Functional mapping of pain-related activation with echo-planar MRI: significance of the SII-insular region

Activation in numerous regions of the brain is likely to be involved in the complex neural network function of pain perception. To detect the cortical representation during nonpainful and painful stimuli, which were presented using electrical finger stimulation in six normal right-handed male volunteers, we performed echo-planar functional magnetic resonance imaging (fMRI). Using a 1.5-T MR system that scanned the supratentorial region of the brain, we obtained multislice BOLD-based functional MR images with single-shot gradient-echo echo-planar imaging (EPI). The data show that dispersed brain regions are activated during painful stimulation, and especially demonstrate the significance of the SII-insular region in pain perception.     

Acute plasticity in the human somatosensory cortex following amputation

We studied a patient after amputation of an arm and found that in less than 24 h stimuli applied on the ipsilateral face were referred in a precise, topographically organized, modality-specific manner to distinct points on the phantom. Functional magnetic resonance imaging (fMRI) performed one month later showed that brush-evoked activity in the brain demonstrates objective signal changes which correlate with perceptual changes in the phantom hand. This finding in humans corresponds to the observations of immediate plasticity in cortical pathways described in animals, including primates. The results suggest that reorganization of sensory pathways occurs very soon after amputation in humans, potentially due to the unmasking of ordinarily silent inputs rather than sprouting of new axon terminals.     

Parcellation of the human prefrontal cortex using MRI

NMR spectroscopy and NMR imaging with magnetic field gradients make strange bedfellows, the requirements for one seemingly ruling out the other for human applications. Nevertheless, their stories are intertwined; the advent of high field imaging systems arose because of the desire for human spectroscopy. Localized spectroscopy is possible because of NMR imaging. Both have links to physics at Nottingham, at least in the personalized account that follows. Today, virtually all NMR spectroscopy experiments can be conceived with a localized in vivo spectroscopy counterpart.     

EEG evidence of stimulus-directed response dynamics in human somatosensory cortex

Dense multichannel recordings of scalp electroencephalogram (EEG) were obtained in the vicinity of primary somatosensory cortex, time-locked to repetitive vibrotactile stimulation of sites on the right index finger of a single human subject. Frequency-domain analysis of cross-trial averages revealed prominent 'driving' responses in the EEG at the frequency of stimulation, which under specific stimulus conditions displayed pronounced changes in amplitude and topographic organization over brief (4 s) durations of stimulus exposure. The changes were systematic and physiologically coherent, evolving toward driving-response topographies observed in the same subject in conjunction with periodic microstimulation of single mechanoreceptive afferents whose receptive fields occupied corresponding positions on the digit. This dynamic process was orderly and reproducible, and could be controlled by manipulating factors such as the amplitude, frequency, and temporal spacing of the stimuli. The results are tentatively interpreted in light of a previously proposed neurophysiological model of stimulus-driven response plasticity in mammalian somatosensory cortex.     

Activation of human mesial cortex during somatosensory target detection task

We recorded somatosensory evoked fields (SEFs) from 10 healthy subjects to ulnar and median nerve stimuli presented at random intervals of 2.4-21.6 s. The subjects either counted the stimuli or ignored them by reading a book. The stimuli activated in both conditions the contralateral SI cortex, the ipsi- and contralateral SII cortices, and the posterior parietal cortex (PPC), in line with earlier observations. In addition, a novel response was observed in nine subjects at 120-160 ms. It was clearly enhanced by attention and was generated in the mesial cortex of the paracentral lobule, close to the end of the central sulcus.     

Pain affect encoded in human anterior cingulate but not somatosensory cortex

Recent evidence demonstrating multiple regions of human cerebral cortex activated by pain has prompted speculation about their individual contributions to this complex experience. To differentiate cortical areas involved in pain affect, hypnotic suggestions were used to alter selectively the unpleasantness of noxious stimuli, without changing the perceived intensity. Positron emission tomography revealed significant changes in pain-evoked activity within anterior cingulate cortex, consistent with the encoding of perceived unpleasantness, whereas primary somatosensory cortex activation was unaltered. These findings provide direct experimental evidence in humans linking frontal-lobe limbic activity with pain affect, as originally suggested by early clinical lesion studies.     

