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Cortical responses to thermal pain depend on stimulus size: a functional MRI study.

Cortical activity patterns to thermal painful stimuli of two different sizes were examined in normal volunteers using functional magnetic resonance imaging (fMRI). Seven right-handed subjects were studied when the painful stimulus applied to the right hand fingers covered either 1,074-mm(2)-area large stimulator or 21-mm(2)-area small stimulator. Stimulus temperatures were adjusted to give rise to equivalent moderately painful ratings. fMRI signal increases and decreases were determined for the contralateral parietal and motor areas. When the overall activity in these regions was compared across subjects, increased fMRI activity was observed over more brain volume with the larger stimulator, whereas decreased fMRI activity was seen in more brain volume for the smaller stimulator. The individual subject and group-averaged activity patterns indicated regional specific differences in increased and decreased fMRI activity. The small stimulator resulted in decreased fMRI responses throughout the upper body representation in both primary somatosensory and motor cortices. In contrast, no decreased fMRI signals were seen in the secondary somatosensory cortex and in the insula. In another seven volunteers, the effects of the size of the thermal painful stimulus on vibrotactile thresholds were examined psychophysically. Painful stimuli were delivered to the fingers and vibrotactile thresholds were measured on the arm just distal to the elbow. Consistent with the fMRI results in the primary somatosensory cortex, painful thermal stimuli using the small stimulator increased vibrotactile thresholds on the forearm, whereas similarly painful stimuli using the large stimulator had no effect on forearm vibrotactile thresholds. These results are discussed in relation to the cortical dynamics for pain perception and in relation to the center-surround organization of cortical neurons.

Adolescent↗

Reorganization of cortical language areas in patients with aphasia: a functional MRI study.

The purpose of this study is to delineate the pattern of reorganization of cortical language areas using functional magnetic resonance imaging (fMRI) after rehabilitation therapy in patients with aphasia. Six right-handed aphasic patients were investigated. Causes of aphasia were intracerebral hemorrhages of the left basal ganglia in 3 patients, cerebral infarction of the left MCA in 2, and surgical resection of the frontotemporal lobes to control intractable epilepsy in 1. An auditory sentence completion task was used to activate brain language areas during the fMRI. Three patients with left frontal lesions showed activation in the right inferior frontal lobes while performing language tasks, whereas the other 3, whose lesions located at subcortical areas, showed activation in the bilateral frontal and temporal lobes. Our results demonstrated the differences in interhemispheric reorganization of the language network depending on the location of the lesion in aphasic patients. While the patients with subcortical lesion showed tendency of bilateral frontal activation, those with cortical lesion showed activation of the right frontal lobe.

Adult↗

[Principles of functional MRI imaging and its possibilities in the study of cerebral cortex activation].

While MR imaging of anatomic structures has long been widely appreciated, the emergence of functional magnetic resonance imaging (FMRI) methods for localising brain activity has emerged in the beginning of the 90s. This new MRI technique produces images of activated brain regions by detecting the indirect effects of neural activity on local blood volume, flow and oxygen saturation, and it is a promising new tool for further understanding of the relationships among brain structure, function and pathology. The information revealed by FMRI is partially overlapping with PET and SPECT, but it is non-invasive and has a better spatial and temporal resolution. The authors briefly summarise the concept and basics of FMRI and demonstrate the first successful FMRI examination performed in Hungary. The potential role of FMRI in the clinical practice is presented.

Animals↗

Functional MRI of pain- and attention-related activations in the human cingulate cortex.

The aims of the study were to use functional magnetic resonance imaging (fMRI) to 1) locate pain-related regions in the anterior cingulate cortex (ACC) of normal human subjects and 2) determine whether each subject's pain-related activation is congruent with ACC regions involved in attention-demanding cognitive processes. Ten normal subjects underwent fMRI with a 1.5-T standard commercial MRI scanner. A conventional gradient echo technique was used to obtain data from a single 4-mm sagittal slice of the left ACC, approximately 3.5 mm from midline. For each subject, interleaved sets of 6 images were obtained during a pain task, an attention-demanding task, and at rest, for a total of 36 images per task. Pain of different intensities was evoked via electrical stimulation of the right median nerve. The attention-demanding task consisted of silent word generation (verbal fluency). Additional experiments obtained data from the right ACC. A pixel-by-pixel statistical analysis of task versus rest images was used to determine task-related activated regions. The pain task resulted in a 1.6-4.0% increase in mean signal intensity within a small region of the ACC. The exact location of this activation varied from subject to subject, but was typically in the posterior part of area 24. The signal intensity changes within this region correlated with pain intensity reported by the subject. The attention-demanding tasks increased the mean signal intensity by 1.3-3.3% in a region anterior and/or superior to the pain-related activation in each subject. The activated region was typically larger than the pain-related activation. In some cases this activation was at or superior to the ACC border, near the supplementary motor area. These regions did not show any pain-intensity-related activation. In one subject both right and left ACC were imaged, revealing bilateral ACC activation during the attention task but only contralateral pain-related activation. These findings shed light on pain- and attention-related cognitive processes. The results provide evidence for a region in the posterior part of the ACC that is involved in pain and a more anterior region involved in other attention-demanding cognitive tasks.

