Temporal spatial differences observed by functional MRI and human intraoperative optical imaging.

Pre-operative functional magnetic resonance imaging (fMRI), cortical evoked potentials (EPs) and intraoperative optical imaging of intrinsic signals (iOIS) were employed to relate the temporal-spatial characteristics of sensorimotor responses in human brain. Peripheral somasthetic stimulation (2 s) was provided either by a 110 Hz finger vibrator or transcutaneous median nerve stimulation in eight patients undergoing neurosurgical procedures. Each technique provided unique spatial patterns and temporal response profiles. EPs and iOIS activities were observed over the surface of pre- and post-central gyri (at the level of the superior genu) with very similar spatial distributions. In contrast, fMRI spatial distributions depended upon the model used for statistical correlation analysis. Using a monophasic response model, fMRI primarily localized within the central sulcus and did not demonstrate large signal changes over the pre- and post-central gyri (areas with iOIS/EP activity). However, as initial negative responses were incorporated into the response model, fMRI progressively localized closer to the iOIS and somatosensory EP maps. Temporally, responses to single stimuli differed between the fMRI and iOIS techniques. Using a monophasic model for fMRI analysis, the total fMRI response was delayed by 2--3 s relative to iOIS. As initial negative responses were incorporated in the analysis, the fMRI time course developed temporal characteristics similar to iOIS. Ultimately, when fMRI time courses were examined over pixels co-localizing with iOIS activation (without using statistical correlation analysis), the fMRI temporal profile included an initial decrease in signal (an initial dip) that closely resembled the time course of iOIS response. This is the first study to experimentally co-localize (temporally and spatially) iOIS and fMRI signals in human subjects. The spatial/temporal differences in this study likely reflect the capillary versus venous contributions of iOIS and fMRI, respectively. The temporal/spatial co-localization of the iOIS signal and the fMRI initial dip suggests the initial fMRI dip and the iOIS signal may result from similar physiologic events.

Optical imaging of bilingual cortical representations. Case report.

The organization of language in the brains of multilingual persons remains controversial. The authors investigated language representations in a proficient bilingual patient by using a novel neuroimaging technique, intraoperative optical imaging of intrinsic signals (iOIS), and a visual object naming task. The results indicate that there are cortical areas that are activated by the use of both English and Spanish languages (superior temporal sulcus, superior and middle temporal gyri, and parts of the supramarginal gyrus). In addition, language-specific areas were identified in the supramarginal (Spanish) and precentral (English) gyri. These results suggest that cortical language representations in bilingual persons may consist of both overlapping and distinct components. Furthermore, this study demonstrates the utility of iOIS in detecting topographical segregation of cognitively distinct cortices.

Characterization of optical intrinsic signals and blood volume during cortical spreading depression.

Cortical spreading depression (CSD) was imaged in vivo in a rodent model with optical intrinsic signals (OIS). This is the first study to identify a triphasic OIS response and to characterize the rate and timing of the response. The initial OIS phase had a highly uniform wavefront, which spread at a rate characteristic of CSD, 3.5 mm/min. Later phases were more diffuse and inhomogeneous. Blood volume changes, measured with intravascular fluorescent dye, correlated in time and location with the later phases of OIS response. This suggests that the inhomogeneity of the late OIS response may be due to complex residual hemodynamic contributions, as opposed to underlying cortical circuitry.

Temporal and topographical characterization of language cortices using intraoperative optical intrinsic signals.

We used intraoperative optical imaging of intrinsic signals (iOIS) and electrocortical stimulation mapping (ESM) to compare functionally active brain regions in 10 awake patients undergoing neurosurgical resection. Patients performed two to four tasks, including visual and auditory naming, word discrimination, and/or orofacial movements. All iOIS maps included areas identified by ESM mapping. However, iOIS also revealed topographical specificity dependent on language task. In Broca's area, naming paradigms activated both anterior and posterior inferior frontal gyrus (IFG), while the word discrimination paradigm activated only posterior IFG. In Wernicke's area, object naming produced activations localizing over the inferior and anterior/posterior regions, while the word discrimination task activated superior and anterior cortices. These results may suggest more posterior phonological activation and more anterior semantic activations in Broca's area, and more anterior/superior phonological activation and more posterior/inferior semantic activations in Wernicke's area. Although similar response onset was observed in Broca's and Wernicke's areas, temporal differences were revealed during block paradigm (20-s) activations. In Broca's area, block paradigms yielded a boxcar temporal activation profile (in all tasks) that resembled response profiles observed in motor cortex (with orofacial movements). In contrast, activations in Wernicke's area responded with a more dynamic profile (including early and late peaks) which varied with paradigm performance. Wernicke's area profiles were very similar to response profiles observed in sensory and visual cortex. The differing temporal patterns may therefore reflect unique processing performed by receptive (Wernicke's) and productive (Broca's) language centers. This study is consistent with task-specific semantic and phonologic regions within Broca's and Wernicke's areas and also is the first report of response profile differences dependent on cortical region and language task.

Mapping morphology of the corpus callosum in schizophrenia.

The nature and extent of callosal morphological alterations in schizophrenia remain unresolved. A parametric surface modeling approach using magnetic resonance (MR) images was employed. This provided spatially accurate representations of midsagittal callosal surfaces in schizophrenic patients (n = 25; 15 males) and normal controls (n = 28; 15 males). Areas of functionally relevant callosal channels and measures reflecting callosal shape were visualized and compared across groups. To register neuroanatomical landmarks surrounding the corpus callosum, each three-dimensional MR volume was scaled according to Talairach AC-PC distance, and raw distances included as covariates in multivariate analyses. Results revealed: (i) a marked vertical displacement of the corpus callosum in patients (P < 0.01); (ii) increases in curvature of superior and inferior callosal surfaces (P < 0.001); and (iii) significant increases in maximum widths in anterior and posterior regions in male patients compared to male controls; as well as (iv) increased patterns of callosal variability in female patients but no effects of diagnosis between female groups. These findings demonstrate a clear index of structural neuropathology in male schizophrenic patients. Displacement and curvature increases were highly correlated with structural differences in surrounding neuroanatomical regions, including increased volume of the lateral ventricles (P < 0.01).

