Accommodation of the Spinal Cat to a Tripping Perturbation

Adult cats with a complete spinal cord transection at T12–T13 can relearn over a period of days-to-weeks how to generate full weight-bearing stepping on a treadmill or standing ability if trained specifically for that task. In the present study, we assessed short-term (milliseconds to minutes) adaptations by repetitively imposing a mechanical perturbation on the hindlimb of chronic spinal cats by placing a rod in the path of the leg during the swing phase to trigger a tripping response. The kinematics and EMG were recorded during control (10 steps), trip (1–60 steps with various patterns), and then release (without any tripping stimulus, 10–20 steps) sequences. Our data show that the muscle activation patterns and kinematics of the hindlimb in the step cycle immediately following the initial trip (mechanosensory stimulation of the dorsal surface of the paw) was modified in a way that increased the probability of avoiding the obstacle in the subsequent step. This indicates that the spinal sensorimotor circuitry reprogrammed the trajectory of the swing following a perturbation prior to the initiation of the swing phase of the subsequent step, in effect “attempting” to avoid the re-occurrence of the perturbation. The average height of the release steps was elevated compared to control regardless of the pattern and the length of the trip sequences. In addition, the average impact force on the tripping rod tended to be lower with repeated exposure to the tripping stimulus. EMG recordings suggest that the semitendinosus, a primary knee flexor, was a major contributor to the adaptive tripping response. These results demonstrate that the lumbosacral locomotor circuitry can modulate the activation patterns of the hindlimb motor pools within the time frame of single step in a manner that tends to minimize repeated perturbations. Furthermore, these adaptations remained evident for a number of steps after removal of the mechanosensory stimulation

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Oscillatory EEG correlates of arithmetic strategies: A training study

There has been a long tradition of research on mathematics education showing that children and adults use different strategies to solve arithmetic problems. Neurophysiological studies have recently begun to investigate the brain correlates of these strategies. The existing body of data, however, reflect static end points of the learning process and do not provide information on how brain activity changes in response to training or intervention. In this study, we explicitly address this issue by training participants in using fact retrieval strategies. We also investigate whether brain activity related to arithmetic fact learning is domain-specific or whether this generalizes to other learning materials, such as the solution of figural-spatial problems. Twenty adult students were trained on sets of two-digit multiplication problems and figural-spatial problems. After the training, they were presented with the trained and untrained problems while their brain activity was recorded by means of electroencephalography (EEG) . In both problem types, the training resulted in accuracies over 90 % and significant decreases in solution times. Analyses of the oscillatory EEG data also revealed training effects across both problem types. Specifically, we observed training-related activity increases in the theta band (3-6 Hz) and decreases in the lower alpha band (8-10 Hz), especially over parieto-occipital and parietal brain regions. These results provide the first evidence that a short term fact retrieval training results in significant changes in oscillatory EEG activity. These findings further corroborate the role of the theta band in the retrieval of semantic information from memory and suggest that theta activity is not only sensitive to fact retrieval in mental arithmetic but also in other domains

Unanswered questions in the transcranial magnetic stimulation treatment of patients with depression

According to the WHO fact sheet depression is a common mental disorder affecting 350 million people of all ages worldwide. Transcranial Magnetic Stimulation (TMS) is a technique which allows the investigator to stimulate and study cortical functions in healthy subjects and patients suffering from various mental and neurological disorders. In the early 1990s, studies revealed that it is possible to evoke long term mood changes in healthy volunteers by rapid rate repetitive, TMS (rTMS) over the frontal cortex. Subsequent studies involving depressed patients found frontal cortical rTMS administered daily to be clinically effective. In the past two decades, numerous trials examined the therapeutic potential of rTMS application in the treatment of mood disorders with constantly evolving treatment protocols. The aim of this paper is to review the literature of the past two decades, focusing on trials addressing the efficacy and safety of rTMS in depressed patients. Our primary goal is to evaluate the results in order to direct future studies which may help investigators in the development of treatment protocols suitable in hospital settings. The time is not far when TMS devices will be used routinely by practitioners primarily for therapeutic purpose rather than clinical research. To our knowledge, a widely accepted “gold standard" that would offer the highest efficacy, with the best tolerability has not been established yet. In order to approach this goal, the most important factors to be addressed by further studies are: localization, frequency, intensity, concurrent medication, maintenance treatments, number of pulses, trains, unilateral, or bilateral mode of application