Dynamic shifts in the organization of primary somatosensory cortex induced by bimanual spatial coupling of motor activity

Previous work has shown that training and learning can induce powerful changes in the homuncular organization of the primary somatosensory cortex (SI). Moreover, a number of studies suggest the existence of short-term adaptation of representational maps in SI. Recently, motor activity has been shown to induce rapid modulation of somatosensory cortical maps. It is hypothesized that there is a task-related influence of motor and premotor areas upon the organization of somatosensory cortex. In order to test this hypothesis, we studied the functional organization of somatosensory cortex by examining coupling effects in a bimanual movement task. Bimanual coupling is known to be related to an activation of the premotor cortex and the supplementary motor area. The functional organization of the somatosensory cortex for known bimanual coupling effects was compared to the organization of the somatosensory cortex during the same movements but with only a small effort in coupling. Topography of the functional organization of the somatosensory cortex was assessed using neuromagnetic source imaging based on tactile stimulation of the first (D1) and fifth digit (D5). We could show that the cortical representations of D1 and D5 moved further apart during the bimanual coupling task in comparison to the same task without coupling and rest. Our data suggest that somatosensory cortical maps undergo fast and dynamic modulation as a result of a task-related influence of motor or premotor areas.     

Attention to action: specific modulation of corticocortical interactions in humans

The prefrontal cortex may exert cognitive control by a general mechanism of attentional selection of neuronal representations. We used functional magnetic resonance imaging to test this hypothesis in the motor system. Normal volunteers were scanned during performance of a simple motor task, with their attention either directed towards their actions, or diverted towards a visual search task, or neither. Attention to action increased activity in prefrontal, premotor and parietal cortex, compared with unattended performance of the same movements. Analysis of cortical activity by structural equation modelling of regional fMRI time series was used to measure effective connectivity among prefrontal, premotor and parietal cortices. Attention to action enhanced effective connectivity between dorsal prefrontal cortex and premotor cortex, whereas non-motor attention diminished it. These effects were not attributable to common inputs from parietal cortex to the prefrontal and premotor cortex. The results suggest a supra-modal role for the dorsal prefrontal cortex in attentional selection, operating within the motor system as well as sensory and mnemonic domains.     

Multi-task functional MRI in multiple sclerosis patients without clinical disability

While the majority of individuals with multiple sclerosis (MS) develop significant clinical disability, a subset experiences a disease course with minimal impairment even in the presence of significant apparent tissue damage on magnetic resonance imaging (MRI). Functional magnetic resonance imaging (fMRI) in MS patients with low disability suggests that increased use of the cognitive control system may limit the clinical manifestation of the disease. The current fMRI studies tested the hypothesis that nondisabled MS patients show increased recruitment of cognitive control regions while performing sensory, motor and cognitive tasks. Twenty two patients with relapsing-remitting MS and an Expanded Disability Status Scale (EDSS) score of ≤ 1.5 and 23 matched healthy controls were recruited. Subjects underwent fMRI while observing flashing checkerboards, performing right or left hand movements, or executing the 2-back working memory task. Compared to control subjects, patients demonstrated increased activation of the right dorsolateral prefrontal cortex and anterior cingulate cortex during the performance of the working memory task. This pattern of functional recruitment also was observed during the performance of non-dominant hand movements. These results support the mounting evidence of increased functional recruitment of cognitive control regions in the working memory system of MS patients with low disability and provide new evidence for the role of increased cognitive control recruitment in the motor system.     

Task-specific plasticity of somatosensory cortex in patients with writer's cramp

Focal dystonias such as writer's cramp are characterized by muscular cramps that accompany the execution of specific motor tasks. Until now, the pathophysiology of focal dystonia remains incompletely understood. Recent studies suggest that the development of writer's cramp is related to abnormal organization of primary somatosensory cortex (SI), which in turn leads to impaired motor function. To explore contributions of SI on mechanisms of task specificity in focal dystonia, we investigated dynamic alterations in the functional organization of SI as well as sensory-motor gating for rest, left- and right-handed writing and brushing in writer's cramp patients and healthy controls. The functional organization of somatosensory cortex was assessed by neuromagnetic source imaging (151 channel whole-head MEG). In accordance with previous reports, distances between cortical representations of thumb and little finger of the affected hand were smaller in patients compared to healthy subjects. However, similar to healthy controls, patients showed normal modulation of the functional organization of SI as induced by the execution of different motor tasks. Both in the control subjects and patients, cortical distances between representations of thumb and little finger increased when writing and brushing compared to the resting condition. Although, cramps only occured during writing, no differences in the organization of SI were seen among motor tasks. Our data suggest that despite alterations in the organization of primary somatosensory cortex in writer's cramp, the capability of SI to adapt dynamically to different tasks is not impaired.     

