Differential effects of painful and non-painful stimulation on tactile processing in fibromyalgia syndrome and subjects with masochistic behaviour

Background

In healthy subjects repeated tactile stimulation in a conditioning test stimulation paradigm yields attenuation of primary (S1) and secondary (S2) somatosensory cortical activation, whereas a preceding painful stimulus results in facilitation.

Methodology/Principal Findings

Since previous data suggest that cognitive processes might affect somatosensory processing in S1, the present study aims at investigating to what extent cortical reactivity is altered by the subjective estimation of pain. To this end, the effect of painful and tactile stimulation on processing of subsequently applied tactile stimuli was investigated in patients with fibromyalgia syndrome (FMS) and in subjects with masochistic behaviour (MB) by means of a 122-channel whole-head magnetoencephalography (MEG) system. Ten patients fulfilling the criteria for the diagnosis of FMS, 10 subjects with MB and 20 control subjects matched with respect to age, gender and handedness participated in the present study. Tactile or brief painful cutaneous laser stimuli were applied as conditioning stimulus (CS) followed by a tactile test stimulus (TS) 500 ms later. While in FMS patients significant attenuation following conditioning tactile stimulation was evident, no facilitation following painful stimulation was found. By contrast, in subjects with MB no attenuation but significant facilitation occurred. Attenuation as well as facilitation applied to cortical responses occurring at about 70 ms but not to early S1 or S2 responses. Additionally, in FMS patients the amount of attenuation was inversely correlated with catastrophizing tendency.

Conclusion

The present results imply altered cortical reactivity of the primary somatosensory cortex in FMS patients and MB possibly reflecting differences of individual pain experience.     

Influence of body position on cortical pain-related somatosensory processing: an ERP study

Background

Despite the consistent information available on the physiological changes induced by head down bed rest, a condition which simulates space microgravity, our knowledge on the possible perceptual-cortical alterations is still poor. The present study investigated the effects of 2-h head-down bed rest on subjective and cortical responses elicited by electrical, pain-related somatosensory stimulation.

Methodology/Principal Findings

Twenty male subjects were randomly assigned to two groups, head-down bed rest (BR) or sitting control condition. Starting from individual electrical thresholds, Somatosensory Evoked Potentials were elicited by electrical stimuli administered randomly to the left wrist and divided into four conditions: control painless condition, electrical pain threshold, 30% above pain threshold, 30% below pain threshold. Subjective pain ratings collected during the EEG session showed significantly reduced pain perception in BR compared to Control group. Statistical analysis on four electrode clusters and sLORETA source analysis revealed, in sitting controls, a P1 component (40–50 ms) in the right somatosensory cortex, whereas it was bilateral and differently located in BR group. Controls'' N1 (80–90 ms) had widespread right hemisphere activation, involving also anterior cingulate, whereas BR group showed primary somatosensory cortex activation. The P2 (190–220 ms) was larger in left-central locations of Controls compared with BR group.

Conclusions/Significance

Head-down bed rest was associated to an overall decrease of pain sensitivity and an altered pain network also outside the primary somatosensory cortex. Results have implications not only for astronauts'' health and spaceflight risks, but also for the clinical aspects of pain detection in bedridden patients at risk of fatal undetected complications.     

Effects of Sensory Behavioral Tasks on Pain Threshold and Cortical Excitability

Background/Objective

Transcutaneous electrical stimulation has been proven to modulate nervous system activity, leading to changes in pain perception, via the peripheral sensory system, in a bottom up approach. We tested whether different sensory behavioral tasks induce significant effects in pain processing and whether these changes correlate with cortical plasticity.

Methodology/Principal Findings

This randomized parallel designed experiment included forty healthy right-handed males. Three different somatosensory tasks, including learning tasks with and without visual feedback and simple somatosensory input, were tested on pressure pain threshold and motor cortex excitability using transcranial magnetic stimulation (TMS). Sensory tasks induced hand-specific pain modulation effects. They increased pain thresholds of the left hand (which was the target to the sensory tasks) and decreased them in the right hand. TMS showed that somatosensory input decreased cortical excitability, as indexed by reduced MEP amplitudes and increased SICI. Although somatosensory tasks similarly altered pain thresholds and cortical excitability, there was no significant correlation between these variables and only the visual feedback task showed significant somatosensory learning.

