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Ausgehend vom Prinzip der freien Energie sowie der aktiven Inferenz beschreibt dieser Beitrag die Gesamtheit der zur räumlichen und bewegungsbezogenen Eigenwahrnehmung sowie zu willkürlichen Bewegungen beitragenden, interagierenden Partialmechanismen als ein dynamisches komplexes funktionelles System. Dieses System befindet sich in einem fortlaufenden Prozess der Selbsterhaltung sowie -bestätigung, der zu einem dynamischen Gleichgewichtszustand führt. Ziel des umschriebenen Systems ist es, ein Modell für die Bewegungsregulation unter Führung multimodaler sensorischer Zuflüsse zu generieren, über das der Organismus in eine dynamische Wahrnehmungs-Handlungs-Interaktion mit der Umwelt tritt. Funktionsstörungen der räumlichen und bewegungsbezogenen Eigenwahrnehmung sowie der Wahrnehmung der relativen Umwelt können Funktionsstörungen des Bewegungssystem bedingen und auf Verarbeitungs- und Wahrnehmungsstörungen der Sinnessysteme beruhen. Entsprechend liefert das Prinzip der freien Energie und die einhergehende Denkweise Impulse zur Reflexion und Weiterentwicklung von bestehenden manualmedizinischen Praktiken, aber auch zur Innovation.

Inactivating variants in PIEZO2, which encodes a stretch-gated ion channel, impair touch perception and proprioception. Visual cues partially compensate for these impairments, allowing affected persons to perform complex movements with greater accuracy. The ability to sense force, which is known as mechanosensation, provides humans and other animals with important information about the environment; it is crucial for social interactions, such as comforting or caressing, and is required for motor coordination. A number of anatomical classes of somatosensory neurons with distinct selectivity for mechanical stimuli have been identified, but the way in which these inputs combine to provide the richness of the human sense of touch remains unclear. 1 , 2 Similarly, proprioception is considered to be essential for posture and controlled movement, but little is known about the underlying mechanisms and the precise role . . .

PIEZO2 is the essential transduction channel for touch discrimination, vibration, and proprioception. Mice and humans lacking Piezo2 experience severe mechanosensory and proprioceptive deficits and fail to develop tactile allodynia. Bradykinin, a proalgesic agent released during inflammation, potentiates PIEZO2 activity. Molecules that decrease PIEZO2 function could reduce heightened touch responses during inflammation. Here, we find that the dietary fatty acid margaric acid (MA) decreases PIEZO2 function in a dose-dependent manner. Chimera analyses demonstrate that the PIEZO2 beam is a key region tuning MA-mediated channel inhibition. MA reduces neuronal action potential firing elicited by mechanical stimuli in mice and rat neurons and counteracts PIEZO2 sensitization by bradykinin. Finally, we demonstrate that this saturated fatty acid decreases PIEZO2 currents in touch neurons derived from human induced pluripotent stem cells. Our findings report on a natural product that inhibits PIEZO2 function and counteracts neuronal mechanical sensitization and reveal a key region for channel inhibition. PIEZO2 is a critical component of the mechanism by which innocuous touch causes pain (tactile allodynia). Here, authors find that the dietary fatty acid margaric acid decreases PIEZO2 function in a dose-dependent manner and counteracts neuronal mechanical sensitization by a proalgesic agent.

Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT2A receptor signaling, supporting their evaluation as a therapeutic for neuroinflammation associated with neurodegenerative disease.ObjectiveThis study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally repeated administration of 5 μg, 10 μg, and 20 μg LSD in older healthy individuals. In the current paper, we present safety, tolerability, pharmacokinetics, and pharmacodynamic measures that relate to safety, tolerability, and dose response.MethodsThis was a phase 1 double-blind, placebo-controlled, randomized study. Volunteers were randomly assigned to 1 of 4 dose groups (5 μg, 10 μg, 20 μg LSD, and placebo), and received their assigned dose on six occasions (i.e., every 4 days).ResultsForty-eight older healthy volunteers (mean age = 62.9 years) received placebo (n = 12), 5 μg (n = 12), 10 μg (n = 12), or 20 μg (n = 12) LSD. LSD plasma levels were undetectable for the 5 μg group and peak blood plasma levels for the 10 μg and 20 μg groups occurred at 30 min. LSD was well tolerated, and the frequency of adverse events was no higher than for placebo. Assessments of cognition, balance, and proprioception revealed no impairment.ConclusionsOur results suggest safety and tolerability of orally administered 5 μg, 10 μg, and 20 μg LSD every fourth day over a 21-day period and support further clinical development of LSD for the treatment and prevention of Alzheimer’s disease (AD).

