Impact of multisensory learning on perceptual and lexical processing of unisensory Morse code.

Multisensory learning profits from stimulus congruency at different levels of processing. In the current study, we sought to investigate whether multisensory learning can potentially be based on high-level feature congruency (same meaning) without perceptual congruency (same time) and how this relates to changes in brain function and behaviour. 50 subjects learned to decode Morse code (MC) either in unisensory or different multisensory manners. During unisensory learning, the MC was trained as sequences of auditory trains. For low-level congruent (perceptual) multisensory learning, MC was applied as tactile stimulation to the left hand simultaneously to the auditory stimulation. In contrast, high-level congruent multisensory learning involved auditory training, followed by the production of MC sequences requiring motor actions and thereby excludes perceptual congruency. After learning, group differences were observed within three distinct brain regions while processing unisensory (auditory) MC. Both types of multisensory learning were associated with increased activation in the right inferior frontal gyrus. Multisensory low-level learning elicited additional activation in the somatosensory cortex, while multisensory high-level learners showed a reduced activation in the inferior parietal lobule, which is relevant for decoding MC. Furthermore, differences in brain function associated with multisensory learning was related to behavioural reaction times for both multisensory learning groups. Overall, our data support the idea that multisensory learning is potentially based on high-level features without perceptual congruency. Furthermore, learning of multisensory associations involves neural representations of stimulus features involved in learning, but also share common brain activation (i.e. the right IFG), which seems to serve as a site of multisensory integration.

[Second look: practical diagnostic and therapeutic checks in neurorehabilitation]. / Der zweite Blick: praktische diagnostische und therapeutische Checks in der rehabilitativen Neurologie.

Post-acute inpatient neurorehabilitation facilities are increasingly treating patients who are not only severely ill and multimorbid but who are also referred from non-neurological departments. These patients are still often medically unstable so that the previous diagnostics and treatment must be reevaluated and when necessary adapted or supplemented. Certain interdisciplinary diagnostic and therapeutic problems, such as antithrombotic therapy, regularly reoccur. This article presents these problems in a checklist fashion, which should provide indications in individual cases when previously carried out measures need to be questioned and adapted.

Muscle diffusion tensor imaging in glycogen storage disease V (McArdle disease).

PURPOSE: To evaluate differences in diffusion parameters in thigh muscles in patients with glycogen storage disease type V (McArdle disease) using muscle diffusion tensor imaging (mDTI) compared to healthy controls METHODS: In this prospective study, we evaluated thigh muscles from hip to knee of 10 McArdle patients (5 female, mean age 33.7 ± 14.4 years) and 10 healthy age- and gender-matched volunteers. MRI scans were performed at 3 T and comprised mDTI, T1-weighted and T2-weighted imaging between May 2015 and May 2017. Needle biopsy of the vastus lateralis muscle was performed in three McArdle patients. The muscle tissue was analyzed by using histochemical and enzyme-histochemical techniques for glycogen content and histopathological changes. Mean values of the eigenvalues (λ1-λ3), fractional anisotropy (FA), and mean diffusivity (MD) were obtained for the vastus lateralis, vastus medialis, rectus femoris, biceps femoris, semitendinosus, and semimembranosus and compared between groups using Student's t tests, as well as ANCOVA; significance level was set at p < 0.05. RESULTS: Needle biopsy showed intracellular glycogen accumulation in skeletal muscle fibers of three McArdle patients. Extracellular histopathological changes were not found. Muscle DTI analysis did not show statistically significant differences between patients and controls for any of the muscles. CONCLUSION: Despite intracellular glycogen accumulation in the three biopsy samples, mDTI parameters were not altered in McArdle patients compared to controls. We conclude that the currently used mDTI acquisition and processing lack the sensitivity to detect intracellular changes due to accumulated glycogen in this cohort of McArdle patients. KEY POINTS: • Despite intracellular glycogen accumulation in three examined biopsy samples, mDTI parameters were not altered in McArdle patients compared to controls. • In its current form, diffusion MR does not provide additional information in quantifying intracellular glycogen accumulations within skeletal muscle fibers in McArdle patients.