Adult↗

Functional MRI of the cervical spinal cord on 1.5 T with fingertapping: to what extent is it feasible?

INTRODUCTION: Until recently, functional magnetic resonance imaging (fMRI) with blood oxygen level-dependent (BOLD) contrast, was mainly used to study brain physiology. The activation signal measured with fMRI is based upon the changes in the concentration of deoxyhaemoglobin that arise from an increase in blood flow in the vicinity of neuronal firing. Technical limitations have impeded such research in the human cervical spinal cord. The purpose of this investigation was to determine whether a reliable fMRI signal can be elicited from the cervical spinal cord during fingertapping, a complex motor activity. Furthermore, we wanted to determine whether the fMRI signal could be spatially localized to the particular neuroanatomical location specific for this task. METHODS: A group of 12 right-handed healthy volunteers performed the complex motor task of fingertapping with their right hand. T2*-weighted gradient-echo echo-planar imaging on a 1.5-T clinical unit was used to image the cervical spinal cord. Motion correction was applied. Cord activation was measured in the transverse imaging plane, between the spinal cord levels C5 and T1. RESULTS: In all subjects spinal cord responses were found, and in most of them on the left and the right side. The distribution of the activation response showed important variations between the subjects. While regions of activation were distributed throughout the spinal cord, concentrated activity was found at the anatomical location of expected motor innervation, namely nerve root C8, in 6 of the 12 subjects. CONCLUSION: fMRI of the human cervical spinal cord on an 1.5-T unit detects neuronal activity related to a complex motor task. The location of the neuronal activation (spinal cord segment C5 through T1 with a peak on C8) corresponds to the craniocaudal anatomical location of the neurons that activate the muscles in use.

Adolescent↗

Characterizing function-structure relationships in the human visual system with functional MRI and diffusion tensor imaging.

A key objective in neuroscience is to improve our understanding of the relationship between brain function and structure. We investigated this in the posterior visual pathways of healthy volunteers by applying functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) with tractography. The optic radiations were segmented using the Probabilistic Index of Connectivity (PICo) tractography algorithm and extracted at several thresholds of connection confidence. The mean fractional anisotropy (FA) of the estimated tracts was found to correlate significantly with fMRI measures of visual cortex activity (induced by a photic stimulation paradigm). The results support the hypothesis that the visual cortical fMRI response is constrained by the external anatomical connections of the subserving optic radiations.

Adult↗

Functional MRI of the newborn.

In order to provide accurate prognosis and developmental intervention to newborns, new methods of assessing cerebral functions are needed. The non-invasive technique of functional magnetic resonance imaging (fMRI) can be considered as the leading technique for functional exploration of the infant's brain. Several studies have previously applied fMRI in both healthy and diseased newborns with different sensory and cognitive tasks. In this chapter, the methodological issues that are proper to the use of fMRI in the newborn are detailed. In addition, an overview of the major findings of previous fMRI studies is provided, with a focus on notable differences from those in adult subjects. More specifically, the functional responses and the localization of cortical activations in healthy and diseased newborns are discussed. We expect a rapid expansion of this field and the establishment of fMRI as a valid clinical diagnostic tool in the newborn.

Brain↗

Evaluation of preoperative high magnetic field motor functional MRI (3 Tesla) in glioma patients by navigated electrocortical stimulation and postoperative outcome.

