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A central challenge in the study of conscious perception lies in dissociating the neural correlates of perceptual awareness from those reflecting its precursors and consequences. No-report paradigms have been instrumental in this endeavor, demonstrating that the event-related potential P300, recorded from the human scalp, reflects reports rather than awareness. However, these paradigms cannot probe the degree to which stimuli are consciously processed from trial to trial and, thus, leave open the possibility that the P300 is a genuine correlate of conscious access enabling reports. Here, instead of removing report requirements, we took the opposite approach and equated postperceptual task demands across conscious and unconscious trials by orthogonalizing target detection and overt reports in a somatosensory detection task. We used Bayesian model selection to track the transformation from physical to perceptual processing stages in the EEG data of 24 male and female participants and show that the early P50 component scaled with physical stimulus intensity, whereas the N140 component was the first correlate of target detection. The late P300 component was elicited for both perceived and unperceived stimuli and was not substantially modulated by target detection. This was in stark contrast to a control experiment using a classical direct report task, which replicated the P50 and N140 effects but additionally showed a strong effect of target detection in the P300 time range. Our results demonstrate the task dependence of the P300 in the somatosensory modality and show that late cortical potentials dissociate from perceptual awareness even when stimuli are always reported.SIGNIFICANCE STATEMENTThe time it takes for sensory information to enter our conscious experience can be an indicator of the neural processing stages that lead to perceptual awareness. However, because many cognitive processes routinely correlate with perception, isolating those signals that uniquely reflect perceptual awareness is not a trivial task. Here, we show that late electroencephalography signals cease to correlate with somatosensory awareness when common task confounds are controlled. Importantly, by balancing report requirements instead of abolishing them, we show that the lack of late effects cannot be explained by a lack of conscious access. Instead, we propose that conscious access occurs earlier, at ∼150 ms, supporting the view that early activity in sensory cortices is a neural correlate of conscious perception.

The study of perceptual decision making has made significant progress owing to major contributions from two experimental paradigms: the sequential vibrotactile frequency comparison task for the somatosensory domain requiring working memory, and the random-dot motion task in the visual domain requiring evidence accumulation over time. On the one hand, electrophysiological recordings in nonhuman primates and humans have identified changes in firing rates and power modulations of beta band oscillations with the vibrotactile frequencies held in working memory, as well as with the mental operation required for decision making. On the other hand, firing rates and centro-parietal potentials were found to increase to a fixed level at the time of responding during the random-dot motion task, possibly reflecting an underlying evidence accumulation mechanism until a decision threshold is met. Here, to bridge these two paradigms, we presented two visual random-dot motion stimuli in a sequential comparison task while recording EEG from human volunteers. We identified a modulation of prefrontal beta band power that scaled with the level of dot motion coherence of the first stimulus during a short retention interval. Furthermore, beta power in premotor areas was modulated by participants’ choices approximately 700 ms before responses were given via button press. At the same time, dot motion patches of the second stimulus evoked a pattern of broadband centro-parietal signal build-up till responses were made, whose peak varied with trial difficulty. Hence, we show that known modulations of beta power during working memory and decision making extend from the vibrotactile to the visual domain and provide support for the notion of evidence accumulation as an unconfined decision-making mechanism generalizing over distinct decision types.

Tracking statistical regularities of the environment is important for shaping human behavior and perception. Evidence suggests that the brain learns environmental dependencies using Bayesian principles. However, much remains unknown about the employed algorithms, for somesthesis in particular. Here, we describe the cortical dynamics of the somatosensory learning system to investigate both the form of the generative model as well as its neural surprise signatures. Specifically, we recorded EEG data from 40 participants subjected to a somatosensory roving-stimulus paradigm and performed single-trial modeling across peri-stimulus time in both sensor and source space. Our Bayesian model selection procedure indicates that evoked potentials are best described by a non-hierarchical learning model that tracks transitions between observations using leaky integration. From around 70ms post-stimulus onset, secondary somatosensory cortices are found to represent confidence-corrected surprise as a measure of model inadequacy. Indications of Bayesian surprise encoding, reflecting model updating, are found in primary somatosensory cortex from around 140ms. This dissociation is compatible with the idea that early surprise signals may control subsequent model update rates. In sum, our findings support the hypothesis that early somatosensory processing reflects Bayesian perceptual learning and contribute to an understanding of its underlying mechanisms., Author summary Our environment features statistical regularities, such as a drop of rain predicting imminent rainfall. Despite the importance for behavior and survival, much remains unknown about how these dependencies are learned, particularly for somatosensation. As surprise signalling about novel observations indicates a mismatch between one’s beliefs and the world, it has been hypothesized that surprise computation plays an important role in perceptual learning. By analyzing EEG data from human participants receiving sequences of tactile stimulation, we compare different formulations of surprise and investigate the employed underlying learning model. Our results indicate that the brain estimates transitions between observations. Furthermore, we identified different signatures of surprise computation and thereby provide a dissociation of the neural correlates of belief inadequacy and belief updating. Specifically, early surprise responses from around 70ms were found to signal the need for changes to the model, with encoding of its subsequent updating occurring from around 140ms. These results provide insights into how somatosensory surprise signals may contribute to the learning of environmental statistics.

Decision‐making in the somatosensory domain has been intensively studied using vibrotactile frequency discrimination tasks. Results from human and monkey electrophysiological studies from this line of research suggest that perceptual choices are encoded within a sensorimotor network. These findings, however, rely on experimental settings in which perceptual choices are inextricably linked to sensory and motor components of the task. Here, we devised a novel version of the vibrotactile frequency discrimination task with saccade responses which has the crucial advantage of decoupling perceptual choices from sensory and motor processes. We recorded human fMRI data from 32 participants while they performed the task. Using a whole‐brain searchlight multivariate classification technique, we identify the left lateral prefrontal cortex and the oculomotor system, including the bilateral frontal eye fields (FEF) and intraparietal sulci, as representing vibrotactile choices. Moreover, we show that the decoding accuracy of choice information in the right FEF correlates with behavioral performance. Not only are these findings in remarkable agreement with previous work, they also provide novel fMRI evidence for choice coding in human oculomotor regions, which is not limited to saccadic decisions, but pertains to contexts where choices are made in a more abstract form.

Working memory (WM) studies have been essential for ascertaining how the brain flexibly handles mentally represented information in the absence of sensory stimulation. Most studies on the memory of sensory stimulus features have focused, however, on the visual domain. Here, we report a human WM study in the tactile modality where participants had to memorize the spatial layout of patterned Braille-like stimuli presented to the index finger. We used a whole-brain searchlight approach in combination with multi-voxel pattern analysis (MVPA) to investigate tactile WM representations without a priori assumptions about which brain regions code tactospatial information. Our analysis revealed that posterior and parietal cortices, as well as premotor regions, retained information across the twelve-second delay phase. Interestingly, parts of this brain network were previously shown to also contain information of visuospatial WM. Also, by specifically testing somatosensory regions for WM representations, we observed content-specific activation patterns in primary somatosensory cortex (SI). Our findings demonstrate that tactile WM depends on a distributed network of brain regions in analogy to the representation of visuospatial information.

