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Painful diabetic polyneuropathy (PDPN) and painful polyneuropathies of other origins are associated with significant personal and societal burdens with treatments limited to symptomatic management. Treatment options include antidepressants, gamma-aminobutyric acid (GABA) analogs, opioids, and topical analgesics, which are intended to alleviate pain and symptoms of neuropathy, but limited data are available on their efficacy. selleck products Paresthesia-based low-frequency spinal cord stimulation (LF-SCS) is considered a last-resort treatment modality for PDPN patients. In a large-scale RCT of neuropathic low back and leg pain, high-frequency SCS at 10 kHz (10 kHz SCS) was shown to provide superior pain relief that is not dependent on paresthesia and a higher responder rate than LF SCS. This retrospective case series includes data from six patients with painful peripheral neuropathies, including PDPN, idiopathic polyneuropathy, and chronic inflammatory demyelinating polyneuropathy, who were candidates for 10 kHz SCS in routine commercial practice. All patients reported a reduction in verbal numerical rating scale (VNRS) pain score at last follow-up (2.7 ± 0.9) compared with baseline (7.0 ± 0.9). Out of five patients with information available at last follow-up, two were completely off their pain medications and two reduced their dose by over 40%. Similarly, at last follow-up, three out of five patients reported sensory improvement in their lower limbs. In conclusion, 10 kHz SCS treatment resulted in significant pain relief in all the patients, decreased reliance on pain medication, and improved lower limb sensory function in the majority of patients.Our sense of number rests on the activity of neurons that are tuned to the number of items and show great invariance across display formats and modalities. Whether numerosity coding becomes abstracted from local spatial representations characteristic of visual input is not known. We mapped the visual receptive fields (RFs) of numerosity-selective neurons in the pFC and ventral intraparietal area in rhesus monkeys. We found numerosity selectivity in pFC and ventral intraparietal neurons irrespective of whether they exhibited an RF and independent of the location of their RFs. RFs were not predictive of the preference of numerosity-selective neurons. Furthermore, the presence and location of RFs had no impact on tuning width and quality of the numerosity-selective neurons. These findings show that neurons in frontal and parietal cortices integrate abstract visuospatial stimuli to give rise to global and spatially released number representations as required for number perception.It is well documented that providing advanced information regarding the spatial location of a target stimulus (i.e., spatial anticipation) or its timing of occurrence (i.e., temporal anticipation) influences reach preparation, reducing RTs. Yet, it remains unknown whether the RT gains attributable to temporal and spatial anticipation are subtended by similar preparatory dynamics. Here, this issue is addressed in humans by investigating EEG beta-band activity during reach preparation. Participants performed a reach RT task in which they initiated a movement as fast as possible toward visual targets following their appearance. Temporal anticipation was manipulated by having the target appear after a constant or variable delay period, whereas spatial anticipation was manipulated by precueing participants about the upcoming target location in advance or not. Results revealed that temporal and spatial anticipation both reduced reach RTs, with no interaction. Interestingly, temporal and spatial anticipation were associated with fundamentally different patterns of beta-band modulations. Temporal anticipation was associated with beta-band desynchronization over contralateral sensorimotor regions specifically around the expected moment of target onset, the magnitude of which was correlated with RT modulations across participants. In contrast, spatial anticipation did not influence sensorimotor activity but rather led to increased beta-band power over bilateral parieto-occipital regions during the entire delay period. These results argue for distinct states of preparation incurred by temporal and spatial anticipation. In particular, sensorimotor beta-band desynchronization may reflect the timely disinhibition of movement-related neuronal ensembles at the expected time of movement initiation, without reflecting its spatial parameters per se.The nature of the mapping process that imbues number symbols with their numerical meaning-known as the "symbolgrounding process"-remains poorly understood and the topic of much debate. The aim of this study was to enhance insight into how the nonsymbolic-symbolic number mapping process and its neurocognitive correlates might differ between small (1-4; subitizing range) and larger (6-9) numerical ranges. Hereto, 22 young adults performed a learning task in which novel symbols acquired numerical meaning by mapping them onto nonsymbolic magnitudes presented as dot arrays (range 1-9). Learning-dependent changes in accuracy and RT provided evidence for successful novel symbol quantity mapping in the subitizing (1-4) range only. Corroborating these behavioral results, the number processing related P2p component was only modulated by the learning/mapping of symbols representing small numbers 1-4. The symbolic N1 amplitude increased with learning independent of symbolic numerical range but dependent on the set size of the preceding dot array; it only occurred when mapping on one to four item dot arrays that allow for quick retrieval of a numeric value, on the basis of which, with learning, one could predict the upcoming symbol causing perceptual expectancy violation when observing a different symbol. These combined results suggest that exact nonsymbolic-symbolic mapping is only successful for small quantities 1-4 from which one can readily extract cardinality. Furthermore, we suggest that the P2p reflects the processing stage of first access to or retrieval of numeric codes and might in future studies be used as a neural correlate of nonsymbolic-symbolic mapping/symbol learning.

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