Category-specific activations during word generation reflect experiential sensorimotor modalities

According to the sensorimotor theory of lexicosemantic organization, semantic representations are neurally distributed and anatomically linked to category-specific sensory areas. Previous functional neuroimaging studies have demonstrated category specificity in lexicosemantic representations. However, little evidence is available from word generation paradigms, which provide access to semantic representations while minimizing confounds resulting from low-level perceptual features of stimulus presentation. In this study, 13 healthy young adults underwent fMRI scanning while performing a word generation task, generating exemplars to nine different semantic categories. Each semantic category was assigned to one of three superordinate category types, based upon sensorimotor modalities (visual, motor, somatosensory) presumed to predominate in lexical acquisition. For word generation overall, robust activation was seen in left inferior frontal cortex. Analyses by sensorimotor modality categories yielded activations in brain regions related to perceptual and motor processing: Visual categories activated extrastriate cortex, motor categories activated the intraparietal sulcus and posterior middle temporal cortex, and somatosensory categories activated postcentral and inferior parietal regions. Our results are consistent with the sensorimotor theory, according to which lexicosemantic representations are distributed across brain regions participating in sensorimotor processing associated with the experiential components of lexicosemantic acquisition.     

Information processing in human parieto-frontal circuits during goal-directed bimanual movements

It is known that, in macaques, movements guided by somatosensory information engage anterior parietal and posterior precentral regions. Movements performed with both visual and somatosensory feedback additionally activate posterior parietal and anterior precentral areas. It remains unclear whether the human parieto-frontal circuits exhibit a similar functional organization. Here, we employed a directional interference task requiring a continuous update of sensory information for the on-line control of movement direction, while brain activity was measured by functional magnetic resonance imaging (fMRI). Directional interference arises when bimanual movements occur along different directions in joint space. Under these circumstances, the presence of visual information does not substantially alter performance, such that we could vary the amount and type of sensory information used during on-line guidance of goal-directed movements without affecting motor output. Our results confirmed that in humans, as in macaques, movements guided by somatosensory information engages anterior parietal and posterior precentral regions, while movements performed with both visual and somatosensory information activate posterior parietal and anterior precentral areas. We provide novel evidence on how the interaction of specific portions of the dorsal parietal and precentral cortex in the right hemisphere might generate spatial representations by integrating different sensory modalities during goal-directed movements.     

The neural correlates and functional integration of cognitive control in a Stroop task

It is well known that performance on a given trial of a cognitive task is affected by the nature of previous trials. For example, conflict effects on interference tasks, such as the Stroop task, are reduced subsequent to high-conflict trials relative to low-conflict trials. This interaction effect between previous and current trial types is called "conflict adaptation" and thought to be due to processing adjustments in cognitive control. The current study aimed to identify the neural substrates of cognitive control during conflict adaptation by isolating neural correlates of reduced conflict from those of increased cognitive control. We expected cognitive control to be implemented by prefrontal cortex through context-specific modulation of posterior regions involved in sensory and motor aspects of task performance. We collected event-related fMRI data on a color-word naming Stroop task and found distinct fronto-parietal networks of current trial conflict detection and conflict adaptation through cognitive control. Conflict adaptation was associated with increased activity in left middle frontal gyrus (GFm) and superior frontal gyrus (GFs), consistent with increased cognitive control, and with decreased activity in bilateral prefrontal and parietal cortices, consistent with reduced response conflict. Psychophysiological interaction analysis (PPI) revealed that cognitive control activation in GFs and GFm was accompanied by increased functional integration with bilateral inferior frontal, right temporal and parietal areas, and the anterior cerebellum. These data suggest that cognitive control is implemented by medial and lateral prefrontal cortices that bias processes in regions that have been implicated in high-level perceptual and motor processes.     

