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.     

Cortical activation associated with passive movements of the human index finger: an MEG study

We recorded somatosensory evoked fields to passive extensions of the left and right index fingers in eight healthy adults. A new nonmagnetic device was designed to produce calibrated extensions of 19 degrees, with a mean angular velocity of 630 degrees/s. The responses, recorded with a 306-channel neuromagnetometer, were modeled with current dipoles. The earliest activation was in the primary somatosensory cortex, with peaks at 36-58 and 30-82 ms for left and right index finger extensions, respectively. Later signals were observed in the left second somatosensory (SII) cortex in six of eight subjects at 75-175 and 75-155 ms for left- and right-sided extensions, respectively; three subjects showed bilateral SII activation in at least one condition. Our results suggest a predominant role for the human left SII cortex in proprioceptive processing.     

Differentiation of somatosensory cortices by high-resolution fMRI at 7 T

This study aimed to evaluate the ability of BOLD signals at high MRI field (7 T) to map fine-scale single-digit activations in subdivisions (areas 3b and 1) of the human primary somatosensory cortex (SI) in individual subjects. We acquired BOLD fMRI data from cortical areas around the central suclus in six healthy human subjects while stimulating individual finger pads with 2-Hz air puffs. Discrete, single-digit responses were identified in an area along the posterior bank of the central sulcus corresponding to area 3b and in an area along the crest of the postcentral gyrus corresponding to area 1. In single subjects, activations of digits 1 to 4 in both areas 3b and 1 were organized in a somatotopic manner. The separation of digit representations was measured for adjacent digits and was approximately 1.6 times greater in area 3b than in area 1. Within individual subjects, the cortical responses to single-digit stimulations and the magnitude of the BOLD signals were reproducible across imaging runs and were comparable across subjects. Our findings demonstrate that BOLD fMRI at 7 T is capable of revealing the somatotopic organization of single-digit activations with good within-subject reliability and reproducibility, and activation maps can be acquired within a reasonably short time window, which are essential characteristics for several neurological applications within patient populations.     

Somatosensory Homunculus as Drawn by MEG

We studied a detailed somatosensory representation map of the human primary somatosensory cortex using magnetoencephalography. Somatosensory-evoked magnetic fields following tactile stimulation of multiple points in the right hemibody (including the tongue, lips, fingers, arm, trunk, leg, and foot) were analyzed in five normal subjects. We were able to estimate equivalent current dipoles (ECDs) following stimulation of the tongue, lips, fingers, palm, forearm, elbow, upper arm, and toes in most subjects and those following the stimulation of the chest, ankle, and thigh in one subject. The ECDs were located in the postcentral gyrus and generally arranged in order along the central sulcus, which is compatible with the somatosensory “homunculus.” Linear distances, averaged in five subjects, from the receptive area of the thumb to that of the tongue, little finger, forearm, upper arm, and toes were estimated to be 2.42 ± 0.28, 1.25 ± 0.28, 2.21 ± 0.72, 2.75 ± 0.63, and 5.29 ± 0.48 cm, respectively. The moment of each ECD, which suggested the size of the cortical areas responsive to the stimulation, was also compatible with the bizarre proportion of the homunculus with a large tongue, lips, and fingers. According to these results, we were able to reproduce a large part of the somatosensory homunculus quantitatively on an individual brain MRI.     

Functional organization of primary somatosensory cortex depends on the focus of attention

We used magnetic source imaging in human subjects to reveal within-subject variations of the homuncular hand representation within the primary somatosensory cortex modulated by attention. In one condition subjects were trained to detect sequential leftward or rightward stimulus motion across the fingers of the left hand ("hand" condition) and in a different condition to detect stimulus motion at a specific finger on this hand ("finger" condition). Afferent input was controlled by applying exactly the same stimulus pattern to the digits in the two tasks. Segregation of the somatotopic hand representation (an increase in the distance between the representations of digits 2 and 5) was observed, commencing with the onset of practice, in the finger relative to the hand condition. Subsequent training in the hand and finger conditions with feedback for correctness did not modify segregation, indicating that segregation was a task effect and not a training effect. These findings indicate that the hand representation within the primary somatosensory cortex is not statically fixed but is dynamically modulated by top-down mechanisms to support task requirements. A greater capacity for modulation of the functional cortical organization was positively correlated with superior learning and task performance.     