Brain structural alterations associated with dysfunctional cognitive control of pain in patients with low back pain.

BACKGROUND: Recent evidence has shown that chronic back pain (CBP) can lead to functional alterations in the circuitry underlying the cognitive control of pain. Thought suppression (TS) is a common type of cognitive control of pain. Previous research has shown that TS has paradoxical effects that may increase the awareness of pain. Pain-related TS may also increase individuals' attention to pain, which may also increase pain sensation, but thus far, the relationship between pain-related TS and structural brain alterations is unknown. METHODS: In this study, we investigated a group of 30 patients 6 months after lumbar disc surgery by applying voxel-based morphometry (VBM) to identify brain regions correlated with TS scores. RESULTS: Since pain-related TS has been positively correlated with depression, all calculations were controlled for depression and age. VBM revealed a negative correlation between the TS score and regional grey matter volume (GMV) in the left superior temporal gyrus (LSTG) and the left middle temporal gyrus (L MTG), which is part of the left temporoparietal junction (L TPJ). In addition, a mediation analysis revealed a significant mediation effect of the pain-related TS on the association between GMV of the left TPJ and reported pain intensity in the last 7 days. CONCLUSIONS: These findings are consistent with previous research on the dysfunctional cognitive control of pain and may therefore provide potential insights into the neural substrates of obstructive cognitive control in chronic low back pain, with a special emphasis on pain-related TS. SIGNIFICANCE: The link between pain-related thought suppression and brain morphology may provide a new perspective on the understanding of cognitive control of pain in chronic low back pain, which may help improve cognitive behavioural therapy.

Structural changes in brain morphology induced by brief periods of repetitive sensory stimulation.

There is a growing interest in identifying the neural mechanisms by which the human brain allows for improving performance. Tactile perceptual measurements, e.g. two-point discrimination (2ptD), can be used to investigate neural mechanisms of perception as well as perceptual improvement. Improvement can be induced in a practice-independent manner, e.g. in the tactile domain through repetitive somatosensory stimulation (rSS). With respect to tactile perception, the role of cortical excitability and activation within the somatosensory cortex has been investigated extensively. However, the role of structural properties, such as regional gray matter (GM) volume, is unknown. Using high resolution imaging and voxel-based morphometry (VBM), we sought to investigate how regional GM volume relates to individual 2ptD performance. Furthermore, we wanted to determine if electrical rSS has an influence on regional GM volume. 2ptD thresholds of the index fingers were assessed bilaterally. High-resolution (1 mm3), T1-weighted images were obtained using a 3T scanner pre-and post-stimulation. RSS was applied for 45 min to the dominant right hand, specifically to the fingertips of all fingers. At baseline, performance in the 2ptD task was associated with regional GM volume in the thalamus, primary somatosensory cortex, and primary visual cortex (negative association). After 45 min of rSS, we observed an improvement in 2ptD of the stimulated hand, whereas no improvement in tactile performance was seen on the non-stimulated side. These perceptual changes were accompanied by an increase in GM volume in the left somatosensory cortex and the degree of improvement correlated with GM volume changes in the insular cortex. Our results show that structural changes in the brain, specifically in regions receiving afferent input from the stimulated body site can be induced via a short-term intervention lasting only 45 min. However, the neurobiological correlates of these changes and the dynamics need to be further elucidated.

GABA-from Inhibition to Cognition: Emerging Concepts.

Neural functioning and plasticity can be studied on different levels of organization and complexity ranging from the molecular and synaptic level to neural circuitry of whole brain networks. Across neuroscience different methods are being applied to better understand the role of various neurotransmitter systems in the evolution of perception and cognition. GABA is the main inhibitory neurotransmitter in the adult mammalian brain and, depending on the brain region, up to 25% of the total number of cortical neurons are GABAergic interneurons. At the one end of the spectrum, GABAergic neurons have been accurately described with regard to cell morphological, molecular, and electrophysiological properties; at the other end researchers try to link GABA concentrations in specific brain regions to human behavior using magnetic resonance spectroscopy. One of the main challenges of modern neuroscience currently is to integrate knowledge from highly specialized subfields at distinct biological scales into a coherent picture that bridges the gap between molecules and behavior. In the current review, recent findings from different fields of GABA research are summarized delineating a potential strategy to develop a more holistic picture of the function and role of GABA.