In recent electroencephalography (EEG) studies, the vibrotactile frequency comparison task has been used to study oscillatory signatures of perceptual decision making in humans, revealing a choice‐selective modulation of premotor upper beta band power shortly before decisions were reported. Importantly, these studies focused on decisions that were (1) indicated immediately after stimulus presentation, and (2) for which a direct motor mapping was provided. Here, we investigated whether the putative beta band choice signal also extends to postponed decisions, and how such a decision signal might be influenced by a response mapping that is dissociated from a specific motor command. We recorded EEG data in two separate experiments, both employing the vibrotactile frequency comparison task with delayed decision reports. In the first experiment, delayed choices were associated with a fixed motor mapping, whereas in the second experiment, choices were mapped onto a color code concealing a specific motor response until the end of the delay phase. In between stimulus presentations, as well as after the second stimulus, prefrontal beta band power indexed stimulus information held in working memory. Beta band power also encoded choices during the response delay, notably, in different cortical areas depending on the provided response mapping. In particular, when decisions were associated with a specific motor mapping, choices were represented in premotor cortices, whereas the color mapping resulted in a choice‐selective modulation of beta band power in parietal cortices. Together, our findings imply that how a choice is expressed (i.e., the decision consequence) determines where in the cortical sensorimotor hierarchy an according decision signal is processed.

Working memory (WM) representations are generally known to be influenced by task demands, but it is not clear whether this extends to the somatosensory domain. One way to investigate the influence of task demands is with categorization paradigms, wherein either a single stimulus or an associated category is maintained in WM. In the somatosensory modality, category representations have been identified in the premotor cortex (PMC) and the intraparietal sulcus (IPS). In this study we used multivariate-pattern-analysis with human fMRI data to investigate whether the WM representations in the PMC, IPS or other regions are influenced by changing task demands. We ensured the task-dependent, categorical WM information was decorrelated from stimulus features by (1) teaching participants arbitrary, non-rule based stimulus groupings and (2) contrasting identical pairs of stimuli across experimental conditions, where either a single stimulus or the associated group was maintained in WM. Importantly, we also decoupled the decision and motor output from the WM representations. With these experimental manipulations, we were able to pinpoint stimulus-specific WM information to the left frontal and parietal cortices and context-dependent, group-specific WM information to the left IPS. By showing that grouped stimuli are represented more similarly in the Group condition than in the Stimulus condition, free from stimulus and motor output confounds, we provide novel evidence for the adaptive nature of somatosensory WM representations in the IPS with changing task-demands.

Recent working memory (WM) research has focused on identifying brain regions that retain different types of mental content. Only few neuroimaging studies have explored the mechanism of attention‐based refreshing, which is a type of rehearsal and is thought to implement the dynamic components of WM allowing for update of WM contents. Here, we took advantage of the distinct coding properties of the superior parietal lobe (SPL), which retains spatial layout information, and the right inferior frontal gyrus (IFG), which retains frequency information of vibrotactile stimuli during tactile WM. In an fMRI delayed match‐to‐sample task, participants had to internally rehearse sequences of spatial layouts or vibratory frequencies. Our results replicate the dissociation of SPL and IFG for the retention of layout and frequency information in terms of activation differences between conditions. Additionally, we found strong premotor cortex (PMC) activation during rehearsal of either stimulus type. To explore interactions between these regions we used dynamic causal modeling and found that activation within the network was best explained by a model that allows the PMC to drive activity in the SPL and IFG during rehearsal. This effect was content‐specific, meaning that the PMC showed stronger influence on the SPL during pattern rehearsal and stronger influence on the IFG during frequency rehearsal. In line with previously established PMC contributions to sequence processing, our results suggest that it acts as a content‐independent area that flexibly recruits content‐specific regions to bring a WM item into the focus of attention during the rehearsal of tactile stimulus sequences., In an fMRI delayed match‐to‐sample task, participants had to internally rehearse sequences of spatial layouts or vibratory frequencies of tactile stimuli. To explore interactions between task activated regions we used dynamic causal modeling and found that activation within the network was best explained by a model that allows the premotor cortex to drive activity in the SPL and IFG during rehearsal.

Previous electrophysiological studies in monkeys and humans suggest that premotor regions are the primary loci for the encoding of perceptual choices during vibrotactile comparisons. However, these studies employed paradigms wherein choices were inextricably linked with the stimulus order and selection of manual movements. It remains largely unknown how vibrotactile choices are represented when they are decoupled from these sensorimotor components of the task. To address this question, we used fMRI-MVPA and a variant of the vibrotactile frequency discrimination task which enabled the isolation of choice-related signals from those related to stimulus order and selection of the manual decision reports. We identified the left contralateral dorsal premotor cortex (PMd) and intraparietal sulcus (IPS) as carrying information about vibrotactile choices. Our finding provides empirical evidence for an involvement of the PMd and IPS in vibrotactile decisions that goes above and beyond the coding of stimulus order and specific action selection. Considering findings from recent studies in animals, we speculate that the premotor region likely serves as a temporary storage site for information necessary for the specification of concrete manual movements, while the IPS might be more directly involved in the computation of choice. Moreover, this finding replicates results from our previous work using an oculomotor variant of the task, with the important difference that the informative premotor cluster identified in the previous work was centered in the bilateral frontal eye fields rather than in the PMd. Evidence from these two studies indicates that categorical choices in human vibrotactile comparisons are represented in a response modality-dependent manner.

To accurately guide one's actions online, the brain predicts sensory action feedback ahead of time based on internal models, which can be updated by sensory prediction errors. The underlying operations can be experimentally investigated in sensorimotor adaptation tasks, in which moving under perturbed sensory action feedback requires internal model updates. Here we altered healthy participants’ visual hand movement feedback in a virtual reality setup, while assessing brain activity with functional magnetic resonance imaging (fMRI). Participants tracked a continually moving virtual target object with a photorealistic, three-dimensional (3D) virtual hand controlled online via a data glove. During the continuous tracking task, the virtual hand's movements (i.e., visual movement feedback) were repeatedly periodically delayed, which participants had to compensate for to maintain accurate tracking. This realistic task design allowed us to simultaneously investigate processes likely operating at several levels of the brain's motor control hierarchy. FMRI revealed that the length of visual feedback delay was parametrically reflected by activity in the inferior parietal cortex and posterior temporal cortex. Unpredicted changes in visuomotor mapping (at transitions from synchronous to delayed visual feedback periods or vice versa) activated biological motion-sensitive regions in the lateral occipitotemporal cortex (LOTC). Activity in the posterior parietal cortex (PPC), focused on the contralateral anterior intraparietal sulcus (aIPS), correlated with tracking error, whereby this correlation was stronger in participants with higher tracking performance. Our results are in line with recent proposals of a wide-spread cortical motor control hierarchy, where temporoparietal regions seem to evaluate visuomotor congruence and thus possibly ground a self-attribution of movements, the LOTC likely processes early visual prediction errors, and the aIPS computes action goal errors and possibly corresponding motor corrections.

According to one view, neural oscillations structure information processing in time, determining whether sensory inputs have a strong or weak impact on behavior. Recent work showed that during sequential integration of visual inputs, stimuli that fall in the preferred phase of slow (1–3 Hz), endogenous EEG activity carry greater weight in subsequent judgment. Here, we asked two questions. Firstly, is this phenomenon modality-specific, or is it supramodal? Secondly, does this effect occur at the level of sequential encoding, or only during decision formation? We analyzed scalp EEG recordings from healthy human participants while they compared the approximate number of visual, auditory or somatosensory pulses in two successive intervals (N1 and N2). Despite differences in activity evoked in different domains, a common, slowly-oscillating (~ 3 Hz) choice-predictive signal was observed in all three modalities with a maximum coincident with pulse onset. Critically, this signal was present during N2 (when a decision was being formed) but absent during N1 (when perceptual information was encoded, but no decision could be made). In other words, rhythmic gain control during sequential processing is a supramodal phenomenon that occurs while information is integrated towards a categorical decision.

