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Parkinson’s disease (PD) is characterised by the emergence of beta frequency oscillatory synchronisation across the cortico-basal-ganglia circuit. The relationship between the anatomy of this circuit and oscillatory synchronisation within it remains unclear. We address this by combining recordings from human subthalamic nucleus (STN) and internal globus pallidus (GPi) with magnetoencephalography, tractography and computational modelling. Coherence between supplementary motor area and STN within the high (21–30 Hz) but not low (13-21 Hz) beta frequency range correlated with ‘hyperdirect pathway’ fibre densities between these structures. Furthermore, supplementary motor area activity drove STN activity selectively at high beta frequencies suggesting that high beta frequencies propagate from the cortex to the basal ganglia via the hyperdirect pathway. Computational modelling revealed that exaggerated high beta hyperdirect pathway activity can provoke the generation of widespread pathological synchrony at lower beta frequencies. These findings suggest a spectral signature and a pathophysiological role for the hyperdirect pathway in PD. In Parkinson’s disease (PD), beta frequency oscillations are synchronised across the cortico-basal-ganglia circuit. The authors show in human participants that high beta frequencies propagate from the cortex to the basal ganglia via the hyperdirect pathway, indicating a pathophysiological role for this pathway in PD.

Background and objectiveDeep brain stimulation (DBS) is used for treating dystonia, commonly targeting the subthalamic nucleus (STN). Optimal stimulation parameters are required to achieve satisfying results. However, recommended parameters for STN-DBS remain to be identified. In this review, we aimed to assess the optimal stimulation parameters by analyzing previously published STN-DBS data of patients with dystonia.MethodsWe examined the STN-DBS stimulation parameters used in studies on dystonia selected on the PubMed/Medline database.ResultsOf the 86 publications retrieved from the PubMed/Medline database, we included 24, which consisted of data from 94 patients and 160 electrodes. Overall, the following average stimulation parameters were observed: amplitude, 2.59 ± 0.67 V; pulse width, 83.87 ± 34.70 μs; frequency, 142.08 ± 37.81 Hz. The average improvement rate was 64.72 ± 24.74%. The improvement rate and stimulation parameters were linearly dependent. The average improvement rate increased by 3.58% at each 10-Hz increase in frequency. In focal and segmental dystonia, the improvement rate and stimulation parameters were linearly dependent. The improvement rate increased by 6.06% and decreased by 2.14% at each 10-Hz increase in frequency and pulse width, respectively. Seventeen publications (83 patients) mentioned stimulation-related adverse effects, including dyskinesia (17), depression (8), transient dysarthria (5), weight gain (4), transient dysphasia (3), transient paresthesia (2), and sustained hyperkinesia (2).ConclusionsThe optimal stimulation parameter for STN-DBS varies across patients. Our findings may be useful for DBS programming based on the specific dystonia subtypes, especially for patients with focal and segmental dystonia.

Deep brain stimulation (DBS) of structures in the brain’s reward system is a promising therapeutic option for patients with treatment-resistant depression (TRD). Recently, DBS of the habenula (HB) in the brain’s anti-reward system has also been reported to alleviate depressive symptoms in patients with TRD or bipolar disorder (BD). In this pilot open-label prospective study, we explored the safety and clinical effectiveness of HB–DBS treatment in seven patients with TRD or BD. Also, local field potentials (LFPs) were recorded from the patients’ left and right HB to explore the power and asymmetry of oscillatory activities as putative biomarkers of the underlying disease state. At 1-month follow-up (FU), depression and anxiety symptoms were both reduced by 49% ( n  = 7) along with substantial improvements in patients’ health status, functional impairment, and quality of life. Although the dropout rate was high and large variability in clinical response existed, clinical improvements were generally maintained throughout the study [56%, 46%, and 64% reduction for depression and 61%, 48%, and 70% reduction for anxiety at 3-month FU ( n  = 5), 6-month FU ( n  = 5), and 12-month FU ( n  = 3), respectively]. After HB–DBS surgery, sustained improvements in mania symptoms were found in two patients who presented with mild hypomania at baseline. Another patient, however, experienced an acute manic episode 2 months after surgery that required hospitalization. Additionally, weaker and more symmetrical HB LFP oscillatory activities were associated with more severe depression and anxiety symptoms at baseline, in keeping with the hypothesis that HB dysfunction contributes to MDD pathophysiology. These preliminary findings indicate that HB–DBS may offer a valuable treatment option for depressive symptoms in patients who suffer from TRD or BD. Larger and well-controlled studies are warranted to examine the safety and efficacy of HB–DBS for treatment-refractory mood disorders in a more rigorous fashion.

