Mapping Subcortico-Cortical Coupling-A Comparison of Thalamic and Subthalamic Oscillations.

BACKGROUND: The ventral intermediate nucleus of the thalamus (VIM) is an effective target for deep brain stimulation in tremor patients. Despite its therapeutic importance, its oscillatory coupling to cortical areas has rarely been investigated in humans. OBJECTIVES: The objective of this study was to identify the cortical areas coupled to the VIM in patients with essential tremor. METHODS: We combined resting-state magnetoencephalography with local field potential recordings from the VIM of 19 essential tremor patients. Whole-brain maps of VIM-cortex coherence in several frequency bands were constructed using beamforming and compared with corresponding maps of subthalamic nucleus (STN) coherence based on data from 19 patients with Parkinson's disease. In addition, we computed spectral Granger causality. RESULTS: The topographies of VIM-cortex and STN-cortex coherence were very similar overall but differed quantitatively. Both nuclei were coupled to the ipsilateral sensorimotor cortex in the high-beta band; to the sensorimotor cortex, brainstem, and cerebellum in the low-beta band; and to the temporal cortex, brainstem, and cerebellum in the alpha band. High-beta coherence to sensorimotor cortex was stronger for the STN (P = 0.014), whereas low-beta coherence to the brainstem was stronger for the VIM (P = 0.017). Although the STN was driven by cortical activity in the high-beta band, the VIM led the sensorimotor cortex in the alpha band. CONCLUSIONS: Thalamo-cortical coupling is spatially and spectrally organized. The overall similar topographies of VIM-cortex and STN-cortex coherence suggest that functional connections are not necessarily unique to one subcortical structure but might reflect larger frequency-specific networks involving VIM and STN to a different degree. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Slowing of Frontal ß Oscillations in Atypical Parkinsonism.

BACKGROUND: Diagnosis of atypical parkinsonian syndromes (APS) mostly relies on clinical presentation as well as structural and molecular brain imaging. Whether parkinsonian syndromes are distinguishable based on neuronal oscillations has not been investigated so far. OBJECTIVE: The aim was to identify spectral properties specific to atypical parkinsonism. METHODS: We measured resting-state magnetoencephalography in 14 patients with corticobasal syndrome (CBS), 16 patients with progressive supranuclear palsy (PSP), 33 patients with idiopathic Parkinson's disease, and 24 healthy controls. We compared spectral power as well as amplitude and frequency of power peaks between groups. RESULTS: Atypical parkinsonism was associated with spectral slowing, distinguishing both CBS and PSP from Parkinson's disease (PD) and age-matched healthy controls. Patients with atypical parkinsonism showed a shift in ß peaks (13-30 Hz) toward lower frequencies in frontal areas bilaterally. A concomitant increase in θ/α power relative to controls was observed in both APS and PD. CONCLUSION: Spectral slowing occurs in atypical parkinsonism, affecting frontal ß oscillations in particular. Spectral slowing with a different topography has previously been observed in other neurodegenerative disorders, such as Alzheimer's disease, suggesting that spectral slowing might be an electrophysiological marker of neurodegeneration. As such, it might support differential diagnosis of parkinsonian syndromes in the future. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Spontaneous network activity <35 ​Hz accounts for variability in stimulus-induced gamma responses.

Gamma activity is thought to serve several cognitive processes, including attention and memory. Even for the simplest stimulus, the occurrence of gamma activity is highly variable, both within and between individuals. The sources of this variability, however, are largely unknown. In this paper, we address one possible cause: the cross-frequency influence of spontaneous, whole-brain network activity on visual stimulus processing. By applying Hidden Markov modelling to MEG data, we reveal that the trial-averaged gamma response to a moving grating depends on the individual network dynamics, inferred from slower brain activity (<35 â€‹Hz) in the absence of stimulation (resting-state and task baseline). In addition, we demonstrate that modulations of network activity in task baseline influence the gamma response on the level of trials. In summary, our results reveal a cross-frequency and cross-session association between gamma responses induced by visual stimulation and spontaneous network activity. These findings underline the dependency of visual stimulus processing on the individual, functional network architecture.