Research on somatosensory awareness has yielded highly diverse findings with putative neural correlates ranging from activity within somatosensory cortex to activation of widely distributed frontoparietal networks. Divergent results from previous studies may reside in cognitive processes that often coincide with stimulus awareness in experimental settings. To scrutinise the specific relevance of regions implied in the target detection network, we used functional magnetic resonance imaging (n = 27) on a novel somatosensory detection task that explicitly controls for stimulus uncertainty, behavioural relevance, overt reports, and motor responses. Using Bayesian Model Selection, we show that responses reflecting target detection are restricted to secondary somatosensory cortex, whereas activity in insular, cingulate, and motor regions is best explained in terms of stimulus uncertainty and overt reports. Our results emphasise the role of sensory-specific cortex for the emergence of perceptual awareness and dissect the contribution of the frontoparietal network to classical detection tasks.

Recent studies suggest that a centro-parietal positivity (CPP) in the EEG signal tracks the absolute (unsigned) strength of accumulated evidence for choices that require the integration of noisy sensory input. Here, we investigated whether the CPP might also reflect the evidence for decisions based on a quantitative comparison between two sequentially presented stimuli (a signed quantity). We recorded EEG while participants decided whether the latter of two vibrotactile frequencies was higher or lower than the former in six variants of this task (n = 116). To account for biases in sequential comparisons, we applied a behavioral model based on Bayesian inference that estimated subjectively perceived frequency differences. Immediately after the second stimulus, parietal ERPs reflected the signed value of subjectively perceived differences and afterwards their absolute value. Strikingly, the modulation by signed difference was evident in trials without any objective evidence for either choice and correlated with choice-selective premotor beta band amplitudes. Modulations by the absolute strength of subjectively perceived evidence – a direct indicator of task difficulty - exhibited all features of statistical decision confidence. Together, our data suggest that parietal EEG signals first index subjective evidence, and later include a measure of confidence in the context of perceptual decision making.

It is a long-standing question in neurolinguistics, to what extent language can have a causal effect on perception. A recent behavioural study reported that participants improved their discrimination ability of Braille-like tactile stimuli after one week of implicit association training with language stimuli being co-presented redundantly with the tactile stimuli. In that experiment subjects were exposed twice a day for 1 h to the joint presentation of tactile stimuli presented to the fingertip and auditorily presented pseudowords. Their discrimination ability improved only for those tactile stimuli that were consistently paired with pseudowords, but not for those that were discordantly paired with different pseudowords. Thereby, a causal effect of verbal labels on tactile perception has been demonstrated under controlled laboratory conditions. This raises the question as to what the neuronal mechanisms underlying this implicit learning effect are. Here, we present fMRI data collected before and after the aforementioned behavioral learning to test for changes in brain connectivity as the underlying mechanism of the observed behavioral effects. The comparison of pre- and post-training revealed a language-driven increase in connectivity strength between auditory and secondary somatosensory cortex and the hippocampus as an association-learning related region.

The analysis of the structural architecture of the human brain in terms of connectivity between its subregions has provided profound insights into its underlying functional organization and has coined the concept of the "connectome", a structural description of the elements forming the human brain and the connections among them. Here, as a proof of concept, we introduce a novel group connectome in standard space based on a large sample of 169 subjects from the Enhanced Nathan Kline Institute-Rockland Sample (eNKI-RS). Whole brain structural connectomes of each subject were estimated with a global tracking approach, and the resulting fiber tracts were warped into standard stereotactic (MNI) space using DARTEL. Employing this group connectome, the results of published tracking studies (i.e., the JHU white matter and Oxford thalamic connectivity atlas) could be largely reproduced directly within MNI space. In a second analysis, a study that examined structural connectivity between regions of a functional network, namely the default mode network, was reproduced. Voxel-wise structural centrality was then calculated and compared to others' findings. Furthermore, including additional resting-state fMRI data from the same subjects, structural and functional connectivity matrices between approximately forty thousand nodes of the brain were calculated. This was done to estimate structure-function agreement indices of voxel-wise whole brain connectivity. Taken together, the combination of a novel whole brain fiber tracking approach and an advanced normalization method led to a group connectome that allowed (at least heuristically) performing fiber tracking directly within MNI space. Such an approach may be used for various purposes like the analysis of structural connectivity and modeling experiments that aim at studying the structure-function relationship of the human connectome. Moreover, it may even represent a first step toward a standard DTI template of the human brain in stereotactic space. The standardized group connectome might thus be a promising new resource to better understand and further analyze the anatomical architecture of the human brain on a population level.

Brain activity in frontal regions has been found to represent frequency information with a parametric code during working memory delay phases. The mental representation of frequencies has furthermore been shown to be modality independent in non-human primate electrophysiology and human EEG studies, suggesting frontal regions encoding quantitative information in a supramodal manner. A recent fMRI study using multivariate pattern analysis (MVPA) supports an overlapping multimodal network for the maintenance of visual and tactile frequency information over frontal and parietal brain regions. The present study extends the investigation of working memory representation of frequency information to the auditory domain. To this aim, we used MVPA on fMRI data recorded during an auditory frequency maintenance task. A support vector regression analysis revealed working memory information in auditory association areas and, consistent with earlier findings of parametric working memory, in a frontoparietal network. A direct comparison to an analogous dataset of vibrotactile parametric working memory revealed an overlap of information coding in prefrontal regions, particularly in the right inferior frontal gyrus. Therefore, our findings indicate that the prefrontal cortex represents frequency-specific working memory content irrespective of the modality as has been now also revealed for the auditory modality.

An important implication of several recent accounts of motor control is that sensory feedback from self-generated movements is relatively attenuated based on predictions issued by the agent's motor system. Such a relative attenuation of sensory information during actions has already been demonstrated in the somatosensory domain. Here, we used functional magnetic resonance imaging (fMRI) and a virtual reality-based setup to investigate a potential attenuation of brain responses to realistic visual movement feedback during active vs. passive right-hand movements. The participants' right unseen hand was rotated either by the participants themselves or by the experimenter, while the participants received visual movement feedback via a photorealistic virtual 3D hand driven by their real hand movements, or received no visual feedback. We observed a significant interaction between movement type (active vs. passive) and movement feedback (vision vs. no vision) in the right superior temporal sulcus (STS), which showed relatively attenuated blood-oxygen-level-dependent (BOLD) signal differences in movements with vs. without visual feedback when those movements were actively vs. passively executed. This finding suggests that STS activity caused by visual feedback from the moving body may be attenuated based on the agent's motor predictions.