Non-invasive functional mapping of the human motor cortex using near-infrared spectroscopy

We applied non-invasive multisite near-infrared spectroscopy (NIRS) to assess oxygenation changes during performance of a sequential finger opposition task in five healthy human adults. Oxygenation response was localized anatomically using three-dimensional high-resolution magnetic resonance imaging (3D MRI). NIRS measurements showed a localized increase in [oxy-Hb] and a decrease in [deoxy-Hb] in all subjects. The largest response was obtained when the measurement position was over the primary motor and sensory cortex hand area. Interestingly, changes in [deoxy-Hb] seemed to be more localized than changes in [oxy-Hb]. We conclude that this simple, non-invasive and flexible optical bedside method may be used for functional brain mapping.     

Interaction of finger representation in the human first somatosensory cortex: a neuromagnetic study

The authors studied immunologic features of saliva in 1714 workers exposed to vibration and other occupational hazards in microbiologic, chemical enterprises. The examinees demonstrated lower activity of lysozyme and concentrations of IgA, higher levels of IgG. Immunologic features of saliva was proved to have extreme diagnostic importance, therefore could be used to detect early signs of exposure to occupational hazards and to diagnose pathologic conditions caused by those hazards.     

The somatosensory cortex of human: cytoarchitecture and regional distributions of receptor-binding sites

Engineering degradation tests allow industry to assess the potential life span of long-life products that do not fail readily under accelerated conditions in life tests. A general statistical model is presented here for performance degradation of an item of equipment. The degradation process in the model is taken to be a Wiener diffusion process with a time scale transformation. The model incorporates Arrhenius extrapolation for high stress testing. The lifetime of an item is defined as the time until performance deteriorates to a specified failure threshold. The model can be used to predict the lifetime of an item or the extent of degradation of an item at a specified future time. Inference methods for the model parameters, based on accelerated degradation test data, are presented. The model and inference methods are illustrated with a case application involving self-regulating heating cables. The paper also discusses a number of practical issues encountered in applications.     

Interhemispheric connections of somatosensory cortex in the flying fox

The interhemispheric connections of somatosensory cortex in the gray-headed flying fox (Pteropus poliocephalus) were examined. Injections of anatomical tracers were placed into five electrophysiologically identified somatosensory areas: the primary somatosensory area (SI or area 3b), the anterior parietal areas 3a and 1/2, and the lateral somatosensory areas SII (the secondary somatosensory area) and PV (pairetal ventral area). In two animals, the hemisphere opposite to that containing the injection sites was explored electrophysiologically to allow the details of the topography of interconnections to be assessed. Examination of the areal distribution of labeled cell bodies and/or axon terminals in cortex sectioned tangential to the pial surface revealed several consistent findings. First, the density of connections varied as a function of the body part representation injected. For example, the area 3b representation of the trunk and structures of the face are more densely interconnected than the representation of distal body parts (e.g., digit 1, D1). Second, callosal connections appear to be both matched and mismatched to the body part representations injected in the opposite hemisphere. For example, an injection of retrograde tracer into the trunk representation of area 3b revealed connections from the trunk representation in the opposite hemisphere, as well as from shoulder and forelimb/wing representations. Third, the same body part is differentially connected in different fields via the corpus callosum. For example, the D1 representation in area 3b in one hemisphere had no connections with the area 3b D1 representation in the opposite hemisphere, whereas the D1 representation in area 1/2 had relatively dense reciprocal connections with area 1/2 in the opposite hemisphere. Finally, there are callosal projections to fields other than the homotopic, contralateral field. For example, the D1 representation in area 1/2 projects to contralateral area 1/2, and also to area 3b and SII.     

Mechanisms of directed attention in the human extrastriate cortex as revealed by functional MRI

A typical scene contains many different objects, but the capacity of the visual system to process multiple stimuli at a given time is limited. Thus, attentional mechanisms are required to select relevant objects from among the many objects competing for visual processing. Evidence from functional magnetic resonance imaging (MRI) in humans showed that when multiple stimuli are present simultaneously in the visual field, their cortical representations within the object recognition pathway interact in a competitive, suppressive fashion. Directing attention to one of the stimuli counteracts the suppressive influence of nearby stimuli. This mechanism may serve to filter out irrelevant information in cluttered visual scenes.     

Brain functional MRI of the visual cortex with echo planar imaging

Brain functional MR imaging (fMRI) is a non invasive imaging method for detecting neural activity. We performed functional MRI of the visual cortex with gradient-echo echo planar imaging (GE-EPI) and spin-echo EPI (SE-EPI) using 1.5T MRI system. Visual stimuli was performed with a checkerboard patterns. Magnitude and temporal phase of correlation between each pixel's time-course and sine functions at the frequency of the stimulus was calculated. In all subjects, the activation area in visual cortex obtained from SE-EPI was smaller than that from GE-EPI. Temporal phase delay images from both GE-EPI and SE-EPI showed signal spread from the primary visual cortex to peripheral supplementary areas. Temporal phase analysis is important to discriminate the source of the hemodynamic response to neural activation in fMRI.     