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.     

Distal-to-proximal representation of volar index finger in human area 3b

In area 3b of the monkey primary somatosensory cortex SI, the proximal phalanges of the fingers are represented close to the surface and the fingertips in the depth of the central sulcus. To study whether a similar arrangement might exist in humans, we applied tactile stimuli to the distal and proximal phalanges of the index finger in 11 healthy adults. Cortical somatosensory evoked fields were recorded with a whole-scalp neuromagnetometer. The sources of the responses were situated in the posterior wall of the central sulcus, statistically significantly more superior to proximal than distal stimuli, with a mean difference of 3.1 mm. Thus the distal-to-proximal representation of the index finger shows a similar order in human and monkey SI cortex.     

Finger Somatotopy in Human Motor Cortex

Although qualitative reports about somatotopic representation of fingers in the human motor cortex exist, up to now no study could provide clear statistical evidence. The goal of the present study was to reinvestigate finger motor somatotopy by means of a thorough investigation of standardized movements of the index and little finger of the right hand. Using high resolution fMRI at 3 Tesla, blood oxygenation level-dependent (BOLD) responses in a group of 26 subjects were repeatedly measured to achieve reliable statistical results. The center of mass of all activated voxels within the primary motor cortex was calculated for each finger and each run. Results of all runs were averaged to yield an individual index and little finger representation for each subject. The mean center of mass localizations for all subjects were then submitted to a paired t test. Results show a highly significant though small scale somatotopy of fingerspecific activation patterns in the order indicated by Penfields motor homunculus. In addition, considerable overlap of finger specific BOLD responses was found. Comparing various methods of analysis, the mean center of mass distance for the two fingers was 2–3 mm with overlapping voxels included and 4–5 mm with overlapping voxels excluded. Our data may be best understood in the context of the work of Schieber (1999) who recently described overlapping somatotopic gradients in lesion studies with humans.     

Somatosensory activation of two fingers can be discriminated with ultrahigh-density diffuse optical tomography

Topographic non-invasive near infrared spectroscopy (NIRS) has become a well-established tool for functional brain imaging. Applying up to 100 optodes over the head of a subject, allows achieving a spatial resolution in the centimeter range. This resolution is poor compared to other functional imaging tools.However, recently it was shown that diffuse optical tomography (DOT) as an extension of NIRS based on high-density (HD) probe arrays and supplemented by an advanced image reconstruction procedure allows describing activation patterns with a spatial resolution in the millimeter range. Building on these findings, we hypothesize that HD-DOT may render very focal activations accessible which would be missed by the traditionally used sparse arrays.We examined activation patterns in the primary somatosensory cortex, since its somatotopic organization is very fine-grained. We performed a vibrotactile stimulation study of the first and fifth finger in eight human subjects, using a 900-channel continuous-wave DOT imaging system for achieving a higher resolution than conventional topographic NIRS. To compare the results to a well-established high-resolution imaging technique, the same paradigm was investigated in the same subjects by means of functional magnetic resonance imaging (fMRI).In this work, we tested the advantage of ultrahigh-density probe arrays and show that highly focal activations would be missed by classical next-nearest neighbor NIRS approach, but also by DOT, when using a sparse probe array. Distinct activation patterns for both fingers correlated well with the expected neuroanatomy in five of eight subjects. Additionally we show that activation for different fingers is projected to different tissue depths in the DOT image. Comparison to the fMRI data yielded similar activation foci in seven out of ten finger representations in these five subjects when comparing the lateral localization of DOT and fMRI results.     

