Approximation to pain-signaling network in humans by means of migraine.

Nociceptive signals are processed within a pain-related network of the brain. Migraine is a rather specific model to gain insight into this system. Brain networks may be described by white matter tracts interconnecting functionally defined gray matter regions. Here, we present an overview of the migraine-related pain network revealed by this strategy. Based on diffusion tensor imaging data from subjects in the Human Connectome Project (HCP) database, we used a global tractography approach to reconstruct white matter tracts connecting brain regions that are known to be involved in migraine-related pain signaling. This network includes an ascending nociceptive pathway, a descending modulatory pathway, a cortical processing system, and a connection between pain-processing and modulatory areas. The insular cortex emerged as the central interface of this network. Direct connections to visual and auditory cortical association fields suggest a potential neural basis of phono- or photophobia and aura phenomena. The intra-axonal volume (Vintra ) as a measure of fiber integrity based on diffusion microstructure was extracted using an innovative supervised machine learning approach in form of a Bayesian estimator. Self-reported pain levels of HCP subjects were positively correlated with tract integrity in subcortical tracts. No correlation with pain was found for the cortical processing systems.

Substance P signalling in primary motor cortex facilitates motor learning in rats.

Among the genes that are up-regulated in response to a reaching training in rats, Tachykinin 1 (Tac1)-a gene that encodes the neuropeptide Substance P (Sub P)-shows an especially strong expression. Using Real-Time RT-PCR, a detailed time-course of Tac1 expression could be defined: a significant peak occurs 7 hours after training ended at the first and second training session, whereas no up-regulation could be detected at a later time-point (sixth training session). To assess the physiological role of Sub P during movement acquisition, microinjections into the primary motor cortex (M1) contralateral to the trained paw were performed. When Sub P was injected before the first three sessions of a reaching training, effectiveness of motor learning became significantly increased. Injections at a time-point when rats already knew the task (i.e. training session ten and eleven) had no effect on reaching performance. Sub P injections did not influence the improvement of performance within a single training session, but retention of performance between sessions became strengthened at a very early stage (i.e. between baseline-training and first training session). Thus, Sub P facilitates motor learning in the very early phase of skill acquisition by supporting memory consolidation. In line with these findings, learning related expression of the precursor Tac1 occurs at early but not at later time-points during reaching training.

A High-Resolution Analysis on the Meteorological Influences on Spontaneous Intracerebral Hemorrhage Incidence.

OBJECTIVE: To investigate the influence of meteorological factors on the incidence of intracerebral hemorrhage (ICH). METHODS: We included 295 ICH admissions between 2005 and 2013. The hourly meteorological parameters considered were surface pressure, temperature, relative humidity, wind gusts, and precipitation. To minimize confounding effects of seasonality, data were analyzed with the following 3 complementary statistical approaches: 1) deviation of daily measure from the 10-year monthly mean at the day of ictus; 2) deviation from monthly average with respect to changes in daily measures between the day of ictus and 2 days before; and 3) evolution of daily measures from 5 days before to 5 days after the ICH occurred. For 1) and 2), the statistical significance of the results was determined with a Monte Carlo simulation combined with a resampling technique (1000×). RESULTS: Regarding all patients, no statistically significant and meteorologically meaningful signal could be found. With respect to subgroup-analysis, ICH related to vascular pathologies occurred significantly more frequently at days with especially low relative humidity, whereas an opposite relation was present in patients with cerebral amyloid angiopathy. However, as absolute deviations were small, a strong functional effect is questionable. With respect to seasonal distribution, a greater incidence of ICH could be detected during the cold season, in line with previous reports. CONCLUSIONS: By using high-quality meteorological data analyzed with a sophisticated and robust statistical method that minimizes the confounding effect of seasonality, no clearly identifiable meteorological influence for the ICH events considered can be found.

Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats.

Neuroplasticity and reorganization of brain motor networks are thought to enable recovery of motor function after ischemic stroke. Especially in the cortex surrounding the ischemic scar (i.e., peri-infarct cortex), evidence for lasting reorganization has been found at the level of neurons and networks. This reorganization depends on expression of specific genes and subsequent protein synthesis. To test the functional relevance of the peri-infarct cortex for recovery we assessed the effect of protein synthesis inhibition within this region after experimental stroke. Long-Evans rats were trained to perform a skilled-reaching task (SRT) until they reached plateau performance. A photothrombotic stroke was induced in the forelimb representation of the primary motor cortex (M1) contralateral to the trained paw. The SRT was re-trained after stroke while the protein synthesis inhibitor anisomycin (ANI) or saline were injected into the peri-infarct cortex through implanted cannulas. ANI injections reduced protein synthesis within the peri-infarct cortex by 69% and significantly impaired recovery of reaching performance through re-training. Improvement of motor performance within a single training session remained intact, while improvement between training sessions was impaired. ANI injections did not affect infarct size. Thus, protein synthesis inhibition within the peri-infarct cortex impairs recovery of motor deficits after ischemic stroke by interfering with consolidation of motor memory between training sessions but not short-term improvements within one session.

Postnatal differentiation of basket cells from slow to fast signaling devices.

Gamma frequency (30-100 Hz) oscillations in the mature cortex underlie higher cognitive functions. Fast signaling in GABAergic interneuron networks plays a key role in the generation of these oscillations. During development of the rodent brain, gamma activity appears at the end of the first postnatal week, but frequency and synchrony reach adult levels only by the fourth week. However, the mechanisms underlying the maturation of gamma activity are unclear. Here we demonstrate that hippocampal basket cells (BCs), the proposed cellular substrate of gamma oscillations, undergo marked changes in their morphological, intrinsic, and synaptic properties between postnatal day 6 (P6) and P25. During maturation, action potential duration, propagation time, duration of the release period, and decay time constant of IPSCs decreases by approximately 30-60%. Thus, postnatal development converts BCs from slow into fast signaling devices. Computational analysis reveals that BC networks with young intrinsic and synaptic properties as well as reduced connectivity generate oscillations with moderate coherence in the lower gamma frequency range. In contrast, BC networks with mature properties and increased connectivity generate highly coherent activity in the upper gamma frequency band. Thus, late postnatal maturation of BCs enhances coherence in neuronal networks and will thereby contribute to the development of cognitive brain functions.