Networks with lateral connectivity. III. Plasticity and reorganization of somatosensory cortex

1. Mechanisms underlying cortical reorganizations were studied using a three-layered neural network model with neuronal groups already formed in the cortical layer. 2. Dynamic changes induced in cortex by behavioral training or intracortical microstimulation (ICMS) were simulated. Both manipulations resulted in reassembly of neuronal groups and formation of stimulus-dependent assemblies. Receptive fields of neurons and cortical representation of inputs also changed. Many neurons that had been weakly responsive or silent became active. 3. Several types of learning models were examined in simulating behavioral training, ICMS-induced dynamic changes, deafferentation, or cortical lesion. Each learning model most accurately reproduced features of experimental data from different manipulations, suggesting that more than one plasticity mechanism might be able to induce dynamic changes in cortex. 4. After skin or cortical stimulation ceased, as spontaneous activity continued, the stimulus-dependent assemblies gradually reverted into structure-dependent neuronal groups. However, relationships among individual neurons and identities of many neurons did not return to their original states. Thus a different set of neurons would be recruited by the same training stimulus sequence on its next presentation. 5. We also reproduced several typical long-term reorganizations caused by pathological manipulations such as cortical lesions, input loss, and digit fusion. 6. In summary, with Hebbian plasticity rules on lateral connections, the network model is capable of reproducing most characteristics of experiments on cortical reorganization. We propose that an important mechanism underlying cortical plastic changes is formation of temporary assemblies that are related to receipt of strongly synchronized localized input. Such stimulus-dependent assemblies can be dissolved by spontaneous activity after removal of the stimuli.     

Localization of functional regions of human mesial cortex by somatosensory evoked potential recording and by cortical stimulation

Previous studies have shown that characteristics of posttraumatic temporomandibular disorders (pTMD) differ considerably from those of nontraumatic or idiopathic temporomandibular disorders (iTMD). Both the rate of recovery and the amount of treatment required appear to be different for both groups. In this blinded study, 14 patients with iTMD and 13 patients with pTMD were examined. Patients submitted to a variety of reaction-time tests and neuropsychologic assessments to test their ability to cope with simple and more complex tasks with and without a variety of cognitive interferences. Clinical examination was used to assess signs of TMD. Eleven of the subjects (six iTMD, five pTMD) consented to a second phase of the investigation, whereby the patients were studied with single-photon emission computerized tomography (SPECT) using 99mTc-hexamethylpropyleneamineoxime (HMPAO). For simple and complex reaction-time tests, the pTMD group was significantly slower than the iTMD group (P < .05 to P < .001). Other neuropsychologic assessment tools such as the Consonant Trigram Test and the California Verbal Learning Test indicated that pTMD patients were more affected by both proactive and retroactive interferences and were more likely to perseverate on a single thought. In clinical examination, pTMD patients demonstrated greater reaction to muscle palpation than did iTMD patients (P < .05). The SPECT results suggested that there were mild differences between the two populations, and further ther studies are required to confirm this finding. The results lend support to the concept that there are differences between pTMD and iTMD populations. It is suggested that although patients with pTMD may have some similarities to those with iTMD, the former population may benefit from being handled somewhat differently and should be assessed and treated using a more broad, multidisciplinary treatment paradigm. These results must be confirmed in studies of larger populations.     

Somatotopy in the human motor cortex hand area. A high-resolution functional MRI study

Fine-scale somatotopic encoding in brain areas devoted to sensorimotor processing has recently been questioned by functional neuroimaging studies which suggested its absence within the hand area of the human primary motor cortex. We re-examined this issue by addressing somatotopy both in terms of functional segregation and of cortical response preference using oxygenation-sensitive magnetic resonance imaging at high spatial resolution. In a first step, spatial representations of self-paced isolated finger movements were mapped by using motor rest as a control state. A subsequent experimental design studied the predominance of individual finger movements by using contrasting finger movements as the control task. While the first approach confirmed previous reports of extensive overlap in spatial representations, the second approach revealed foci of differential activation which displayed an orderly mediolateral progression in accordance with the classical cortical motor homunculus. We conclude that somatotopy within the hand area of the primary motor cortex does not present as qualitative functional segregation but as quantitative predominance of certain movement or digit representation embedded in an overall joint hand area.     