Somatosensory dynamic gamma-band synchrony: a neural code of sensorimotor dexterity

To investigate neural coding characteristics in the human primary somatosensory cortex, two fingers with different levels of functional skill were studied. Their dexterity was scored by the Fingertip writing test. Each finger was separately provided by a passive simple sensory stimulation and the responsiveness of each finger cortical representation was studied by a novel source extraction method applied to magnetoencephalographic signals recorded in a 14 healthy right handed subject cohort. In the two hemispheres, neural oscillatory activity synchronization was analysed in the three characteristic alpha, beta and gamma frequency bands by two dynamic measures, one isolating the phase locking between neural network components, the other reflecting the total number of synchronous recruited neurons. In the dominant hemisphere, the gamma band phase locking was higher for the thumb than for the little finger and it correlated with the contra-lateral finger dexterity. Neither in the dominant nor in the non-dominant hemisphere, any effect was observed in the alpha and beta bands. In the gamma band, the amplitude showed similar tendency to the phase locking, without reaching statistical significance. These findings suggest the dynamic gamma band phase locking as a code for finger dexterity, in addition to the magnification of somatotopic central maps.     

应用脑磁图对人脑初级体感皮质功能定位的研究

目的　通过脑磁图确定脑初级体感皮质的位置。方法　对 16名右利手健康受试者腕部正中神经进行电刺激 ,引起支配手的脑初级感觉皮质兴奋 ,脑初级感觉皮质的兴奋产生微弱的颅外磁场 ,用脑磁图机对这个微弱的颅外磁场进行测量。脑磁图检查后 ,受试者进行MRI检查 ,扫描序列为SE序列 ,矢状T1WI。结果　所有受试者均出现M 2 0波峰及M 3 5波峰 ,只有 2例出现明显的M 60波峰。将同一受试者M 2 0波峰及M 3 5波峰的等电流偶极与MRI叠加 ,即可明确显示手区初级体感皮质在左、右侧半球的位置。同一受试者M 2 0偶极位置与相应半球的M 3 5偶极位置相近。结论　将脑磁图获得的脑电生理学资料与MRI获得的解剖学资料叠加到一起所得到的磁源性影像可准确地确定脑的手区初级体感皮质的位置。     

Functional representation of the finger and face in the human somatosensory cortex: intraoperative intrinsic optical imaging

We applied the intrinsic optical imaging technique to the human primary somatosensory cortex during brain tumor/epilepsy surgery for nine patients. The cortical surface was illuminated with a Xenon light through an operating microscope, and the reflected light, which passed through a 605 nm bandpass filter, was detected by a CCD camera-based optical imaging system. Individual electrical stimulation of five digits induced changes in the reflected light intensities. Visualizing the intrinsic optical responses, we constructed maps of finger representation in Brodmann's area 1. In the maps, response areas of Digits I to V were sequentially aligned along the central sulcus in the crown of the postcentral gyrus from the latero-inferior region (Digit I) to the medio-superior region (Digit V). The neighboring response areas partially overlapped each other, as previously described in the monkey somatosensory cortex. Similar results were obtained in the face region with stimulation of the three branches of the trigeminal nerve. These results suggest that the overlap of the response areas is a common feature in the somatosensory cortex not only in monkeys, but also in humans.     