The bilateral effects of deep brain stimulation (DBS) on motor and non-motor symptoms of Parkinson’s disease (PD) have been extensively studied and reviewed. However, the unilateral effects—in particular, the potential lateralized effects of left- versus right-sided DBS—have not been adequately recognized or studied. Here we summarized the current evidence and controversies in the literature regarding the lateralized effects of DBS on motor and non-motor outcomes in PD patients. Publications in English language before February 2021 were obtained from the PubMed database and included if they directly compared the effects of unilateral versus contralateral side DBS on motor or non-motor outcomes in PD. The current literature is overall of low-quality and is biased by various confounders. Researchers have investigated mainly PD patients receiving subthalamic nucleus (STN) DBS while the potential lateralized effects of globus pallidus interna (GPi) DBS have not been adequately studied. Evidence suggests potential lateralized effects of STN DBS on axial motor symptoms and deleterious effects of left-sided DBS on language-related functions, in particular, the verbal fluency, in PD. The lateralized DBS effects on appendicular motor symptoms as well as other neurocognitive and neuropsychiatric domains remain inconclusive. Future studies should control for varying methodological approaches as well as clinical and DBS management heterogeneities, including symptom laterality, stimulation parameters, location of active contacts, and lead trajectories. This would contribute to improved treatment strategies such as personalized target selection, surgical planning, and postoperative management that ultimately benefit patients.

A homogeneity-adjusted dataset of total cloud cover from weather stations in the contiguous United States is compared with cloud cover in four state-of-the-art global reanalysis products: the Climate Forecast System Reanalysis from NCEP, the Modern-Era Retrospective Analysis for Research and Applications from NASA, ERA-Interim from ECMWF, and the Japanese 55-year Reanalysis Project from the Japan Meteorological Agency. The reanalysis products examined in this study generally show much lower cloud amount than visual weather station data, and this underestimation appears to be generally consistent with their overestimation of downward surface shortwave fluxes when compared with surface radiation data from the Surface Radiation Network. Nevertheless, the reanalysis products largely succeed in simulating the main aspects of interannual variability of cloudiness for large-scale means, as measured by correlations of 0.81–0.90 for U.S. mean time series. Trends in the reanalysis datasets for the U.S. mean for 1979–2009, ranging from −0.38% to −1.8% decade−1, are in the same direction as the trend in surface data (−0.50% decade−1), but further effort is needed to understand the discrepancies in their magnitudes.

•L-dopa enhances β power in motor cortex, improving motor symptoms.•STN-DBS reduces β oscillations in motor cortex, correlating with symptom relief.•Distinct β band effects observed with L-dopa vs. STN-DBS treatment.•Motor state alterations linked with clinical scales for Parkinson's assessment.•HMM reveals critical insights into Parkinson's disease cortical dynamics. Parkinson's disease (PD) is a movement disorder caused by dopaminergic neurodegeneration. Both Levodopa (L-dopa) and Subthalamic Deep Brain Stimulation (STN-DBS) effectively alleviate symptoms, yet their cerebral effects remain under-explored. Understanding these effects is essential for optimizing treatment strategies and assessing disease severity. Magnetoencephalogram (MEG) data provide a continuous time series signal that reflects the dynamic changes in brain activity. The hidden Markov model (HMM) can capture and model the temporal features and underlying states of the MEG signal to extract potential brain states and monitor dynamic changes. In this study, we employed HMM to investigate the cortical mechanism underlying the treatment of PD patients using MEG recordings. 21 PD patients treated with medication underwent MEG recording in both L-dopa medoff and medon conditions. Additionally, 11 PD patients receiving STN-DBS treatment underwent MEG recording in both dbsoff and dbson conditions. The MEG data were segmented into four states by Time-delay embedded Hidden Markov Model (TDE-HMM) algorithm. The state parameters including Fractional Occupancy (FO), Interval Times (IT), and Life Time (LT) for each state and power spectrum of β band were analyzed to study the effects of L-dopa and STN-DBS treatment respectively. L-dopa significantly increased the motor state of HMM and power in the motor area of both high β (21–35 Hz) and low β (13–20 Hz); the motor state of high β in medoff were correlated with the Unified Parkinson's Disease Rating Scale III (UPDRS III). Conversely, DBS significantly diminishes the motor state of HMM and power in motor area of high β oscillations. The score changes of tremor and limb rigidity after DBS treatment were significantly correlated with the changes of motor state of high β. This study demonstrates that L-dopa and STN-DBS exert differing effects on β oscillations in the motor cortex of PD patients, primarily in high β band. Understanding these distinct neurophysiological impacts can provide valuable insights for refining therapeutic approaches in motor control for PD patients.