Dynamic changes of resting state connectivity related to the acquisition of a lexico-semantic skill.

The brain undergoes adaptive changes during learning. Spontaneous neural activity has been proposed to play an important role in acquiring new information and/or improve the interaction of task related brain regions. A promising approach is the investigation of resting state functional connectivity (rs-fc) and resting state networks, which rely on the detection of interregional correlations of spontaneous BOLD fluctuations. Using Morse Code (MC) as a model to investigate neural correlates of lexico-semantic learning we sought to identify patterns in rs-fc that predict learning success and/or undergo dynamic changes during a 10-day training period. Thirty-five participants were trained to decode twelve letters of MC. Rs-fMRI data were collected before and after the training period and rs-fc analyses were performed using a group independent component analysis. Baseline connectivity between the language-network (LANG) and the anterior-salience-network (ASN) predicted learning success and learning was associated with an increase in LANG - ASN connectivity. Furthermore, a disconnection between the default mode network (DMN) and the ASN as well as the left fusiform gyrus, which is critically involved in MC deciphering, was observed. Our findings demonstrate that rs-fc can undergo behaviorally relevant changes within 10 training days, reflecting a learning dependent modulation of interference between task specific networks.

Altered fMRI resting-state connectivity in individuals with fibromyalgia on acute pain stimulation.

BACKGROUND: Fibromyalgia is a chronic widespread pain condition, with patients commonly reporting other symptoms such as sleep difficulties, memory complaints and fatigue. The use of magnetic resonance imaging (MRI) in fibromyalgia has allowed for the detection of neural abnormalities, with alterations in brain activation elicited by experimental pain and alterations in resting state connectivity related to clinical pain. METHODS: In this study, we sought to monitor state changes in resting brain connectivity following experimental pressure pain in fibromyalgia patients and healthy controls. Twelve fibromyalgia patients and 15 healthy controls were studied by applying discrete pressure stimuli to the thumbnail bed during MRI. Resting-state functional MRI scanning was performed before and immediately following experimental pressure pain. We investigated changes in functional connectivity to the thalamus and the insular cortex. RESULTS: Acute pressure pain increased insula connectivity to the anterior cingulate and the hippocampus. Additionally, we observed increased thalamic connectivity to the precuneus/posterior cingulate cortex, a known part of the default mode network, in patients but not in controls. This connectivity was correlated with changes in clinical pain. CONCLUSIONS: These data reporting changes in resting-state brain activity following a noxious stimulus suggest that the acute painful stimuli may contribute to the alteration of the neural signature of chronic pain. WHAT DOES THIS STUDY/ADD?: In this study acute pain application shows an echo in functional connectivity and clinical pain changes in chronic pain.

Transcutaneous spinal DC stimulation reduces pain sensitivity in humans.

Non-invasive approaches to pain management are needed to manage patient pain escalation and to providing sufficient pain relief. Here, we evaluate the potential of transcutaneous spinal direct current stimulation (tsDCS) to modulate pain sensitivity to electrical stimuli and mechanical pinpricks in 24 healthy subjects in a sham-controlled, single-blind study. Pain ratings to mechanical pinpricks and electrical stimuli were recorded prior to and at three time points (0, 30, and 60min) following 15min of anodal tsDCS (2.5mA, "active" electrode centered over the T11 spinous process, return electrode on the left posterior shoulder). Pain ratings to the pinpricks of the highest forces tested (128, 256, 512mN) were reduced at 30min and 60min following anodal tsDCS. These findings demonstrate that pain sensitivity in healthy subjects can be suppressed by anodal tsDCS and suggest that tsDCS may provide a non-invasive tool to manage mechanically-induced pain.

Resting state connectivity correlates with drug and placebo response in fibromyalgia patients.