Functional MRI reveals spatially specific attentional modulation in human primary visual cortex

Selective visual attention can strongly influence perceptual processing, even for apparently low-level visual stimuli. Although it is largely accepted that attention modulates neural activity in extrastriate visual cortex, the extent to which attention operates in the first cortical stage, striate visual cortex (area V1), remains controversial. Here, functional MRI was used at high field strength (3 T) to study humans during attentionally demanding visual discriminations. Similar, robust attentional modulations were observed in both striate and extrastriate cortical areas. Functional mapping of cortical retinotopy demonstrates that attentional modulations were spatially specific, enhancing responses to attended stimuli and suppressing responses when attention was directed elsewhere. The spatial pattern of modulation reveals a complex attentional window that is consistent with object-based attention but is inconsistent with a simple attentional spotlight. These data suggest that neural processing in V1 is not governed simply by sensory stimulation, but, like extrastriate regions, V1 can be strongly and specifically influenced by attention.     

Single-cell correlates of a representational boundary in rat somatosensory cortex

In primary somatosensory cortex (S1), the transition from one representation to the next is typically abrupt when assayed physiologically. However, the extent of anatomical projections to and within the cortex do not strictly respect these physiologically defined transitions. Physiological properties, such as synaptic strengths or intracortical inhibition, have been hypothesized to account for the functionally defined precision of these representational borders. Because these representational borders can be translocated across the cortex by manipulations or behaviors that change the activity patterns of inputs to the cortex, understanding the physiological mechanisms that delimit representations is also an important starting point for understanding cortical plasticity. A novel in vivo and in vitro preparation has been developed to examine the cellular and synaptic mechanisms that underlie representational borders in the rat. In vivo, a short segment of the border between the forepaw-lower jaw representations in rat S1 was mapped using standard electrophysiological methods and was visibly marked using iontophoresis of pontamine sky blue dye. Slices were then obtained from this marked region and maintained in vitro. Intracellularly recorded responses to electrical stimulation of supragranular cortex were obtained from single neurons near the border in response to stimulation within the representational zone or across the border. Both excitatory and inhibitory responses were smaller when evoked by stimuli that activated projections that crossed borders, as compared with stimuli to projections that did not. These findings indicate that intracortical network properties are contributing to the expressions of representational discontinuities in the cortex.     

Development of the barrels and barrel field in the somatosensory cortex of the mouse

Barrels of the PMBSF of the mouse somatosensory cortex become apparent in Nissl-stained tangential sections simultaneously, on the fourth postnatal day. At this time they are miniatures of those in the adult and are situated in the deepest sublamina of the trilaminar cortical plate. An early barrel appears as a patch of decreased cell density: the prospective hollow of the barrel. Septa become noticeable during the sixth postnatal day. From that period to adulthood, the relative contribution of the PMBSF to the total cortical surface area increases -- an increase that goes against one's expectation: the barrel related periphery matures very early and so does the central, lateral region of the cortex. Barrel growth parallel to the pial surface is greater along the major axes than along the minor axes. By using the barrels to identify prospective layer IV in immature cortex, we could determine that layers V and VI attain their adult height during the sixth postnatal day -- an age when prospective layers I-IV are only half their adult height. The onset of barrel formation coincides with the moment after which injury to the pertinent somatosensory periphery (the vibrissal papillae) no longer causes profound alterations in barrel morphology.     

Fuzzy clustering of gradient-echo functional MRI in the human visual cortex. Part I: reproducibility

Reproducibility of human functional MRI (fMRI) studies is essential for clinical and neuroresearch applications of this new human brain mapping method. Based on a recently presented study on reproducibility of gradient-echo fMRI in the human visual cortex (Moser et al. Magn Reson Imaging 1996; 14:567-579), comparing the performance of three different threshold strategies for correlation analysis, we demonstrate that (a) fuzzy clustering is a robust, model-independent method to extract functional information in time and space; (b) intertrial reproducibility of cortical activation is significantly improved by the capability of fuzzy clustering to separate signal contributions from larger vessels, running perpendicular to the slice orientation, from activation apparently close to the primary visual cortex; and (c) for repeated single subject studies, SDs of <20% for signal enhancement in approximately 80% of the studies and SDs of <30% for activated area size in approximately 65% of the studies are obtained. This, however, depends also on signal-to-noise ratio, (motion) artifacts, and subject cooperation.