Preparatory activity and connectivity in dorsal anterior cingulate cortex for cognitive control

Dorsal anterior cingulate cortex (dACC) is composed of functionally distinct subregions that may contribute to the top-down control of response selection and preparation. Multiple motor areas have been identified in dACC, including an anterior zone implicated in conflict monitoring and a caudal zone involved in movement execution. This study tested the involvement of a third cingulate area, the posterior zone of dACC, in the top-down control of response selection and preparation. Sixteen healthy young adults were scanned with event-related functional magnetic resonance imaging while performing a cued go/no-go task that was designed to minimize response conflicts. The activation and functional connectivity of dACC were tested with standard convolution models and psychophysiological interaction analyses, respectively. Ready cues that informed the direction of the impending response triggered preparatory neural activity in the posterior zone of dACC and strengthened functional connectivity with the anterior and caudal zones of dACC, as well as perigenual anterior cingulate cortex, frontal operculum, dorsolateral prefrontal cortex, sensory association cortices, and extra-pyramidal motor areas. The preparatory cues activated dACC above and beyond the general arousing effects common to cues despite negligible conflict in the go/no-go task. The integration of cognitive, sensorimotor, and incentive signals in dACC places the region in an ideal position to select and prepare appropriate behavioral responses to achieve higher-level goals.     

Task-relevant modulation of contralateral and ipsilateral primary somatosensory cortex and the role of a prefrontal-cortical sensory gating system.

Electrophysiological studies have shown that task-relevant somatosensory information leads to selective facilitation within the primary somatosensory cortex (SI). The purpose of the present study was (1) to further explore the relationship between the relevancy of stimuli and activation within the contralateral and ipsilateral SI and (2) to provide further insight into the specific sensory gating network responsible for modulating neural activity within SI. Functional MRI of 12 normal subjects was performed with vibrotactile stimuli presented to the pad of the index finger. In experiment 1, the stimulus was presented to either the left or the right hand. Subjects were required to detect transient changes in stimulus frequency. In experiment 2, stimuli were presented to either the right hand alone or both hands simultaneously. Stimuli were applied either (A) passively or (B) when subjects were asked to detect frequency changes that occurred to the right hand only. In experiment 1, task-relevant somatosensory stimulation led not only to enhanced contralateral SI activity, but also to a suppression of activity in the ipsilateral SI. In experiment 2, SI activation was enhanced when stimuli were task-relevant, compared to that observed with passive input. When stimuli were presented simultaneously to both hands, only those that were task-relevant increased SI activation. This was associated with recruitment of a network of cortical regions, including the right prefrontal cortex (Brodmann area 9). We conclude that SI modulation is dependent on task relevancy and that this modulation may be regulated, at least in part, by the prefrontal cortex.     

A regulation role of the prefrontal cortex in the fist-edge-palm task: evidence from functional connectivity analysis

The Fist-Edge-Palm (FEP) task is a motor sequencing task that is widely used in neurological examination. Deficits in this task are believed to reflect impairment in the frontal lobe regions. However, two recent functional brain imaging studies of the FEP task using conventional subtraction analysis failed to demonstrate FEP-induced activation in the prefrontal cortex (PFC), which contradicts existing neuropsychological literature. In this study, psychophysiological interaction (PPI) analysis was used to reanalyze our previous neuroimaging dataset from 10 healthy subjects in order to evaluate the changes of functional connectivity between the sensorimotor cortex and the prefrontal regions during the performances of the FEP task relative to simple motor control tasks. The PPI analysis revealed significantly increased functional connectivity between bilateral sensorimotor cortex and the right inferior and middle frontal cortex during the performance of the FEP task compared with the control tasks. However, regional signal changes showed no significant activation differences in these prefrontal regions. These results provide evidence supporting the involvement of the frontal lobe in the performance of the FEP task, and suggest a role of regulation, rather than direct participation, of the prefrontal cortex in the execution of complex motor sequence tasks such as the FEP task.     

fMRI investigation of unexpected somatosensory feedback perturbation during speech

