Dissociating pain from its anticipation in the human brain.

The experience of pain is subjectively different from the fear and anxiety caused by threats of pain. Functional magnetic resonance imaging in healthy humans was applied to dissociate neural activation patterns associated with acute pain and its anticipation. Expectation of pain activated sites within the medial frontal lobe, insular cortex, and cerebellum distinct from, but close to, locations mediating pain experience itself. Anticipation of pain can in its own right cause mood changes and behavioral adaptations that exacerbate the suffering experienced by chronic pain patients. Selective manipulations of activity at these sites may offer therapeutic possibilities for treating chronic pain.

Comparison of Multiple Sclerosis Cortical Lesion Types Detected by Multicontrast 3T and 7T MRI.

BACKGROUND AND PURPOSE: Our aims were the following: 1) to compare multicontrast cortical lesion detection using 3T and 7T MR imaging, 2) to compare cortical lesion type frequency in relapsing-remitting and secondary-progressive MS, and 3) to assess whether detectability is related to the magnetization transfer ratio, an imaging marker sensitive to myelin content. MATERIALS AND METHODS: Multicontrast 3T and 7T MR images from 10 participants with relapsing-remitting MS and 10 with secondary-progressive MS. We used the following 3T contrast sequences: 3D-T1-weighted, quantitative T1, FLAIR, magnetization-transfer, and 2D proton-density- and T2-weighted. We used the following 7T contrast sequences: 3D-T1-weighted, quantitative T1, and 2D-T2*-weighted. RESULTS: Cortical lesion counts at 7T were the following: 720 total cortical lesions, 420 leukocortical lesions (58%), 27 intracortical lesions (4%), and 273 subpial lesions (38%). Cortical lesion counts at 3T were the following: 424 total cortical, 393 leukocortical (93%), zero intracortical, and 31 subpial (7%) lesions. Total, intracortical, and subpial 3T lesion counts were significantly lower than the 7T counts (P < .002). Leukocortical lesion counts were not significantly different between scanners. Total and leukocortical lesion counts were significantly higher in secondary-progressive MS, at 3T and 7T (P ≤ .02). Subpial lesions were significantly higher in secondary-progressive MS at 7T (P = .006). The magnetization transfer ratio values of leukocortical lesions visible on both scanners were significantly lower than the magnetization transfer ratio values of leukocortical lesions visible only at 3T. No significant difference was found in magnetization transfer ratio values between subpial lesions visible only at 7T and subpial lesions visible on both 3T and 7T. CONCLUSIONS: Detection of leukocortical lesions at 3T is comparable with that at 7T MR imaging. Imaging at 3T is less sensitive to intracortical and subpial lesions. Leukocortical lesions not visible on 7T T2*-weighted MRI may be associated with less demyelination than those that are visible. Detectability of subpial lesions does not appear to be related to the degree of demyelination.

An fMRI study of the selective activation of human extrastriate form vision areas by radial and concentric gratings.

The ventral form vision pathway of the primate brain comprises a sequence of areas that include V1, V2, V4 and the inferior temporal cortex (IT) [1]. Although contour extraction in the V1 area and responses to complex images, such as faces, in the IT have been studied extensively, much less is known about shape extraction at intermediate cortical levels such as V4. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate that the human V4 is more strongly activated by concentric and radial patterns than by conventional sinusoidal gratings. This is consistent with global pooling of local V1 orientations to extract concentric and radial shape information in V4. Furthermore, concentric patterns were found to be effective in activating the fusiform face area. These findings support recent psychophysical [2,3] and physiological [4,5] data indicating that analysis of concentric and radial structure represents an important aspect of processing at intermediate levels of form vision.

The effects of visual object priming on brain activation before and after recognition.

