EEG signatures of auditory activity correlate with simultaneously recorded fMRI responses in humans

We recorded auditory-evoked potentials (AEPs) during simultaneous, continuous fMRI and identified trial-to-trial correlations between the amplitude of electrophysiological responses, characterised in the time domain and the time–frequency domain, and the hemodynamic BOLD response. Cortical AEPs were recorded from 30 EEG channels within the 3 T MRI scanner with and without the collection of simultaneous BOLD fMRI. Focussing on the Cz (vertex) EEG response, single-trial AEP responses were measured from time-domain waveforms. Furthermore, a novel method was used to characterise the single-trial AEP response within three regions of interest in the time–frequency domain (TF-ROIs). The latency and amplitude values of the N1 and P2 AEP peaks during fMRI scanning were not significantly different from the Control session (p > 0.16). BOLD fMRI responses to the auditory stimulation were observed in bilateral secondary auditory cortices as well as in the right precentral and postcentral gyri, anterior cingulate cortex (ACC) and supplementary motor cortex (SMC). Significant single-trial correlations were observed with a voxel-wise analysis, between (1) the magnitude of the EEG TF-ROI1 (70–800 ms post-stimulus, 1–5 Hz) and the BOLD response in right primary (Heschl's gyrus) and secondary (STG, planum temporale) auditory cortex; and (2) the amplitude of the P2 peak and the BOLD response in left pre- and postcentral gyri, the ACC and SMC. No correlation was observed with single-trial N1 amplitude on a voxel-wise basis. An fMRI-ROI analysis of functionally-identified auditory responsive regions identified further single-trial correlations of BOLD and EEG responses. The TF amplitudes in TF-ROI1 and TF-ROI2 (20–400 ms post-stimulus, 5–15 Hz) were significantly correlated with the BOLD response in all bilateral auditory areas investigated (planum temporale, superior temporal gyrus and Heschl's gyrus). However the N1 and P2 peak amplitudes, occurring at similar latencies did not show a correlation in these regions. N1 and P2 peak amplitude did correlate with the BOLD response in bilateral precentral and postcentral gyri and the SMC. Additionally P2 and TF-ROI1 both correlated with the ACC. TF-ROI3 (400–900 ms post-stimulus, 4–10 Hz) correlations were only observed in the ACC and SMC. Across the group, the subject-mean N1 peak amplitude correlated with the BOLD response amplitude in the primary and secondary auditory cortices bilaterally, as well as the right precentral gyrus and SMC. We confirm that auditory-evoked EEG responses can be recorded during continuous and simultaneous fMRI. We have presented further evidence of an empirical single-trial coupling between the EEG and BOLD fMRI responses, and show that a time–frequency decomposition of EEG signals can yield additional BOLD fMRI correlates, predominantly in auditory cortices, beyond those found using the evoked response amplitude alone.     

Activity in ventromedial prefrontal cortex covaries with sympathetic skin conductance level: a physiological account of a "default mode" of brain function

We examined neural activity related to modulation of skin conductance level (SCL), an index of sympathetic tone, using functional magnetic resonance imaging (fMRI) while subjects performed biofeedback arousal and relaxation tasks. Neural activity within the ventromedial prefrontal cortex (VMPFC) and the orbitofrontal cortex (OFC) covaried with skin conductance level (SCL), irrespective of task. Activity within striate and extrastriate cortices, anterior cingulate and insular cortices, thalamus, hypothalamus and lateral regions of prefrontal cortex reflected the rate of change in electrodermal activity, highlighting areas supporting transient skin conductance responses (SCRs). Successful performance of either biofeedback task (where SCL changed in the intended direction) was associated with enhanced activity in mid-OFC. The findings point to a dissociation between neural systems controlling basal sympathetic tone (SCL) and transient skin conductance responses (SCRs). The level of activity in VMPFC has been related to a default mode of brain function and our findings provide a physiological account of this state, indicating that activity within VMPFC and OFC reflects a dynamic between exteroceptive and interoceptive deployment of attention.     

