Gamma oscillations in human primary somatosensory cortex reflect pain perception

Pain is a highly subjective sensation of inherent behavioral importance and is therefore expected to receive enhanced processing in relevant brain regions. We show that painful stimuli induce high-frequency oscillations in the electrical activity of the human primary somatosensory cortex. Amplitudes of these pain-induced gamma oscillations were more closely related to the subjective perception of pain than to the objective stimulus attributes. They correlated with participants' ratings of pain and were stronger for laser stimuli that caused pain, compared with the same stimuli when no pain was perceived. These findings indicate that gamma oscillations may represent an important mechanism for processing behaviorally relevant sensory information

Impact of coastal polynyas on dense shelf water formation in the Weddell Sea

Dense shelf water is an essential ingredient to the formation of Antarctic Bottom Water (AABW). It is formed on the continental shelves surrounding Antarctica, when freezing rates are sufficiently high to push ocean salinity to values of 34.65 and higher. Coastal polynyas, where the ice is driven away from the coastline, maintain the highest freezing rates in Antarctic winter. Since theWeddell Sea is considered the most productive source region of AABW, we investigate the dense water formation on the continental shelves of the southwestern Weddell Sea, with a focus on the role of coastal polynyas, using the Finite Element Sea ice-Ocean Model (FESOM), a primitive-equation, hydrostatic ocean model coupled with a dynamic-thermodynamic sea ice model. The horizontal resolution of the global, unstructured mesh is up to 3 km at the southwestern Weddell Sea coastline; in vertical direction the mesh features 37 depth levels (resolution increases toward the surface). The model was initialized on 01/01/1980 with data from the Polar Hydrographic Climatology and forced with NCEP/NCAR Reanalysis data. The 20-year period 1990-2009 is used for analysis. Our results indicate that in an average year, the polynya freezing rates of 9 cm d--1 (corresponding to a salt input of 2.5 kg m--2d--1) cause a seasonal variation in salinity of 0.3 psu under the Ronne polynya and result in the production of 5.10-4 km-3 dense shelf water, which leaves the continental shelf (outlined by the 700 m isobath in this study) at a long-term mean volume flux of 5.2 Sv. Some of this water contributes to the formation of Weddell Sea Deep/BottomWater, but a large fraction is diluted by mixing with ambient water and leaves the Weddell Sea at intermediate levels

Probabilistic tractography in the ventrolateral thalamic nucleus: cerebellar and pallidal connections

The ventrolateral thalamic nucleus (VL), as part of the ‘motor thalamus’, is main relay station of cerebellar and pallidal projections. It comprises anterior (VLa) and posterior (VLpd and VLpv) subnuclei. Though the fibre architecture of cerebellar and pallidal projections to of the VL nucleus has already been focus in a numerous amount of in vitro studies mainly in animals, probabilistic tractography now offers the possibility of an in vivo comparison in healthy humans. In this study we performed a (a) qualitative and (b) quantitative examination of VL-cerebellar and VL-pallidal pathways and compared the probability distributions between both projection fields in the VL after an (I) atlas-based and (II) manual-based segmentation procedure. Both procedures led to high congruent results of cerebellar and pallidal connectivity distributions: the maximum of pallidal projections was located in anterior and medial parts of the VL nucleus, whereas cerebellar connectivity was more located in lateral and posterior parts. The median connectivity for cerebellar connections in both approaches (manual and atlas-based segmentation) was VLa > VLpv > VLpd, whereas the pallidal median connectivity was VLa ~ VLpv > VLpd in the atlas-based approach and VLpv > VLa > VLpd in the manual approach.Peer reviewe

Safety perception in patients with advanced idiopathic Parkinson’s disease – a qualitative study