OBJECTIVES: The validity of 3 Tesla motor functional magnetic resonance imaging (fMRI) in patients with gliomas involving the primary motor cortex was investigated by intraoperative navigated motor cortex stimulation (MCS). METHODS: Twenty two patients (10 males, 12 females, mean age 39 years, range 10-65 years) underwent preoperative fMRI studies, performing motor tasks including hand, foot, and mouth movements. A recently developed high field clinical fMRI technique was used to generate pre-surgical maps of functional high risk areas defining a motor focus. Motor foci were tested for validity by intraoperative motor cortex stimulation (MCS) employing image fusion and neuronavigation. Clinical outcome was assessed using the Modified Rankin Scale. RESULTS: FMRI motor foci were successfully detected in all patients preoperatively. In 17 of 22 patients (77.3%), a successful stimulation of the primary motor cortex was possible. All 17 correlated patients showed 100% agreement on MCS and fMRI motor focus within 10 mm. Technical problems during stimulation occurred in three patients (13.6%), no motor response was elicited in two (9.1%), and MCS induced seizures occurred in three (13.6%). Combined fMRI and MCS mapping results allowed large resections in 20 patients (91%) (gross total in nine (41%), subtotal in 11 (50%)) and biopsy in two patients (9%). Pathology revealed seven low grade and 15 high grade gliomas. Mild to moderate transient neurological deterioration occurred in six patients, and a severe hemiparesis in one. All patients recovered within 3 months (31.8% transient, 0% permanent morbidity). CONCLUSIONS: The validation of clinically optimised high magnetic field motor fMRI confirms high reliability as a preoperative and intraoperative adjunct in glioma patients selected for surgery within or adjacent to the motor cortex.

Adolescent↗

Neural correlates for the suppression of habitual behavior: a functional MRI study.

It has been suggested that inhibitory executive control of behavior is directed by the frontal lobes. We used functional magnetic resonance imaging to explore the brain regions that are involved in the inhibition of habitual manual responses. Fifteen right-handed subjects performed the rock-scissors-paper game against computer-simulated pictures of hands during the scanning procedure. The subjects were required to win, lose, or draw against the presented picture in a separate block. We considered that the situation in which subjects intentionally lost the game required the suppression of habitual behavior, because it is natural behavior for people to attempt to win the game. Compared with the WIN and DRAW conditions, the left premotor and sensorimotor areas were activated for both hand sessions with a positive correlation with error rates. Importantly, the LOSE condition in the case of the right hand yielded brain activation exclusively in the anterior part of the left inferior frontal gyrus, the activity which showed a negative correlation with error rates. Overall brain activations were predominant in the left hemisphere, irrespective of the hand used for the response. The results suggest that the anterior part of the left inferior frontal gyrus plays a critical role in the inhibition of habitual manual behavior, and that the left hemisphere is dominant for the selection of well-learned manual behavior.

Adult↗

Age-dependent plasticity in the superior temporal sulcus in deaf humans: a functional MRI study.

BACKGROUND: Sign-language comprehension activates the auditory cortex in deaf subjects. It is not known whether this functional plasticity in the temporal cortex is age dependent. We conducted functional magnetic-resonance imaging in six deaf signers who lost their hearing before the age of 2 years, five deaf signers who were >5 years of age at the time of hearing loss and six signers with normal hearing. The task was sentence comprehension in Japanese sign language. RESULTS: The sign-comprehension tasks activated the planum temporale of both early- and late-deaf subjects, but not that of hearing signers. In early-deaf subjects, the middle superior temporal sulcus was more prominently activated than in late-deaf subjects. CONCLUSIONS: As the middle superior temporal sulcus is known to respond selectively to human voices, our findings suggest that this subregion of the auditory-association cortex, when deprived of its proper input, might make a functional shift from human voice processing to visual processing in an age-dependent manner.

Adult↗

[Motor cortex by real-time imaging process functional MRI during finger movements].

OBJECTIVE: To explore the techniques of RTIP-fMRI scanning and the correspondence between structure and functional changes of motor cortex during self-paced finger movements by RTIP-fMRI in normal volunteers. METHODS: The 15 healthy volunteers were studied by RTIP-fMRI, and the activation tasks consisted of self-paced finger movements performed with the right and the left hands. Image postprocessing was done on the workstation by "correlation coefficient" algorithm analysis method, IAC and SPM software. RESULTS: There was a good correspondence between the anatomical landmarks of the somatotopical organization of primary motor areas in the 15 volunteers; during the finger tasks, the functional changes occurred in the contralateral primary motor-somatosensory cortex (M1/S1), the supplementary motor area (SMA), and the ipsilateral primary motor cortex. CONCLUSION: RTIP, a promising new technique, can localize the motor cortex accurately. It is superior to any other fMRI techniques, and may be used widely in the function research of the brain.

