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Brain processing during mechanical hyperalgesia in complex regional pain syndrome: a functional MRI study.

Complex Regional Pain Syndromes (CRPS) are characterized by a triad of sensory, motor and autonomic dysfunctions of still unknown origin. Pain and mechanical hyperalgesia are hallmarks of CRPS. There are several lines of evidence that central nervous system (CNS) changes are crucial for the development and maintenance of mechanical hyperalgesia. However, little is known about the cortical structures associated with the processing of hyperalgesia in pain patients. This study describes the use of functional magnetic resonance imaging (fMRI) to delineate brain activations during pin-prick hyperalgesia in CRPS. Twelve patients, in whom previous quantitative sensory testing revealed the presence of hyperalgesia to punctuate mechanical stimuli (i.e. pin-prick hyperalgesia), were included in the study. Pin-prick-hyperalgesia was elicited by von-Frey filaments at the affected limb. For control, the identical stimulation was performed on the unaffected limb. fMRI was used to explore the corresponding cortical activations. Mechanical stimulation at the unaffected limb was non-painful and mainly led to an activation of the contralateral primary somatosensory cortex (S1), insula and bilateral secondary somatosensory cortices (S2). The stimulation of the affected limb was painful (mechanical hyperalgesia) and led to a significantly increased activation of the S1 cortex (contralateral), S2 (bilateral), insula (bilateral), associative-somatosensory cortices (contralateral), frontal cortices and parts of the anterior cingulate cortex. The results of our study indicate a complex cortical network activated during pin-prick hyperalgesia in CRPS. The underlying neuronal matrix comprises areas not only involved in nociceptive, but also in cognitive and motor processing.

Adult↗

Functional MRI statistical software packages: a comparative analysis.

Currently, there are many choices of software packages for the analysis of fMRI data, each offering many options. Since no one package can meet the needs of all fMRI laboratories, it is helpful to know what each package offers. Several software programs were evaluated for comparison of their documentation, ease of learning and use, referencing, data input steps required, types of statistical methods offered, and output choices. The functionality of each package was detailed and discussed. AFNI 2.01, SPM96, Stimulate 5.0, MEDIMAX 2.01, and FIT were tested. FIASCO, Yale, and MEDx 2.0 were described but not tested. A description of each package is provided.

Algorithms↗

Functional MRI changes before and after onset of reported emotions.

The social nature of emotion is evident in the importance of facial and vocal displays in emotion-related behavior. This is the first brain-imaging study to use simulated face-to-face social interactions to evoke emotional responses and to compare valence-related activations before and after subjective onset of emotional response. Videotapes were prepared with actresses who described happy or unhappy experiences. Functional magnetic resonance imaging (fMRI) at 1.5 T was used to acquire BOLD images in 21 healthy young adults before, after, and during viewing of the happy and sad tapes. Subjects pushed buttons to indicate the onset of subjective emotional responses. Group data were analyzed by a bootstrap randomization method after anatomical normalization. Significant activation was detected in frontal and sensory regions prior to the reported onset of emotional response, and this activity showed a marked decrease after the report of conscious emotional experience. Significant differences between happy and sad conditions were evident in multiple brain regions both before and after the reported onset of emotional response, including the middle and superior temporal gyri, the middle frontal gyrus, the caudate, and the hippocampus. Socially relevant emotional stimulation is feasible and evokes robust responses. The neural correlates of the evoked emotion are multiple, widely distributed, and inclusive of areas important in many cognitive tasks. Positive and negative emotional responses include activation of common and distinctive brain regions.

Adult↗

Neural correlates of perceptual learning: a functional MRI study of visual texture discrimination.

Visual texture discrimination has been shown to induce long-lasting behavioral improvement restricted to the trained eye and trained location in visual field [Karni, A. & Sagi, D. (1991) Proc. Natl. Acad. Sci. USA 88, 4966-4970]. We tested the hypothesis that such learning involves durable neural modifications at the earliest cortical stages of the visual system, where eye specificity, orientation, and location information are mapped with highest resolution. Using functional magnetic resonance imaging in humans, we measured neural activity 24 h after a single session of intensive monocular training on visual texture discrimination, performed in one visual quadrant. Within-subject comparisons between trained and untrained eye for targets presented within the same quadrant revealed higher activity in a corresponding retinotopic area of visual cortex. Functional connectivity analysis showed that these learning-dependent changes were not associated with an increased engagement of other brain areas remote from early visual cortex. We suggest that these new data are consistent with recent proposals that the cellular mechanisms underlying this type of perceptual learning may involve changes in local connections within primary visual cortex. Our findings provide a direct demonstration of learning-dependent reorganization at early processing stages in the visual cortex of adult humans.