BACKGROUND: Recognizing an object is improved by recent experience with that object even if one cannot recall seeing the object. This perceptual facilitation as a result of previous experience is called priming. In neuroimaging studies, priming is often associated with a decrease in activation in brain regions involved in object recognition. It is thought that this occurs because priming causes a sharpening of object representations which leads to more efficient processing and, consequently, a reduction in neural activity. Recent evidence has suggested, however, that the apparent effect of priming on brain activation may vary as a function of whether the neural activity is measured before or after recognition has taken place. RESULTS: Using a gradual 'unmasking' technique, we presented primed and non-primed objects to subjects, and measured activation time courses using high-field functional magnetic resonance imaging (fMRI). As the objects were slowly revealed, but before recognition had occurred, activation increased from baseline level to a peak that corresponded in time to the subjects' behavioural recognition responses. The activation peak for primed objects occurred sooner than the peak for non-primed objects, and subjects responded sooner when presented with a primed object than with a non-primed object. During this pre-recognition phase, primed objects produced more activation than non-primed objects. After recognition, activation declined rapidly for both primed and non-primed objects, but now activation was lower for the primed objects. CONCLUSIONS: Priming did not produce a general decrease in activation in the brain regions involved in object recognition but, instead, produced a shift in the time of peak activation that corresponded to the shift in time seen in the subjects' behavioural recognition performance.

Differences in perceived shape from shading correlate with activity in early visual areas.

The perception of shape from shading depends on the orientation of the shading gradient [1] [2] [3] [4]. Displays composed of elements with vertically oriented shading gradients of opposite polarity produce a strong and stable percept of 'concave' and 'convex' elements. If the shading gradients are rotated 90 degrees , the depth percept is reduced and appears much more ambiguous. Results from psychophysical [1] [2] [3] [4] [5] [6], neuropsychological [7] and computational studies [8] [9] suggest that the perception of shape from shading engages specific mechanisms in early cortical visual areas. In a three-dimensional functional magnetic resonance imaging (fMRI) study at 1.5 Tesla using a three-dimensional, interleaved-echoplanar imaging technique and a surface radio frequency (RF) coil placed under the visual cortex, we investigated the activity in these early visual areas associated with viewing shape from shading displays at two different orientations. We found significantly greater activation in area V1 and neighbouring low-level visual areas of cortex when subjects viewed displays that led to weak and unstable depth percepts than when they viewed displays that led to strong and stable depth percepts.

Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation.

OBJECTIVE: The neuronal circuitry underlying posttraumatic stress disorder (PTSD) was studied in traumatized subjects with and without PTSD. METHOD: Traumatized subjects with (N=9) and without (N=9) PTSD were studied by using the script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging at a 4-T field strength. RESULTS: PTSD subjects showed significantly less activation of the thalamus, the anterior cingulate gyrus (Brodmann's area 32), and the medial frontal gyrus (Brodmann's area 10/11) than did the comparison subjects. CONCLUSIONS: The findings suggest anterior cingulate, frontal, and thalamic involvement in the neuronal circuitry underlying PTSD.

Repetition priming and the time course of object recognition: an fMRI study.

We investigated the effects of repetition priming on the time course of recognition in several visual areas of the brain using fMRI. We slowed down recognition by gradually revealing the stimuli, in order to prolong the pre-recognition phase. Activation was lower for primed than for non-primed objects overall in both the occipitotemporal region (OTR) and the intraparietal region (IPR). A difference was found between primed and non-primed objects in the rate of increase of OTR activation. We concluded that the IPR, in addition to the OTR, was affected by repetition priming, and that this effect was different from that seen in the OTR.

Imaging of current density and current pathways in rabbit brain during transcranial electrostimulation.

A magnetic resonance imaging (MRI) method was used for a noninvasive study of current density (CD) and current pathways (CP's) inside the skull during transcranial electrostimulation in rabbits. The transcranial impulse current directions studied were those previously used in transcranial electric treatment either sagittally or bilaterally. MRI data were collected from slices perpendicular to the direction of current application. In these slices, only the perpendicular component of the CD was measured. Computer methods for accurate topographic mapping of the main areas with high CD and for reconstruction of CP's are described. It was revealed that current applied on the head sagittally passed mostly through the cerebrospinal fluid in the basal brain cisternas connected in series, and through the anterior horns of the lateral ventricles, foramina of Monro, ventrocaudal part of the third ventricle, aqueductus, and fourth ventricle. Possible connections between these CP's are suggested. Bilaterally applied current passed through the brain and skull core more diffusely without concentrations in cisternas and ventricles. The results of the present study suggest an explanation for the observation that sagittally applied current more effectively stimulates brain structures with antinociceptive function and elicits more pronounced analgesic effect.