Conclusions/Significance

Lack of correlation between cortical excitability and pain thresholds and lack of differential effects across tasks, but significant changes in pain thresholds suggest that analgesic effects of somatosensory tasks are not primarily associated with motor cortical neural mechanisms, thus, suggesting that subcortical neural circuits and/or spinal cord are involved with the observed effects. Identifying the neural mechanisms of somatosensory stimulation on pain may open novel possibilities for combining different targeted therapies for pain control.     

The effects of neck flexion on cerebral potentials evoked by visual,auditory and somatosensory stimuli and focal brain blood flow in related sensory cortices

Background

A flexed neck posture leads to non-specific activation of the brain. Sensory evoked cerebral potentials and focal brain blood flow have been used to evaluate the activation of the sensory cortex. We investigated the effects of a flexed neck posture on the cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in the related sensory cortices.

Methods

Twelve healthy young adults received right visual hemi-field, binaural auditory and left median nerve stimuli while sitting with the neck in a resting and flexed (20° flexion) position. Sensory evoked potentials were recorded from the right occipital region, Cz in accordance with the international 10–20 system, and 2 cm posterior from C4, during visual, auditory and somatosensory stimulations. The oxidative-hemoglobin concentration was measured in the respective sensory cortex using near-infrared spectroscopy.

Results

Latencies of the late component of all sensory evoked potentials significantly shortened, and the amplitude of auditory evoked potentials increased when the neck was in a flexed position. Oxidative-hemoglobin concentrations in the left and right visual cortices were higher during visual stimulation in the flexed neck position. The left visual cortex is responsible for receiving the visual information. In addition, oxidative-hemoglobin concentrations in the bilateral auditory cortex during auditory stimulation, and in the right somatosensory cortex during somatosensory stimulation, were higher in the flexed neck position.

Conclusions

Visual, auditory and somatosensory pathways were activated by neck flexion. The sensory cortices were selectively activated, reflecting the modalities in sensory projection to the cerebral cortex and inter-hemispheric connections.     

Differential neural responses to food images in women with bulimia versus anorexia nervosa

Background

Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known.

Methods

We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI).

Results

In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area.

Conclusions

Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.     

Effect of Transcranial Magnetic Stimulation (TMS) on Parietal and Premotor Cortex during Planning of Reaching Movements

Background

Cerebral activation during planning of reaching movements occurs both in the superior parietal lobule (SPL) and premotor cortex (PM), and their activation seems to take place in parallel.

Methodology

The activation of the SPL and PM has been investigated using transcranial magnetic stimulation (TMS) during planning of reaching movements under visual guidance.

Principal Findings

A facilitory effect was found when TMS was delivered on the parietal cortex at about half of the time from sight of the target to hand movement, independently of target location in space. Furthermore, at the same stimulation time, a similar facilitory effect was found in PM, which is probably related to movement preparation.

Conclusions

This data contributes to the understanding of cortical dynamics in the parieto-frontal network, and suggests that it is possible to interfere with the planning of reaching movements at different cortical points within a particular time window. Since similar effects may be produced at similar times on both the SPL and PM, parallel processing of visuomotor information is likely to take place in these regions.     

Evidence of Impaired Brain Activity Balance after Passive Sensorimotor Stimulation in Multiple Sclerosis

Objectives

Examination of sensorimotor activation alone in multiple sclerosis (MS) patients may not yield a comprehensive view of cerebral response to task stimulation. Additional information may be obtained by examining the negative BOLD response (deactivation). Aim of this work was to characterize activation and deactivation patterns during passive hand movements in MS patients.

Methods

13 relapsing remitting-MS patients (RRMS), 18 secondary progressive-MS patients (SPMS) and 15 healthy controls (HC) underwent an fMRI study during passive right-hand movements. Activation and deactivation contrasts in the three groups were entered into ANOVA, age and gender corrected. Post-hoc analysis was performed with one-sample and two-sample t-tests. For each patient we obtained lesion volume (LV) from both T1- and T2-weighted images.

