaptive Closed Loop Stimulation.

Deep brain stimulation has developed into an established treatment for movement disorders and is being actively investigated for numerous other neurological as well as psychiatric disorders. An accurate electrode placement in the target area and the effective programming of DBS devices are considered the most important factors for the individual outcome. Recent research in humans highlights the relevance of widespread networks connected to specific DBS targets. Improving the targeting of anatomical and functional networks involved in the generation of pathological neural activity will improve the clinical DBS effect and limit side-effects. Here, we offer a comprehensive overview over the latest research on target structures and targeting strategies in DBS. In addition, we provide a detailed synopsis of novel technologies that will support DBS programming and parameter selection in the future, with a particular focus on closed-loop stimulation and associated biofeedback signals.

The applause sign in frontotemporal lobar degeneration and related conditions.

The applause sign, i.e., the inability to execute the same amount of claps as performed by the examiner, was originally reported as a sign specific for progressive supranuclear palsy (PSP). Recent research, however, has provided evidence for the occurrence of the applause sign in various conditions. The aim of this study was to determine the prevalence of the applause sign and correlate its presence with neuropsychological and MRI volumetry findings in frontotemporal lobar degeneration and related conditions. The applause sign was elicited with the three clap test (TCT), with a higher score indicating poorer performance. Data were recorded from 272 patients from the cohort of the German consortium for frontotemporal lobar degeneration (FTLDc): 111 with behavioral variant frontotemporal dementia (bvFTD), 98 with primary progressive aphasia (PPA), 30 with progressive supranuclear palsy Richardson's syndrome, 17 with corticobasal syndrome (CBS) and 16 with amyotrophic lateral sclerosis with frontotemporal dementia (ALS/FTD). For comparison, 29 healthy elderly control subjects (HC) were enrolled in the study. All subjects underwent detailed language and neuropsychological assessment. In a subset of 156 subjects, atlas-based volumetry was performed. The applause sign occurred in all patient groups (40% in PSP, 29.5% in CBS, 25% in ALS/FTD, 13.3% in PPA and 9.0% in bvFTD) but not in healthy controls. The prevalence was highest in PSP patients. It was significantly more common in PSP as compared to bvFTD, PPA and HC. The comparison between the other groups failed to show a significant difference regarding the occurrence of the applause sign. The applause sign was highly correlated to a number of neuropsychological findings, especially to measures of executive, visuospatial, and language function as well as measures of disease severity. TCT scores showed an inverse correlation with the volume of the ventral diencephalon and the pallidum. Furthermore the volume of the ventral diencephalon and pallidum were significantly smaller in patients displaying the applause sign. Our study confirms the occurrence of the applause sign in bvFTD, PSP and CBS and adds PPA and ALS/FTD to these conditions. Although still suggestive of PSP, clinically it must be interpreted with caution. From the correlation with various cognitive measures we suggest the applause sign to be indicative of disease severity. Furthermore we suggest that the applause sign represents dysfunction of the pallidum and the subthalamic nucleus, structures which are known to play important roles in response inhibition.

Subthalamic oscillatory activity and connectivity during gait in Parkinson's disease.

Local field potentials (LFP) of the subthalamic nucleus (STN) recorded during walking may provide clues for determining the function of the STN during gait and also, may be used as biomarker to steer adaptive brain stimulation devices. Here, we present LFP recordings from an implanted sensing neurostimulator (Medtronic Activa PC + S) during walking and rest with and without stimulation in 10 patients with Parkinson's disease and electrodes placed bilaterally in the STN. We also present recordings from two of these patients recorded with externalized leads. We analyzed changes in overall frequency power, bilateral connectivity, high beta frequency oscillatory characteristics and gait-cycle related oscillatory activity. We report that deep brain stimulation improves gait parameters. High beta frequency power (20-30 Hz) and bilateral oscillatory connectivity are reduced during gait, while the attenuation of high beta power is absent during stimulation. Oscillatory characteristics are affected in a similar way. We describe a reduction in overall high beta burst amplitude and burst lifetimes during gait as compared to rest off stimulation. Investigating gait cycle related oscillatory dynamics, we found that alpha, beta and gamma frequency power is modulated in time during gait, locked to the gait cycle. We argue that these changes are related to movement induced artifacts and that these issues have important implications for similar research.

Improving the Standard for Deep Brain Stimulation Therapy: Target Structures and Feedback Signals for Adaptive Stimulation. Current Perspectives and Future Directions.

Deep brain stimulation (DBS) is an established therapeutic option for the treatment of various neurological disorders and has been used successfully in movement disorders for over 25 years. However, the standard stimulation schemes have not changed substantially. Two major points of interest for the further development of DBS are target-structures and novel adaptive stimulation techniques integrating feedback signals. We describe recent research results on target structures and on neural and behavioural feedback signals for adaptive deep brain stimulation (aDBS), as well as outline future directions.

Subthalamic stimulation, oscillatory activity and connectivity reveal functional role of STN and network mechanisms during decision making under conflict.

Inhibitory control is an important executive function that is necessary to suppress premature actions and to block interference from irrelevant stimuli. Current experimental studies and models highlight proactive and reactive mechanisms and claim several cortical and subcortical structures to be involved in response inhibition. However, the involved structures, network mechanisms and the behavioral relevance of the underlying neural activity remain debated. We report cortical EEG and invasive subthalamic local field potential recordings from a fully implanted sensing neurostimulator in Parkinson's patients during a stimulus- and response conflict task with and without deep brain stimulation (DBS). DBS made reaction times faster overall while leaving the effects of conflict intact: this lack of any effect on conflict may have been inherent to our task encouraging a high level of proactive inhibition. Drift diffusion modelling hints that DBS influences decision thresholds and drift rates are modulated by stimulus conflict. Both cortical EEG and subthalamic (STN) LFP oscillations reflected reaction times (RT). With these results, we provide a different interpretation of previously conflict-related oscillations in the STN and suggest that the STN implements a general task-specific decision threshold. The timecourse and topography of subthalamic-cortical oscillatory connectivity suggest the involvement of motor, frontal midline and posterior regions in a larger network with complementary functionality, oscillatory mechanisms and structures. While beta oscillations are functionally associated with motor cortical-subthalamic connectivity, low frequency oscillations reveal a subthalamic-frontal-posterior network. With our results, we suggest that proactive as well as reactive mechanisms and structures are involved in implementing a task-related dynamic inhibitory signal. We propose that motor and executive control networks with complementary oscillatory mechanisms are tonically active, react to stimuli and release inhibition at the response when uncertainty is resolved and return to their default state afterwards.