Refractory periods observed by intrinsic signal and fluorescent dye imaging.

All perfusion-based imaging modalities depend on the relationship between neuronal and vascular activity. However, the relationship between stimulus and response was never fully characterized. With the use of optical imaging (intrinsic signals and intravascular fluorescent dyes) during repetitive stimulation paradigms, we observed reduced responses with temporally close stimuli. Cortical evoked potentials, however, did not produce the same reduced responsiveness. We therefore termed these intervals of reduced responsiveness "refractory periods." During these refractory periods an ability to respond was retained, but at a near 60% reduction in the initial magnitude. Although increasing the initial stimulus duration lengthened the observed refractory periods, significantly novel or temporally spaced stimuli overcame them. We observed this phenomenon in both rodent and human subjects in somatosensory and auditory cortices. These results have significant implications for understanding the capacities, mechanisms, and distributions of neurovascular coupling and thereby possess relevance to all perfusion-dependent functional imaging techniques.

Topographical and temporal specificity of human intraoperative optical intrinsic signals.

The goal of this study was to determine the topographical and temporal specificity of neuronal and vascular responses using an intraoperative optical technique (iOIS). The face, thumb, index, and middle fingers were stimulated individually to obtain separate maps of cortical activation. Peak optical responses provided unique, non-overlapping cortical brain maps. Non-peak signals were more dispersed and produced overlapping responses from different digits. Peak iOIS responses colocalized with electrocortical stimulation mapping and evoked potentials. Temporally, we observed statistically significant specificity corresponding to sequential cortical activation during early optical signals (500-1750 ms), but later perfusion responses were non-specific. To our knowledge, this is the first report of either topographical specificity in overlapping spatial patterns, and/or temporal specificity in early perfusion profiles. These results therefore may have significant implications for other perfusion dependent functional imaging techniques.

A three-dimensional multimodality brain map of the nemestrina monkey.

A three-dimensional multimodality computerized map of the nemestrina monkey brain was created with serial sectioning and digital imaging techniques. An adult female Macaca nemestrina (pigtail macaque) weighing 7.2 kg was used in constructing this atlas. CT, PET, and MRI were performed on the monkey before the specimen's head was frozen and cryoplaned. Closely spaced (50 microns) images of the specimen blockface were then digitally acquired and modified to produce whole head and brain-only 3D image sets. The resulting data sets were organized into a digital volume and repositioned into a stereotaxic coordinate system defined by Horsley and Clark in 1908 [7]. Orthogonal images were obtained by digitally resampling the volume in order to produce a full set of coronal, sagittal, and horizontal images. Stereotaxic reference grids were applied to each image indicating the A/P, M/L, or Ho position within the digital volume. Specific anatomic structures were outlined from the cryosection data set and 3D surface models reconstructed. Structural labels indicating nuclei, tracts, and other neuroanatomical features were incorporated into coronally sliced cryosection images spaced at 500 microns. The CT, PET, and MRI data sets were reconstructed into a digital volume and coregistered to the cryosection volume. All images constructed from this 3D map are available for public access via the internet using an anonymous file transfer protocol (FTP) and the World Wide Web (http:@www.loni.ucla.edu). The foremost advantage of this digital map is an integrated multimodality three-dimensional representation of the Macaca nemestrina brain, which is not possible with traditional atlases.

The evolution of optical signals in human and rodent cortex.

The time course of optical intrinsic signals was examined in order to characterize the evolution of response in human and rodent cortex. Both subtraction/ratio and principal component analyses were used to construct time-course curves. The time course began at a prestimulus baseline, responded with a finite delay, overcompensated, reduced to a maintenance level, and then disappeared. The magnitude, spatial involvement, and principal components demonstrated similar time-course curves both in human and in rodent. For acute stimuli, peak response was reached between 2 and 3 s and returned to baseline by 6 s poststimulation. The shape of the time-course curve is consistent with the need to satisfy neuronal demand and the contributions of vascular smooth muscle properties to the response behavior. The temporal delays and nonlinear phenomena observed in the time-course curves are consistent with a hydraulic model of neurovascular supply/demand behavior.

The temporal/spatial evolution of optical signals in human cortex.

Intraoperative measures of functioning brain are an important aspect to understanding normal and diseased cortical response. Previous studies, in animal models, have used optical reflectance maps to illustrate the location and timing of functional activity. We used optical reflectance mapping in patients undergoing parietal tumor resection to reveal the temporal/spatial evolution of perfusion and other related metabolic responses of sensorimotor cortex to peripheral somesthetic stimulation. The somatosensory cortex of seven anesthetized patients was mapped in response to transcutaneous electrical median and ulnar nerve stimulation using optical reflectance imaging. The time course and spatial extent of this response were measured and correlated with evoked potential maps collected during the same conditions. Observable signals first appeared within 1-2 sec, peaked at 3 sec, and disappeared by 9 sec. These signals colocalized with the largest evoked potentials in both the sensory and motor regions and demonstrated topological specificity with median and ulnar nerve stimulation. Maps of this temporal/spatial resolution illustrate the integrative and dynamic nature of the neuronal, vascular, and metabolic responses of human cortex. These data also provide insight to the mechanisms responsible for signals obtained using other brain imaging techniques such as PET and fMRI.