Adult↗

A functional MRI study: cerebral laterality for lexical-semantic processing and human voice perception.

BACKGROUND AND PURPOSE: Language dominance research using functional neuroimaging has made important contributions to clinical applications. Nevertheless, although recent neuroimaging studies demonstrated right-lateralized activation by human voice perception, the influence of voice perception in terms of language dominance has not been adequately studied. We aimed to accurately clarify language dominance for lexical-semantic processing in the temporal cortices by focusing on human voice perception. METHODS: Thirty normal right-handed subjects were scanned by functional MR imaging while listening to sentences (SEN), reverse sentences (rSEN), and identifiable nonvocal sounds (SND). We investigated cerebral activation and the distribution of individual Laterality Index under 3 contrasts: rSEN-SND, SEN-SND, and SEN-rSEN. RESULTS: The rSEN-SND contrast, including human voice perception, revealed right-lateralized activation in the anterior temporal cortices. Both SEN-SND and SEN-rSEN contrasts, including lexical-semantic processing, showed left-lateralized activation in the inferior and middle frontal gyrus and middle temporal gyrus. The SEN-rSEN contrast, without the influence of human voice perception, showed no temporal activation in the right hemisphere. Symmetrical or right-lateralized activation was observed in 22 of 27 subjects (81.4%) under the rSEN-SND contrast in the temporal cortices. Although 9 of 27 subjects (33.3%) showed symmetrical or right-lateralized activation under the SEN-SND contrast in the temporal cortices, all subjects showed left-lateralized activation under the SEN-rSEN contrast. CONCLUSION: Our results demonstrated that right-lateralized activation by human voice perception could mask left-lateralized activation by lexical-semantic processing. This finding suggests that the influence of human voice perception should be adequately taken into account when language dominance is determined.

Adult↗

Functional MRI with simultaneous EEG recording: feasibility and application to motor and visual activation.

The possibility of combining the high spatial resolution of functional magnetic resonance imaging (fMRI) with the high temporal resolution of electroencephalography (EEG) may provide a new tool in cognitive neurophysiology, as well as in clinical applications such as epilepsy. However, the simultaneous recording of EEG and fMRI raises important practical problems: 1) the patients' safety, in particular the risk of skin burns due to electrodes heating; 2) the impairment of the EEG recording by the static magnetic field, as well as by RF and magnetic field gradients used during MRI; and 3) the quality of MR images, which may be affected by the presence of conductors and electronic devices in the MRI bore. Here we present our experiences on 19 normal volunteers who underwent combined fMRI and 16-channel EEG examination. Consistent with previous reports, safety could be assured when performing EEG recordings during fMRI acquisition. Electrophysiological signals recorded with surface EEG were similar inside and outside the 1.5 T magnet. Furthermore, fMRI using motor or visual tasks revealed similar areas of activation when performed with and without 16-channel EEG recording. J. Magn. Reson. Imaging 2001;13:943-948.

Attention↗

Influence of body segment position during in-phase and antiphase hand and foot movements: a kinematic and functional MRI study.

Behavioral studies have provided important insights into the mechanisms governing interlimb coordination. In this study, we combined kinematic and functional magnetic resonance imaging (fMRI) analysis to investigate the brain cortical and subcortical areas involved in interlimb coordination and the influence of direction of movement and of body segment position on the activity of those areas. Fifteen right-handed healthy subjects were studied while performing cyclic in-phase and antiphase hand and foot movements with the dominant, right limbs, with the upper limb positioned either prone or supine, and in front or behind with respect to the trunk. When contrasting antiphase to in-phase movements, fMRI analysis demonstrated an increased recruitment of a widespread sensorimotor network (including regions in the frontal and parietal lobes, bilaterally, the cingulated motor area, the thalami, the visual cortex, and the cerebellum) considered to function in motor, sensory, and multimodal integration processing. When contrasting the anterior to the posterior position of the upper limb with respect to the trunk, we found different recruitment patterns in the frontal and parietal regions as well as the preferential recruitment of the basal ganglia, the insula, and the cerebellum during the first condition and of regions located in the temporal lobes during the second one. Different brain areas are engaged at a different extent during interlimb coordination. In addition to the relative difficulty of the movement, the different cognitive and sensorial loads needed to control and perform the motor act might be responsible for these findings.

Adult↗

Systematic investigation of balanced steady-state free precession for functional MRI in the human visual cortex at 3 Tesla.