Results

Activations showed a progressive extension to the ipsilateral brain hemisphere according to the group and the clinical form (HC<RRMS<SPMS). Significant deactivation of the ipsilateral cortical sensorimotor areas was reduced in both patient groups with respect to HC. Deactivation of posterior cortical areas belonging to the default mode network (DMN), was increased in RRMS, but not in SPMS, with respect to HC. The amount of activation in the contralateral sensorimotor cortex was significantly correlated with that of deactivation in the DMN in HC and RRMS, but not in SPMS. Both increased activation and decreased deactivation patterns correlated with LV.

Conclusion

In RRMS patients, increased cortical activation was associated with increased deactivation of the posterior cortex suggesting a greater resting-state activity in the DMN, probably aimed at facilitating sensorimotor circuit engagement during task performance. In SPMS the coupling between increased sensorimotor activation/increased DMN deactivation was not observed suggesting disorganization between anticorrelated functional networks as a consequence of a higher level of disconnection.     

Theta-burst stimulation-induced plasticity over primary somatosensory cortex changes somatosensory temporal discrimination in healthy humans

Background

The somatosensory temporal discrimination threshold (STDT) measures the ability to perceive two stimuli as being sequential. Precisely how the single cerebral structures contribute in controlling the STDT is partially known and no information is available about whether STDT can be modulated by plasticity-inducing protocols.

Methodology/Principal Findings

To investigate how the cortical and cerebellar areas contribute to the STDT we used transcranial magnetic stimulation and a neuronavigation system. We enrolled 18 healthy volunteers and 10 of these completed all the experimental sessions, including the control experiments. STDT was measured on the left hand before and after applying continuous theta-burst stimulation (cTBS) on the right primary somatosensory area (S1), pre-supplementary motor area (pre-SMA), right dorsolateral prefrontal cortex (DLPFC) and left cerebellar hemisphere. We then investigated whether intermittent theta-burst stimulation (iTBS) on the right S1 improved the STDT. After right S1 cTBS, STDT values increased whereas after iTBS to the same cortical site they decreased. cTBS over the DLPFC and left lateral cerebellum left the STDT statistically unchanged. cTBS over the pre-SMA also left the STDT statistically unchanged, but it increased the number of errors subjects made in distinguishing trials testing a single stimulus and those testing paired stimuli.

Conclusions/Significance

Our findings obtained by applying TBS to the cortical areas involved in processing sensory discrimination show that the STDT is encoded in S1, possibly depends on intrinsic S1 neural circuit properties, and can be modulated by plasticity-inducing TBS protocols delivered over S1. Our findings, giving further insight into mechanisms involved in somatosensory temporal discrimination, help interpret STDT abnormalities in movement disorders including dystonia and Parkinson''s disease.     

The Brain Effects of Laser Acupuncture in Healthy Individuals: An fMRI Investigation

Background

As laser acupuncture is being increasingly used to treat mental disorders, we sought to determine whether it has a biologically plausible effect by using functional magnetic resonance imaging (fMRI) to investigate the cerebral activation patterns from laser stimulation of relevant acupoints.

Methodology/Principal Findings

Ten healthy subjects were randomly stimulated with a fibreoptic infrared laser on 4 acupoints (LR14, CV14, LR8 and HT7) used for depression following the principles of Traditional Chinese Medicine (TCM), and 1 control non-acupoint (sham point) in a blocked design (alternating verum laser and placebo laser/rest blocks), while the blood oxygenation level-dependent (BOLD) fMRI response was recorded from the whole brain on a 3T scanner. Many of the acupoint laser stimulation conditions resulted in different patterns of neural activity. Regions with significantly increased activation included the limbic cortex (cingulate) and the frontal lobe (middle and superior frontal gyrus). Laser acupuncture tended to be associated with ipsilateral brain activation and contralateral deactivation that therefore cannot be simply attributed to somatosensory stimulation.

Conclusions/Significance

We found that laser stimulation of acupoints lead to activation of frontal-limbic-striatal brain regions, with the pattern of neural activity somewhat different for each acupuncture point. This is the first study to investigate laser acupuncture on a group of acupoints useful in the management of depression. Differing activity patterns depending on the acupoint site were demonstrated, suggesting that neurological effects vary with the site of stimulation. The mechanisms of activation and deactivation and their effects on depression warrant further investigation.     