Background In clinical practice, analgesic drug doses applied during general anaesthesia are considered sufficient when clinical responses (e.g. movement, blood pressure and heart rate elevations) are suppressed during noxious stimulation. We investigated whether absent clinical responses are indicative of suppressed spinal and brain responsiveness to noxious stimulation in anaesthetised subjects. Methods Ten healthy volunteers were investigated during deep propofol anaesthesia supplemented with increasing doses of remifentanil in a stepwise manner. Noxious electrical stimuli at an intensity comparable with surgical stimulation were repeatedly administered at each targeted remifentanil concentration. During stimulation, we monitored both clinical responses (blood pressure, heart rate, and movement) and neuronal responses. Neuronal responses were assessed using functional magnetic resonance imaging, spinal reflex responses, and somatosensory evoked potentials. Results This monitoring combination was able to faithfully detect brain and spinal neuronal responses to the noxious stimulation. Although clinical responses were no longer detected at analgesic dosages similar to those used for general anaesthesia in clinical practice, spinal and brain neuronal responses were consistently observed. Opioid doses that are significantly larger than is usually used in clinical practice only reduced neuronal responses to 41% of their maximal response. Conclusions Nociceptive activation persists during deep general anaesthesia despite abolished clinical responses. Absent clinical responses are therefore not indicative of absent nociception-specific activation. Thus, commonly accepted clinical responses might be inadequate surrogate markers to assess anti-nociception during general anaesthesia. Further research is required to investigate whether persistent nociception causes adverse effects on patient outcome.

To understand how the brain handles mentally represented information flexibly in the absence of sensory stimulation, working memory (WM) studies have been essential. A seminal finding in monkey research is that neurons in the prefrontal cortex (PFC) retain stimulus-specific information when vibrotactile frequencies were memorized. A direct mapping between monkey studies and human research is still controversial. Although oscillatory signatures, in terms of frequency-dependent parametric beta-band modulation, have been observed recently in human EEG studies, the content specificity of these representations in terms of multivariate pattern analysis has not yet been shown. Here, we used fMRI in combination with multivariate classification techniques to determine which brain regions retain information during WM. In a retro-cue delayed-match-to-sample task, human subjects memorized the frequency of vibrotactile stimulation over a 12 s delay phase. Using an assumption-free whole-brain searchlight approach, we tested with support vector regression which brain regions exhibited multivariate parametric WM codes of the maintained frequencies during the WM delay. Interestingly, our analysis revealed an overlap with regions previously identified in monkeys composed of bilateral premotor cortices, supplementary motor area, and the right inferior frontal gyrus as part of the PFC. Therefore, our results establish a link between the WM codes found in monkeys and those in humans and emphasize the importance of the PFC for information maintenance during WM also in humans.SIGNIFICANCE STATEMENTWorking memory (WM) research in monkeys has identified a network of regions, including prefrontal regions, to code stimulus-specific information when vibrotactile frequencies are memorized. Here, we performed an fMRI study during which human subjects had to memorize vibratory frequencies in parallel to previous monkey research. Using an assumption-free, whole-brain searchlight decoding approach, we identified for the first time regions in the human brain that exhibit multivariate patterns of activity to code the vibratory frequency parametrically during WM. Our results parallel previous monkey findings and show that the supplementary motor area, premotor, and the right prefrontal cortex are involved in vibrotactile WM coding in humans.

An emerging field of human brain imaging deals with the characterization of the connectome, a comprehensive global description of structural and functional connectivity within the human brain. However, the question of how functional and structural connectivity are related has not been fully answered yet. Here, we used different methods to estimate the connectivity between each voxel of the cerebral cortex based on functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data in order to obtain observer-independent functional–structural connectomes of the human brain. Probabilistic fiber-tracking and a novel global fiber-tracking technique were used to measure structural connectivity whereas for functional connectivity, full and partial correlations between each voxel pair's fMRI-timecourses were calculated. For every voxel, two vectors consisting of functional and structural connectivity estimates to all other voxels in the cortex were correlated with each other. In this way, voxels structurally and functionally connected to similar regions within the rest of the brain could be identified. Areas forming parts of the ‘default mode network’ (DMN) showed the highest agreement of structure–function connectivity. Bilateral precuneal and inferior parietal regions were found using all applied techniques, whereas the global tracking algorithm additionally revealed bilateral medial prefrontal cortices and early visual areas. There were no significant differences between the results obtained from full and partial correlations. Our data suggests that the DMN is the functional brain network, which uses the most direct structural connections. Thus, the anatomical profile of the brain seems to shape its functional repertoire and the computation of the whole-brain functional–structural connectome appears to be a valuable method to characterize global brain connectivity within and between populations.

Numerosity can be assessed by analog estimation, similar to a continuous magnitude, or by discrete quantification of the individual items in a set. While the extent to which these two processes rely on common neural mechanisms remains debated, recent studies of sensory working memory (WM) have identified an oscillatory signature of continuous magnitude information, in terms of quantitative modulations of prefrontal upper beta activity (20–30 Hz). Here, we examined how such parametric oscillatory WM activity may also reflect the abstract assessment of the numerosity of discrete items. We recorded EEG while participants (n= 24) processed the number of stimulus pulses presented in the visual, auditory, or tactile modality, under otherwise identical experimental conditions. Behavioral response profiles showed varying degrees of analog estimation and of discretized quantification in the different modalities. During sustained processing in WM, the amplitude of posterior alpha oscillations (8–13 Hz) reflected the increased memory load associated with maintaining larger sets of discrete items. In contrast, earlier numerosity-dependent modulations of right prefrontal upper beta (20–30 Hz) specifically reflected the extent to which numerosity was assessed by analog estimation, both between and within presentation modalities. Together, the analog approximation—but not the discretized representation—of numerosity information exhibited a parametric oscillatory signature akin to a continuous sensory magnitude. The results suggest dissociable oscillatory mechanisms of abstract numerosity integration, at a supramodal processing stage in human WM.

The human motion complex hMT+/V5 is activated not only by visual motion, but also by tactile and auditory motion. Whilst direction-selectivity has been found within this complex for visual and auditory stimuli, it is unknown whether hMT+/V5 also contains direction-specific information from the tactile modality. In the current study, we sought to investigate whether hMT+/V5 contains direction-specific information about visual/tactile moving stimuli. Leftward and rightward moving stimuli were presented in the visual and tactile modalities in an event-related fMRI design. Using region-of-interest-based multivariate pattern analysis we could decode the two motion directions for both tactile and visual stimuli in hMT+/V5. The activity patterns of the two modalities differed significantly, indicating that motion direction information from different modalities may be carried by distinct sets of neuronal populations. Our findings show that hMT+/V5 contains specific information about the direction of a moving stimulus in both the tactile and visual modalities, supporting the theory of hMT+/V5 being a multimodal motion area.

Building on evidence for working memory (WM) coding of vibrotactile frequency information in monkey prefrontal cortex, recent electroencephalography studies found frequency processing in human WM to be reflected by quantitative modulations of prefrontal upper beta activity (20-30 Hz) as a function of the to-be-maintained stimulus attribute. This kind of stimulus-dependent activity has been observed across different sensory modalities, suggesting a generalized role of prefrontal beta during abstract WM processing of quantitative magnitude information. However, until now the available empirical evidence for such quantitative WM representation remains critically limited to the retention of periodic stimulus frequencies. In the present experiment, we used retrospective cueing to examine the quantitative WM processing of stationary (intensity) and temporal (duration) attributes of a previously presented tactile stimulus. We found parametric modulations of prefrontal beta activity during cued WM processing of each type of quantitative information, in a very similar manner as had before been observed only for periodic frequency information. In particular, delayed prefrontal beta modulations systematically reflected the magnitude of the retrospectively selected stimulus attribute and were functionally linked to successful behavioral task performance. Together, these findings converge on a generalized role of stimulus-dependent prefrontal beta-band oscillations during abstract scaling of analog quantity information in human WM.