Somatosensory feedback plays a critical role in the coordination of articulator movements for speech production. In response to unexpected resistance to lip or jaw movements during speech, fluent speakers can use the difference between the somatosensory expectations of a speech sound and the actual somatosensory feedback to adjust the trajectories of functionally relevant but unimpeded articulators. In an effort to investigate the neural substrates underlying the somatosensory feedback control of speech, we used an event-related sparse sampling functional magnetic resonance imaging paradigm and a novel pneumatic device that unpredictably blocked subjects' jaw movements. In comparison to speech, perturbed speech, in which jaw perturbation prompted the generation of compensatory speech motor commands, demonstrated increased effects in bilateral ventral motor cortex, right-lateralized anterior supramarginal gyrus, inferior frontal gyrus pars triangularis and ventral premotor cortex, and bilateral inferior posterior cerebellum (lobule VIII). Structural equation modeling revealed a significant increased influence from left anterior supramarginal gyrus to right anterior supramarginal gyrus and from left anterior supramarginal gyrus to right ventral premotor cortex as well as a significant increased reciprocal influence between right ventral premotor cortex and right ventral motor cortex and right anterior supramarginal gyrus and right inferior frontal gyrus pars triangularis for perturbed speech relative to speech. These results suggest that bilateral anterior supramarginal gyrus, right inferior frontal gyrus pars triangularis, right ventral premotor and motor cortices are functionally coupled and influence speech motor output when somatosensory feedback is unexpectedly perturbed during speech production.     

Frontostriatal system in planning complexity: a parametric functional magnetic resonance version of Tower of London task

In the present study, we sought to investigate which brain structures are recruited in planning tasks of increasing complexity. For this purpose, a parametric self-paced pseudo-randomized event-related functional MRI version of the Tower of London task was designed. We tested 22 healthy subjects, enabling assessment of imaging results at a second (random effects) level of analysis. Compared with baseline, planning activity was correlated with increased blood oxygenation level-dependent (BOLD) signal in the dorsolateral prefrontal cortex, striatum, premotor cortex, supplementary motor area, and visuospatial system (precuneus and inferior parietal cortex). Task load was associated with increased activity in these same regions. In addition, increasing task complexity was correlated with activity in the left anterior prefrontal cortex, a region supposed to be specifically involved in third-order higher cognitive functioning.     

Mapping motor inhibition: conjunctive brain activations across different versions of go/no-go and stop tasks

Conjunction analysis methods were used in functional magnetic resonance imaging to investigate brain regions commonly activated in subjects performing different versions of go/no-go and stop tasks, differing in probability of inhibitory signals and/or contrast conditions. Generic brain activation maps highlighted brain regions commonly activated in (a) two different go/no-go task versions, (b) three different stop task versions, and (c) all 5 inhibition task versions. Comparison between the generic activation maps of stop and go/no-go task versions revealed inhibitory mechanisms specific to go/no-go or stop task performance in 15 healthy, right-handed, male adults. In the go/no-go task a motor response had to be selectively executed or inhibited in either 50% or 30% of trials. In the stop task, the motor response to a go-stimulus had to be retracted on either 50 or 30% of trials, indicated by a stop signal, shortly (250 ms) following the go-stimulus. The shared "inhibitory" neurocognitive network by all inhibition tasks comprised mesial, medial, and inferior frontal and parietal cortices. Generic activation of the go/no-go task versions identified bilateral, but more predominantly left hemispheric mesial, medial, and inferior frontal and parietal cortices. Common activation to all stop task versions was in predominantly right hemispheric anterior cingulate, supplementary motor area, inferior prefrontal, and parietal cortices. On direct comparison between generic stop and go/no-go activation maps increased BOLD signal was observed in left hemispheric dorsolateral prefrontal, medial, and parietal cortices during the go/no-go task, presumably reflecting a left frontoparietal specialization for response selection.     