Fibromyalgia is a chronic pain syndrome characterized by widespread pain, fatigue, and memory and mood disturbances. Despite advances in our understanding of the underlying pathophysiology, treatment is often challenging. New research indicates that changes in functional connectivity between brain regions, as can be measured by magnetic resonance imaging (fcMRI) of the resting state, may underlie the pathogenesis of this and other chronic pain states. As such, this parameter may be able to be used to monitor changes in brain function associated with pharmacological treatment, and might also be able to predict treatment response. We performed a resting state fcMRI trial using a randomized, placebo-controlled, cross-over design to investigate mechanisms of action of milnacipran (MLN), a selective serotonin and norepinephrine reuptake inhibitor (SNRI), in fibromyalgia patients. Our aim was to identify functional connectivity patterns at baseline that would differentially predict treatment response to MLN as compared to placebo. Since preclinical studies of MLN suggest that this medication works by augmenting antinociceptive processes, we specifically investigated brain regions known to be involved in pain inhibition. 15 fibromyalgia patients completed the study, consisting of 6 weeks of drug and placebo intake (order counterbalanced) with an interspersed 2 week wash out period. As a main finding we report that reductions in clinical pain scores during MLN were associated with decreased functional connectivity between pro-nociceptive regions and antinociceptive pain regions at baseline, specifically between the rostral part of the anterior cingulate cortex (ACC) and the insular cortex (IC), as well as between the periaqueductal gray (PAG) and the IC: patients with lower preexisting functional connectivity had the greatest reduction in clinical pain. This pattern was not observed for the placebo period. However a more robust placebo response was associated with lower baseline functional connectivity between the ACC and the dorsolateral prefrontal cortex. This study indicates that ACC-IC connectivity might play a role in the mechanism of action of MLN, and perhaps more importantly fcMRI might be a useful tool to predict pharmacological treatment response.

Juggling revisited - a voxel-based morphometry study with expert jugglers.

Juggling is a highly interesting tool to investigate neuroplasticity associated with motor-learning. Several brain-imaging studies have reported changes in regional brain morphology in visual association cortices in individuals learning how to juggle a three-ball cascade. However, to our knowledge there are no studies that investigated expert jugglers, looking for specific features in regional brain morphology related to this highly specialized skill. Using T1-weighted images and voxel-based morphometry we investigated in a cross-sectional study design 16 expert jugglers, able to juggle at least five balls and an age- and gender-matched group of non-jugglers. We hypothesized that expert jugglers would show higher gray matter density in regions involved in visual motion perception and eye-hand coordination. Images were pre-processed and analyzed using SPM8. Age was included in the analyses as covariate of no interest. As compared to controls jugglers displayed several clusters of higher, regional gray matter density in the occipital and parietal lobes including the secondary visual cortex, the hMT+/V5 area bilaterally and the intraparietal sulcus bilaterally. Within the jugglers group we also found a correlation between performance and regional gray matter density in the right hMT+/V5 area. Our study provides evidence that expert jugglers show increased gray matter density in brain regions involved in visual motion perception and eye-hand coordination, i.e. brain areas that have previously been shown to undergo dynamic changes in terms of gray matter increases in subjects learning a basic three-ball cascade. The extent to which transient increases in beginners and the differences in experts and non-experts are based on the same neurobiological correlates remains to be fully elucidated.

Sports and brain morphology - a voxel-based morphometry study with endurance athletes and martial artists.

Physical exercises and motor skill learning have been shown to induce changes in regional brain morphology, this has been demonstrated for various activities and tasks. Also individuals with special skills show differences in regional brain morphology. This has been indicated for professional musicians, London taxi drivers, as well as for athletes like dancers, golfers and judokas. However little is known about whether sports with different metabolic profiles (aerobic vs. anaerobic) are associated with different patterns of altered brain morphology. In this cross-sectional study we investigated two groups of high-performance athletes, one group performing sports that are thought to be mainly aerobic, and one group performing sports known to have intermittent phases of anaerobic metabolism. Using high-resolution structural imaging and voxel-based morphometry (VBM), we investigated a group of 26 male athletes consisting of 13 martial artists and 13 endurance athletes as well as a group of non-exercising men (n=13). VBM analyses revealed higher gray matter (GM) volumes in the supplementary motor area/dorsal premotor cortex (BA 6) in both athlete groups as compared to the control group. In addition, endurance athletes showed significantly higher GM volume in the medial temporal lobe (MTL), specifically in the hippocampus and parahippocampal gyrus, which was not seen in the martial arts group. Our data suggest that high-performance sports are associated with changes in regional brain morphology in areas implicated in motor planning and motor learning. In addition high-level endurance sports seem to affect MTL structures, areas that have previously been shown to be modulated by aerobic exercise.