Study Design Randomised controlled trial.BackgroundWhile some authors reported significant effect of balance training on proprioception, however the others reported non-significant findings.ObjectivesResearch shows that balance training can be effective to reduce injuries and improving balance but less is known about the effect of balance training on proprioceptive improvement and the current results are inconclusive regarding the ability of balance training to improve proprioception.Methods and MeasuresTwelve men (age: 22.5±4.58 years, height: 181.58±7.57 cm, weight:85.25±10.67 kg, BMI: 25.87±3.01 kg/m2) and 16 women (age: 20.87±3.4 years, height: 164.13±6.15 cm, weight: 63.75±13.3 kg, BMI: 23.53±3.94 kg/m2 ) volunteered to participate in this study. All participants completed 12 supervised balance-training sessions over 4 weeks . Each session consisted of a combination of dynamic unstable-surface tasks that incorporated a BOSU ball and lasted about 30 min . In order to assess the ankle proprioception a passive reproduction of passive positioning protocol was used. Target angles were determined as 10° and 20° of inversion.ResultsAt the end of 4 weeks dynamic balance training ankle proprioception did not change significantly from pre (100 Inversion: 2.290 ; 200 Inversion: 2.270) to post test (100 Inversion: 2.090 ; 200 Inversion: 2.440), respectively.ConclusionsThe lack of a significant improvement in joint position sense could be due to dose response, and participants characteristic (healthy persons).

The hand endows us with unparalleled precision and versatility in our interactions with objects, from mundane activities such as grasping to extraordinary ones such as virtuoso pianism. The complex anatomy of the human hand combined with expansive and specialized neuronal control circuits allows a wide range of precise manual behaviours. To support these behaviours, an exquisite sensory apparatus, spanning the modalities of touch and proprioception, conveys detailed and timely information about our interactions with objects and about the objects themselves. The study of manual dexterity provides a unique lens into the sensorimotor mechanisms that endow the nervous system with the ability to flexibly generate complex behaviour.Hands enable us to interact with objects in precise and versatile ways. In this Review, Sobinov and Bensmaia discuss aspects of mundane and expert manual behaviours, the anatomical complexity of the human hand and neural mechanisms that underlie manual dexterity.

BackgroundSensory ganglionopathy is typified by selective peripheral sensory axonal loss on nerve conduction studies (NCS) and can occur with CANVAS (cerebellar ataxia with neuropathy and bilateral vestibular areflexia) syndrome.Case: A 53-year old woman had a 4-year history of some unsteadiness, slurred speech and distal sensory symptoms. She also reported a daily cough over the past 10 years. Clinically, she had dysarthria and mild sensory ataxia. Proprioception and deep tendon reflexes were preserved.Results of Investigations: NCS demonstrated markedly reduced sensory nerve action potential (SNAP) amplitudes in upper and lower limbs with normal motor NCS. The tibial H-reflexes were strikingly retained. Genetic testing confirmed biallelic RFC1 intronic repeat expansion mutation consistent with CANVAS syndrome.DiscussionThe retained H-reflexes (and tendon reflexes) indicates relative sparing of the group Ia muscle afferents that originate from muscle spindle primary endings and are known to contribute significantly to proprioception. This accounts for the relatively mild gait ataxia in the setting of CANVAS syndrome despite marked sensory NCS abnormalities.

Epidural electrical stimulation (EES) of the spinal cord restores locomotion in animal models of spinal cord injury but is less effective in humans. Here we hypothesized that this interspecies discrepancy is due to interference between EES and proprioceptive information in humans. Computational simulations and preclinical and clinical experiments reveal that EES blocks a significant amount of proprioceptive input in humans, but not in rats. This transient deafferentation prevents modulation of reciprocal inhibitory networks involved in locomotion and reduces or abolishes the conscious perception of leg position. Consequently, continuous EES can only facilitate locomotion within a narrow range of stimulation parameters and is unable to provide meaningful locomotor improvements in humans without rehabilitation. Simulations showed that burst stimulation and spatiotemporal stimulation profiles mitigate the cancellation of proprioceptive information, enabling robust control over motor neuron activity. This demonstrates the importance of stimulation protocols that preserve proprioceptive information to facilitate walking with EES.