fMRI reflects functional connectivity of human somatosensory cortex

Unilateral sensory stimulation reliably elicits contralateral somatotopic activation of primary (SI) and secondary (SII) somatosensory cortex. There is an ongoing debate about the occurrence and nature of concomitant ipsilateral SI and SII activation. Here we used functional magnetic resonance imaging (fMRI) in healthy human subjects with unilateral tactile stimulation of fingers and lips, to compare somatosensory activation patterns from distal and proximal body parts. We hypothesized that fMRI in humans should reflect the functional connectivity of somatosensory cortex as predicted by animal studies. We show that both unilateral finger and lip stimulations activate contra- and ipsilateral SI and SII cortices with high detection frequency. Correlations of BOLD-signals to the applied hemodynamic reference function were significantly higher in contralateral as compared to ipsilateral SI and SII cortices for both finger and lip stimulation, reflecting strong contribution of contralateral thalamocortical input. Furthermore, BOLD-signal correlations were higher in SI than in SII activations on the contralateral but not on the ipsilateral side. While these asymmetries within and across hemispheres were consistent for finger and lip stimulations, indicating analogous underlying organizing principles, they were less prominent for lip stimulation. Somatotopic organization was detected in SI but not in SII representations of fingers and lips. These results qualitatively and quantitatively support the prevalent concepts of anatomical and functional connectivity in the somatosensory system and therefore may allow interpretation of sensory evoked fMRI signals in terms of normal human brain function. Thus, the assessment of human somatosensory function with fMRI may permit in the future investigations of pathological conditions.     

Cortical networks subserving upper limb movements in primates

In all primates, the cortical control of hand and arm movements is initiated and controlled by a network of cortical regions including primary motor cortex (M1), premotor cortex (PMC), and posterior parietal cortex (PPC). These interconnected regions are influenced by inputs from especially visual and somatosensory cortical areas, and prefrontal cortex. Here we discuss recent evidence showing M1, PMC, and PPC can be subdivided into a number of functional zones or domains, including several that participate in guiding and controlling hand and arm movements. Functional zones can be defined by the movement sequences evoked by microstimulation within them, and functional zones related to the same type of movement in all three cortical regions are interconnected. The inactivation of a functional zone in each of the regions has a different impact on motor behavior. Finally, there is considerable plasticity within the networks so that behavioral recoveries can occur after damage to functional zones within a network.     

Fingertip Representation in the Human Somatosensory Cortex: An fMRI Study

Eight right-handed adult humans underwent functional magnetic resonance imaging (fMRI) of their brain while a vibratory stimulus was applied to an individual digit tip (digit 1, 2, or 5) on the right hand. Multislice echoplanar imaging techniques were utilized during digit stimulation to investigate the organization of the human primary somatosensory (SI) cortex, cortical regions located on the upper bank of the Sylvian fissure (SII region), insula, and posterior parietal cortices. Thettest and cluster size analyses were performed to produce cortical activation maps, which exhibited significant regions of interest (ROIs) in all four cortical regions investigated. The frequency of significant ROIs was much higher in SI and the SII region than in the insula and posterior parietal region. Multiple digit representations were observed in the primary somatosensory cortex, corresponding to the four anatomic subdivisions of this cortex (areas 3a, 3b, 1, and 2), suggesting that the organization of the human somatosensory cortex resembles that described in other primates. Overall, there was no simple medial to lateral somatotopic representation in individual subject activity maps. However, the spatial distance between digit 1 and digit 5 cortical representations was the greatest in both SI and the SII region within the group. Statistical analyses of multiple activity parameters showed significant differences between cortical regions and between digits, indicating that vibrotactile activations of the cortex are dependent on both the stimulated digit and cortical region investigated.     

Pain-related cerebral activation is altered by a distracting cognitive task

It has previously been suggested that the activity in sensory regions of the brain can be modulated by attentional mechanisms during parallel cognitive processing. To investigate whether such attention-related modulations are present in the processing of pain, the regional cerebral blood flow was measured using [(15)O]butanol and positron emission tomography in conditions involving both pain and parallel cognitive demands. The painful stimulus consisted of the standard cold pressor test and the cognitive task was a computerised perceptual maze test. The activations during the maze test reproduced findings in previous studies of the same cognitive task. The cold pressor test evoked significant activity in the contralateral S1, and bilaterally in the somatosensory association areas (including S2), the ACC and the mid-insula. The activity in the somatosensory association areas and periaqueductal gray/midbrain were significantly modified, i.e. relatively decreased, when the subjects also were performing the maze task. The altered activity was accompanied with significantly lower ratings of pain during the cognitive task. In contrast, lateral orbitofrontal regions showed a relative increase of activity during pain combined with the maze task as compared to only pain, which suggests the possibility of the involvement of frontal cortex in modulation of regions processing pain.     

