Mike Brügger

Brain activity during stepping: A novel MRI-compatible device

Little is known about the impact of supraspinal centers on the control of human locomotion. Analyzing brain activity can help to clarify their impact and to improve the effects of locomotor training. A fMRI-compatible pneumatic robotic device is presented that can generate freely programmable, highly repetitive periodic active and passive leg movements comprised by hip, knee, and ankle joint displacements. Forces of up to 400N can be applied to each foot while the subject is lying in a supine position. Magnetic interference of the device with the magnetic field of the scanner is measurable, but does not affect the image quality as obtained by a usual image analysis procedure. In a first experiment, brain activity of one healthy subject was acquired during nine different gait-like movement conditions. Brain activity in the somatosensory and motor function related areas increased more when the subject actively moved the legs than when the legs were passively moved by the device. In almost all conditions, mean head motion could be limited to 2mm within the duration of one fMRI scan by a specifically developed head and trunk fixation system. Based on these results, it is concluded that our device will significantly contribute to a better understanding of human locomotor control and related therapeutic effects in spinal cord injured and stroke patients, and thereby, to improve training approaches.

Taking Sides with Pain – Lateralization aspects Related to Cerebral Processing of Dental Pain

The current fMRI study investigated cortical processing of electrically induced painful tooth stimulation of both maxillary canines and central incisors in 21 healthy, right-handed volunteers. A constant current, 150% above tooth specific pain perception thresholds was applied and corresponding online ratings of perceived pain intensity were recorded with a computerized visual analog scale during fMRI measurements. Lateralization of cortical activations was investigated by a region of interest analysis. A wide cortical network distributed over several areas, typically described as the pain or nociceptive matrix, was activated on a conservative significance level. Distinct lateralization patterns of analyzed structures allow functional classification of the dental pain processing system. Namely, certain parts are activated independent of the stimulation site, and hence are interpreted to reflect cognitive emotional aspects. Other parts represent somatotopic processing and therefore reflect discriminative perceptive analysis. Of particular interest is the observed amygdala activity depending on the stimulated tooth that might indicate a role in somatotopic encoding.

Interindividual differences in the perception of dental stimulation and related brain activity

For identical diagnoses in the trigeminal innervation territory, individual differences have been clinically observed among the symptoms reported, such as dysesthesia and pain. Different subjective perceptions of unpleasantness and pain intensity may have different cortical substrates. The aim of this study was to identify brain areas in which activation depends on the subjective perception (intensity and unpleasantness) of electric dental stimulation. Electrical stimuli of increasing intensity were applied to maxillary canines in 14 healthy volunteers. Ratings for stimulus intensity and unpleasantness perceived across the stimulation session were reported postscan on 11-point numerical scales. The rating values were then included as covariates in the functional magnetic resonance imaging (fMRI) group analysis. Interindividual differences of intensity ratings were reflected in differential activity of the following brain areas: superior parietal lobule, superior temporal gyrus/anterior insula, inferior and middle temporal gyrus, lingual gyrus, anterior cingulate, and caudate nucleus. Differences related to unpleasantness ratings were reflected in the lingual gyrus. In conclusion, differences of perceived intensity between individuals are reflected in the differential activity of a set of brain areas distinct from those regions, reflecting rating differences of unpleasantness.

Fear-learning deficits in subjects with fibromyalgia syndrome?

Fibromyalgia syndrome (FMS) is frequently associated with psychiatric conditions, particularly anxiety. Deficits in contingency learning during fear conditioning have been hypothesized to increase anxiety and, consequently, pain sensation in susceptible individuals. The goal of this study was to examine the relationship between contingency learning and pain experience in subjects with FMS and rheumatoid arthritis (RA).