Thinking about eating food activates visual cortex with reduced bilateral cerebellar activation in females with anorexia nervosa: an fMRI study

Background

Women with anorexia nervosa (AN) have aberrant cognitions about food and altered activity in prefrontal cortical and somatosensory regions to food images. However, differential effects on the brain when thinking about eating food between healthy women and those with AN is unknown.

Methods

Functional magnetic resonance imaging (fMRI) examined neural activation when 42 women thought about eating the food shown in images: 18 with AN (11 RAN, 7 BPAN) and 24 age-matched controls (HC).

Results

Group contrasts between HC and AN revealed reduced activation in AN in the bilateral cerebellar vermis, and increased activation in the right visual cortex. Preliminary comparisons between AN subtypes and healthy controls suggest differences in cortical and limbic regions.

Conclusions

These preliminary data suggest that thinking about eating food shown in images increases visual and prefrontal cortical neural responses in females with AN, which may underlie cognitive biases towards food stimuli and ruminations about controlling food intake. Future studies are needed to explicitly test how thinking about eating activates restraint cognitions, specifically in those with restricting vs. binge-purging AN subtypes.     

Brain Processing of Biologically Relevant Odors in the Awake Rat,as Revealed by Manganese-Enhanced MRI

Background

So far, an overall view of olfactory structures activated by natural biologically relevant odors in the awake rat is not available. Manganese-enhanced MRI (MEMRI) is appropriate for this purpose. While MEMRI has been used for anatomical labeling of olfactory pathways, functional imaging analyses have not yet been performed beyond the olfactory bulb. Here, we have used MEMRI for functional imaging of rat central olfactory structures and for comparing activation maps obtained with odors conveying different biological messages.

Methodology/Principal Findings

Odors of male fox feces and of chocolate flavored cereals were used to stimulate conscious rats previously treated by intranasal instillation of manganese (Mn). MEMRI activation maps showed Mn enhancement all along the primary olfactory cortex. Mn enhancement elicited by male fox feces odor and to a lesser extent that elicited by chocolate odor, differed from that elicited by deodorized air. This result was partly confirmed by c-Fos immunohistochemistry in the piriform cortex.

Conclusion/Significance

By providing an overall image of brain structures activated in awake rats by odorous stimulation, and by showing that Mn enhancement is differently sensitive to different stimulating odors, the present results demonstrate the interest of MEMRI for functional studies of olfaction in the primary olfactory cortex of laboratory small animals, under conditions close to natural perception. Finally, the factors that may cause the variability of the MEMRI signal in response to different odor are discussed.     

Reduced Responsiveness to Long-Term Monocular Deprivation of Parvalbumin Neurons Assessed by c-Fos Staining in Rat Visual Cortex

Background

It is generally assumed that visual cortical cells homogeneously shift their ocular dominance (OD) in response to monocular deprivation (MD), however little experimental evidence directly supports this notion. By using immunohistochemistry for the activity-dependent markers c-Fos and Arc, coupled with staining for markers of inhibitory cortical sub-populations, we studied whether long-term MD initiated at P21 differentially affects visual response of inhibitory neurons in rat binocular primary visual cortex.

Methodology/Principal Findings

The inhibitory markers GAD67, parvalbumin (PV), calbindin (CB) and calretinin (CR) were used. Visually activated Arc did not colocalize with PV and was discarded from further studies. MD decreased visually induced c-Fos activation in GAD67 and CR positive neurons. The CB population responded to MD with a decrease of CB expression, while PV cells did not show any effect of MD on c-Fos expression. The persistence of c-Fos expression induced by deprived eye stimulation in PV cells is not likely to be due to a particularly low threshold for activity-dependent c-Fos induction. Indeed, c-Fos induction by increasing concentrations of the GABAA antagonist picrotoxin in visual cortical slices was similar between PV cells and the other cortical neurons.

Conclusion

These data indicate that PV cells are particularly refractory to MD, suggesting that different cortical subpopulation may show different response to MD.     