Comparison of multiecho postprocessing schemes for SWI with use of linear and nonlinear mask functions.

BACKGROUND AND PURPOSE: SWI is an MR technique conventionally implemented with single-echo gradient-echo data. The purpose of this study was to compare single-echo SWI processing and 2 multiecho SWI processing schemes: postaverage, where an SWI image is created for each echo and then averaged to create a single volume; and frequency-based, where a SWI image is generated from an average frequency image. Linear and nonlinear mask functions were investigated for all 3 processing schemes. MATERIALS AND METHODS: Comprehensive optimizations were performed. Single and multigradient-echo data were acquired at 3T in 10 volunteers. Contrast-to-noise ratio was measured in various structures. Visibilities of the same structures were ranked in different SWI images by trained raters. RESULTS: When image evaluation was based on measurements of contrast-to-noise ratio, the nonlinear mask and frequency-based scheme were superior. However, when image evaluation was based on ranks of qualitative visibility, the linear mask and postaverage scheme were superior. Although the nonlinear mask and frequency-based scheme allow increased contrast of paramagnetic perturbers such as the globus pallidus, periventricular veins, red nucleus, and subthalamic nucleus, they do not necessarily increase the information content of the image; rather, they result in a harsh contrast that is visually unpleasing to radiologists and wherein more subtle structure is relatively less apparent. CONCLUSIONS: Linearly masked postaverage SWI is the recommended implementation of multiecho SWI for radiologic use; however, nonlinearly masked frequency-based SWI may have use in computer-based segmentation or registration.

A cradle-shaped gradient coil to expand the clear-bore width of an animal MRI scanner.

The never ending quest for higher magnetic field strengths in MRI and MRS has led to small and medium bore scanners at 9.4 T and above for both human and animal use; however, these bore diameters restrict the size of object that can be accommodated when using a conventional gradient coil. By replacing a cylindrical gradient-coil insert with a single-sided gradient coil, the scanner's functionality can be extended to include localized imaging of wider samples. As a prototype, a three-axis, cradle-shaped gradient coil was designed, fabricated and implemented in a 9.4 T animal MRI scanner. Since gradient fields are required only to be monotonic over the desired field of view, the cradle gradient coil was designed to produce high gradient efficiencies (up to 2.25 mT m(-1) A(-1) over a 5 cm imaging region) at the expense of gradient linearity. A dedicated three-dimensional algorithm was developed to correct the resultant image distortion. Preliminary images of a grid phantom and a mouse demonstrated the fidelity of the algorithm in correcting image distortion of greater than 200%. Eddy currents were measured along each gradient axis. A large 65.2 (Hz mT(-1) m) B(0) eddy current was produced by the y-axis, suggesting potential limitations of single-sided gradient coils.

Brain reorganization in patients with spinal cord compression evaluated using fMRI.