Adult↗

Differential coding of hyperalgesia in the human brain: a functional MRI study.

Neuropathic pain can be both ongoing or stimulus-induced. Stimulus-induced pain, also known as hyperalgesia, can be differentiated into primary and secondary hyperalgesia. The former results from sensitization of peripheral nociceptive structures, the latter involves sensitization processes within the central nervous system (CNS). Hypersensitivity towards heat stimuli, i.e. thermal hyperalgesia, is a key feature of primary hyperalgesia, whereas secondary hyperalgesia is characterized by hypersensitivity towards mechanical (e.g. pin-prick) stimulation. Using functional magnetic resonance imaging (fMRI), we investigated if brain activation patterns associated with primary and secondary hyperalgesia might differ. Thermal and pin-prick hyperalgesia were induced on the left forearm in 12 healthy subjects by topical capsaicin (2.5%, 30 min) application. Equal pain intensities of both hyperalgesia types were applied during fMRI experiments, based on previous quantitative sensory testing. Simultaneously, subjects had to rate the unpleasantness of stimulus-related pain. Pin-prick hyperalgesia (i.e. subtraction of brain activations during pin-prick stimulation before and after capsaicin exposure) led to activations of primary and secondary somatosensory cortices (S1 and S2), associative-somatosensory cortices, insula and superior and inferior frontal cortices (SFC, IFC). Brain areas activated during thermal hyperalgesia (i.e. subtraction of brain activations during thermal stimulation before and after capsaicin exposure) were S1 and S2, insula, associative-somatosensory cortices, cingulate cortex (GC), SFC, middle frontal cortex (MFC) and IFC. When compared to pin-prick hyperalgesia, thermal hyperalgesia led to an increased activation of bilateral anterior insular cortices, MFC, GC (Brodmann area 24' and 32') and contralateral SFC and IFC, despite equal pain intensities. Interestingly, stronger activations of GC, contralateral MFC and anterior insula significantly correlated to higher ratings of the stimulus-related unpleasantness. We conclude that thermal and mechanical hyperalgesia produce substantially different brain activation patterns. This is linked to different psychophysical properties.

Adult↗

Functional MRI in human somatosensory cortex activated by touching textured surfaces.

MRI revealed activation foci in human somatosensory cortex during protocols involving stimulation of the fingertips with a textured surface. A 2D T2*-weighted gradient echo sequence was used to acquire images. The imaging protocol included acquiring images while subjects performed specific tactile stimulation paradigms (activation scans) or rested. Three different paradigms were used to produce functional activation using a textured surface to rub the fingertips of one hand. First, motor sensory activation was produced by rubbing the textured surface held in one hand against the fingertips of the opposite hand only during the activation scans. Second, the hand holding the textured surface moved throughout the experiment but touched the fingertips of the opposite hand only during the activation scans. Third, subjects remained still in the magnet throughout the entire study while an investigator rubbed the textured surface against the subjects' fingertips during the activation scans. Images were postprocessed using a cross-correlation scheme. The results revealed multiple foci of motor sensory activation near the central sulcus, postcentral sulcus, and prefrontal cortex.

Adult↗

Functional MRI detection of activation in the primary gustatory cortices in humans.

Magnetoencephalography (MEG) has recently revealed that the transitions between the parietal operculum (Pop) and the insula (area G) and the ventral end of the central sulcus (cs) were activated with the shortest latency by instrumental gustatory stimulation, which suggests that the location of the primary gustatory area is in these two regions. However, studies using other noninvasive brain-imaging methods such as positron-emission tomography or functional magnetic resonance imaging (fMRI) with manual application of tastants into the mouth have been unable to confirm this. The present study examined cortical activation by repetitive stimulation of the tongue tip with 1 M NaCl with a computer-controlled stimulator and used fMRI to detect it. In individual brains, activations were detected with multiple comparisons (false discovery rate) across the whole brain corrected (threshold at P < 0.05) at both area G and frontal operculum (Fop) in 8 of 11 subjects and at the rolandic operculum (Rop) in 7 subjects. Activations were also found at the ventral end of the cs (n = 3). Group analysis with random-effect models (multiple comparison using familywise error in regions of interest, P < 0.02) revealed activation at area G in both hemispheres and in the Fop, Rop, and ventral end of the cs on the left side. The present study revealed no activation on the gyrus of the external cerebral surface except for the Rop. Taking MEG findings into consideration, the present findings strongly indicate that the primary gustatory area is present at both the transition between the Pop and insula and the Rop including the gray matter within a ventral part of the cs.

