Brains of endurance athletes differ in the association areas but not in the primary areas.

Regular participation in sports results in a series of physiological adaptations. However, little is known about the brain adaptations to physical activity. Here we aimed to investigate whether young endurance athletes and non-athletes differ in the gray and white matter of the brain and whether cardiorespiratory fitness (CRF) is associated with these differences. We assessed the CRF, volumes of the gray and white matter of the brain using structural magnetic resonance imaging (sMRI), and brain white matter connections using diffusion magnetic resonance imaging (dMRI) in 20 young male endurance athletes and 21 healthy non-athletes. While total brain volume was similar in both groups, the white matter volume was larger and the gray matter volume was smaller in the athletes compared to non-athletes. The reduction of gray matter was located in the association areas of the brain that are specialized in processing of sensory stimuli. In the microstructure analysis, significant group differences were found only in the association tracts, for example, the inferior occipito-frontal fascicle (IOFF) showing higher fractional anisotropy and lower radial diffusivity, indicating stronger myelination in this tract. Additionally, gray and white matter brain volumes, as well as association tracts correlated with CRF. No changes were observed in other brain areas or tracts. In summary, the brain signature of the endurance athlete is characterized by changes in the integration of sensory and motor information in the association areas.

Neural mechanisms of pain processing differ between endurance athletes and nonathletes: A functional connectivity magnetic resonance imaging study.

Pain perception and the ability to modulate arising pain vary tremendously between individuals. It has been shown that endurance athletes possess higher pain tolerance thresholds and a greater effect of conditioned pain modulation than nonathletes, both indicating a more efficient system of endogenous pain inhibition. The aim of the present study was to focus on the neural mechanisms of pain processing in endurance athletes that have not been investigated yet. Therefore, we analyzed the pain processing of 18 male athletes and 19 healthy male nonathletes using functional magnetic resonance imaging. We found lower pain ratings in endurance athletes compared to nonathletes to physically identical painful stimulation. Furthermore, brain activations of athletes versus nonathletes during painful heat stimulation revealed reduced activation in several brain regions that are typically activated by nociceptive stimulation. This included the thalamus, primary and secondary somatosensory cortex, insula, anterior cingulate cortex, midcingulate cortex, dorsolateral prefrontal cortex, and brain stem (BS). Functional connectivity analyses revealed stronger network during painful heat stimulation in athletes between the analyzed brain regions except for connections with the BS that showed reduced functional connectivity in athletes. Post hoc correlation analyses revealed associations of the subject's fitness level and the brain activation strengths, subject's fitness level and functional connectivity, and brain activation strengths and functional connectivity. Together, our results demonstrate for the first time that endurance athletes do not only differ in behavioral variables compared to nonathletes, but also in the neural processing of pain elicited by noxious heat.

Microstructural alterations in medial forebrain bundle are associated with interindividual pain sensitivity.

The perception of pain to noxious stimuli, also known as pain sensitivity, varies among individuals. The comprised brain structures and their white matter pathways are complex and elusive. Here, we aimed to investigate whether variation of microstructure of the medial forebrain bundle (MFB), a tract connecting the basal forebrain with the brain stem, is associated with interindividual pain sensitivity. We assessed interindividual pain sensitivity as a rating of pain intensity to heat stimuli (45, 47, and 48.9°C) in 38 healthy men (age: 27.05 ± 5.7 years). We also reconstructed the MFB using multitensor tractography from diffusion magnetic resonance imaging (dMRI) and calculated free-water corrected dMRI measures of fractional anisotropy (FAt ), radial diffusivity (RDt ), and axial diffusivity (ADt ). Lower ratings of interindividual pain intensity correlated with higher FAt and lower RDt of the MFB. As changes in FAt and RDt may reflect abnormalities in myelination, the results might be interpreted as that a lower pain rating is associated with higher degree of myelination of the MFB and could represent an inhibitory pathway of pain. Our results suggest that alteration of microstructure in the MFB contributes to the interindividual variation of pain perception.

Stimulation of peroneal nerves reveals maintained somatosensory representation in transtibial amputees.

Introduction: Several studies have found changes in the organization of the primary somatosensory cortex (SI) after amputation. This SI reorganization was mainly investigated by stimulating neighboring areas to amputation. Unexpectedly, the somatosensory representation of the deafferented limb has rarely been directly tested. Methods: We stimulated the truncated peroneal nerve in 24 unilateral transtibial amputees and 15 healthy controls. The stimulation intensity was adjusted to make the elicited percept comparable between both stimulation sides. Neural sources of the somatosensory-evoked magnetic fields (SEFs) to peroneal stimulation were localized in the contralateral foot/leg areas of SI in 19 patients and 14 healthy controls. Results: We demonstrated the activation of functionally preserved cortical representations of amputated lower limbs. None of the patients reported evoked phantom limb pain (PLP) during stimulation. Stimulation that evoked perceptions in the foot required stronger intensities on the amputated side than on the intact side. In addition to this, stronger stimulation intensities were required for amputees than for healthy controls. Exploratorily, PLP intensity was neither associated with stimulation intensity nor dipole strength nor with differences in Euclidean distances (between SEF sources of the healthy peroneus and mirrored SEF sources of the truncated peroneus). Discussion: Our results provide hope that the truncated nerve may be used to establish both motor control and somatosensory feedback via the nerve trunk when a permanently functional connection between the nerve trunk and the prosthesis becomes available.