The brain constructs a flexible representation of the body from multisensory information. Previous work on monkeys suggests that the posterior parietal cortex (PPC) and ventral premotor cortex (PMv) represent the position of the upper limbs based on visual and proprioceptive information. Human experiments on the rubber hand illusion implicate similar regions, but since such experiments rely on additional visuo-tactile interactions, they cannot isolate visuo-proprioceptive integration. Here, we independently manipulated the position (palm or back facing) of passive human participants' unseen arm and of a photorealistic virtual 3D arm. Functional magnetic resonance imaging (fMRI) revealed that matching visual and proprioceptive information about arm position engaged the PPC, PMv, and the body-selective extrastriate body area (EBA); activity in the PMv moreover reflected interindividual differences in congruent arm ownership. Further, the PPC, PMv, and EBA increased their coupling with the primary visual cortex during congruent visuo-proprioceptive position information. These results suggest that human PPC, PMv, and EBA evaluate visual and proprioceptive position information and, under sufficient cross-modal congruence, integrate it into a multisensory representation of the upper limb in space.SIGNIFICANCE STATEMENTThe position of our limbs in space constantly changes, yet the brain manages to represent limb position accurately by combining information from vision and proprioception. Electrophysiological recordings in monkeys have revealed neurons in the posterior parietal and premotor cortices that seem to implement and update such a multisensory limb representation, but this has been difficult to demonstrate in humans. Our fMRI experiment shows that human posterior parietal, premotor, and body-selective visual brain areas respond preferentially to a virtual arm seen in a position corresponding to one's unseen hidden arm, while increasing their communication with regions conveying visual information. These brain areas thus likely integrate visual and proprioceptive information into a flexible multisensory body representation.

The neural mechanisms of stimulus detection, despite extensive research, remain elusive. The recurrent processing hypothesis, a prominent theoretical account of perceptual awareness, states that, although stimuli might in principle evoke feedforward activity propagating through the visual cortex, stimuli that become consciously detected are further processed in feedforward–feedback loops established between cortical areas. To test this theory in the tactile modality, we applied dynamic causal modeling to electroencephalography (EEG) data acquired from humans in a somatosensory detection task. In the analysis of stimulation-induced event-related potentials (ERPs), we focused on model-based evidence for feedforward, feedback, and recurrent processing between primary and secondary somatosensory cortices. Bayesian model comparison revealed that, although early EEG components were well explained by both the feedforward and the recurrent models, the recurrent model outperformed the other models when later EEG segments were analyzed. Within the recurrent model, stimulus detection was characterized by a relatively early strength increase of the feedforward connection from primary to secondary somatosensory cortex (>80 ms). At longer latencies (>140 ms), also the feedback connection showed a detection-related strength increase. The modeling results on relative evidence between recurrent and feedforward model comparison support the hypothesis that the ERP responses from sensory areas arising after aware stimulus detection can be explained by increased recurrent processing within the somatosensory network in the later stages of stimulus processing.

Contralesional dorsal premotor cortex (cPMd) may support residual motor function following stroke. We performed two complementary experiments to explore how cPMd might perform this role in a group of chronic human stroke patients. First, we used paired-coil transcranial magnetic stimulation (TMS) to establish the physiological influence of cPMd on ipsilesional primary motor cortex (iM1) at rest. We found that this influence became less inhibitory/more facilitatory in patients with greater clinical impairment. Second, we applied TMS over cPMd during functional magnetic resonance imaging (fMRI) in these patients to examine the causal influence of cPMd TMS on the whole network of surviving cortical motor areas in either hemisphere and whether these influences changed during affected hand movement. We confirmed that hand grip-related activation in cPMd was greater in more impaired patients. Furthermore, the peak ipsilesional sensorimotor cortex activity shifted posteriorly in more impaired patients. Critical new findings were that concurrent TMS-fMRI results correlated with the level of both clinical impairment and neurophysiological impairment (i.e., less inhibitory/more facilitatory cPMd-iM1 measure at rest as assessed with paired-coil TMS). Specifically, greater clinical and neurophysiological impairment was associated with a stronger facilitatory influence of cPMd TMS on blood oxygenation level-dependent signal in posterior parts of ipsilesional sensorimotor cortex during hand grip, corresponding to the posteriorly shifted sensorimotor activity seen in more impaired patients. cPMd TMS was not found to influence activity in other brain regions in either hemisphere. This state-dependent influence on ipsilesional sensorimotor regions may provide a mechanism by which cPMd supports recovered function after stroke.

Comparisons of sequentially presented vibrotactile frequencies have been extensively studied using electrophysiological recordings in nonhuman primates. Although neural signatures for working memory aspects of such tasks were recently also identified in human oscillatory EEG activity, homologue correlates of the comparison process are yet unknown. Here, we recorded EEG activity while participants decided which of two sequentially presented vibrotactile stimuli had a higher frequency. Because choices in this type of task are known to be systematically biased by the time-order effect, we applied Bayesian modeling to account for individual choice behavior. Using model-based EEG analysis, we found that upper beta band amplitude (∼20–30 Hz) was modulated by participants' choices. The modulation emerged ∼750 msec before a behavioral response was given and was source-localized to premotor areas.Importantly, the choice-dependent modulation of beta band amplitude was invariant to different motor response mappings and reflected the categorical outcome of the subjective comparison between the two frequencies. Consistently, this pattern was evident for both correct and incorrect trials, indicating that the beta band amplitude mirrors the internal representation of the comparison outcome. Our data complement previous findings in nonhuman primates and corroborate that the beta band activity in premotor areas reflects the categorical outcome of a sensory comparison prior to translation into an effector-specific motor command.

During voluntary action, dorsal premotor cortex (PMd) may exert influences on motor regions in both hemispheres, but such inter-regional interactions are not well understood. We used transcranial magnetic stimulation (TMS) concurrently with event-related functional magnetic resonance imaging to study such interactions directly. We tested whether causal influences from left PMd upon contralateral (right) motor areas depend on the current state of the motor system, involving regions engaged in a current task. We applied short bursts (360 ms) of high or low intensity TMS to left PMd, during single isometric left-hand grips or during rest. TMS to left PMd affected activity in contralateral right PMd and primary motor cortex (M1), in a state-dependent manner. During active left-hand grip, high (vs low) intensity TMS led to activity increases in contralateral right PMd and M1, whereas activity decreases there due to TMS were observed during no-grip rest. Analyses of condition-dependent functional coupling confirmed topographically-specific stronger coupling between left PMd with right PMd (and right M1), when high intensity TMS was applied to left PMd during left-hand grip. We conclude that left PMd can exert state-dependent interhemispheric influences on contralateral cortical motor areas relevant for a current motor task.

In humans, touching the skin is known to activate, among others, the contralateral primary somatosensory cortex on the postcentral gyrus together with the bilateral parietal operculum (i.e. the anatomical site of the secondary somatosensory cortex). But which brain regions beyond the postcentral gyrus specifically contribute to the perception of touch remains speculative. In this study we collected structural magnetic resonance imaging scans and neurological examination reports of patients with brain injuries or stroke in the left or right hemisphere, but not in the postcentral gyrus as the entry site of cortical somatosensory processing. Using voxel-based lesion-symptom mapping, we compared patients with impaired touch perception (i.e. hypoaesthesia) to patients without such touch impairments. Patients with hypoaesthesia as compared to control patients differed in one single brain cluster comprising the contralateral parietal operculum together with the anterior and posterior insular cortex, the putamen, as well as subcortical white matter connections reaching ventrally towards prefrontal structures. This finding confirms previous speculations on the 'ventral pathway of somatosensory perception' and causally links these brain structures to the perception of touch.