The human prefrontal and parietal association cortices are involved in NO-GO performances: an event-related fMRI study

One of the important roles of the prefrontal cortex is inhibition of movement. We applied an event-related functional magnetic resonance imaging (fMRI) technique to observe changes in fMRI signals of the entire brain during a GO/NO-GO task to identify the functional fields activated in relation to the NO-GO decision. Eleven normal subjects participated in the study, which consisted of a random series of 30 GO and 30 NO-GO trials. The subjects were instructed to press a mouse button immediately after the GO signal was presented. However, they were instructed not to move when the NO-GO signal was presented. We detected significant changes in MR signals in relation to the preparation phases, GO responses, and NO-GO responses. The activation fields related to the NO-GO responses were located in the bilateral middle frontal cortices, left dorsal premotor area, left posterior intraparietal cortices, and right occipitotemporal area. The fields of activation in relation to the GO responses were found in the left primary sensorimotor, right cerebellar anterior lobule, bilateral thalamus, and the area from the anterior cingulate to the supplementary motor area (SMA). Brain activations related to the preparation phases were identified in the left dorsal premotor, left lateral occipital, right ventral premotor, right fusiform, and the area from the anterior cingulate to the SMA. The results indicate that brain networks consisting of the bilateral prefrontal, intraparietal, and occipitotemporal cortices may play an important role in executing a NO-GO response.     

Ventral medial prefrontal cortex and cardiovagal control in conscious humans

The autonomic nervous system plays a critical role in regulating the cardiovascular responses to mental and physical stress. Recent neuroimaging studies have demonstrated that sympathetic outflow to the heart is modulated by the activity of the anterior cingulate cortex (ACC). However, the cortical modulation of cardiovagal activity is still unclear in humans. The present study used functional MRI to investigate the cortical network involved in cardiovagal control. Seventeen healthy individuals performed graded handgrip exercise while heart rate (HR) and cortical activity were recorded. Muscle sympathetic nerve activity (MSNA), mean arterial pressure (MAP) and HR were measured while participants repeated the same protocol in a parallel experiment session. The handgrip exercise elevated HR and MAP without concurrent elevations in MSNA supporting earlier conclusions that the cardiovascular responses are mainly modulated by vagal withdrawal. The imaging data showed activation in the insular cortex, thalamus, parietal cortices and cerebellum during the exercise period. Consistently across all the participants, the HR response correlated with the deactivation in the ventral medial prefrontal cortex (vMPFC), which has substantial anatomical connection with the subcortical autonomic structures. The deactivation of the vMPFC was independent of the motor control and was observed commonly in both left and right hand exercise. Stronger vMPFC deactivation was observed when participants completed a higher intensity exercise that elicited a larger HR response. Our findings support the hypothesis that the vMPFC is involved in modulating the vagal efferent outflow to the heart and the suppression of its activity elevates cardiovascular arousal in conscious humans.     

Functional activity mapping of the mesial hemispheric wall during anticipation of pain

The relative contributions of autonomic arousal and of cognitive processing to cortical activity during anticipation of pain, and the role of changes in thalamic outflow, are still largely unknown. To address these issues, we investigated with functional magnetic resonance imaging (fMRI) the activity of the contralateral mesial hemispheric wall in 56 healthy volunteers while they expected the stimulation of one foot, which could be either painful or innocuous. The waiting period was characterized by emotional arousal, a moderate rise in heart rate, and by increases in mean fMRI signals in the medial thalamus, mid- and posterior cingulate cortex, and in the putative foot area of the primary somatosensory and motor cortex. The same brain regions, excepting posterior cingulate, were also activated by somatosensory stimulation. We identified by cross-correlation analysis a cluster population whose fMRI signal time course was related to the mean heart rate (HR) profile, showing selective changes of activity during the waiting period. Positively correlated clusters were found mainly in sensorimotor areas, mid- and posterior cingulate, and dorsomedial prefrontal cortex. Negatively correlated clusters predominated in the perigenual anterior cingulate and ventromedial prefrontal cortex. HR clusters had different characteristics from, and showed limited spatial overlap with, clusters whose fMRI signals were related to the psychophysical pain intensity profile; however, both cluster populations were affected by anticipation. These findings unravel a complex pattern of brain activity during uncertain anticipation of noxious input, likely related both to changes in the level of arousal and to cognitive modulation of the pain system.     