Different Brain Activation under Left and Right Ventricular Stimulation: An fMRI Study in Anesthetized Rats

Background

Myocardial ischemia in the anterior wall of the left ventricule (LV) and in the inferior wall and/or right ventricle (RV) shows different manifestations that can be explained by the different innervations of cardiac afferent nerves. However, it remains unclear whether information from different areas of the heart, such as the LV and RV, are differently processed in the brain. In this study, we investigated the brain regions that process information from the LV or RV using cardiac electrical stimulation and functional magnetic resonance imaging (fMRI) in anesthetized rats because the combination of these two approaches cannot be used in humans.

Methodology/Principal Findings

An electrical stimulation catheter was inserted into the LV or RV (n = 12 each). Brain fMRI scans were recorded during LV or RV stimulation (9 Hz and 0.3 ms width) over 10 blocks consisting of alternating periods of 2 mA for 30 sec followed by 0.2 mA for 60 sec. The validity of fMRI signals was confirmed by first and second-level analyses and temporal profiles. Increases in fMRI signals were observed in the anterior cingulate cortex and the right somatosensory cortex under LV stimulation. In contrast, RV stimulation activated the right somatosensory cortex, which was identified more anteriorly compared with LV stimulation but did not activate the anterior cingulate cortex.

Conclusion/Significance

This study provides the first evidence for differences in brain activation under LV and RV stimulation. These different brain processes may be associated with different clinical manifestations between anterior wall and inferoposterior wall and/or RV myocardial ischemia.     

Lesions to primary sensory and posterior parietal cortices impair recovery from hand paresis after stroke

Background

Neuroanatomical determinants of motor skill recovery after stroke are still poorly understood. Although lesion load onto the corticospinal tract is known to affect recovery, less is known about the effect of lesions to cortical sensorimotor areas. Here, we test the hypothesis that lesions of somatosensory cortices interfere with the capacity to recover motor skills after stroke.

Methods

Standardized tests of motor skill and somatosensory functions were acquired longitudinally over nine months in 29 patients with stroke to the pre- and postcentral gyrus, including adjacent areas of the frontal, parietal and insular cortices. We derived the recovery trajectories of each patient for five motor subtest using least-squares curve fitting and objective model selection procedures for linear and exponential models. Patients were classified into subgroups based on their motor recovery models. Lesions were mapped onto diffusion weighted imaging scans and normalized into stereotaxic space using cost-function masking. To identify critical neuranatomical regions, voxel-wise subtractions were calculated between subgroup lesion maps. A probabilistic cytoarchitectonic atlas was used to quantify of lesion extent and location.

Results

Twenty-three patients with moderate to severe initial deficits showed exponential recovery trajectories for motor subtests that relied on precise distal movements. Those that retained a chronic motor deficit had lesions that extended to the center of the somatosensory cortex (area 2) and the intraparietal sulcus (areas hIP1, hIP2). Impaired recovery outcome correlated with lesion extent on this areas and somatosensory performance. The rate of recovery, however, depended on the lesion load onto the primary motor cortex (areas 4a, 4p).

Conclusions

Our findings support a critical role of uni-and multimodal somatosensory cortices in motor skill recovery. Whereas lesions to these areas influence recovery outcome, lesions to the primary motor cortex affect recovery dynamics. This points to a possible dissociation of neural substrates for different aspects of post-stroke recovery.     

When the Sun Prickles Your Nose: An EEG Study Identifying Neural Bases of Photic Sneezing

Background

Exposure to bright light such as sunlight elicits a sneeze or prickling sensation in about one of every four individuals. This study presents the first scientific examination of this phenomenon, called ‘the photic sneeze reflex’.

Methodology and Principal Findings

In the present experiment, ‘photic sneezers’ and controls were exposed to a standard checkerboard stimulus (block 1) and bright flashing lights (block 2) while their EEG (electro-encephalogram) was recorded. Remarkably, we found a generally enhanced excitability of the visual cortex (mainly in the cuneus) to visual stimuli in ‘photic sneezers’ compared with control subjects. In addition, a stronger prickling sensation in the nose of photic sneezers was found to be associated with activation in the insula and stronger activation in the secondary somatosensory cortex.