With congruent stimulation of one's limb together with a fake counterpart, an illusory self-attribution of the fake limb can be induced. Such illusions have brought profound insights into the cognitive and neuronal mechanisms underlying temporary changes in body representation, but to put them in perspective, they need to be compared with ownership as experienced for one's real body. We used functional magnetic resonance imaging (fMRI) to compare the neuronal correlates of touch under different degrees of body ownership. Participants' left and right arms were stimulated either alone or together with a fake counterpart while this stimulation was synchronous, ambiguous or asynchronous. Synchronous stimulation induced illusory fake arm ownership, but the brain still differentiated between touch to one's real arm and to an illusory 'owned' arm: the degree of arm ownership was encoded positively by activity in the ventromedial prefrontal cortex and lateral occipitotemporal cortex and negatively in the temporoparietal cortex. Conversely, the ventral premotor cortex responded more strongly to synchronous stimulation compared with asynchronous stimulation and with real arm only stimulation. These results offer new insights into the differential representation of the real body vs a body that is temporarily self-attributed following the resolution of multisensory conflict.

The Rubber Hand Illusion (RHI) is an established paradigm for studying body ownership, and several studies have implicated premotor and temporo-parietal brain regions in its neuronal foundation. Here we used an automated setup to induce a novel multi-site version of the RHI in healthy human participants inside an MR-scanner, with a RHI and control condition that were matched in terms of synchrony of visual and tactile stimulation. Importantly, as previous research has shown that most of the ownership-related brain areas also respond to observed human actions and touch, or body parts of others, here such potential effects of the experimenter were eliminated by the automated procedure. The RHI condition induced a strong ownership illusion; we found correspondingly stronger brain activity during the RHI versus control condition in contralateral middle occipital gyrus (mOCG) and bilateral anterior insula, which have previously been related to illusory body ownership. Using independent functional localizers, we confirmed that the activity in mOCG was located within the body-part selective extrastriate body area (EBA). Crucially, activity differences in participants' peak voxels within the left EBA correlated strongly positively with their behavioral illusion scores. Thus EBA activity also reflected interindividual differences in the experienced intensity of illusory limb ownership. Moreover, psychophysiological interaction analyses (PPI) revealed that contralateral primary somatosensory cortex had stronger brain connectivity with EBA during the RHI versus control condition, while EBA was more strongly interacting with temporo-parietal multisensory regions. In sum, our findings demonstrate a direct involvement of EBA in limb ownership.

Previous studies of delayed-match-to-sample (DMTS) frequency discrimination in animals and humans have succeeded in delineating the neural signature of frequency processing in somatosensory working memory (WM). During retention of vibrotactile frequencies, stimulus-dependent single-cell and population activity in prefrontal cortex was found to reflect the task-relevant memory content, whereas increases in occipital alpha activity signaled the disengagement of areas not relevant for the tactile task. Here, we recorded EEG from human participants to determine the extent to which these mechanisms can be generalized to frequency retention in the visual and auditory domains. Subjects performed analogous variants of a DMTS frequency discrimination task, with the frequency information presented either visually, auditorily, or by vibrotactile stimulation. Examining oscillatory EEG activity during frequency retention, we found characteristic topographical distributions of alpha power over visual, auditory, and somatosensory cortices, indicating systematic patterns of inhibition and engagement of early sensory areas, depending on stimulus modality. The task-relevant frequency information, in contrast, was found to be represented in right prefrontal cortex, independent of presentation mode. In each of the three modality conditions, parametric modulations of prefrontal upper beta activity (20–30 Hz) emerged, in a very similar manner as recently found in vibrotactile tasks. Together, the findings corroborate a view of parametric WM as supramodal internal scaling of abstract quantity information and suggest strong relevance of previous evidence from vibrotactile work for a more general framework of quantity processing in human working memory.

Accumulating empirical evidence suggests a role of Bayesian inference and learning for shaping neural responses in auditory and visual perception. However, its relevance for somatosensory processing is unclear. In the present study we test the hypothesis that cortical somatosensory processing exhibits dynamics that are consistent with Bayesian accounts of brain function. Specifically, we investigate the cortical encoding of Bayesian surprise, a recently proposed marker of Bayesian perceptual learning, using EEG data recorded from 15 subjects. Capitalizing on a somatosensory mismatch roving paradigm, we performed computational single-trial modeling of evoked somatosensory potentials for the entire peri-stimulus time period in source space. By means of Bayesian model selection, we find that, at 140 ms post-stimulus onset, secondary somatosensory cortex represents Bayesian surprise rather than stimulus change, which is the conventional marker of EEG mismatch responses. In contrast, at 250 ms, right inferior frontal cortex indexes stimulus change. Finally, at 360 ms, our analyses indicate additional perceptual learning attributable to medial cingulate cortex. In summary, the present study provides novel evidence for anatomical-temporal/functional segregation in human somatosensory processing that is consistent with the Bayesian brain hypothesis.

We used functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to study the negative blood oxygenation level dependent (BOLD) signal and its underlying blood flow changes in healthy human subjects. This was combined with psychophysiological measurements to test that the negative BOLD signal is associated with functional inhibition. Electrical stimulation of the median nerve at 7 Hz evoked robust negative BOLD signals in the primary somatosensory cortex (SI) ipsilateral to stimulation, and positive BOLD signals in contralateral SI. The negative BOLD signal in ipsilateral SI was accompanied by commensurate decreases in relative regional cerebral blood flow (rCBF). Conjunction analysis of the fMRI and PET data revealed a region in the ipsilateral postcentral gyrus showing overlap of negative BOLD signals and relative rCBF decreases. The current perception threshold (CPT) at the ipsilateral finger during concomitant stimulation of the contralateral median nerve increased significantly, suggesting augmented functional inhibition. Since the CPT in the ipsilateral hallux did not significantly change in response to median nerve stimulation, it is more likely that the CPT-increase for the finger is due to functional inhibition (Kastrup et al., 2008) than to changes in selective attention. In conclusion, our data provide evidence that stimulus-induced reductions in relative rCBF may underlie the negative BOLD signal, which in turn may reflect increments in functional inhibition.

Processing of motion and pattern has been extensively studied in the visual domain, but much less in the somatosensory system. Here, we used ultra-high-field functional magnetic resonance imaging (fMRI) at 7 Tesla to investigate the neuronal correlates of tactile motion and pattern processing in humans under tightly controlled stimulation conditions. Different types of dynamic stimuli created the sensation of moving or stationary bar patterns during passive touch. Activity in somatosensory cortex was increased during both motion and pattern processing and modulated by motion directionality in primary and secondary somatosensory cortices (SI and SII) as well as by pattern orientation in the anterior intraparietal sulcus. Furthermore, tactile motion and pattern processing induced activity in the middle temporal cortex (hMT+/V5) and in the inferior parietal cortex (IPC), involving parts of the supramarginal und angular gyri. These responses covaried with subjects' individual perceptual performance, suggesting that hMT+/V5 and IPC contribute to conscious perception of specific tactile stimulus features. In addition, an analysis of effective connectivity using psychophysiological interactions (PPI) revealed increased functional coupling between SI and hMT+/V5 during motion processing, as well as between SI and IPC during pattern processing. This connectivity pattern provides evidence for the direct engagement of these specialized cortical areas in tactile processing during somesthesis.