Central autonomic network alterations in male endurance athletes.

Physical exercise causes marked adjustments in brain function and the cardiovascular system. Brain regions of the so-called central autonomic network (CAN) are likely to show exercise-related alterations due to their involvement in cardiac control, yet exercise-induced CAN changes remain unclear. Here we investigate the effects of intensive exercise on brain regions involved in cardiac autonomic regulation using resting-state functional connectivity (rsFC). We explored rsFC of six core regions within CAN, namely ventromedial prefrontal cortex, dorsolateral anterior cingulate cortex, left/right amygdala, and left/right anterior insula, in 20 endurance athletes and 21 non-athletes. We showed that athletes had enhanced rsFC within CAN and sensorimotor areas compared to non-athletes. Likewise, we identified two networks with increased rsFC encompassing autonomic and motor-related areas using network-based statistics analysis. In addition, rsFC displayed an inverse relationship with heart rate, where the stronger rsFC in athletes correlates with their slower heart rate. Despite this significant relationship, mediation analysis revealed that heart rate is a weak mediator of the effect of intensive physical training on rsFC. Our findings prove that physical exercise enhances brain connectivity in central autonomic and sensorimotor networks and highlight the close link between brain and heart.

Dissociation of Endogenous Pain Inhibition Due to Conditioned Pain Modulation and Placebo in Male Athletes Versus Nonathletes.

Animals and humans are able to inhibit pain by activating their endogenous pain-inhibition system. Endurance athletes possess a higher pain-tolerance threshold and a greater conditioned pain modulation (CPM) effect than nonathletes, suggesting better endogenous pain inhibition. In addition to CPM, placebo is another prominent paradigm used to test endogenous pain inhibition. However, whether the placebo effect and the CPM effect share the same mechanisms of pain inhibition has not been investigated. If there is a shared mechanism, then endurance athletes should show not only a better CPM effect than nonathletes but also a greater placebo effect. Here, we investigated 16 male endurance athletes and 17 male nonathletes in well-established placebo and CPM paradigms to assess whether endurance athletes have a better endogenous pain-inhibition system than nonathletes. As expected, we find a significantly greater CPM effect in athletes than in nonathletes. In contrast, we could only find a significant placebo effect in nonathletes. Explorative analyses reveal negative associations between the placebo effect and heart rate variability as well as between the placebo effect and interoceptive awareness. Together, the results demonstrate a dissociation of endogenous pain inhibition of CPM and placebo effect between endurance athletes and nonathletes. This suggests that both effects are based, at least in part, on different biological mechanisms.

Expectation of exercise in trained athletes results in a reduction of central processing to nociceptive stimulation.

A single endurance exercise session was shown to lead to a reduction of pain perception and an elevation of mood. We hypothesized that athletes, who regularly practice endurance, might also induce changes in mood and pain processing in expectation of an endurance session. We compared the expectation effects of a 2-h-run on mood and pain processing to a run-free control day (RFC). Fifteen trained runners were assessed with repeated painful and nonpainful pinprick stimulation in a functional magnetic resonance imaging (fMRI) scanner prior to a 2-h-run and at RFC. Pain ratings, pressure pain stimulus-response functions, and euphoria ratings were also assessed. There were no mean expectation effects on any of the behavioral measures. However, highly trained athletes needed more pressure to evoke a pain rating of 46 pre-run vs. RFC but were less euphoric pre-run vs. RFC. Furthermore, analysis of brain activities to painful stimuli applied immediately before the 2-h-run compared to RFC revealed increased activation in the medial prefrontal cortex (mPFC) and reduced activation in posterior insula. Additionally, less trained athletes had reduced activation in posterior insula to painful stimulation pre-run vs. RFC compared to highly trained athletes. The results suggest reduced central pain processing in expectation of an endurance run and an association between the amount of the expectation effect and training frequency which differs depending on the stimuli applied.

Large-scale mapping of mutations affecting zebrafish development.

BACKGROUND: Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers. RESULTS: We have selected a set of microsatellite markers and developed methods and scoring criteria suitable for efficient, high-throughput genome scanning. We have used these methods to successfully obtain a rough map position for 319 mutant loci from the Tübingen I mutagenesis screen and subsequent screening of the mutant collection. For 277 of these the corresponding gene is not yet identified. Mapping was successful for 80 % of the tested loci. By comparing 21 mutation and gene positions of cloned mutations we have validated the correctness of our linkage group assignments and estimated the standard error of our map positions to be approximately 6 cM. CONCLUSION: By obtaining rough map positions for over 300 zebrafish loci with developmental phenotypes, we have generated a dataset that will be useful not only for cloning of the affected genes, but also to suggest allelism of mutations with similar phenotypes that will be identified in future screens. Furthermore this work validates the usefulness of our methodology for rapid, systematic and inexpensive microsatellite mapping of zebrafish mutations.