Functional MRI BOLD response to Tower of London performance of first-episode schizophrenia patients using cortical pattern matching

Due to its three-dimensional folding pattern, the human neocortex poses a challenge for accurate co-registration of grouped functional brain imaging data. The present study addressed this problem by employing three-dimensional continuum-mechanical image-warping techniques to derive average anatomical representations for co-registration of functional magnetic resonance brain imaging data obtained from 10 male first-episode schizophrenia patients and 10 age-matched male healthy volunteers while they performed a version of the Tower of London task. This novel technique produced an equivalent representation of blood oxygenation level dependent (BOLD) response across hemispheres, cortical regions, and groups, respectively, when compared to intensity average co-registration, using a deformable Brodmann area atlas as anatomical reference. Somewhat closer association of Brodmann area boundaries with primary visual and auditory areas was evident using the gyral pattern average model. Statistically-thresholded BOLD cluster data confirmed predominantly bilateral prefrontal and parietal, right frontal and dorsolateral prefrontal, and left occipital activation in healthy subjects, while patients' hemispheric dominance pattern was diminished or reversed, particularly decreasing cortical BOLD response with increasing task difficulty in the right superior temporal gyrus. Reduced regional gray matter thickness correlated with reduced left-hemispheric prefrontal/frontal and bilateral parietal BOLD activation in patients. This is the first study demonstrating that reduction of regional gray matter in first-episode schizophrenia patients is associated with impaired brain function when performing the Tower of London task, and supports previous findings of impaired executive attention and working memory in schizophrenia.     

The sensory somatotopic map of the human hand demonstrated at 4 Tesla.

Recent attempts at high-resolution sensory-stimulated fMRI performed at 1.5 T have had very limited success at demonstrating a somatotopic organization for individual digits. Our purpose was to determine if functional MRI at 4 T can demonstrate the sensory somatotopic map of the human hand. Sensory functional MRI was performed at 4 T in five normal volunteers using a low-frequency vibratory stimulus on the pad of each finger of the left hand. A simple motor control task was also performed. The data were normalized to a standard atlas, and individual and group statistical parametric maps (SPMs) were computed for each task. Volume of activation and distribution of cluster maxima were compared for each task. For three of the subjects, the SPMs demonstrated a somatotopic organization of the sensory cortex. The group SPMs demonstrated a clear somatotopic organization of the sensory cortex. The thumb to fifth finger were organized, in general, with a lateral to medial, inferior to superior, and anterior to posterior relationship. There was overlap in the individual SPMs between fingers. The sensory activation spanned a space of 12-18 mm (thumb to fifth finger) on the primary sensory cortex. The motor activation occurred consistently at the superior-most extent of the sensory activation within and across subjects. The sensory somatotopic map of the human hand can be identified at 4 T. High-resolution imaging at 4 T can be useful for detailed functional imaging studies.     

Morphing the body: illusory feeling of an elongated arm affects somatosensory homunculus

Recent studies suggest that in contrast to traditional views of the body map the topographic representation in primary somatosensory cortex (SI) reflects the perceived rather than the physical aspects of peripheral stimulation. Here, we created a simple illusion of feeling an elongated arm by using the dominance of the visual domain over the tactile sense: employing an artificial hand and arm, which were connected to the body, subjects were given the visual impression that they had an extended arm. Since it is known from animal studies that tactile illusions alter early sensory processing in SI, we expected a modulation of the topography in SI corresponding to this illusion. Behavioral results showed that during the illusion the participants felt that their arm was elongated. Neuromagnetic source imaging of the functional organization in SI revealed that the cortical distance between first (D1) and fifth digit (D5) decreased when subjects felt the arm elongated. Since this modulation was significantly positively correlated with the illusionary feeling of an extended arm, the results suggest an involvement of SI during perceived changes in the size of body parts. We discuss the results as possible top-down modulations of SI by higher order somatosensory areas.