Functional segregation of the human cingulate cortex is confirmed by functional connectivity based neuroanatomical parcellation

The four-region model with 7 specified subregions represents a theoretical construct of functionally segregated divisions of the cingulate cortex based on integrated neurobiological assessments. Under this framework, we aimed to investigate the functional specialization of the human cingulate cortex by analyzing the resting-state functional connectivity (FC) of each subregion from a network perspective. In 20 healthy subjects we systematically investigated the FC patterns of the bilateral subgenual (sACC) and pregenual (pACC) anterior cingulate cortices, anterior (aMCC) and posterior (pMCC) midcingulate cortices, dorsal (dPCC) and ventral (vPCC) posterior cingulate cortices and retrosplenial cortices (RSC). We found that each cingulate subregion was specifically integrated in the predescribed functional networks and showed anti-correlated resting-state fluctuations. The sACC and pACC were involved in an affective network and anti-correlated with the sensorimotor and cognitive networks, while the pACC also correlated with the default-mode network and anti-correlated with the visual network. In the midcingulate cortex, however, the aMCC was correlated with the cognitive and sensorimotor networks and anti-correlated with the visual, affective and default-mode networks, whereas the pMCC only correlated with the sensorimotor network and anti-correlated with the cognitive and visual networks. The dPCC and vPCC involved in the default-mode network and anti-correlated with the sensorimotor, cognitive and visual networks, in contrast, the RSC was mainly correlated with the PCC and thalamus. Based on a strong hypothesis driven approach of anatomical partitions of the cingulate cortex, we could confirm their segregation in terms of functional neuroanatomy, as suggested earlier by task studies or exploratory multi-seed investigations.     

帕金森病静息态脑功能MRI研究

目的：应用血氧水平依赖的功能MRI（BOLD-fMRI）,探索帕金森病（PD）患者静息态脑功能可能存在的异常。材料与方法对68例PD患者和36例健康志愿者进行静息态BOLD-fMRI检查。分析PD组与正常对照组标准化脑功能低频振荡幅度（mALFF）的差异。结果与正常对照组比较,PD组在双侧辅助运动区、中后扣带回、楔前叶、海马、海马旁回、外侧苍白球、背侧丘脑、小脑前叶以及右侧局部初级运动皮层、岛叶、尾状核、壳核、小脑后叶等广泛区域mALFF值显著减低（P〈0.05,AlphaSim校正）,在双侧前额叶、顶叶及颞叶的广泛外侧皮层、左侧枕叶初级视觉皮层等区域mALFF值显著增高（P〈0.05,AlphaSim校正）。结论 PD患者静息态脑功能存在广泛异常,主要表现为PD患者在运动调节相关脑区、默认网络关键节点、边缘系统等部位神经元活动减弱,在前额叶、顶叶、颞叶的广泛外侧皮层以及初级视觉皮层等部位神经元活动增强。     

An fMRI investigation of syllable sequence production

Fluent speech comprises sequences that are composed from a finite alphabet of learned words, syllables, and phonemes. The sequencing of discrete motor behaviors has received much attention in the motor control literature, but relatively little has been focused directly on speech production. In this paper, we investigate the cortical and subcortical regions involved in organizing and enacting sequences of simple speech sounds. Sparse event-triggered functional magnetic resonance imaging (fMRI) was used to measure responses to preparation and overt production of non-lexical three-syllable utterances, parameterized by two factors: syllable complexity and sequence complexity. The comparison of overt production trials to preparation only trials revealed a network related to the initiation of a speech plan, control of the articulators, and to hearing one's own voice. This network included the primary motor and somatosensory cortices, auditory cortical areas, supplementary motor area (SMA), the precentral gyrus of the insula, and portions of the thalamus, basal ganglia, and cerebellum. Additional stimulus complexity led to increased engagement of the basic speech network and recruitment of additional areas known to be involved in sequencing non-speech motor acts. In particular, the left hemisphere inferior frontal sulcus and posterior parietal cortex, and bilateral regions at the junction of the anterior insula and frontal operculum, the SMA and pre-SMA, the basal ganglia, anterior thalamus, and the cerebellum showed increased activity for more complex stimuli. We hypothesize mechanistic roles for the extended speech production network in the organization and execution of sequences of speech sounds.     