Adaptive behavior requires the ability to shift responding within (intra-dimensional) or between (extra-dimensional) stimulus dimensions when reward contingencies change. Studies of shifting in humans have focused mainly on the prefrontal cortex and/ or have been restricted to indirect measures of neural activity such as fMRI and lesions. Here, we demonstrate the importance of the amygdala and hippocampus by recording local field potentials directly from these regions intracranially in human epilepsy patients. Reward signals were coded in the high frequency gamma activity (HFG; 60-250 Hz) of both regions and synchronised via low frequency (3-5 Hz) phase-locking only after a shift when patients did not already know the rule and it signalled to stop shifting (“Win-Stay”). In contrast, HFG punishment signals were only seen in the amygdala when the rule then changed and it signalled to start shifting (“Lose-Shift”). During decision-making, hippocampal HFG was more inhibited on non-shift relative to shift trials, suggesting a role in preventing interference in rule representation and amygdala HFG was sensitive to stimulus novelty. The findings expand our understanding of human amygdala-hippocampal function and shifting processes, the disruption of which could contribute to shifting deficits in neuropsychiatric disorders. Studies of rule shifts have focused mainly on prefrontal cortex. Here, the authors show that activity in amygdala and hippocampus and their connectivity is important for several processes involved in rule shifts.

Lateral habenula is believed to encode negative motivational stimuli and plays key roles in the pathophysiology of psychiatric disorders. However, how habenula activities are modulated during the processing of emotional information is still poorly understood. We recorded local field potentials from bilateral habenula areas with simultaneous cortical magnetoencephalography in nine patients with psychiatric disorders during an emotional picture-viewing task. Transient activity in the theta/alpha band (5–10 Hz) within the habenula and prefrontal cortical regions, as well as the coupling between these structures, is increased during the perception and processing of negative emotional stimuli compared to positive emotional stimuli. The increase in theta/alpha band synchronization in the frontal cortex-habenula network correlated with the emotional valence but not the arousal score of the stimuli. These results provide direct evidence for increased theta/alpha synchrony within the habenula area and prefrontal cortex-habenula network in the perception of negative emotion in human participants.

Diabetes and Alzheimer’s disease (AD) place a significant burden on health care systems in the Western world and its aging populations. These diseases have long been regarded as separate entities; however, advanced glycation end products (AGEs) and the receptors for AGEs (RAGE) may be a link between diabetes and AD. In our study, mice injected with AGEs through stereotaxic surgery showed significant AD-like features: behavior showed decreased memory; immunofluorescence showed increased phosphorylated tau and APP. These results suggest links between diabetes and AD. Patients with diabetes are at a higher risk of developing AD, and the possible underlying molecular components of this association are now beginning to emerge.

Collocated global atmospheric temperature, humidity, and refractivity profiles from radiosondes and from Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) radio occultation data for April 2008 to October 2009 are compared for two purposes. The first is to quantify the error characteristics of 12 radiosonde types flown in the global operational network, as a function of height and for both day and nighttime observations, for each of the three variables. The second is to determine the effects of imperfect temporal and spatial collocation on the radiosonde‐COSMIC differences, for application to the general problem of satellite calibration and validation using in situ sounding data. Statistical analyses of the comparisons reveal differences among radiosonde types in refractivity, relative humidity, and radiation‐corrected temperature data. Most of the radiosonde types show a dry bias, particularly in the upper troposphere, with the bias in daytime drier than in nighttime. Weather‐scale variability, introduced by collocation time and distance mismatch, affects the comparison of radiosonde and COSMIC data by increasing the standard deviation errors, which are generally proportional to the size of the time and distance mismatch within the collocation window of 6 h and 250 km considered. Globally, in the troposphere (850–200 hPa), the collocation mismatch impacts on the comparison standard deviation errors for temperature are 0.35 K per 3 h and 0.42 K per 100 km and, for relative humidity, are 3.3% per 3 h and 3.1% per 100 km, indicating an approximate equivalence of 3 h to 100 km in terms of mismatch impact.