Adult↗

[Functional MRI activation in area V4 alpha during a hue arrangement test].

BACKGROUND: Recent studies of cerebral information processing have shown that area V4 alpha, the area anterior to area V4, which is known as the human color center, is also associated with color. However, our clinical study has shown that lesions associated with hue arrangement test failures are more anterior than those associated with pseudoisochromatic plate test failure. PURPOSE AND METHODS: We studied area V4 alpha, and planned two functional magnetic resonance experiments for V4 alpha activity during the hue arrangement test. The task in the first experiment was virtual simulation of the hue arrangement test. The second experiment involved a task more specific to color information processing. RESULTS: We found significant activity in area V4 alpha in healthy subjects. CONCLUSIONS: We have reported that one of our patients with a more anterior lesion excluding area V4 had dyschromatopsia, as revealed by a panel D-15 test. Our experimental data and the clinical findings suggest that area V4 alpha plays an important role in processing during the hue arrangement test.

Cerebral Cortex↗

The counting Stroop: an interference task specialized for functional neuroimaging--validation study with functional MRI.

The anterior cingulate cortex has been activated by color Stroop tasks, supporting the hypothesis that it is recruited to mediate response selection or allocate attentional resources when confronted with competing information-processing streams. The current study used the newly developed "Counting Stroop" to identify the mediating neural substrate of cognitive interference. The Counting Stroop, a Stroop variant allowing on-line response time measurements while obviating speech, was created because speaking produces head movements that can exceed those tolerated by functional magnetic resonance imaging (fMRI), preventing the collection of vital performance data. During this task, subjects report by button-press the number of words (1-4) on the screen, regardless of word meaning. Interference trials contain number words that are incongruent with the correct response (e.g., "two" written three times), while neutral trials contain single semantic category common animals (e.g., "bird"). Nine normal right-handed adult volunteers underwent fMRI while performing the Counting Stroop. Group fMRI data revealed significant (P < or = 10(-4) activity in the cognitive division of anterior cingulate cortex when contrasting the interference vs. neutral conditions. On-line performance data showed 1) longer reaction times for interference blocks than for neutral ones, and 2) decreasing reaction times with practice during interference trials (diminished interference effects), indicating that learning occurred. The performance data proved to be a useful guide in analyzing the image data. The relative difference in anterior cingulate activity between the interference and neutral conditions decreased as subjects learned the task. These findings have ramifications for attentional, cognitive interference, learning, and motor control mechanism theories.

Adult↗

Spatial imagery in deductive reasoning: a functional MRI study.

Various cognitive theories aim to explain human deductive reasoning: (1) mental logic theories claim syntactic language-based proofs of derivation, (2) the mental model theory proposes cognitive processes of constructing and manipulating spatially organized mental models, and (3) imagery theories postulate that such abilities are based on visual mental images. To explore the neural substrates of human deductive reasoning, we examined BOLD (blood oxygen level dependent) contrasts of twelve healthy participants during relational and conditional reasoning with whole-brain functional magnetic resonance imaging (fMRI). The results indicate that, in the absence of any correlated visual input, reasoning activated an occipitoparietal-frontal network, including parts of the prefrontal cortex (Brodmann's area, BA, 6, 9) and the cingulate gyrus (BA 32), the superior and inferior parietal cortex (BA 7, 40), the precuneus (BA 7), and the visual association cortex (BA 19). In the discussion, we first focus on the activated occipito-parietal pathway that is well known to be involved in spatial perception and spatial working memory. Second, we briefly relate the activation in the prefrontal cortical areas and in the anterior cingulate gyrus to other imaging studies on higher cognitive functions. Finally, we draw some general conclusions and argue that reasoners envisage and inspect spatially organized mental models to solve deductive inference problems.

Adult↗

Functional MRI using multiple receiver coils: BOLD signal changes and signal-to-noise ratio for three-dimensional-PRESTO vs. single shot EPI in comparison to a standard quadrature head coil.