The role of higher-order motor areas in voluntary movement as revealed by high-resolution EEG and fMRI

In the human motor cortex structural and functional differences separate motor areas related to motor output from areas essentially involved in higher-order motor control. Little is known about the function of these higher-order motor areas during simple voluntary movement. We examined a simple finger flexion movement in six healthy subjects using a novel brain-imaging approach, integrating high-resolution EEG with the individual structural and functional MRI. Electrical source reconstruction was performed in respect to the individual brain morphology from MRI. Highly converging results from EEG and fMRI were obtained for both executive and higher-order motor areas. All subjects showed activation of the primary motor area (MI) and of the frontal medial wall motor areas. Two different types of medial wall activation were observed with both methods: Four of the subjects showed an anterior type of activation, and two of the subjects a posterior type of activation. In the former, activity started in the anterior cingulate motor area (CMA) and subsequently shifted its focus to the intermediate supplementary motor area (SMA). Approximately 120 ms before the movement started, the intermediate SMA showed a drop of source strength, and simultaneously MI showed an increase of source strength. In the posterior type, activation was restricted to the posterior SMA. Further, three of the subjects investigated showed activation in the inferior parietal lobe (IPL) starting during early movement preparation. In all subjects showing activation of higher-order motor areas (anterior CMA, intermediate SMA, IPL) these areas became active before the executive motor areas (MI and posterior SMA). We suggest that the early activation of the anterior CMA and the IPL may be related to attentional functions of these areas. Further, we argue that the intermediate part of the SMA triggers the actual motor act via the release of inhibition of the primary motor area. Our results demonstrate that a noninvasive, multimodal brain imaging technique can reveal individual cortical brain activity with high temporal and spatial resolution, independent of a priori physiological assumptions.     

Inhibitory impact of subliminal electrical finger stimulation on SI representation and perceptual sensitivity of an adjacent finger

Simultaneous stimulation of two adjacent fingers above sensory perception threshold (supraliminal stimulation) leads to an inhibitory interaction effect on responses in primary somatosensory cortex (SI). Moreover, during electrical finger stimulation closely below threshold for conscious perception (subliminal stimulation) inhibitory interneurons in cortical layer 4 are assumed to be activated preferentially as compared to excitatory interneurons. Using fMRI in humans, here we show that interspersed subliminal electrical stimulation of an adjacent finger reduces the response to target finger stimulation in contralateral SI. This effect was shown in a complementary study to be associated behaviorally with a diminished detectability of test pulses on the target finger. We propose the mechanism underlying this lateral inhibitory effect to be related to a representational overlap of inhibitory interneurons in SI based on the divergence of thalamocortical feedforward projections, or to intracortical lateral inhibitory projections targeting juxtaposed receptive fields, or both.     

3D mapping of somatotopic reorganization with small animal functional MRI

There are few in vivo noninvasive methods to study neuroplasticity in animal brains. Functional MRI (fMRI) has been developed for animal brain mapping, but few fMRI studies have analyzed functional alteration due to plasticity in animal models. One major limitation is that fMRI maps are characterized by statistical parametric mapping making the apparent boundary dependent on the statistical threshold used. Here, we developed a method to characterize the location of center-of-mass in fMRI maps that is shown not to be sensitive to statistical threshold. Utilizing centers-of-mass as anchor points to fit the spatial distribution of the BOLD response enabled quantitative group analysis of altered boundaries of functional somatosensory maps. This approach was used to study cortical reorganization in the rat primary somatosensory cortex (S1) after sensory deprivation to the barrel cortex by follicle ablation (F.A.). FMRI demonstrated an enlarged nose S1 representation in the 3D somatotopic functional maps. This result clearly demonstrates that fMRI enables the spatial mapping of functional changes that can characterize multiple regions of S1 cortex and still be sensitive to changes due to plasticity.     