OBJECTIVE: This prospective study characterizes the reorganization that occurs within the primary sensorimotor cortices following decompression of cervical spinal stenosis. METHODS: Twelve right-handed patients with cervical myelopathy underwent blood oxygenation level dependent functional MRI (fMRI) prior to decompression and 6 months following surgery. Ten right-handed controls also underwent fMRI. All subjects performed a finger-tapping paradigm with the right hand. Volume time course data were corrected for temporal serial correlation and % normalized before inclusion in the general linear model. Activation maps were created for each group using a threshold of p < 0.005 with Bonferroni correction. Between-group differences in left hemisphere volume of activation (VOA) were measured along the precentral gyrus (PrCG) and postcentral gyrus (PoCG). Each subject also completed clinical questionnaires. RESULTS: Prior to surgery, patients demonstrated a larger VOA (1.23 cm(3), t(max) = 11.8) in comparison to controls within the PrCG. This difference increased following surgery (2.99 cm(3), t(max) = 13.6). Within the PoCG, controls demonstrated a larger VOA (0.53 cm(3), t(max) = 8.28) than preoperative patients. This difference decreased by 0.12 cm(3) (t(max) = 7.05) following surgery. Preoperatively, patients had a 21.7 cm(3) VOA (t(max) = 29.4) within the sensorimotor cortex with the center of gravity located within Brodmann area (BA) 3. Following surgery, the VOA increased to 23.1 cm(3) (t(max) = 26.1) within BA 3. There were significant improvements in clinical outcomes following surgery. CONCLUSIONS: Spinal cord compression resulted in an increase in volume of activation (VOA) within the precentral gyrus (PrCG) and a loss of VOA within the postcentral gyrus (PoCG) in comparison to controls. Surgical decompression results in cortical reorganization with enlarging VOA within both the PrCG and PoCG.

Perirhinal and hippocampal contributions to visual recognition memory can be distinguished from those of occipito-temporal structures based on conscious awareness of prior occurrence.

The ability of humans to distinguish consciously between new and previously encountered objects can be probed with visual recognition memory tasks that require explicit old-new discriminations. Medial temporal-lobe (MTL) lesions impair performance on such tasks. Within the MTL, both perirhinal cortex and the hippocampus have been implicated. Cognitive processes can also be affected by past object encounters in the absence of conscious recognition, as in repetition priming tasks. Past functional neuroimaging findings in healthy individuals suggest that even in tasks that require conscious recognition decisions for visual stimuli, posterior cortical structures in the ventral visual pathway distinguish between old and new objects at a nonconscious level. Conclusive evidence that differentiates the neural underpinnings of conscious from nonconscious processes in recognition memory, however, is still missing. In particular, functional magnetic resonance imaging (fMRI) findings for the MTL have been inconsistent towards this end. In the present fMRI study, we tested whether perirhinal and hippocampal contributions to recognition memory can be distinguished from those of occipito-temporal structures in the ventral visual pathway based on the participants' reported conscious awareness of prior occurrence. Images of objects with a large degree of feature overlap served as stimuli; they were selected to ensure an involvement of perirhinal cortex in the present recognition task, based on evidence from past lesion-based research. We found that both perirhinal cortex and occipito-temporal cortex showed a differential old-new response that reflected a repetition-related decrease in activity (i.e., new > old). Whereas in perirhinal cortex this decrease was observed with respect to whether subjects reported objects to be old or new, irrespective of the true item status, in occipito-temporal cortex it occurred in relation to whether objects were truly old or new, irrespective of the participants' conscious reports. Hippocampal responses differed in their exact pattern from those of perirhinal cortex, but were also related to the conscious recognition reports. These results indicate that both perirhinal and hippocampal contributions can be distinguished from those of occipito-temporal structures in the ventral visual pathway based on the participants' reported conscious awareness of prior occurrence.

4 T MRI of chondrocalcinosis in combination with three-dimensional CT, radiography, and arthroscopy: a report of three cases.

OBJECTIVE: To describe 4 T MRI techniques in imaging chondrocalcinosis within the knee and examine the results together with those demonstrated using three-dimensional (3D) computed tomography, conventional radiography, and arthroscopy. DESIGN AND PATIENTS: From a larger clinical imaging study of early osteoarthritis, knee arthroscopy patients were imaged using high-field MRI and high-resolution 3D CT prior to their surgery. Retrospective review of the imaging data diagnosed three patients with chondrocalcinosis. Fat-suppressed 3D spoiled gradient (3D SPGR) and two-dimensional fat-suppressed fast spin echo (FSE) imaging was performed at 4 T. The MR images, multi-planar reformatted CT (MPR-CT) and maximum intensity projection CT (MIP-CT) images, and radiographs were examined by a musculoskeletal radiologist for the presence and location of chondrocalcinosis. The findings from arthroscopy were also included. RESULTS: MRI showed 16 sites of punctate hypointense regions from 18 articular surfaces and five of six menisci with similar signal characteristics. Both meniscal chondrocalcinosis and meniscal tears were clearly visible using the 3D SPGR sequence. Only three sites were demonstrated to have calcification using MPR-CT and MIP-CT revealed an additional three. In articular cartilage surfaces showing surface disruption, arthroscopy demonstrated 11 sites with crystal deposition. Arthroscopy also revealed five menisci with calcification present. CONCLUSION: Our preliminary findings suggest that imaging chondrocalcinosis using spoiled gradient 4 T MRI is superior and complementary to the other imaging modalities in the detection of crystal deposition in both articular cartilage and menisci.