单侧踝背屈等长运动对双侧大脑皮质的影响

摘要 目的：利用fMRI技术研究人体单侧主动踝背屈时双侧脑功能区激活情况,为力量训练交叉迁移的中枢机制提供理论依据,并为进一步临床康复应用提供理论支持。 方法：选取8名健康青年男性右利腿志愿者,以右踝关节背屈主动用力最大等长收缩为刺激模式,采用组块设计,使用1.5T磁共振全身扫描仪进行fMRI数据采集,利用SPM5软件进行数据分析和脑功能区定位。 结果：右踝背屈主动运动主要激活脑区为双侧初级躯体运动区、双侧次级躯体感觉区、双侧运动前区、双侧运动辅助区、双侧小脑、双侧扣带回及对侧初级躯体感觉区。 结论：单侧踝背屈主动运动引起双侧大脑皮质多个运动相关皮质的激活,说明主动运动引起的交叉迁移现象可能存在大脑皮质机制,支持皮质参与的神经机制学说,也为进一步将交叉迁移效果应用到临床提供了理论依据。     

Cortical dynamics of human scalp EEG origins in a visually guided motor execution

The EEG mu rhythm is often used as an index of activation in the sensorimotor cortex. However, the blur caused by volume conduction makes it difficult to identify the exact origin of the EEG rhythm in the brain using only the human scalp EEG. In this study, simultaneous fMRI and EEG measurements were performed during a visually guided motor execution task in order to investigate whether the mu rhythm in the scalp EEG is an indication of the activity in the sensorimotor cortex. In addition, a new method was proposed for reconstruction of the cortical EEG activity through the fusion of fMRI and EEG data. A suppression of mu rhythm appeared around the lateral central electrode sites, just above the sensorimotor cortex, in association with the activity in that region. During a visually guided motor execution task, the alpha rhythms at the occipital electrode sites and the alpha rhythm at the central electrode sites also showed a correlation with the fMRI signal in the occipital and the supplementary motor cortices, respectively. This method allows the investigation of the scalp EEG origin with the spatial precision of fMRI, while retaining dynamic properties of the cortex with the temporal precision of EEG.     

High opiate receptor binding potential in the human lateral pain system

To determine how opiate receptor distribution is co-localized with the distribution of nociceptive areas in the human brain, eleven male healthy volunteers underwent one PET scan with the subtype-nonselective opioidergic radioligand [(18)F]fluoroethyl-diprenorphine under resting conditions. The binding potential (BP), a parameter for the regional cerebral opioid receptor availability, was computed using the occipital cortex as reference region. The following regions of interest (ROIs) were defined on individual MR images: thalamus, sensory motor strip (SI/MI area), frontal operculum, parietal operculum, anterior insular cortex, posterior insular cortex, anterior cingulate cortex (ACC; peri- and subgenual part of "classical ACC" only), midcingulate cortex (MCC, posterior part of "classical ACC"), putamen, caudate nucleus and the amygdala. BP for [(18)F]fluoroethyl-diprenorphine was lowest in the sensory motor strip (0.30). Highest BP was found in thalamus (1.36), basal ganglia (putamen 1.22, caudate 1.16) and amygdala (1.21). In the cingulate cortex, ACC (1.11) had higher BP than MCC (0.86). In the operculo-insular region, we found high BPs in all ROIs: anterior insula (1.16), posterior insula (1.05), frontal operculum (0.99) and parietal operculum (0.77). Factor analysis of interindividual variability of opiate receptor BP revealed four factors (95% explained variance): (1) operculo-insular areas, ACC, MCC and putamen, (2) amygdala and thalamus, (3) caudate and thalamus, (4) SI/MI and MCC. Nociceptive areas of the lateral pain system (frontoparietal operculum and insula) have opiate receptor BPs significantly higher than SI/MI, comparable to anterior and midcingulate areas of the medial pain system. These findings suggest that the cortical anti-nociceptive effects of opiates are not only mediated by ACC and MCC, but also by the operculo-insular cortex, if it can be assumed that opioid binding mediates anti-nociception in those structures.     