Unilateral deep brain stimulation suppresses alpha and beta oscillations in sensorimotor cortices.

Deep brain stimulation (DBS) is an established therapy to treat motor symptoms in movement disorders such as Parkinson's disease (PD). The mechanisms leading to the high therapeutic effectiveness of DBS are poorly understood so far, but modulation of oscillatory activity is likely to play an important role. Thus, investigating the effect of DBS on cortical oscillatory activity can help clarifying the neurophysiological mechanisms of DBS. Here, we aimed at scrutinizing changes of cortical oscillatory activity by DBS at different frequencies using magnetoencephalography (MEG). MEG data from 17 PD patients were acquired during DBS of the subthalamic nucleus (STN) the day after electrode implantation and before implanting the pulse generator. We stimulated the STN unilaterally at two different stimulation frequencies, 130 Hz and 340 Hz using an external stimulator. Data from six patients had to be discarded due to strong artefacts and two other datasets were excluded since these patients were not able to finalize the paradigm. After DBS artefact removal, power spectral density (PSD) values of MEG were calculated for each individual patient and averaged over the group. DBS at both 130 Hz and 340 Hz led to a widespread suppression of cortical alpha/beta band activity (8-22 Hz) specifically over bilateral sensorimotor cortices. No significant differences were observed between the two stimulation frequencies. Our finding of a widespread suppression of cortical alpha/beta band activity is particularly interesting as PD is associated with pathologically increased levels of beta band activity in the basal ganglia-thalamo-cortical circuit. Therefore, suppression of such oscillatory activity might be an essential effect of DBS for relieving motor symptoms in PD and can be achieved at different stimulation frequencies above 100 Hz.

Bicycling suppresses abnormal beta synchrony in the Parkinsonian basal ganglia.

OBJECTIVE: Freezing of gait is a poorly understood symptom of Parkinson disease, and can severely disrupt the locomotion of affected patients. However, bicycling ability remains surprisingly unaffected in most patients suffering from freezing, suggesting functional differences in the motor network. The purpose of this study was to characterize and contrast the oscillatory dynamics underlying bicycling and walking in the basal ganglia. METHODS: We present the first local field potential recordings directly comparing bicycling and walking in Parkinson disease patients with electrodes implanted in the subthalamic nuclei for deep brain stimulation. Low (13-22Hz) and high (23-35Hz) beta power changes were analyzed in 22 subthalamic nuclei from 13 Parkinson disease patients (57.5 ± 5.9 years old, 4 female). The study group consisted of 5 patients with and 8 patients without freezing of gait. RESULTS: In patients without freezing of gait, both bicycling and walking led to a suppression of subthalamic beta power (13-35Hz), and this suppression was stronger for bicycling. Freezers showed a similar pattern in general. Superimposed on this pattern, however, we observed a movement-induced, narrowband power increase around 18Hz, which was evident even in the absence of freezing. INTERPRETATION: These results indicate that bicycling facilitates overall suppression of beta power. Furthermore, movement leads to exaggerated synchronization in the low beta band specifically within the basal ganglia of patients susceptible to freezing. Abnormal ∼18Hz oscillations are implicated in the pathophysiology of freezing of gait, and suppressing them may form a key strategy in developing potential therapies. Ann Neurol 2017;82:592-601.

Parkinsonian Rest Tremor Is Associated With Modulations of Subthalamic High-Frequency Oscillations.