Conclusion

We propose that the photic sneeze phenomenon might be the consequence of higher sensitivity to visual stimuli in the visual cortex and of co-activation of somatosensory areas. The ‘photic sneeze reflex’ is therefore not a classical reflex that occurs only at a brainstem or spinal cord level but, in stark contrast to many theories, involves also specific cortical areas.     

Monitoring Cortical Excitability during Repetitive Transcranial Magnetic Stimulation in Children with ADHD: A Single-Blind,Sham-Controlled TMS-EEG Study

Background

Repetitive transcranial magnetic stimulation (rTMS) allows non-invasive stimulation of the human brain. However, no suitable marker has yet been established to monitor the immediate rTMS effects on cortical areas in children.

Objective

TMS-evoked EEG potentials (TEPs) could present a well-suited marker for real-time monitoring. Monitoring is particularly important in children where only few data about rTMS effects and safety are currently available.

Methods

In a single-blind sham-controlled study, twenty-five school-aged children with ADHD received subthreshold 1 Hz-rTMS to the primary motor cortex. The TMS-evoked N100 was measured by 64-channel-EEG pre, during and post rTMS, and compared to sham stimulation as an intraindividual control condition.

Results

TMS-evoked N100 amplitude decreased during 1 Hz-rTMS and, at the group level, reached a stable plateau after approximately 500 pulses. N100 amplitude to supra-threshold single pulses post rTMS confirmed the amplitude reduction in comparison to the pre-rTMS level while sham stimulation had no influence. EEG source analysis indicated that the TMS-evoked N100 change reflected rTMS effects in the stimulated motor cortex. Amplitude changes in TMS-evoked N100 and MEPs (pre versus post 1 Hz-rTMS) correlated significantly, but this correlation was also found for pre versus post sham stimulation.

Conclusion

The TMS-evoked N100 represents a promising candidate marker to monitor rTMS effects on cortical excitability in children with ADHD. TMS-evoked N100 can be employed to monitor real-time effects of TMS for subthreshold intensities. Though TMS-evoked N100 was a more sensitive parameter for rTMS-specific changes than MEPs in our sample, further studies are necessary to demonstrate whether clinical rTMS effects can be predicted from rTMS-induced changes in TMS-evoked N100 amplitude and to clarify the relationship between rTMS-induced changes in TMS-evoked N100 and MEP amplitudes. The TMS-evoked N100 amplitude reduction after 1 Hz-rTMS could either reflect a globally decreased cortical response to the TMS pulse or a specific decrease in inhibition.     

Motor-cortical interaction in Gilles de la Tourette syndrome

Background

In Gilles de la Tourette syndrome (GTS) increased activation of the primary motor cortex (M1) before and during movement execution followed by increased inhibition after movement termination was reported. The present study aimed at investigating, whether this activation pattern is due to altered functional interaction between motor cortical areas.

Methodology/Principal Findings

10 GTS-patients and 10 control subjects performed a self-paced finger movement task while neuromagnetic brain activity was recorded using Magnetoencephalography (MEG). Cerebro-cerebral coherence as a measure of functional interaction was calculated. During movement preparation and execution coherence between contralateral M1 and supplementary motor area (SMA) was significantly increased at beta-frequency in GTS-patients. After movement termination no significant differences between groups were evident.

Conclusions/Significance

The present data suggest that increased M1 activation in GTS-patients might be due to increased functional interaction between SMA and M1 most likely reflecting a pathophysiological marker of GTS. The data extend previous findings of motor-cortical alterations in GTS by showing that local activation changes are associated with alterations of functional networks between premotor and primary motor areas. Interestingly enough, alterations were evident during preparation and execution of voluntary movements, which implies a general theme of increased motor-cortical interaction in GTS.     

Entacapone Reduces Cortical Activation in Parkinson's Disease with Wearing-Off: A f-MRI Study

Background and Purpose

Wearing-off is one of the most frequent problems encountered by levodopa-treated patients. Entacapone, a peripheral inhibitor of catechol-O-methyltransferase (COMT), reduces this motor complication by prolonging the effect of levodopa. We sought to understand the impact of COMT-inhibition on movement execution in PD patients with wearing-off by comparing functional magnetic resonance imaging (f-MRI) activation patterns prior to and during entacapone treatment. Our hypothesis was to determine whether changes in cortical activation are associated to COMT-inhibitor treatment.