Impact of brain networks involved in vigilance on processing irrelevant visual motion

The ability to sustain attention over prolonged periods of time is called vigilance. Vigilance is a fundamental component of attention which impacts on performance in many situations. We here investigate whether similar neural mechanisms are responsible for vigilant attention over long and short durations of time and whether neural activity in brain regions sensitive to vigilant attention is related to processing irrelevant information. Brain activity was measured by means of functional magnetic resonance imaging (fMRI) in a 32 min visual vigilance task with varying inter-target intervals and irrelevant peripheral motion stimuli. Changes in neural activity were analysed as a function of time on task to capture long-term aspects of vigilance and as a function of time between target stimuli to capture short-term aspects of vigilance. Several brain regions including the inferior frontal, posterior parietal, superior and middle temporal cortices and the anterior insular showed decreases in neural activity as a function of time on task. In contrast, increasing inter-target intervals resulted in increased neural activity in a widespread network of regions involving lateral and medial frontal areas, temporal areas, cuneus and precuneus, inferior occipital cortex (right), posterior insular cortices, the thalamus, nucleus accumbens and basal forebrain. A partial least square analysis revealed that neural activity in this latter network covaried with neural activity related to processing irrelevant motion stimuli. Our results provide neural evidence that two separate mechanisms are responsible for sustaining attention over long and short durations. We show that only brain areas involved in sustaining attention over short durations of time are related to processing irrelevant stimuli and suggest that these areas can be segregated into two functionally different networks, one possibly involved in motivation, the other in arousal.     

完全性脊髓损伤亚急性期脑运动控制功能变化的功能磁共振研究

目的 探讨完全性脊髓损伤患者脑运动控制功能的变化情况。方法 2017年1月至2019年1月,病程3~6个月完全性脊髓损伤患者11例与健康人12例,在试图/实际运动、意象运动(MI)任务下行功能磁共振成像(fMRI)扫描,观察不同运动任务引发激活效应的空间分布和信号强度。结果 患者试图运动时的脑激活区域显著多于健康人实际运动时的激活区域,包括双侧初级感觉/运动皮质(S1/M1)、辅助运动区(SMA)、外侧苍白球(PA)、小脑、左侧丘脑和壳核等。健康人意象运动的比较,患者激活簇主要存在于右M1、SMA、背侧运动前区(PMd)、左SMA、岛叶和基底核。患者试图运动比意象运动在左M1、双SMA、扣带回运动区和右小脑诱发更多的兴奋。结论 亚急性期完全性脊髓损伤患者执行运动任务时,M1、SMA的兴奋模式基本正常,顶叶和小脑等感觉运动整合区域激活增加,提示发生适应性重组。     

Dissection of perceptual,motor and autonomic components of brain activity evoked by noxious stimulation

In the past two decades, functional brain imaging has considerably advanced our knowledge of cerebral pain processing. However, many important links are still missing in our understanding of brain activity in relation to the regulation of pain-related physiological responses. This fMRI study investigates the cerebral correlates of pain (rating), motor responses (RIII-reflex) and autonomic activity (skin conductance response; SCR) evoked by noxious electrical stimulation. Stimulus intensity was adjusted individually based on the RIII threshold to control for differences in peripheral processes and baseline spinal activation. Covariance analyses were used to reveal individual differences in brain activity uniquely associated with individual differences in pain, RIII and SCR. Shock-evoked activity in cingulate, medial orbitofrontal and parahippocampal regions predicted pain sensitivity. Moreover, lateral orbitofrontal and cingulate areas showed strong positive associations with individual differences in motor reactivity but negative associations with autonomic reactivity. Notably, individual differences in OFC activation was almost fully accounted by the combination of individual measures of autonomic and motor reactivity (R² = 0.93). Additionally, trial-to-trial fluctuations of RIII-reflex and SCR (within-subjects) were proportional to shock-evoked responses in subgenual cingulate cortex (RIII), anterior insula (SCR) and midcingulate cortex (SCR and RIII). Together, these results confirm that individual differences in perceptual, motor, and autonomic components of pain reflect robust individual differences in brain activity. Furthermore, the brain correlates of trial-to-trial fluctuations in pain responses provide additional evidence for a partial segregation of sub-systems involved more specifically in the ongoing monitoring, and possibly the regulation, of pain-related motor and autonomic responses.     

