Andrew F. Cannestra

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 Brocas area, naming paradigms activated both anterior and posterior inferior frontal gyrus (IFG), while the word discrimination paradigm activated only posterior IFG. In Wernickes 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 Brocas area, and more anterior/superior phonological activation and more posterior/inferior semantic activations in Wernickes area. Although similar response onset was observed in Brocas and Wernickes areas, temporal differences were revealed during block paradigm (20-s) activations. In Brocas 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 Wernickes area responded with a more dynamic profile (including early and late peaks) which varied with paradigm performance. Wernickes 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 (Wernickes) and productive (Brocas) language centers. This study is consistent with task-specific semantic and phonologic regions within Brocas and Wernickes areas and also is the first report of response profile differences dependent on cortical region and language task.

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.

Spatial/temporal correlation of BOLD and optical intrinsic signals in humans

Comparing the BOLD signal with electrophysiological maps and other perfusion‐dependent signals, such as the optical intrinsic signal (OIS), within subjects should provide insight into the etiology of the BOLD signal. Tongue activations were compared in five human subjects using BOLD fMRI, 610‐nm OIS, and the electrocortical stimulation map (ESM). Robust fMRI activations centered on the lateral inferior aspect of the central sulcus and extended into pre‐ and post‐central gyri, adjacent to ESM tongue loci. OIS and fMRI maps colocalized, although optical responses were spatially larger (P < .001 across multiple thresholds) and contained more gyral components. The timecourses of the fMRI and OIS signals were similar, appearing within 2.5 s and peaking 6–8 s after task onset. Although many processes contribute to increased 610‐nm reflectance, optical spectroscopy and fluorescent dye imaging suggest that a significant part of this signal is due to a concomitant decrease in deoxyhemoglobin and increase in oxyhemoglobin concentrations. The spatial/temporal correlation of BOLD and the positive 610‐nm response within subjects suggests that the two signals may share similar etiologies. The OIS/fMRI inconsistencies may be due to cell swelling and light‐scattering contributions to OIS and fMRI sensitivity. This study also demonstrates that fMRI maps do not precisely colocalize with ESM, rather they emphasize changes in adjacent venous/sulcal structures. Magn Reson Med 47:766–776, 2002.

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.

Functional assessment of Broca's area using near infrared spectroscopy in humans.

We used near-infrared spectroscopy (NIRS) to compare functional hemoglobin concentration changes (delta[oxy-Hb] and delta[deoxy-Hb]) over human language and motor cortices. Eight subjects performed finger opposition, tongue movement, and covert visual object naming in an interleaved block paradigm design. NIRS revealed paradigm specific patterns of delta[oxy-Hb] and delta[deoxy-Hb] providing cortical localization of each function. During each task, significant response overlap was observed when comparing the [oxy-Hb] signals, whereas delta[deoxy-Hb] seemed more localized. Furthermore, by applying magnitude and time to significance measures to the delta[deoxy-Hb] response profile, Brocas area was easily distinguished from neighboring tongue (and hand) motor representation. Delta[oxy-Hb] did not provide this level of specificity. These findings suggest delta[deoxy-Hb] as the preferential NIRS parameter to map language cortices.

Functional Magnetic Resonance Imaging and Optical Imaging for Dominant-hemisphere Perisylvian Arteriovenous Malformations

OBJECTIVE:In this study, we developed an a priori system to stratify surgical intervention of perisylvian arteriovenous malformations (AVMs) in 20 patients. We stratified the patients into three categories based on preoperative functional magnetic resonance imaging (fMRI) language activation pattern and relative location of the AVM. METHODS:In Group I (minimal risk), the AVM was at least one gyrus removed from language activation, and patients subsequently underwent asleep resection. In Group II (high risk), the AVM and language activation were intimately associated. Because the risk of postoperative language deficit was high, these patients were then referred to radiosurgery. In Group III (indeterminate risk), the AVM and language were adjacent to each other. The risk of language deficit could not be predicted on the basis of the fMRI alone. These patients underwent awake craniotomy with electrocortical stimulation mapping and optical imaging of intrinsic signals for language mapping. RESULTS:All patients from Group I (minimal risk) underwent asleep resection without deficit. All Group II (high-risk) patients tolerated radiosurgery without complication. In Group III (indeterminate risk), three patients underwent successful resection, whereas two underwent aborted resection after intracranial mapping. CONCLUSION:We advocate the use of fMRI to assist in the preoperative determination of operability by asleep versus awake craniotomy versus radiosurgery referral. In addition, we advocate the use of all three functional mapping (fMRI, electrocortical stimulation mapping, and optical imaging of intrinsic signals) techniques to clarify the eloquence score of the Spetzler-Martin system before definitive treatment (anesthetized resection versus radiosurgery versus intraoperative resection versus intraoperative closure and radiosurgery referral).

Near-infrared spectroscopy (NIRS) in cognitive neuroscience of the primate brain

We describe the use of near-infrared spectroscopy (NIRS) as a suitable means of assessing hemodynamic changes in the cerebral cortex of awake and behaving monkeys. NIRS can be applied to animals performing cognitive tasks in conjunction with electrophysiological methods, thus offering the possibility of investigating cortical neurovascular coupling in cognition. Because it imposes fewer constraints on behavior than fMRI, NIRS appears more practical than fMRI for certain studies of cognitive neuroscience on the primate cortex. In the present study, NIRS and field potential signals were simultaneously recorded from the association cortex (posterior parietal and prefrontal) of monkeys performing two delay tasks, one spatial and the other non-spatial. Working memory was accompanied by an increase in oxygenated hemoglobin mirrored by a decrease in deoxygenated hemoglobin. Both the trends and the amplitudes of these changes differed by task and by area. Field potential records revealed slow negative potentials that preceded the task trials and persisted during their memory period. The negativity during that period was greater in prefrontal than in parietal cortex. Between tasks, the potential differences were less pronounced than the hemodynamic differences. The present feasibility study lays the groundwork for future correlative studies of cognitive function and neurovascular coupling in the primate.

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 specimens 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.

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 reponse. This suggests that the inhomogeneity of the late OIS response may be due to complex residual hemodynamic contributions, as opposed to underlying cortical circuitry.

Optical imaging of bilingual cortical representations

✓ 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.