Methods

Nine levodopa-treated non-demented PD patients with wearing-off were prospectively studied in two f-MRI session, prior to and during entacapone treatment. A group of control subjects were also studied for comparison.

Results

The patients significantly improved under COMT-inhibitor treatment based on home diaries. F-MRI results showed that at baseline the patients presented a bilateral activation of the primary motor, controlateral premotor cortex and supplementary motor area, as well as ipsilateral cerebellum. During treatment with entacapone, PD patients showed reductions in the activations of these cortical areas and a decreased activation in the ipsilateral cerebellum.

Conclusions

Our preliminary findings indicate that f-MRI is able to detect cortical activation changes during long-term modulation of dopaminergic treatment in PD patients with wearing-off, and thus, this technique could be further investigated in advanced PD patients.     

Diffuse Optical Tomography Activation in the Somatosensory Cortex: Specific Activation by Painful vs. Non-Painful Thermal Stimuli

Background

Pain is difficult to assess due to the subjective nature of self-reporting. The lack of objective measures of pain has hampered the development of new treatments as well as the evaluation of current ones. Functional MRI studies of pain have begun to delineate potential brain response signatures that could be used as objective read-outs of pain. Using Diffuse Optical Tomography (DOT), we have shown in the past a distinct DOT signal over the somatosensory cortex to a noxious heat stimulus that could be distinguished from the signal elicited by innocuous mechanical stimuli. Here we further our findings by studying the response to thermal innocuous and noxious stimuli.

Methodology/Principal Findings

Innocuous and noxious thermal stimuli were applied to the skin of the face of the first division (ophthalmic) of the trigeminal nerve in healthy volunteers (N = 6). Stimuli temperatures were adjusted for each subject to evoke warm (equivalent to a 3/10) and painful hot (7/10) sensations in a verbal rating scale (0/10 = no/max pain). A set of 26 stimuli (5 sec each) was applied for each temperature with inter-stimulus intervals varied between 8 and 15 sec using a Peltier thermode. A DOT system was used to capture cortical responses on both sides of the head over the primary somatosensory cortical region (S1). For the innocuous stimuli, group results indicated mainly activation on the contralateral side with a weak ipsilateral response. For the noxious stimuli, bilateral activation was observed with comparable amplitudes on both sides. Furthermore, noxious stimuli produced a temporal biphasic response while innocuous stimuli produced a monophasic response.

Conclusions/Significance

These results are in accordance with fMRI and our other DOT studies of innocuous mechanical and noxious heat stimuli. The data indicate the differentiation of DOT cortical responses for pain vs. innocuous stimuli that may be useful in assessing objectively acute pain.     

Simultaneous fMRI and EEG during the Multi-Source Interference Task

Background

fMRI and EEG are two non-invasive functional imaging techniques within cognitive neuroscience that have complementary advantages to obtain both temporal and spatial information. The multi-source interference task (MSIT) has been shown to generate robust activations of the dorsal anterior cingulate cortex (dACC) on both a single-subject level and in group averages, in fMRI studies. We have now simultaneously acquired fMRI and EEG during a cognitive interference task.

Materials and Methods

Healthy volunteers were tested in an MRI scanner with simultaneous EEG and fMRI recordings during the MSIT.

Results

The interference condition significantly increased the reaction time in the task. The fMRI analyses revealed activation of dACC as expected, in all subjects at the individual level and in group analyses. The posterior cingulate cortex was de-activated. Simultaneous EEG showed the expected anterior distribution of the interference effect, as it was restricted to frontal sites within a time frame of 80–120 ms post response.

Conclusion

The MSIT task is a reliable task for interference evaluation. fMRI shows robust activation of dACC and by adding EEG, an interference effect can be noticed within a temporal interval of 80–120 ms after the response, as a CRN (correct response negativity). This means that EEG could add a more detailed temporal aspect to the fMRI data from an interference task, and that despite the hostile environment within an MRI scanner, EEG data could be used.