Numerous studies in animals and humans have related central aspects of somatosensory working memory function to neural activity in the inferior frontal gyrus (IFG). However, as previous studies have almost exclusively used correlational analyses, the question whether sustained neural activity in the IFG is causally involved in successful maintenance of somatosensory information remains unanswered. We used an online repetitive transcranial magnetic stimulation (rTMS) protocol to disrupt neuronal activity in the IFG while participants were maintaining tactile information throughout the delay for later comparison against a probe stimulus. rTMS impaired participants' performance in the working memory task, but not in a physically matched perceptual control task. Targeting the IFG in either hemisphere led to comparable working memory impairment. Our results show that the neural activity in the IFG plays a causal role in successful maintenance of somatosensory information.

We used concurrent transcranial magnetic stimulation and functional MRI (TMS-fMRI) during a visuospatial cueing paradigm in humans, to study the causal role of the right angular gyrus (AG) as a source of attentional control. Our findings show that TMS over the right AG (high vs. low intensity) modulates neural responses interhemispherically, in a manner that varies dynamically with the current attentional condition. The behavioural impact of such TMS depended not only on the target hemifield but also on exogenous cue validity, facilitating spatial reorienting to invalidly cued right visual targets. On a neural level, right AG TMS had corresponding interhemispheric effects in the left AG and left retinotopic cortex, including area V1. We conclude that the direction of covert visuospatial attention can involve dynamic interplay between the right AG and remote interconnected regions of the opposite left hemisphere, whereas our findings also suggest that the right AG can influence responses in the retinotopic visual cortex.

Previous animal research has revealed neuronal activity underlying short-term retention of vibrotactile stimuli, providing evidence for a parametric representation of stimulus frequency in primate tactile working memory (Romo et al., 1999). Here, we investigated the neural correlates of vibrotactile frequency processing in human working memory, using noninvasive electroencephalography (EEG). Participants judged the frequencies of vibrotactile stimuli delivered to the fingertip in a delayed match-to-sample frequency discrimination task. As expected, vibrotactile stimulation elicited pronounced steady-state evoked potentials, which were source-localized in primary somatosensory cortex. Furthermore, parametric analysis of induced EEG responses revealed that the frequency of stimulation was reflected by systematic modulations of synchronized oscillatory activity in nonprimary cortical areas. Stimulus processing was accompanied by frequency-dependent alpha-band responses (8–12 Hz) over dorsal occipital cortex. The critical new finding was that, throughout the retention interval, the stimulus frequency held in working memory was systematically represented by a modulation in prefrontal beta activity (20–25 Hz), which was source-localized to the inferior frontal gyrus. This modulation in oscillatory activity during stimulus retention was related to successful frequency discrimination, thus reflecting behaviorally relevant information. Together, the results complement previous findings of parametric working memory correlates in nonhuman primates and suggest that the quantitative representation of vibrotactile frequency in sensory memory entails systematic modulations of synchronized neural activity in human prefrontal cortex.

Do ongoing brain states determine conscious perception of an upcoming stimulus? Using the high temporal resolution of EEG, we investigated the relationship between prestimulus neuronal oscillations and the perceptibility of two competing somatosensory stimuli embedded in a backward masking paradigm. We identified two prestimulus EEG signatures predictive for a suprathreshold yet weak target stimulus to become perceptually resistant against masking by a stronger distractor stimulus: (i) over left frontal cortex a desynchronization of the regional beta rhythm (∼20 Hz) 500 msec prior to a perceived target, and (ii) a subsequent additional attenuation of both mu (∼10 Hz) and beta “idling” rhythms over those pericentral sensorimotor cortices which are going to process the upcoming target stimulus. Furthermore, across subjects the probability for target perception strongly correlates with the individual absolute level of pre-target amplitudes in these frequency bands and locations. These signatures significantly differed from the EEG characteristics preceding detected and undetected single stimuli. We suggest that the early activation of left frontal areas involved in top–down attentional control is critical for preventing backward masking and leads the preparation of primary sensory cortices: The ensuing prestimulus suppression of sensory idling rhythms warrants an intensified poststimulus processing, and thus, effectively promotes conscious perception of suprathreshold target stimuli embedded into an ecologically relevant condition featuring competing environmental stimuli.

Reinforcing effects of reward on action are well established, but possible effects on sensory function are less well explored. Here, using functional magnetic resonance imaging, we assessed whether reward can influence somatosensory judgments and modulate activity in human somatosensory cortex. Participants discriminated electrical somatosensory stimuli on an index finger with correct performance rewarded financially at trial end, at one of four different anticipated levels. Higher rewards improved tactile performance and led to increased hemodynamic signals from ventral striatum on rewarded trials. Remarkably, primary somatosensory cortex contralateral to the judged hand was reactivated at the point of reward delivery, despite the absence of concurrent somatosensory input at that time point. This side-specific reactivation of primary somatosensory cortex increased monotonically with level of reward. Moreover, the level of reward received on a particular trial influenced somatosensory performance and neural activity on the subsequent trial, with better discrimination and enhanced hemodynamic response in contralateral primary somatosensory cortex for trials that followed higher rewards. These results indicate that rewards can influence not only classical reward-related regions, but also early somatosensory cortex when a decision is required for that modality.

We investigated correlates of somatosensory awareness for supratheshold stimuli using event-related potentials in a masking paradigm: Conscious perception of a weak, but suprathreshold ‘‘target’’ stimulus was suppressed in a significant number of trials when followed by a higher-intensity ‘‘mask’’ stimulus. ERPswere compared for trials with perceived versus unperceived target stimuli. Early ERPs (P60, N80), generated in the contralateral S1, were found independent of stimulus perception. In contrast, for consciously perceived target stimuli, amplitude enhancements were observed for the P100 and N140. Thus, early activation of S1 is not sufficient to warrant conscious stimulus perception. Conscious stimulus processing differs significantly from unconscious processing starting around 100 ms after stimulus presentation when the signal is processed in parietal and frontal cortices, brain regions crucial for stimulus access into conscious perception. Descriptors: Perceptualawareness, Somatosensoryevent-relatedpotentials,Masking,Primary somatosensorycortex, Frontoparietal network, Spatial attention

The neural processes underlying tactile decisions in the human brain remain elusive. We addressed this question in a functional magnetic resonance imaging study using a somatosensory discrimination task, requiring participants to compare the frequency of two successive tactile stimuli. Tactile stimuli per se engaged somatosensory, parietal, and frontal cortical regions. Using a statistical model that accounted for the relative difference in frequencies (i.e., Weber fraction) and discrimination accuracy (i.e., correct or incorrect), we show that trial-by-trial relative frequency difference is represented linearly by activity changes in the left dorsolateral prefrontal cortex (DLPFC), the dorsal anterior cingulate cortex, and bilateral anterior insular cortices. However, a circumscribed region within the left DLPFC showed a different response pattern expressed as activity changes that were monotonically related to relative stimulation difference only for correct but not for incorrect trials. Our findings suggest that activity in the left DLPFC encodes stimulus representations that underlie veridical tactile decisions in humans.