PURPOSE: To compare the performance of single shot echo planar imaging (SSEPI) with three-dimensional-multishot echo-planar imaging (EPI) based on principles-of-echo-shifting-with-a-train-of-observations (PRESTO) in combination with a standard quadrature head coil and, as an alternative, a multiple receiver coil in intraoperative functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: Six healthy subjects underwent fMRI with visual stimulation using a SSEPI and a PRESTO-sequence with both coil systems. Statistical evaluation was done with a scanner-based post-processing software and SPM 99. The number of activated voxels in the visual cortex, the percent signal change between rest and activation, and finally the signal-to-noise ratio (SNR) during time course were measured and compared for both coil systems and both sequences, used in four different combinations. RESULTS: Blood oxygen level dependent (BOLD) signal changes were the lowest with PRESTO and standard head coil and the highest for SSEPI and phased array coil. For the latter combination, a significantly higher signal change and larger activation size was observed together with a better SNR. SSEPI yielded similar performance using both coils. CONCLUSION: SSEPI was superior due to its better SNR and a higher BOLD signal change in the defined settings, irrespective of the coil used. In a stereotactical setup the phased array coil can be used to generate fMRI data without loss of image quality.

Adult↗

A new area in the human brain associated with learning and memory: immunohistochemical and functional MRI analysis.

Previous studies identified a new brain area, the marginal division (MrD), at the caudomedial border of the neostriatum in the brain of the rat, cat and monkey. The MrD was distinguishable from the rest of the striatum by the presence of spindle-shaped neurons, specific connections, and dense immunoreactivity for neuropeptides and monoamines in fibers, terminals and neuronal somata. Behavioral testing demonstrated that the MrD contributes to learning and memory in the rat. In the present study, the structure and the function of the MrD were investigated in the human brain. The presence of spindle-shaped neurons and the distribution of neurotransmitters in the MrD were evaluated by immunocytochemical methods. The function of the MrD was identified with functional magnetic resonance imaging (fMRI) of healthy volunteers tested with an auditory digital working memory task. Highly active areas were observed in the prefrontal cortex and MrD with left sided predominance during performance of the task, but other parts of the neostriatum were not excited and the MrD was not activated in a control test of non-working memory. The results of the present investigation therefore indicate the existence of a new area associated with learning and memory function in the human brain. The MrD probably plays an important role in the execution of digital working memory and appears to link the limbic system and the basal nucleus of Meynert. The MrD may also be involved in the mechanism of Alzheimer's disease.

Adult↗

False lateralization of language cortex on functional MRI after a cluster of focal seizures.

fMRI can define language cortex but its limitations are not yet fully understood. This article describes a child in whom fMRI falsely lateralized language cortex when performed after a cluster of left temporal lobe seizures. Multiple language tasks revealed no activation over the left temporal lobe despite a normal neurologic exam at the time of the study. A second fMRI performed 2 weeks later activated sites predominantly over the left, which were confirmed by extra-operative functional language mapping. fMRI may be unhelpful after frequent seizures.

Adolescent↗

Both parietal lobes are involved in drawing: a functional MRI study and implications for constructional apraxia.

In clinical studies, many researchers have reported that drawing can be disturbed by left or right unilateral parietal lobe damage (constructional apraxia). There seem to be two possible predictions about the cerebral laterality for drawing. The first is that drawing requires both parietal lobes, therefore, a lesion to either side can disrupt drawing. The second is that individuals can differ in laterality: some have only right or left activations, and some have bilateral. To test these predictions, we investigated with functional magnetic resonance imaging (fMRI) the cerebral activation whilst 17 right-handed healthy subjects performed a drawing task. The experiment consisted of two conditions: (1). naming an object in a presented picture and drawing it by using right index finger (DRAWING & NAMING); (2). naming an object in a presented picture (NAMING). We considered the brain regions that had greater activity in the DRAWING&NAMING condition than in the NAMING condition were the neural substrates of drawing. Individual analysis revealed that all subjects showed parietal activation bilaterally. We interpret that the results support the first prediction that both parietal lobes are required for drawing. By calculating the laterality indices of the individual parietal activations, it was found that there were more left dominant subjects than right dominant subjects (left, 12; right, 5). The results are inconsistent with previous studies on the incidence of constructional apraxia. In addition, we found activation in regions that were not previously reported in the literature of constructional apraxia: they are the ventral premotor area and posterior part of inferior temporal sulcus.

Adult↗

Hemispheric asymmetry emerges at distinct parts of the occipitotemporal cortex for objects, logograms and phonograms: a functional MRI study.