The event-related optical signal to electrical stimulation of the median nerve

The event-related optical signal (EROS) uses near-infrared light to study changes in neuronal optical properties in response to stimuli and endogenous events. EROS responses to electrical stimulation of the median nerve at 1, 5, and 8 Hz were collected from 80 channels in 7 subjects. Optical recording channels were spatially aligned by co-registering the digitized fiber locations with structural magnetic resonance images (MRI) for each subject separately. The co-registered data sets were then transformed into Talairach space to permit alignment across subjects. After alignment, data from channels underlying pixels of a surface projection were combined to produce maps of Z statistics. Waveforms associated with voxels within an a priori region of interest (ROI) over the hand area of primary somatosensory (SI) cortex were compared across the three stimulus frequencies. Reliable early increases in light propagation time (i.e., increased phase delay) were found in SI as early as 16-32 ms of poststimulus for all three frequency conditions, and both an increase in phase delay and a decrease in signal intensity were observed over SI at longer latencies. A split-half analysis of the 8 Hz condition demonstrated the replicability of the response. This represents the first direct comparison of intensity and delay measures of these components of the somatosensory response; further, it shows that these early cortical components are replicable across subjects and correspond well to individual subjects' anatomical landmarks for SI.     

Functional motor-cortex mapping using corticokinematic coherence

We present a novel method, corticokinematic coherence (CKC), for functional mapping of the motor cortex by computing coherence between cortical magnetoencephalographic (MEG) signals and the kinematics of voluntary movements. Ten subjects performed self-paced flexion-extensions of the right-hand fingers at about 3 Hz, with a three-axis accelerometer attached to the index finger. Cross-correlogram and coherence spectra were computed between 306 MEG channels and the accelerometer signals. In all subjects, accelerometer and coherence spectra showed peaks around 3-5 Hz and 6-10 Hz, corresponding to the movement frequencies. The coherence was statistically significant (P<0.05) in all subjects, with sources at the hand area of the primary motor cortex contralateral to the movement. CKC appears to be a promising and robust method for reliable and convenient functional mapping of the human motor cortex.     

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.     

High-resolution mapping of discrete representational areas in rat somatosensory cortex using blood volume-dependent functional MRI

The present study documents the use of an iron oxide-based blood-pool contrast agent in functional magnetic resonance imaging to monitor activity-related changes in cerebral blood volume (CBV) resulting from peripheral sensory stimulation and the application of this technique to generate high-resolution functional maps. Rats, anesthetized with alpha-chloralose, were imaged during electrical stimulation (3 ms, 3 Hz, 3 V) of forelimb or hindlimb. Activation maps were generated by cross-correlation of the measured signal response and a square-wave function representative of the stimulus for each image pixel. Multislice imaging produced functional maps consistent with the known functional anatomy of rat primary somatosensory (S-I) cortex. Imaging with improved temporal resolution demonstrated rapid (<6 s) CBV increases which were sustained and relatively stable (coefficient of variation = 0.17 +/- 0.02) for forelimb stimulation periods of up to 5 min. Enabled by this sustained response we generated high-resolution (approximately 100 micrometer in-plane) functional maps showing discrete forelimb and hindlimb activation. This technique offers many advantages over other methods for the study of brain activity in the rat and has resolution sufficient to be useful in reorganization studies.     

Alteration in the response properties of primary somatosensory cortex related to differential aversive Pavlovian conditioning

The effects of differential aversive Pavlovian conditioning on the functional organization of primary somatosensory cortex (SI) were examined in 17 healthy participants. Neuroelectric source imaging from 60 electrodes was employed while nine subjects received an innocuous electric stimulus (conditioned stimulus, CS) to one finger (left or right) that was followed by painful electric shock to the lower back (unconditioned stimulus, US) and an innocuous stimulus to the other finger that was never followed by pain. Eight subjects received a presentation of the innocuous and painful stimuli with equal probability to both fingers (control group). The data included the electromyogram (EMG) from the left m. corrugator, and judgments of intensity, aversiveness, and CS-US contingency. Only the experimental group displayed EMG conditioning, differential contingency judgments, as well as a change of dipole orientation for the CS and an enhanced dipole moment for the US in the electroencephalogram. Intensity and unpleasantness ratings were altered in a more unspecific manner and did not differ between groups and stimulus conditions. The data suggest that SI contributes to memory processes in associative learning. Pavlovian conditioning of tactile responses might be important in the altered processing of painful stimuli in chronic pain patients where enhanced conditioning has been demonstrated.