BACKGROUND: High frequency oscillations (>200 Hz) have been observed in the basal ganglia of PD patients and were shown to be modulated by the administration of levodopa and voluntary movement. OBJECTIVE: The objective of this study was to test whether the power of high-frequency oscillations in the STN is associated with spontaneous manifestation of parkinsonian rest tremor. METHODS: The electromyogram of both forearms and local field potentials from the STN were recorded in 11 PD patients (10 men, age 58 [9.4] years, disease duration 9.2 [6.3] years). Patients were recorded at rest and while performing repetitive hand movements before and after levodopa intake. High-frequency oscillation power was compared across epochs containing rest tremor, tremor-free rest, or voluntary movement and related to the tremor cycle. RESULTS: We observed prominent slow (200-300 Hz) and fast (300-400 Hz) high-frequency oscillations. The ratio between slow and fast high-frequency oscillation power increased when tremor became manifest. This increase was consistent across nuclei (94%) and occurred in medication ON and OFF. The ratio outperformed other potential markers of tremor, such as power at individual tremor frequency, beta power, or low gamma power. For voluntary movement, we did not observe a significant difference when compared with rest or rest tremor. Finally, rhythmic modulations of high-frequency oscillation power occurred within the tremor cycle. CONCLUSIONS: Subthalamic high-frequency oscillation power is closely linked to the occurrence of parkinsonian rest tremor. The balance between slow and fast high-frequency oscillation power combines information on motor and medication state. © 2016 International Parkinson and Movement Disorder Society.

Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America.

A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.

Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America.

A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panel's recommendations were developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment of diverse SSTIs ranging from minor superficial infections to life-threatening infections such as necrotizing fasciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments in a timely fashion.

High-frequency oscillations in Parkinson's disease: spatial distribution and clinical relevance.

The pathophysiology of Parkinson's disease (PD) has been related to excessive beta band oscillations in the basal ganglia. Recent recordings from the subthalamic nucleus of PD patients showed that beta oscillations show strong cross-frequency coupling with high-frequency oscillations (>200 Hz). However, little is known about the characteristics and functional properties of these oscillations. We studied the spatial distribution of high-frequency oscillations and their relation to PD motor symptoms. We included 10 PD patients in medication OFF who underwent implantation of deep brain stimulation (DBS) electrodes. Intraoperative five-channel microelectrode recordings were performed at 9 to 10 recording sites within the subthalamic nucleus and its immediate surroundings. We found a focal spatial distribution of high-frequency oscillations with highest power 2 mm below the dorsolateral border of the subthalamic nucleus. Within the subthalamic nucleus, power peaked slightly anterior to the DBS target site. In addition, contralateral akinesia/rigidity scores were negatively correlated with high-frequency oscillation power. Our results demonstrate a focal origin of high-frequency oscillations within the subthalamic nucleus and provide further evidence for their functional association with motor state.

A direct relationship between oscillatory subthalamic nucleus-cortex coupling and rest tremor in Parkinson's disease.

Electrophysiological studies suggest that rest tremor in Parkinson's disease is associated with an alteration of oscillatory activity. Although it is well known that tremor depends on cortico-muscular coupling, it is unclear whether synchronization within and between brain areas is specifically related to the presence and severity of tremor. To tackle this longstanding issue, we took advantage of naturally occurring spontaneous tremor fluctuations and investigated cerebral synchronization in the presence and absence of rest tremor. We simultaneously recorded local field potentials from the subthalamic nucleus, the magnetoencephalogram and the electromyogram of forearm muscles in 11 patients with Parkinson's disease (all male, age: 52-74 years). Recordings took place the day after surgery for deep brain stimulation, after withdrawal of anti-parkinsonian medication. We selected epochs containing spontaneous rest tremor and tremor-free epochs, respectively, and compared power and coherence between subthalamic nucleus, cortex and muscle across conditions. Tremor-associated changes in cerebro-muscular coherence were localized by Dynamic Imaging of Coherent Sources. Subsequently, cortico-cortical coupling was analysed by computation of the imaginary part of coherency, a coupling measure insensitive to volume conduction. After tremor onset, local field potential power increased at individual tremor frequency and cortical power decreased in the beta band (13-30 Hz). Sensor level subthalamic nucleus-cortex, cortico-muscular and subthalamic nucleus-muscle coherence increased during tremor specifically at tremor frequency. The increase in subthalamic nucleus-cortex coherence correlated with the increase in electromyogram power. On the source level, we observed tremor-associated increases in cortico-muscular coherence in primary motor cortex, premotor cortex and posterior parietal cortex contralateral to the tremulous limb. Analysis of the imaginary part of coherency revealed tremor-dependent coupling between these cortical areas at tremor frequency and double tremor frequency. Our findings demonstrate a direct relationship between the synchronization of cerebral oscillations and tremor manifestation. Furthermore, they suggest the feasibility of tremor detection based on local field potentials and might thus become relevant for the design of closed-loop stimulation systems.