Behavioral and neuropsychological studies have suggested that the right hemisphere has a special advantage in the visual recognition of logograms. While this long-standing 'right hemisphere hypothesis' has never been investigated systematically by previous neuroimaging studies, a candidate neural substrate of such asymmetry might be found within the occipitotemporal cortex that is known to exhibit lateralized response to a certain class of stimuli, such as letters and faces. The present study examined the hemispheric specialization of brain activation during naming of objects, logograms and phonograms using functional magnetic resonance imaging. The three types of stimuli overall produced left-predominant activation of the perisylvian and inferior parietal regions relative to the resting baseline. This inter-hemispheric difference was significant irrespective of the stimuli type. In the occipitotemporal cortex, six subregions showing lateralized response were identified. That is, the three stimuli commonly produced left-lateralized response in the posterior fusiform and superior temporal gyri and right-lateralized response in the extrastriate cortex. Only logograms and objects produced a distinct cluster showing right-lateralized activation in the medial anterior fusiform gyrus associated with semantic knowledge, whereas only phonograms produced a left-lateralized activation in the posterior middle temporal cortex close to the site associated with visual perception of alphabetical letters. These findings suggest that while these stimuli similarly recruit the left perisylvian language area as a common neural component for naming, processing of objects and logograms becomes left-lateralized only in the downstream of the occipitotemporal cortex. By contrast, visual processing of phonograms is specialized to the left hemisphere in earlier stages of the area. The present data provide further evidence suggesting that both the left-right and anterior-posterior axes of the occipitotemporal cortex are differentially tuned according to the specific features of visual stimuli.

Adult↗

The temporal response of the brain after eating revealed by functional MRI.

After eating, the human brain senses a biochemical change and then signals satiation, but precisely when this occurs is unknown. Even for well-established physiological systems like glucose-insulin regulation, the timing of interaction between hormonal processes and neural events is inferred mostly from blood sampling. Recently, neuroimaging studies have provided in vivo information about the neuroanatomical correlates of the regulation of energy intake. Temporal orchestration of such systems, however, is crucial to the integration of neuronal and hormonal signals that control eating behaviour. The challenge of this functional magnetic resonance imaging study is to map not only where but also when the brain will respond after food ingestion. Here we use a temporal clustering analysis technique to demonstrate that eating-related neural activity peaks at two different times with distinct localization. Importantly, the differentiated responses are interacting with an internal signal, the plasma insulin. These results support the concept of temporal parcellation of brain activity, which reflects the different natures of stimuli and responses. Moreover, this study provides a neuroimaging basis for detecting dynamic processes without prior knowledge of their timing, such as the acute effects of medication and nutrition in the brain.

Adult↗

Relationship between cerebral blood flow changes during visual stimulation and baseline flow levels investigated with functional MRI.

Using fMRI, the relationship between regional cerebral blood flow (rCBF) changes during visual stimulation and the prevailing baseline global and regional flow levels was evaluated in 22 volunteers. The absolute increase in rCBF was not correlated with baseline rCBF values (r = 0.01, p = 0.8); however, the percentage change in rCBF showed a negative correlation (r=-0.78, p<0.001). Both absolute and relative changes in rCBF were independent of baseline global CBF values. These results indicate that caution should be exercised when comparing relative flow changes during focal brain activation, especially in functional neuroimaging studies dealing with altered baseline flow values.

Adult↗

Attentional modulation of perceptual grouping in human visual cortex: functional MRI studies.

When presented with a complex visual scene, our visual system has to organize the discrete entities present into useful perceptual units. The current work investigated the neural substrates of perceptual grouping defined by Gestalt laws of proximity and similarity of shape, and whether the neural substrates underlying perceptual grouping are modulated by task relevance and spatial attention. In visual discrimination tasks, subjects identified the orientations of perceptual groups formed by proximity or similarity of local elements or alternatively identified colors of either dots around the grouped stimuli or the fixation cross. Using functional magnetic resonance imaging (fMRI), we identified that the calcarine cortex was involved in proximity grouping but not in the grouping process defined by similarity of shape. Moreover, we showed evidence that the neural correlates of proximity grouping in the calcarine cortex were weakened when the elements were of low task relevance and fell outside an attended area of field. The findings reveal the neural basis for basic grouping operations, as well as illustrating how attention and proximity grouping interact in human visual cortex.

Adult↗