Neural correlates of blink suppression and the buildup of a natural bodily urge

Neuroimaging studies have elucidated some of the underlying physiology of spontaneous and voluntary eye blinking; however, the neural networks involved in eye blink suppression remain poorly understood. Here we investigated blink suppression by analyzing fMRI data in a block design and event-related manner, and employed a novel hypothetical time-varying neural response model to detect brain activations associated with the buildup of urge. Blinks were found to activate visual cortices while our block design analysis revealed activations limited to the middle occipital gyri and deactivations in medial occipital, posterior cingulate and precuneus areas. Our model for urge, however, revealed a widespread network of activations including right greater than left insular cortex, right ventrolateral prefrontal cortex, middle cingulate cortex, and bilateral temporo-parietal cortices, primary and secondary face motor regions, and visual cortices. Subsequent inspection of BOLD time-series in an extensive ROI analysis showed that activity in the bilateral insular cortex, right ventrolateral prefrontal cortex, and bilateral STG and MTG showed strong correlations with our hypothetical model for urge suggesting these areas play a prominent role in the buildup of urge. The involvement of the insular cortex in particular, along with its function in interoceptive processing, helps support a key role for this structure in the buildup of urge during blink suppression. The right ventrolateral prefrontal cortex findings in conjunction with its known involvement in inhibitory control suggest a role for this structure in maintaining volitional suppression of an increasing sense of urge. The consistency of our urge model findings with prior studies investigating the suppression of blinking and other bodily urges, thoughts, and behaviors suggests that a similar investigative approach may have utility in fMRI studies of disorders associated with abnormal urge suppression such as Tourette syndrome and obsessive-compulsive disorder.     

Where arousal meets attention: a simultaneous fMRI and EEG recording study

In this fMRI study, we looked for the regions supporting interaction between cortical arousal and attention during three conditions: detection, observation, and rest. Arousal measurements were obtained from the EEG low-frequency (LF) power (5-9.5 Hz) recorded continuously together with fMRI. Whatever the condition, arousal was positively correlated with the fMRI signal of the right dorsal-lateral prefrontal and superior parietal cortices, closely overlapping regions involved in the maintenance of attention. Although the inferior temporal areas also presented a correlation with arousal during detection, path analysis suggests that this influence may be indirect, through the top-down influence of the previously mentioned network. However, those visual-processing areas could account for the correlation between arousal and performances. Lastly, the medial frontal cortex, frontal opercula, and thalamus were inversely correlated with arousal but only during detection and observation so that they could account for the control of arousal.     

The functional neuroanatomy of simple calculation and number repetition: A parametric PET activation study

We examined cerebral activation patterns with positron emission tomography (PET) in 12 right-handed normal volunteers while they were completing simple calculation tasks or merely repeating numbers. Using a parametric experimental design, during calculation we found activation in the medial frontal/cingulate gyri, left dorsolateral prefrontal cortex, left anterior insular cortex and right anterior insular cortex/putamen, left lateral parietal cortex, and the medial thalamus. Number repetition engaged bilateral inferior sensorimotor cortex, bilateral temporal areas, and left inferior frontal cortex. These results suggest a functional anatomical network for simple calculation, which includes aspects of attention, auditory, and motor processing and the phonological store and articulatory loop components of working memory; they add some support for a special role of the parietal cortex in calculation tasks.     