BackgroundA fundamental cornerstone of quality of healthcare is patient safety, which many people with life-limiting illnesses feel is being compromised. Perceptions of impaired safety are associated with the occurrence of psychological distress and healthcare utilization. However, little is known about how people with idiopathic Parkinson’s disease (iPD) perceive their own safety toward the end of life. The aim of our study was therefore to investigate factors that influence the perception of safety of patients with advanced iPD.MethodsWe conducted semi-structured interviews with a purposeful sample of 21 patients with advanced iPD. Participants were recruited at the neurology department of a tertiary care hospital in Germany between August 2021 and June 2022. Data were analyzed using reflexive thematic analysis.ResultsiPD-patients reported relevant impairment of their safety. While most participants expressed safety concerns based on the manifestation of disease, our analysis identified enablers and barriers to establishing safety in patients with advanced iPD, in 10 additional domains: relationship to the disease, informedness, self-perception, utilization of support and care structures, healthcare professionals and structures, treatment, social interaction, social security, spirituality, and environment.ConclusionThis study provides new insights into safety perceptions of patients with advanced iPD, which extend well beyond the physical realm. The findings suggest that clinicians and policy makers should consider a holistic and multidisciplinary approach to assessing and improving patients’ safety taking into account the enablers and barriers identified in this study

A functional micro-electrode mapping of ventral thalamus in Essential Tremor

Deep brain stimulation enables the delivery of therapeutic interventions to otherwise inaccessible areas of the brain while, at the same time, offering the unique opportunity to record from these same regions in awake patients. The posterior ventrolateral thalamus has become a reliable deep brain stimulation target for medically-refractory patients suffering from essential tremor. However, the contribution of the thalamus in essential tremor, and even whether posterior ventrolateral thalamus is the optimal target, remains a matter of ongoing debate. There are several lines of evidence supporting clusters of activity within the posterior ventrolateral thalamus that are important for tremor emergence. In this study we sought to map the functional properties of these clusters through microelectrode recordings during deep brain stimulation surgery. Data were obtained from 10 severely affected patients with essential tremor (12 hemispheres) undergoing deep brain stimulation surgery. Our results demonstrate power and coherence maxima located in the inferior posterior ventrolateral thalamus and immediate ventral region. Moreover, we identified distinct yet overlapping clusters of predominantly efferent (driving) and afferent (feedback) activity, with a preference for more efferent contributors, consistent with a net role in the driving of tremor output. Finally, we demonstrate that resolvable thalamic spiking activity directly relates to background activity and that the strength of tremor may be dictated by phase relationships between efferent and afferent pockets in the posterior ventrolateral thalamus. Taken together, these results provide important evidence for the role of the inferior posterior ventrolateral thalamus and its border region in essential tremor pathophysiology. Such results progress our mechanistic understanding and promote the adoption of next-generation therapies such as high resolution segregated deep brain stimulation electrodes

Patterning and gastrulation defects caused by the tw18 lethal are due to loss of Ppp2r1a

The mouse t haplotype, a variant 20 cM genomic region on Chromosome 17, harbors 16 embryonic control genes identified by recessive lethal mutations isolated from wild mouse populations. Due to technical constraints so far only one of these, the tw5 lethal, has been cloned and molecularly characterized. Here we report the molecular isolation of the tw18 lethal. Embryos carrying the tw18 lethal die from major gastrulation defects commencing with primitive streak formation at E6.5. We have used transcriptome and marker gene analyses to describe the molecular etiology of the tw18 phenotype. We show that both WNT and Nodal signal transduction are impaired in the mutant epiblast, causing embryonic patterning defects and failure of primitive streak and mesoderm formation. By using a candidate gene approach, gene knockout by homologous recombination and genetic rescue, we have identified the gene causing the tw18 phenotype as Ppp2r1a, encoding the PP2A scaffolding subunit PR65alpha. Our work highlights the importance of phosphatase 2A in embryonic patterning, primitive streak formation, gastrulation, and mesoderm formation downstream of WNT and Nodal signaling

Pallidal Deep Brain Stimulation Reduces Sensorimotor Cortex Activation in Focal/Segmental Dystonia