[Etiology and pathophysiology of fibromyalgia syndrome]. / Ätiologie und Pathophysiologie des Fibromyalgiesyndroms.

BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. MATERIALS AND METHODS: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. RESULTS: Current data do not identify distinct etiologic or pathophysiological factors mediating development of FMS. The development of FMS is associated with inflammatory rheumatic diseases (EL2b), with gene polymorphisms of the 5-hydroxytryptamine (HT)(2) receptor (EL3a), lifestyle factors (smoking, obesity, lack of physical activity; EL2b), physical and sexual abuse in childhood and adulthood (EL3a). CONCLUSION: FMS is most likely the result of various pathogenetic factors and pathophysiological mechanisms. The English full-text version of this article is available at SpringerLink (under "Supplemental").

Pharmacotherapy in fibromyalgia (FM)--implications for the underlying pathophysiology.

Although chronic pain states are highly prevalent, the underlying neurobiological mechanisms involved in causing pain are incompletely understood. This is especially true for the so-called chronic functional pain syndromes and pain syndromes of unknown origin, such as fibromyalgia (FM), in which no structural correlates of pain experience, in terms of a nociceptive source, can clearly be defined. In addition to limited therapeutic options and often unsatisfactory treatment, such patients often struggle with socio-medical acceptance of their pain condition. As FM has become more widely recognized, options available for treatment have grown along with our understanding of the neurobiological mechanisms underlying chronic pain experience and concomitant symptoms. The current review aims to provide an overview of existing pharmacotherapies for FM, and their implication for the underlying pathophysiology. Further we discuss some of the potential targets that have been recently identified that may hold promise for the development of novel treatments.

Distinct patterns of functional and structural neuroplasticity associated with learning Morse code.

Learning is based on neuroplasticity, i.e. on the capability of the brain to adapt to new experiences. Different mechanisms of neuroplasticity have been described, ranging from synaptic remodeling to changes in complex neural circuitry. To further study the relationship between changes in neural activity and changes in gray matter density associated with learning, we performed a combined longitudinal functional and morphometric magnetic resonance imaging (MRI) study on healthy volunteers who learned to decipher Morse code. We investigated 16 healthy subjects using functional MR imaging (fMRI) and voxel-based morphometry (VBM) before and after they had learned to decipher Morse code. The same set of Morse-code signals was presented to participants pre- and post-training. We found an increase in task-specific neural activity in brain regions known to be critically involved in language perception and memory, such as the inferior parietal cortex bilaterally and the medial parietal cortex during Morse code deciphering. Furthermore we found an increase in gray matter density in the left occipitotemporal region, extending into the fusiform gyrus. Anatomically neighboring sites of functional and structural neuroplasticity were revealed in the left occipitotemporal/inferior temporal cortex, but these regions only marginally overlapped. Implications of this morpho-functional dissociation for learning concepts are discussed.

[Cognitive impairment in patients suffering from fibromyalgia. An underestimated problem]. / Schmerz und Aufmerksamkeit. Kognitive Defizite bei Fibromyalgiepatienten.

The primary symptom of fibromyalgia (FM) is chronic, widespread pain accompanied by diffuse tenderness to light palpation. However, many patients report a multitude of additional complaints and symptoms. Besides fatigue, exhaustibility and stiffness, a decrease in concentration and memory are further complaints that add significantly to the degree of suffering. This complaint, often termed "fibrofog", is increasingly recognised as an independent symptom that has made its way into the medical literature under the term "dyscognition". Nonetheless there are only a few studies that have specifically investigated neuropsychological deficits in FM patients in order to further specify clinical complaints. The studies performed so far have provided increasing evidence that FM patients have attention and working memory deficits, which are most prominent when patients have to cope with an additional source of distraction. With this review we intend to give an overview of the neuropsychological studies in FM performed so far and to assess possible implications for the underlying pathophysiology. In addition, we discuss potential clinical approaches to these symptoms. A systematic literature review up to June 2009 was carried out using the keywords (pairs) "fibromyalgia" and "cognition", "fibromyalgia" and "dyscognition", "fibromyalgia" and "cognitive deficits".