Parkinsonian rest tremor can be distinguished from voluntary hand movements based on subthalamic and cortical activity.

OBJECTIVE: To distinguish Parkinsonian rest tremor and different voluntary hand movements by analyzing brain activity. METHODS: We re-analyzed magnetoencephalography and local field potential recordings from the subthalamic nucleus of six patients with Parkinson's disease. Data were obtained after withdrawal from dopaminergic medication (Med Off) and after administration of levodopa (Med On). Using gradient-boosted tree learning, we classified epochs as tremor, fist-clenching, forearm extension or tremor-free rest. RESULTS: Subthalamic activity alone was insufficient for distinguishing the four different motor states (balanced accuracy mean: 38%, std: 7%). The combination of cortical and subthalamic features, in contrast, allowed for a much more accurate classification (balanced accuracy mean: 75%, std: 17%). Adding a single cortical area improved balanced accuracy by 17% on average, as compared to classification based on subthalamic activity alone. In most patients, the most informative cortical areas were sensorimotor cortical regions. Decoding performance was similar in Med On and Med Off. CONCLUSIONS: Electrophysiological recordings allow for distinguishing several motor states, provided that cortical signals are monitored in addition to subthalamic activity. SIGNIFICANCE: By combining cortical recordings, subcortical recordings and machine learning, adaptive deep brain stimulation systems might be able to detect tremor specifically and to respond adequately to several motor states.

Exploring the electrophysiology of Parkinson's disease with magnetoencephalography and deep brain recordings.

Aberrant information processing in the basal ganglia and connected cortical areas are key to many neurological movement disorders such as Parkinson's disease. Investigating the electrophysiology of this system is difficult in humans because non-invasive methods, such as electroencephalography or magnetoencephalography, have limited sensitivity to deep brain areas. Recordings from electrodes implanted for therapeutic deep brain stimulation, in contrast, provide clear deep brain signals but are not suited for studying cortical activity. Therefore, we combine magnetoencephalography and local field potential recordings from deep brain stimulation electrodes in individuals with Parkinson's disease. Here, we make these data available, inviting a broader scientific community to explore the dynamics of neural activity in the subthalamic nucleus and its functional connectivity to cortex. The dataset encompasses resting-state recordings, plus two motor tasks: static forearm extension and self-paced repetitive fist clenching. Most patients were recorded both in the medicated and the unmedicated state. Along with the raw data, we provide metadata on channels, events and scripts for pre-processing to help interested researchers get started.

Lower limb cellulitis and its mimics: part II. Conditions that simulate lower limb cellulitis.

Several common conditions can mimic cellulitis, creating a potential for misdiagnosis and incorrect management. The most common disorders mistaken for lower limb cellulitis include venous eczema, lipodermatosclerosis, irritant dermatitis, and lymphedema. The dermatologist is often consulted when a patient has failed to respond to therapy, and a thorough knowledge of the differential diagnosis is essential. This article focuses on entities that can mimic cellulitis, with an emphasis of elements of the history and physical examination that can help to distinguish between lower limb cellulitis and its simulators.