Background Although deep brain stimulation of the globus pallidus internus (GPi-DBS) is an established treatment for many forms of dystonia, including generalized as well as focal forms, its effects on brain (dys-)function remain to be elucidated, particularly for focal and segmental dystonia. Clinical response to GPi-DBS typically comes with some delay and lasts up to several days, sometimes even weeks, once stimulation is discontinued. Objective This study investigated how neural activity during rest and motor activation is affected by GPi-DBS while excluding the potential confound of altered feedback as a result of therapy-induced differences in dystonic muscle contractions. Methods Two groups of patients with focal or segmental dystonia were included in the study: 6 patients with GPi-DBS and 8 without DBS (control group). All 14 patients had cervical dystonia. Using (H2O)-O-15 PET, regional cerebral blood flow was measured at rest and during a motor task performed with a nondystonic hand. Results In patients with GPi-DBS (stimulation ON and OFF), activity at rest was reduced in a prefrontal network, and during the motor task, sensorimotor cortex activity was lower than in patients without DBS. Within-group contrasts (tapping > rest) showed less extensive task-induced motor network activation in GPi-DBS patients than in non-DBS controls. Reduced sensorimotor activation amounted to a significant group-by-task interaction only in the stimulation ON state. Conclusions These findings support previous observations in generalized dystonia that suggested that GPi-DBS normalizes dystonia-associated sensorimotor and prefrontal hyperactivity, indicating similar mechanisms in generalized and focal or segmental dystonia. Evidence is provided that these effects extend into the OFF state, which was not previously demonstrated by neuroimaging. (c) 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.Peer reviewe

Non-invasive vagus nerve stimulation in epilepsy patients enhances cooperative behavior in the prisoner's dilemma task

The vagus nerve constitutes a key link between the autonomic and the central nervous system. Previous studies provide evidence for the impact of vagal activity on distinct cognitive processes including functions related to social cognition. Recent studies in animals and humans show that vagus nerve stimulation is associated with enhanced reward-seeking and dopamine-release in the brain. Social interaction recruits similar brain circuits to reward processing. We hypothesize that vagus nerve stimulation (VNS) boosts rewarding aspects of social behavior and compare the impact of transcutaneous VNS (tVNS) and sham stimulation on social interaction in 19 epilepsy patients in a double-blind pseudo-randomized study with cross-over design. Using a well-established paradigm, i.e., the prisoner's dilemma, we investigate effects of stimulation on cooperative behavior, as well as interactions of stimulation effects with patient characteristics. A repeated-measures ANOVA and a linear mixed-effects model provide converging evidence that tVNS boosts cooperation. Post-hoc correlations reveal that this effect varies as a function of neuroticism, a personality trait linked to the dopaminergic system. Behavioral modeling indicates that tVNS induces a behavioral starting bias towards cooperation, which is independent of the decision process. This study provides evidence for the causal influence of vagus nerve activity on social interaction

Case report: Unilateral GPi DBS in secondary myoclonus-dystonia syndrome after acute disseminated encephalomyelitis

IntroductionDeep brain stimulation (DBS) is an established and effective therapy for movement disorders. Here, we present a case of secondary myoclonus-dystonia syndrome following acute disseminated encephalomyelitis (ADEM) in childhood, which was alleviated by DBS. Using a patient-specific connectome analysis, we sought to characterise the fibres and circuits affected by stimulation.Case reportWe report a case of a 20-year-old man with progressive dystonia, myoclonic jerks, and impaired concentration following childhood ADEM. Motor assessments utilising the Unified Myoclonus Rating Scale (UMRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) revealed a greater improvement in dystonia compared to myoclonus following adjustments of DBS parameters. These adjustments were based on visualisation of electrode position and volume of tissue activated (VTA) 3 years after surgery. A patient-specific connectome analysis using the VTA as a region of interest revealed fibre tracts connecting to the cerebello-thalamo-cortical network and the superior frontal gyrus in addition to basal ganglia circuits as particularly effective.ConclusionGlobus pallidus internus (GPi) DBS shows promise as a treatment for secondary myoclonus-dystonia syndromes. Personalised structural considerations, tailored to individual symptoms and clinical characteristics, can provide significant benefits. Patient-specific connectome analysis, specifically, offers insights into the structures involved and may enable a favourable treatment response