Previous studies have applied balanced steady-state free precession (bSSFP) to functional brain imaging. Methods that exploit the strong frequency dependence of the MR signal in the bSSFP transition band are strongly affected by field inhomogeneity and frequency drifts. Recent bSSFP studies using "on-resonance" (in the bSSFP passband) acquisition claimed that higher sensitivity was achieved compared to traditional fMRI methods. However, the contrast mechanism that generates activation-related signal changes in bSSFP imaging is not yet fully understood. We performed a systematic study of on-resonance bSSFP signal behavior using a multiecho balanced SSFP sequence with different TRs at 3 Tesla. We conclude that intravoxel dephasing, or the off-resonance averaged steady state, dominates the bSSFP signal decay and determines the bSSFP fMRI contrast. Experimental findings were confirmed by simulations based on existing theories for signal formation around blood vessels in inhomogeneous tissues. The activation-induced signal change in on-resonance bSSFP increases with TE, and the TE dependence of the contrast-to-noise ratio (CNR) in bSSFP is similar to that in gradient echo-planar imaging (GE-EPI). However, GE-EPI has a significantly higher CNR efficiency.

Adult↗

A new statistical approach to detecting significant activation in functional MRI.

There are many ways to detect activation patterns in a time series of observations at a single voxel in a functional magnetic resonance imaging study. The critical problem is to estimate the statistical significance, which depends on the estimation of both the magnitude of the response to the stimulus and the serial dependence of the time series and especially on the assumptions made in that estimation. We show that for experimental designs with periodic stimuli, only a few aspects of the serial dependence are important and these can be estimated reliably via nonparametric estimation of the spectral density of the time series, whereas existing techniques are biased by their assumptions. The linear model with (stationary) serially dependent errors can be analyzed entirely in frequency domain, and doing so provides many insights. In particular, we introduce a technique to detect periodic activations and show that it has a distribution theory that enables us to assign significance levels down to 1 in 100,000, levels which are needed when a whole brain image is under consideration. Nonparametric spectral density estimation is shown to be self-calibrating and accurate when compared to several other time-domain approaches. The technique is especially resistant to high frequency artefacts that we have found in some datasets and we demonstrate that time-domain approaches may be sufficiently susceptible to these effects to give misleading results. The method is easily generalized to handle event-related designs. We found it necessary to consider the trends in the time series carefully and use nonlinear filters to remove the trends and robust techniques to remove "spikes." Using this in connection with our techniques allows us to detect activations in clumps of a few (even one) voxel in periodic designs, yet produce essentially no false positive detections at any voxels in null datasets.

Acoustic Stimulation↗

High-resolution, multiple gradient-echo functional MRI at 1.5 T.

A multiple gradient echo, high resolution imaging method is proposed to better visualize different sources of activation in functional magnetic resonance imaging (fMRI) experiments. Eight echoes are collected from 30 ms to 205 ms with an echo spacing of 25 ms. All echoes show significant activation, but each echo reveals its own pattern of activation. From this variability, it appears that large vessel contributions can be separated from small vessel contributions using a fuzzy cluster analysis across echo times. The results demonstrate the importance of a multiple gradient echo data acquisition approach in localizing various vascular contributions to brain activation in fMRI.

Adult↗

Statistical analysis of functional MRI data in the wavelet domain.

The use of the wavelet transform is explored for the detection of differences between brain functional magnetic resonance images (fMRI's) acquired under two different experimental conditions. The method benefits from the fact that a smooth and spatially localized signal can be represented by a small set of localized wavelet coefficients, while the power of white noise is uniformly spread throughout the wavelet space. Hence, a statistical procedure is developed that uses the imposed decomposition orthogonality to locate wavelet-space partitions with large signal-to-noise ratio (SNR), and subsequently restricts the testing for significant wavelet coefficients to these partitions. This results in a higher SNR and a smaller number of statistical tests, yielding a lower detection threshold compared to spatial-domain testing and, thus, a higher detection sensitivity without increasing type I errors. The multiresolution approach of the wavelet method is particularly suited to applications where the signal bandwidth and/or the characteristics of an imaging modality cannot be well specified. The proposed method was applied to compare two different fMRI acquisition modalities. Differences of the respective useful signal bandwidths could be clearly demonstrated; the estimated signal, due to the smoothness of the wavelet representation, yielded more compact regions of neuroactivity than standard spatial-domain testing.

Adult↗