I move, therefore I am: A new theoretical framework to investigate agency and ownership

The neurocognitive structure of the acting self has recently been widely studied, yet is still perplexing and remains an often confounded issue in cognitive neuroscience, psychopathology and philosophy. We provide a new systematic account of two of its main features, the sense of agency and the sense of ownership, demonstrating that although both features appear as phenomenally uniform, they each in fact are complex crossmodal phenomena of largely heterogeneous functional and representational levels. These levels can be arranged within a gradually evolving, onto- and phylogenetically plausible framework which proceeds from basic non-conceptual sensorimotor processes to more complex conceptual and meta-representational processes of agency and ownership, respectively. In particular, three fundamental levels of agency and ownership processing have to be distinguished: The level of feeling, thinking and social interaction. This naturalistic account will not only allow to “ground the self in action”, but also provide an empirically testable taxonomy for cognitive neuroscience and a new tool for disentangling agency and ownership disturbances in psychopathology

Real-time use of audio-biofeedback can improve postural sway in patients with degenerative ataxia

Abstract Objective Cerebellar ataxia essentially includes deficient postural control. It remains unclear whether augmented sensory information might help cerebellar patients, as the cerebellum underlies processing of various sensory modalities for postural control. Here, we hypothesized that patients with cerebellar degeneration can still exploit audio‐biofeedback (ABF) of trunk acceleration as a real‐time assistive signal to compensate for deficient postural control. Methods Effects on postural sway during stance were assessed in an ABF intervention group versus a no‐ABF disease control group (23 vs. 17 cerebellar patients) in a clinico‐experimental study. A single‐session ABF paradigm of standing plus short exergaming under ABF was applied. Postural sway with eyes open and eyes closed was quantified prior to ABF, under ABF, and post ABF. Results Postural sway in the eyes closed condition was significantly reduced under ABF. Both benefit of ABF and benefit of vision correlated with the extent of postural sway at baseline, and both types of sensory benefits correlated with each other. Patients with strongest postural sway exhibited reduced postural sway also with eyes open, thus benefitting from both vision and ABF. No changes were observed in the no‐ABF control group. Interpretation Our findings provide proof‐of‐principle evidence that subjects with cerebellar degeneration are still able to integrate additional sensory modalities to compensate for deficient postural control: They can use auditory cues functionally similar to vision in the absence of vision, and additive to vision in the presence of vision (in case of pronounced postural sway). These findings might inform future assistive strategies for cerebellar ataxia

S100B is increased in Parkinson’s disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-α pathway

Peer reviewedPublisher PD

Case Report: Deep brain stimulation improves tremor in FGF-14 associated spinocerebellar ataxia

ObjectivesSpinocerebellar ataxia 27 (SCA 27) is a rare heredodegenerative disorder caused by mutations in the fibroblast growth factor 14 (FGF14) and characterized by early-onset tremor and progressive ataxia later during the disease course. We investigated the effect of deep brain stimulation (DBS) of the ventralis intermedius nucleus of the thalamus (VIM) and subthalamic projections on tremor and ataxia.MethodsAt baseline, we studied the effects of high-frequency VIM stimulation and low-frequency stimulation of subthalamic projections on tremor and ataxia. The patient then adopted the best individual high-frequency stimulation programme at daytime and either 30 Hz-stimulation of the subthalamic contacts or StimOFF at night during two separate 5-weeks follow-up intervals. Both patient and rater were blinded to the stimulation settings.ResultsHigh-frequency stimulation of the VIM effectively attenuated tremor. At follow-up, intermittent 30 Hz-stimulation at night resulted in a superior tremor response compared to StimOFF at night. Ataxia was not affected.DiscussionStimulation of the VIM and adjacent subthalamic projections effectively attenuated tremor in a patient with confirmed SCA 27. Cycling between daytime high-frequency and night-time low-frequency stimulation led to a more sustained tremor response. This suggests to study in future if low-frequency stimulation of the subthalamic projection fibers may help overcome tolerance of tremor that is observed as a long-term limitation of VIM-DBS

Intracellular Lipid Accumulation and Mitochondrial Dysfunction Accompanies Endoplasmic Reticulum Stress Caused by Loss of the Co-chaperone DNAJC3.

Recessive mutations in DNAJC3, an endoplasmic reticulum (ER)-resident BiP co-chaperone, have been identified in patients with multisystemic neurodegeneration and diabetes mellitus. To further unravel these pathomechanisms, we employed a non-biased proteomic approach and identified dysregulation of several key cellular pathways, suggesting a pathophysiological interplay of perturbed lipid metabolism, mitochondrial bioenergetics, ER-Golgi function, and amyloid-beta processing. Further functional investigations in fibroblasts of patients with DNAJC3 mutations detected cellular accumulation of lipids and an increased sensitivity to cholesterol stress, which led to activation of the unfolded protein response (UPR), alterations of the ER-Golgi machinery, and a defect of amyloid precursor protein. In line with the results of previous studies, we describe here alterations in mitochondrial morphology and function, as a major contributor to the DNAJC3 pathophysiology. Hence, we propose that the loss of DNAJC3 affects lipid/cholesterol homeostasis, leading to UPR activation, β-amyloid accumulation, and impairment of mitochondrial oxidative phosphorylation

Spinocerebellar ataxia 27B: episodic symptoms and acetazolamide response in 34 patients

Ashton C et al report a retrospective multi-centre cohort of 34 patients from Canada, France, Austria and Australia with spinocerebellar ataxia 27B, describing the common feature of episodic ataxia and other episodic features, as well as the inefficacy of acetazolamide in these patients

Correction:Solving unsolved rare neurological diseases—a Solve-RD viewpoint (European Journal of Human Genetics, (2021), 29, 9, (1332-1336), 10.1038/s41431-021-00901-1)

In the original publication of the article, consortium author lists were missing in the article

Are intrinsic neural timescales related to sensory processing? Evidence from abnormal behavioral states

The brain exhibits a complex temporal structure which translates into a hierarchy of distinct neural timescales. An open question is how these intrinsic timescales are related to sensory or motor information processing and whether these dynamics have common patterns in different behavioral states. We address these questions by investigating the brain\u27s intrinsic timescales in healthy controls, motor (amyotrophic lateral sclerosis, locked-in syndrome), sensory (anesthesia, unresponsive wakefulness syndrome), and progressive reduction of sensory processing (from awake states over N1, N2, N3). We employed a combination of measures from EEG resting-state data: auto-correlation window (ACW), power spectral density (PSD), and power-law exponent (PLE). Prolonged neural timescales accompanied by a shift towards slower frequencies were observed in the conditions with sensory deficits, but not in conditions with motor deficits. Our results establish that the spontaneous activity\u27s intrinsic neural timescale is related to the neural capacity that specifically supports sensory rather than motor information processing in the healthy brain