Tracing Toothache Intensity in the Brain

Identification of brain regions that differentially respond to pain intensity may improve our understanding of trigeminally mediated nociception. This report analyzed cortical responses to painless and painful electrical stimulation of a right human maxillary canine tooth. Functional magnetic resonance images were obtained during the application of five graded stimulus strengths, from below, at, and above the individually determined pain thresholds. Study participants reported each stimulus on a visual rating scale with respect to evoked sensation. Based on hemodynamic responses of all pooled stimuli, a cerebral network was identified that largely corresponds to the known lateral and medial nociceptive system. Further analysis of the five graded stimulus strengths revealed positive linear correlations for the anterior insula bilaterally, the contralateral (left) anterior mid-cingulate, as well as contralateral (left) pregenual cingulate cortices. Cerebral toothache intensity coding on a group level can thus be attributed to specific subregions within the cortical pain network.

An fMRI pilot study to evaluate brain activation associated with locomotion adaptation

The goal of robotic therapy is to provoke motor plasticity via the application of robotic training strategies. Although robotic haptic guidance is the commonly used motor-training strategy to reduce performance errors while training, research on motor learning has emphasized that errors are a fundamental neural signal that drives motor adaptation. Thus, researchers have proposed robotic therapy algorithms that amplify movement errors rather than decrease them. Studying the particular brain regions involved in learning under different training strategies might help tailoring motor training conditions to the anatomical location of a focal brain insult. In this paper, we evaluate the brain regions involved in locomotion adaptation when training with three different conditions: without robotic guidance, with a random-varying force disturbance, and with repulsive forces proportional to errors. We performed an fMRI pilot study with four healthy subjects who stepped in an fMRI compatible walking robotic device. Subjects were instructed to actively synchronize their left leg with respect to their right leg (passively guided by the robot) while their left leg was affected by any of the three conditions. We observed activation in areas known to be involved in error processing. Although we found that all conditions required the similar cortical network to fulfill the task, we observed a tendency towards more activity in the motor/sensory network as more “challenged” the subjects were.

Brain activation induced by dentine hypersensitivity pain–an fMRI study

AIM Dentine hypersensitivity (DH) is characterized by a short, sharp pain arising from exposed dentin. Most published literature reports on peripheral neural aspects of this pain condition. The current investigation focused on differential cerebral activity elicited by stimulation of sensitive and insensitive teeth by means of natural air stimuli. MATERIALS AND METHODS Five graded stimulus strengths were randomly applied by means of a multi-injector air jet delivery system, each followed by an individual rating of perceived stimulus intensity. Brain activity was analysed by functional magnetic resonance imaging (fMRI). RESULTS Stimulation of sensitive teeth induced significant activation in the thalamus, somatosensory cortices (SI & SII), anterior, middle and posterior insular cortices, anterior mid cingulate cortex, perigenual anterior cingulate cortex and frontal regions (BA10 and BA46). Differential responses to DH and painless perceptions were observed in the anterior insula and anterior midcingulate cortex. CONCLUSION For the first time, this fMRI study demonstrates the feasibility of investigating cerebral processes related to DH evoked by natural (air) stimuli. Our neuroimaging data additionally provide evidence that differential activity in the anterior Insula (aIC) and anterior midcingulate cortex (aMCC) may represent clinically relevant pain experienced by DH patients.

Equal pain-unequal fear response: Enhanced susceptibility of tooth pain to fear conditioning