Neural correlates of error awareness

Error processing results in a number of consequences on multiple levels. The posterior frontomedian cortex (pFMC) is involved in performance monitoring and signalling the need for adjustments, which can be observed as post-error speed-accuracy shifts at the behavioural level. Furthermore autonomic reactions to an error have been reported. The role of conscious error awareness for this processing cascade has received little attention of researchers so far. We examined the neural correlates of conscious error perception in a functional magnetic resonance imaging (fMRI) study. An antisaccade task known to yield sufficient numbers of aware and unaware errors was used. Results from a metaanalysis were used to guide a region of interest (ROI) analysis of the fMRI data. Consistent with previous reports, error-related activity in the rostral cingulate zone (RCZ), the pre-supplementary motor area (pre-SMA) and the insular cortex bilaterally was found. Whereas the RCZ activity did not differentiate between aware and unaware errors, activity in the left anterior inferior insular cortex was stronger for aware as compared to unaware errors. This could be due to increased awareness of the autonomic reaction to an error, or the increased autonomic reaction itself. Furthermore, post-error adjustments were only observed after aware errors and a correlation between post-error slowing and the hemodynamic activity in the RCZ was revealed. The data suggest that the RCZ activity alone is insufficient to drive error awareness. Its signal appears to be useful for post-error speed-accuracy adjustments only when the error is consciously perceived.     

Representation of cold allodynia in the human brain--a functional MRI study

Cold allodynia, meaning that innocuous cold stimuli become painful, is a characteristic, but enigmatic feature of neuropathic pain. Here, we used functional magnetic resonance imaging (fMRI) and investigated brain activations underlying menthol-induced cold allodynia. 12 healthy volunteers were investigated using a block-design fMRI approach. Firstly, brain activity was measured during application of innocuous cold stimuli (at 5 degrees C above cold pain threshold) and noxious cold stimuli (at 5 degrees C below cold pain threshold) to normal skin of the forearm using a peltier- driven thermostimulator. The stimuli were adjusted to the individual cold pain threshold. Secondly, cold allodynia was induced by topical menthol and cortical activations were measured during previously innocuous cold stimulation (i.e. cold pain threshold +5 degrees C), that were then perceived as painful. On a numeric rating scale for pain (0-10) innocuous cold, cold pain and cold allodynia were rated to 0.9+/-0.3, 4.1+/-0.3 and 4.5+/-0.5, respectively. Sensory and affective components of allodynic and cold pain were equal in the McGill pain questionnaire. All tested conditions (innocuous cold, noxious cold and cold allodynia) led to significant activations of bilateral insular cortices, bilateral frontal cortices and the anterior cingulate cortex. When noxious cold and innocuous cold were compared, noxious cold contributed significantly more to activations of the posterior insula and innocuous cold contributed more to activations of ipsilateral anterior insular cortex. However, comparing cold allodynia and equally intense cold pain conditions, we found significantly increased activations in bilateral dorsolateral prefrontal cortices (DLPFC) and the brainstem (ipsilateral parabrachial nucleus) during cold allodynia. Furthermore, in contrast maps cold allodynia contributed significantly more to activations of the bilateral anterior insula, whereas the contribution to activation of the contralateral posterior insula was equal. It is concluded that cold allodynia activates a network similar to that of normal cold pain but additionally recruits bilateral DLPFC and the midbrain, suggesting that these brain areas are involved in central nociceptive sensitisation processes.     

Multimodal imaging of functional networks and event-related potentials in performance monitoring

The stop-signal task is a prototypical experiment to study cognitive processes that mediate successful performance in a rapidly changing environment. By means of simultaneous recording and combined analysis of electroencephalography and functional magnetic resonance imaging on single trial level, we provide a comprehensive view on brain responses related to performance monitoring in this task. Three types of event-related EEG components were analyzed: a go-related N2/P3-complex devoid of motor-inhibition, the stop-related N2/P3-complex and the error-related negativity with its consecutive error positivity. Relevant functional networks were identified by crossmodal correlation analyses in a parallel independent component analysis framework. Go-related potentials were associated with a midcingulate network known to participate in the processing of conflicts, a left-dominant somatosensory-motor network, and deactivations in visual cortices. Stop-related brain responses in association with the N2/P3-complex were seen with networks known to support motor and cognitive inhibition, including parts of the basal ganglia, the anterior midcingulate cortex and pre-supplementary motor area as well as the anterior insula. Error-related brain responses showed a similar constellation with additional recruitment of the posterior insula and the inferior frontal cortex. Our data clearly indicate that the pre-supplementary motor area is involved in inhibitory mechanisms but not in the processing of conflicts per se.