Lower limb cellulitis and its mimics: part I. Lower limb cellulitis.

An aging population and obesity have both contributed to a rising incidence of lower limb cellulitis; the most important predisposing factors include older age, obesity, venous insufficiency, saphenous venectomy, and edema. Streptococci are the most commonly implicated pathogen, and often reside in the interdigital toes spaces. Any disruption of the skin surface can allow the organism to invade. Effective management requires an appropriate antibiotic and attention to the predisposing factors. This article summarizes the epidemiology and treatment of this common infection.

Neuronal oscillations predict deep brain stimulation outcome in Parkinson's disease.

BACKGROUND: Neuronal oscillations are linked to symptoms of Parkinson's disease. This relation can be exploited for optimizing deep brain stimulation (DBS), e.g. by informing a device or human about the optimal location, time and intensity of stimulation. Whether oscillations predict individual DBS outcome is not clear so far. OBJECTIVE: To predict motor symptom improvement from subthalamic power and subthalamo-cortical coherence. METHODS: We applied machine learning techniques to simultaneously recorded magnetoencephalography and local field potential data from 36 patients with Parkinson's disease. Gradient-boosted tree learning was applied in combination with feature importance analysis to generate and understand out-of-sample predictions. RESULTS: A few features sufficed for making accurate predictions. A model operating on five coherence features, for example, achieved correlations of r > 0.8 between actual and predicted outcomes. Coherence comprised more information in less features than subthalamic power, although in general their information content was comparable. Both signals predicted akinesia/rigidity reduction best. The most important local feature was subthalamic high-beta power (20-35 Hz). The most important connectivity features were subthalamo-parietal coherence in the very high frequency band (>200 Hz) and subthalamo-parietal coherence in low-gamma band (36-60 Hz). Successful prediction was not due to the model inferring distance to target or symptom severity from neuronal oscillations. CONCLUSION: This study demonstrates for the first time that neuronal oscillations are predictive of DBS outcome. Coherence between subthalamic and parietal oscillations are particularly informative. These results highlight the clinical relevance of inter-areal synchrony in basal ganglia-cortex loops and might facilitate further improvements of DBS in the future.

Deep Brain Stimulation Does Not Modulate Auditory-Motor Integration of Speech in Parkinson's Disease.

Deep brain stimulation (DBS) has significant effects on motor symptoms in Parkinson's disease (PD), but existing studies on the effect of DBS on speech are rather inconclusive. It is assumed that deficits in auditory-motor integration strongly contribute to Parkinsonian speech pathology. The aim of the present study was to assess whether subthalamic DBS can modulate these deficits. Twenty PD patients (15 male, 5 female; 62.4 ± 6.7 years) with subthalamic DBS were exposed to pitch-shifted acoustic feedback during vowel vocalization and subsequent listening. Voice and brain activity were measured ON and OFF stimulation using magnetoencephalography (MEG). Vocal responses and auditory evoked responses time locked to the onset of pitch-shifted feedback were examined. A positive correlation between vocal response magnitude and pitch variability was observed for both, stimulation ON and OFF (ON: r = 0.722, p < 0.001, OFF: r = 0.746, p < 0.001). However, no differences of vocal responses to pitch-shifted feedback between the stimulation conditions were found [t (19) = -0.245, p = 0.809, d = -0.055]. P200m amplitudes of event related fields (ERF) of left and right auditory cortex (AC) and superior temporal gyrus (STG) were significantly larger during listening [left AC P200m: F (1, 19) = 10.241, p = 0.005, f = 0.734; right STG P200m: F (1, 19) = 8.393, p = 0.009, f = 0.664]. Subthalamic DBS appears to have no substantial effect on vocal compensations, although it has been suggested that auditory-motor integration deficits contribute to higher vocal response magnitudes in pitch perturbation experiments with PD patients. Thus, DBS seems to be limited in modulating auditory-motor integration of speech in PD.