Experimental fear conditioning in humans is widely used as a model to investigate the neural basis of fear learning and to unravel the pathogenesis of anxiety disorders. It has been observed that fear conditioning depends on stimulus salience and subject vulnerability to fear. It is further known that the prevalence of dental-related fear and phobia is exceedingly high in the population. Dental phobia is unique as no other body part is associated with a specific phobia. Therefore, we hypothesized that painful dental stimuli exhibit an enhanced susceptibility to fear conditioning when comparing to equal perceived stimuli applied to other body sites. Differential susceptibility to pain-related fear was investigated by analyzing responses to an unconditioned stimulus (UCS) applied to the right maxillary canine (UCS-c) vs. the right tibia (UCS-t). For fear conditioning, UCS-c and USC-t consisted of painful electric stimuli, carefully matched at both application sites for equal intensity and quality perception. UCSs were paired to simple geometrical forms which served as conditioned stimuli (CS+). Unpaired CS+ were presented for eliciting and analyzing conditioned fear responses. Outcome parameter were (1) skin conductance changes and (2) time-dependent brain activity (BOLD responses) in fear-related brain regions such as the amygdala, anterior cingulate cortex, insula, thalamus, orbitofrontal cortex, and medial prefrontal cortex. A preferential susceptibility of dental pain to fear conditioning was observed, reflected by heightened skin conductance responses and enhanced time-dependent brain activity (BOLD responses) in the fear network. For the first time, this study demonstrates fear-related neurobiological mechanisms that point toward a superior conditionability of tooth pain. Beside traumatic dental experiences our results offer novel evidence that might explain the high prevalence of dental-related fears in the population.

A reliability study on brain activation during active and passive arm movements supported by an MRI-compatible robot

In neurorehabilitation, longitudinal assessment of arm movement related brain function in patients with motor disability is challenging due to variability in task performance. MRI-compatible robots monitor and control task performance, yielding more reliable evaluation of brain function over time. The main goals of the present study were first to define the brain network activated while performing active and passive elbow movements with an MRI-compatible arm robot (MaRIA) in healthy subjects, and second to test the reproducibility of this activation over time. For the fMRI analysis two models were compared. In model 1 movement onset and duration were included, whereas in model 2 force and range of motion were added to the analysis. Reliability of brain activation was tested with several statistical approaches applied on individual and group activation maps and on summary statistics. The activated network included mainly the primary motor cortex, primary and secondary somatosensory cortex, superior and inferior parietal cortex, medial and lateral premotor regions, and subcortical structures. Reliability analyses revealed robust activation for active movements with both fMRI models and all the statistical methods used. Imposed passive movements also elicited mainly robust brain activation for individual and group activation maps, and reliability was improved by including additional force and range of motion using model 2. These findings demonstrate that the use of robotic devices, such as MaRIA, can be useful to reliably assess arm movement related brain activation in longitudinal studies and may contribute in studies evaluating therapies and brain plasticity following injury in the nervous system.

Insula-Specific 1H Magnetic Resonance Spectroscopy Reactions in Heavy Smokers under Acute Nicotine Withdrawal and after Oral Nicotine Substitution

The aim of this study was to clarify whether addiction-specific neurometabolic reaction patterns occur in the insular cortex during acute nicotine withdrawal in tobacco smokers in comparison to nonsmokers. Fourteen male smokers and 10 male nonsmokers were included. Neurometabolites of the right and the left insular cortices were quantified by magnetic resonance spectroscopy (MRS) on a 3-Tesla scanner. Three separate MRS measurements were performed in each subject: among the smokers, the first measurement was done during normal smoking behavior, the second measurement during acute withdrawal (after 24 h of smoking abstinence), and the third shortly after administration of an oral nicotine substitute. Simultaneously, craving, withdrawal symptoms, and CO levels in exhaled air were determined during the three phases. The participants in the control group underwent the same MR protocol. In the smokers, during withdrawal, the insular cortex showed a significant increase in glutamine (Gln; p = 0.023) as well as a slight increase not reaching significance for glutamine/glutamate (Glx; p = 0.085) and a nonsignificant drop in myoinositol (mI; p = 0.381). These values tended to normalize after oral nicotine substitution treatment, even though differences were not significant: Gln (p = 0.225), Glx (p = 0.107) and mI (p = 0.810). Overall, the nonsmokers (control group) did not show any metabolic changes over all three phases (p > 0.05). In smokers, acute nicotine withdrawal produces a neurometabolic reaction pattern that is partly reversed by the administration of an oral nicotine substitute. The results are consistent with the expression of an addiction-specific neurometabolic shift in the brain and confirm the fact that the insular cortex seems to play a possible role in nicotine dependence.