The functional scout image: immediate mapping of cortical function at 4 Tesla using receiver phase cycling.

A rapid method of generating functional scout images to map cortical activity is presented. Maps were produced immediately "on-line" on the scanner's console using fast low-angle shot gradient-recalled echo and echo-planar imaging sequences without special hardware. To demonstrate the technique, raw data collected during photic stimulation and dark control periods were subtracted through phase alternation of the receiver with constant transmitted radio frequency phase. A blood oxygen level-dependent signal difference map was produced by magnitude reconstruction of the resulting complex-difference data. Maps improved in contrast with an increasing number of stimulation-control cycles and showed similar areas of activation to traditional fMRI processing methods. Such a functional scout procedure allows rapid localization of brain function within the anatomical region of interest. From these functional scout images, slices or voxels may be planned by using the scanner manufacturers prescription tools for further specialized studies.

Mental chronometry using latency-resolved functional MRI.

Vascular responses to neural activity are exploited as the basis of a number of brain imaging techniques. The vascular response is thought to be too slow to resolve the temporal sequence of events involved in cognitive tasks, and hence, imaging studies of mental chronometry have relied on techniques such as the evoked potential. Using rapid functional MRI (fMRI) of single trials of two simple behavioral tasks, we demonstrate that while the microvascular response to the onset of neural activity is delayed consistently by several seconds, the relative timing between the onset of the fMRI responses in different brain areas appears preserved. We examined a number of parameters that characterize the fMRI response and determined that its onset time is best defined by the inflection point from the resting baseline. We have found that fMRI onset latencies determined in this manner correlate well with independently measurable parameters of the tasks such as reaction time or stimulus presentation time and can be used to determine the origin of processing delays during cognitive or perceptual tasks with a temporal accuracy of tens of milliseconds and spatial resolution of millimeters.

Investigation of BOLD contrast in fMRI using multi-shot EPI.

High resolution volume coverage of the brain in fMRI studies can be accomplished using multi-slice, multi-shot EPI. We demonstrate that the optimum contrast sensitivity in BOLD based fMRI experiments using multi-shot EPI is achieved by using the shortest possible TR values between segments and the longest tolerable echo train length. For a fixed paradigm time, acquiring the largest number of images under these conditions yields the best statistical detection thresholds. For a multi-slice multi-shot EPI fMRI study, the best approach is to perform the acquisition of all the segments in a single slice before continuing on to each of the slices in turn. Our results regarding the number of shots and TR are also applicable to other multi-shot techniques such as interleaved spirals.

A transmit-only/receive-only (TORO) RF system for high-field MRI/MRS applications.

The design and operation of a detunable shielded hybrid birdcage RF head coil optimized for human brain imaging at 170 MHz is presented. A high duty-cycle and rapid-switching decoupling scheme that allows uniform RF transmission with the head coil and reception with a surface coil within the volume of the head coil is also demonstrated. In addition, the circumscribing hybrid coil can be biased to operate as a conventional transmit/receive head coil. Our RF design allows the use of higher sensitivity surface coils or phased-array coils at very high magnetic fields where body RF resonators are not currently available or whose use is precluded by specific-absorption ratio restrictions. The design also allows the use of receive-only coils within head gradient inserts, which normally do not allow transmission with an RF body resonator at any field strength.