Repetitive transcranial magnetic stimulation (rTMS) is an established technique for non-invasive stimulation of human cortex. Although studies have shown an influence of rTMS on single cortical regions and on simple behavioral response patterns, its influences on the dynamics of task-related activity in cortical networks have not been characterized. We provide such a characterization by showing that 5 Hz rTMS over primary somatosensory cortex (SI) induces a reconfiguration of activity patterns in a sensorimotor network, comprising the stimulated region and ipsilateral primary motor cortex (MI). These plastic changes endure for up to 120 min and are correlated with behavioral improvement in discrimination. Dynamic causal modeling showed that this reconfiguration could be explained by an rTMS-induced increase in SI excitability (self-connection) and an increase in the effective connectivity from SI to MI. Thus, our data demonstrate that rTMS can temporarily induce behaviorally relevant reorganization within a complex cortical network underlying human somatosensory experience.

Cortical representations may change when somatosensory input is altered. Here, we investigated the functional consequences of partial ‘‘central’’ deafferentation of the somatosensory cortex due to a lesion of the ventroposterior lateral nucleus (VPL) in patients at a chronic stage after solitary infarction of the thalamus. Event-related functional magnetic resonance imaging during electrical index finger stimulation of the affected and nonaffected side was performed in 6 patients exhibiting contralesional sensory deficits (mainly hypesthesia). Involvement of the VPL and additional nuclei was determined by high-resolution magnetic resonance imaging (MRI) and subsequent MRI-to-atlas coregistration. For the group, statistical parametric maps showed a reduced activation of contralateral primary somatosensory cortex (SI) in response to stimulation of the affected side. However, no significant difference in the activation of contralateral secondary somatosensory cortex (SII) compared with stimulation of the nonaffected side was detected. Correspondingly, the ratio of SII-to-SI activation for the ipsilesional hemisphere was markedly elevated as compared with the contralesional hemisphere. For preserved responsiveness of SII in thalamic stroke comparable with that of the contralesional hemisphere, possible explanations are a direct thalamocortical input to SII mediating parallel information processing, nonlinear response behavior of SII in serial processing, or reorganizational processes that evolved over time.

In the primary somatosensory cortex (SI) of non-human primates, receptive field properties have been shown to differ between its sub-areas with increasing convergence in areas 1 and 2 as compared with area 3b. In this study, we searched for a similar functional organization of human SI. We performed fMRI in healthy subjects during separate or simultaneous electrical stimulation of the second and third finger of the right hand. Activation patterns in response to stimulation of single fingers reflected the somatotopical arrangement within the hand area of SI. Somatotopy was more clear-cut in area 3b as compared with areas 1 and 2. The response to simultaneous stimulation was considerably smaller than the summed responses to separate stimulation of each finger alone, pointing to a suppressive interaction effect. A region-of-interest analysis in the representational areas of the second and third finger revealed sub-area-specific differential suppressive interaction with an increase along the rostral-caudal axis (areas 3b, 1 and 2: 26, 32.7 and 42.2%, respectively). These findings on differences in the topographic as well as functional organization between sub-areas of SI support the notion of increasing convergence and integration from area 3b to areas 1 and 2 in human subjects.

We used simultaneous electroencephalogram-functional magnetic resonance imaging (EEG-fMRI) and EEG-near infrared spectroscopy (NIRS) to investigate whether changes of the posterior EEG alpha rhythm are correlated with changes in local cerebral blood oxygenation. Cross-correlation analysis of slowly fluctuating, spontaneous rhythms in the EEG and the fMRI signal revealed an inverse relationship between alpha activity and the fMRI-blood oxygen level dependent signal in the occipital cortex. The NIRS-EEG measurements demonstrated a positive cross-correlation in occipital cortex between alpha activity and concentration changes of deoxygenated hemoglobin, which peaked at a relative shift of about 8 s. Our data suggest that alpha activity in the occipital cortex is associated with metabolic deactivation. Mapping of spontaneously synchronizing distributed neuronal networks is thus shown to be feasible.

Medial-to-lateral somatotopy is a well-established feature of the human primary somatosensory cortex (SI); however, it is unknown whether, similarly to non-human primates, a rostral-to-caudal somatotopic arrangement exists as well. Therefore, in this functional magnetic resonance imaging (fMRI) study on eight healthy human subjects, five circumscribed skin areas sequentially located on the third finger and the palm of the hand were stimulated with innocuous electrical pulses. Within area 3b of contralateral SI, successive cortical representation sites ordered in a rostral-to-caudal fashion were seen in the group analysis and in six individual subjects. The fingertip was located most rostrally, whereas the proximal parts of the finger as well as the distal palm were represented at more caudal locations. Within area 1, the group analysis revealed a similar pattern of discrete representations. However, in contrast to area 3b, the fingertip was located most caudally, whereas the more proximal parts of the finger were found to be represented rostrally within area 1. Thus, the representation pattern of area 1 appeared as a 'mirror image' of that of area 3b. In comparison to the representations of the finger and the distal palm, the proximal palm was found to be represented at a more medial position of the postcentral gyrus.

In this study, the feasibility of dipole source localization (DSL) and coregistration with functional magnetic resonance imaging (fMRI) activation patterns on the basis of simultaneously acquired data is demonstrated. Brain activity was mapped during the performance of a somatosensory single reaction and a choice reaction task at high spatiotemporal resolution in six healthy subjects. The choice reaction task required a categorization of two different stimulus intensities, whereas for the single reaction task merely the perception of a tactile stimulus had to be confirmed by the subjects. An offline artifact correction algorithm was applied to 32-channel EEG data that were acquired between subsequent MRI scans. Using a multiple dipole approach, five distinct dipole sources were identified within areas of the somatosensory system. Coregistration of fMRI and DSL showed consistent spatial activation patterns with a mean distance of 9.2 +/- 6.8 mm between dipole sources and fMRI activation maxima. However, since the number of fMRI activation sites exceeded the number of cerebral dipole sources, it was not possible to assign a dipole source to each fMRI activation site. Dipole moment time courses were consistent with previously reported results of similar experiments. A comparison of brain activation patterns during the two tasks with both fMRI and DSL indicated an involvement of the contralateral secondary somatosensory cortex in somatosensory categorization.

Cortical signal intensity changes due to brief (1 s) innocuous electrical stimuli applied to the second and fifth finger of the right hand were measured by means of fMRI at 1.5 T. The activation pattern in this event-related fMRI approach closely resembled that obtained in recent block-design studies. Activations were found in contralateral primary (SI) and bilaterally in secondary (SII) somato-sensory cortex as well as in posterior parietal cortex, insula, and supplementary motor area (SMA). In SI, the somatotopic organization of the hand area is demonstrated, more clearly to be seen in area 3b than in area 1 and 2. In conclusion, the feasibility to employ event-related somatosensory stimulation paradigms in fMRI studies is demonstrated.

Summary Actions are guided by prior sensory information [1–10], which is inherently uncertain. However, how the motor system is sculpted by trial-by-trial content of current sensory information remains largely unexplored. Previous work suggests that conditional probabilities, learned under a particular context, can be used preemptively to influence the output of the motor system [11–14]. To test this we used transcranial magnetic stimulation (TMS) to read out corticospinal excitability (CSE) during preparation for action in an instructed delay task [15, 16]. We systematically varied the uncertainty about an impending action by changing the validity of the instructive visual cue. We used two information-theoretic quantities to predict changes in CSE, prior to action, on a trial-by-trial basis: entropy (average uncertainty) and surprise (the stimulus-bound information conveyed by a visual cue) [17–19]. Our data show that during preparation for action, human CSE varies according to the entropy and surprise conveyed by visual events guiding action. CSE increases on trials with low entropy about the impending action and low surprise conveyed by an event. Commensurate effects were observed in reaction times. We suggest that motor output is biased according to contextual probabilities that are represented dynamically in the brain.