Working memory performance is correlated with local brain morphology in the medial frontal and anterior cingulate cortex in fibromyalgia patients: structural correlates of pain-cognition interaction.

Fibromyalgia (FM) is a disorder of unknown aetiology, characterized by chronic widespread pain, stiffness and sleep disturbances. In addition, patients frequently complain of memory and attention deficits. Accumulating evidence suggests that FM is associated with CNS dysfunction and with an altered brain morphology. However, few studies have specifically investigated neuropsychological issues in patients suffering from FM. We therefore sought to determine whether neuropsychological deficits found in FM patients may be correlated with changes in local brain morphology specifically in the frontal, temporal or cingulate cortices. Twenty FM patients underwent extensive testing for potential neuropsychological deficits, which demonstrated significantly reduced working memory and impaired non-verbal long-term memory (limited to free recall condition) in comparison with normative data from age- and education-matched control groups. Voxel-based morphometry (VBM) was used to evaluate for potential correlations between test results and local brain morphology. Performance on non-verbal working memory was positively correlated with grey matter values in the left dorsolateral prefrontal cortex, whereas performance on verbal working memory (digit backward) was positively correlated with grey matter values in the supplementary motor cortex. On the other hand, pain scores were negatively correlated with grey matter values in the medial frontal gyrus. White matter analyses revealed comparable correlations for verbal working memory and pain scores in the medial frontal and prefrontal cortex and in the anterior cingulate cortex. Our data suggest that, in addition to chronic pain, FM patients suffer from neurocognitive deficits that correlate with local brain morphology in the frontal lobe and anterior cingulate gyrus, which may be interpreted to indicate structural correlates of pain-cognition interaction.

Subtle grey matter changes between migraine patients and healthy controls.

Local morphological alterations of the brain have recently been detected in cluster headache and chronic tension-type headache, but not in migraine. We investigated 35 patients suffering from migraine and compared them with 31 healthy controls with no headache history. Using magnetic resonance imaging and voxel based morphometry, we found a significant decrease of grey matter in areas ascribable to the transmission of pain (cingulate cortex), but not in areas specific for migraine, such as the brainstem. Our data are in line with recent findings in chronic pain states, such as chronic phantom pain and chronic back pain. We suggest that the grey matter change in migraine patients is the consequence of frequent nociceptive input and should thus be reversible when migraine attacks cease.

Striatal grey matter increase in patients suffering from fibromyalgia--a voxel-based morphometry study.

Fibromyalgia (FM), among other chronic pain syndromes, such as chronic tension type headache and atypical face pain, is classified as a so-called dysfunctional pain syndrome. Patients with fibromyalgia suffer from widespread, "deep" muscle pain and often report concomitant depressive episodes, fatigue and cognitive deficits. Clear evidence for structural abnormalities within the muscles or soft tissue of fibromyalgia patients is lacking. There is growing evidence that clinical pain in fibromyalgia has to be understood in terms of pathological activity of central structures involved in nociception. We applied MR-imaging and voxel-based morphometry, to determine whether fibromyalgia is associated with altered local brain morphology. We investigated 20 patients with the diagnosis of primary fibromyalgia and 22 healthy controls. VBM revealed a conspicuous pattern of altered brain morphology in the right superior temporal gyrus (decrease in grey matter), the left posterior thalamus (decrease in grey matter), in the left orbitofrontal cortex (increase in grey matter), left cerebellum (increase in grey matter) and in the striatum bilaterally (increase in grey matter). Our data suggest that fibromyalgia is associated with structural changes in the CNS of patients suffering from this chronic pain disorder. They might reflect either a consequence of chronic nociceptive input or they might be causative to the pathogenesis of fibromyalgia. The affected areas are known to be both, part of the somatosensory system and part of the motor system.