Experimental determination of the BOLD field strength dependence in vessels and tissue.

High resolution functional MRI (fMRI) experiments were performed in human visual cortex at 0.5, 1.5, and 4 T to determine the blood oxygenation level dependent (BOLD) field strength response within regions of obvious venous vessels and cortical gray matter ("tissue"). T2*-weighted FLASH images were collected in single- and multi-echo mode and used to determine the intrinsic BOLD parameters, namely, signal-to-noise ratio (psi), the apparent transverse relaxation rate (R2*) and the change in R2* (deltaR2*) between the activated and baseline states. The authors find the average percentage signal change (deltaS/S, measured at TE = T2*) to be large in vessels (13.3 +/- 2.3%, 18.4 +/- 4.0%, and 15.1 +/- 1.2%) compared with that in tissue (1.4 +/- 0.7%, 1.9 +/- 0.7%, and 3.3 +/- 0.2%) at 0.5, 1.5, and 4 T, respectively. The signal-to-noise ratio in optimized, fully relaxed proton density weighted gradient echo images was found to increase linearly with respect to the static magnetic field strength (B0). The predicted upper bound on BOLD contrast-to-noise ratio (deltaS/R)max as a function of field strength was calculated and found to behave less than linearly in voxels containing vessels larger than the voxel itself and greater than linearly in voxels containing a mixture of capillaries and veins/venules with a diameter less than that of the voxel.

Cerebral cortical representation of automatic and volitional swallowing in humans.

Although the cerebral cortex has been implicated in the control of swallowing, the functional organization of the human cortical swallowing representation has not been fully documented. Therefore, the present study determined the cortical representation of swallowing in fourteen healthy right-handed female subjects using single-event-related functional magnetic resonance imaging (fMRI). Subjects were scanned during three swallowing activation tasks: a naïve saliva swallow, a voluntary saliva swallow, and a water bolus swallow. Swallow-related laryngeal movement was recorded simultaneously from the output of a bellows positioned over the thyroid cartilage. Statistical maps were generated by computing the difference between the magnitude of the voxel time course during 1) a single swallowing trial and 2) the corresponding control period. Automatic and volitional swallowing produced activation within several common cortical regions, the most prominent and consistent being located within the lateral precentral gyrus, lateral postcentral gyrus, and right insula. Activation foci within the superior temporal gyrus, middle and inferior frontal gyri, and frontal operculum also were identified for all swallowing tasks. In contrast, activation of the caudal anterior cingulate cortex was significantly more likely in association with the voluntary saliva swallow and water bolus swallow than the naïve swallow. These findings support the view that, in addition to known brain stem areas, human swallowing is represented within a number of spatially and functionally distinct cortical loci which may participate differentially in the regulation of swallowing. Activation of the insula was significantly lateralized to the right hemisphere for the voluntary saliva swallow, suggesting a functional hemispheric dominance of the insula for the processing of swallowing.

Eye position signal modulates a human parietal pointing region during memory-guided movements.

Using functional magnetic resonance imaging, we examined the signal in parietal regions that were selectively activated during delayed pointing to flashed visual targets and determined whether this signal was dependent on the fixation position of the eyes. Delayed pointing activated a bilateral parietal area in the intraparietal sulcus (rIPS), rostral/anterior to areas activated by saccades. During right-hand pointing to centrally located targets, the left rIPS region showed a significant increase in activation when the eye position was rightward compared with leftward. As expected, activation in motor cortex showed no modulation when only eye position changed. During pointing to retinotopically identical targets, the left rIPS region again showed a significant increased signal when the eye position was rightward compared with leftward. Conversely, when pointing with the left arm, the right rIPS showed an increase in signal when eye position was leftward compared with rightward. The results suggest that the human parietal hand/arm movement region (rIPS), like monkey parietal areas (Andersen et al., 1985), exhibits an eye position modulation of its activity; modulation that may be used to transform the coordinates of the retinotopically coded target position into a motor error command appropriate for the wrist.