Larry Schuster

With help from navigational MRI, researchers at the University of California, San Francisco have assembled the largest composite map of the brain's language sites ever to appear in the medical literature. They found far greater variability in the location of these sites than other models of language organization suggest.

The study of language mapping was based on navigational MR images from 250 consecutive conscious patients during glioma surgery. 

Prior to the study, the understanding of where language sites were localized was limited, according to first author Dr. Nader Sanai, a senior resident in neurological surgery at UCSF. Historically, it was based on case reports of injuries due to impact trauma, stroke, projectile injury, or surgery, when those injuries caused language problems.

"What this composite map showed us was there is a much larger degree of variation than what had previously been acknowledged," Sanai said.

In the study, surgeons found nearly half of their patients had no positive language sites within 2 cm of the surgical site. More than 94% of cortical stimulations in these patients were negative, yet their functional outcomes remained acceptable. Only 1.6% of surviving patients had a persistent language deficit six months after surgery.

Sanai found during a literature search that no previously published composite brain map of language employed data from as many patients as the UCSF study.

Brain images for the study were acquired in a standard clinical MR scanner before surgery. The resulting images depicted the patient's brain as well the spatial relationship between brain anatomy and fiducial markers that were placed on the patient's scalp before the procedure.

Patients were transported to the operating room after their heads were immobilized using three-point fixation. The surgeon used a wireless wand with an infrared aiming mechanism on its tip to identify the location of the fiducial marks. A computer created a map establishing the spatial relationship of the markers and brain anatomy in 3D space.

The surgeon again employed the wand for real-time guidance during surgery. With the wand aimed at a region of interest, software automatically displayed the corresponding axial, coronal, and sagittal images with a cross-hair on the point that was localized. 

During the mapping procedures, surgeons sequentially stimulated each square centimeter of the patient's cortex to determine presence of a language site. Then, for each square centimeter, they put down a sterile piece of paper with a number to form a grid of markers across the surface of the brain, with each marker corresponding to where language did and did not reside. 

Sanai and colleagues compiled data for the composite map from glioma resections performed at UCSF from 1997 to 2005. Their results were reported in the Jan. 3 issue of 

Clinically, the mapping technique proved effective. Overall, 159 of 250 patients (63.6%) had intact speech, and 91 (36.4%) has some language deficit before surgery. One week after resection, the language function of 194 patients was unaffected from surgery or had improved. Language problems appeared for the first time for 35 patients and worsened for 21 patients. After one month, however, the number of patients with exacerbated preexisting language deficits dropped to 16 (6.4%), and only eight patients (3.2%) who were free of language deficit before surgery developed a new language deficit afterward.

The composite will be used to provide a template for future operative planning and analysis for how language is organized, Sanai said. It already has implications for neurosurgeons.

"Historically, neurosurgeons believed it was essential to identify the areas where language was located before any nonfunctional area could be safely resected," the researchers wrote. "That's no longer the case."

Now, instead of seeking to identify every possible language site on the surface of the cortex prior to resection, surgeons may safely restrict their language mapping activities to a 2-cm area immediately bordering a tumor, Sanai said.

The protocol saves time because less brain is exposed and a smaller area of the brain's surface must be mapped, he said. 

For more information from the Diagnostic Imaging archives: 

Preoperative brain mapping alters tumor surgery

fMRI links brain connectivity pattern with reading problems in dyslexic children

fMRI test assumption about behavior and thought

Articles

With help from navigational MRI, researchers at the University of California, San Francisco have assembled the largest composite map of the brain’s language sites ever to appear in the medical literature. They found far greater variability in the location of these sites than other models of language organization suggest.

Navigational MRI charts language map of brain

Can functional MRI detect the anatomic point of origin of belief in a personal God? That profound physiological and philosophical question has been answered in the affirmative by Mark S. Cohen, Ph.D., and colleagues at the University of California, Los Angeles Center for Cognitive Neuroscience and the UCLA Brain Mapping Center.Their 3T fMRI investigation of seven men and seven women, aged 18 to 45 years, found that states of belief, disbelief, and uncertainty in normal adults differentially activate distinct regions of the prefrontal and parietal cortices as well as the basal ganglia. The same regions are associated with primitive emotions such as disgust and anger. The correlation among beliefs, disbeliefs, and emotions led the UCLA researchers to insights about the heartfelt nature of strong convictions. Cohen, a professor of psychiatry and biobehavioral science, was the senior author of a paper describing the results that was released Dec. 10, ahead of publication in the 

 Sam Harris, a graduate student in UCLA's Ahmanson-Lovelace Brain Mapping Center was first author.

Subjects were presented through a video-goggle display worn over their eyes with a series of short statements, including:

 A personal God exists, just as the Bible describes

 Jesus spoke 2467 words in the New Testament

After reading each statement, they were asked to evaluate its truth content with the press of a button, indicating "true" (belief), "false" (disbelief), and "undecidable" (uncertainty).

Volunteers also responded to statements from mathematics, geography, ethics, and semantics. These were designed to disclose the subject's belief, disbelief, or uncertainty regarding their veracity.Functional data were acquired on a 3T scanner in the anterior commissure-posterior commissure orientation using T2*-weighted echo-planar imaging. Anatomic images were acquired using a magnetization-prepared rapid gradient-echo sequence.Maps of blood oxygen level-dependent signal changes were the result of pairwise contrasts between each of the three task conditions.Cohen told Diagnostic Imaging that the research team was surprised by the high level of limbic system involvement. Previous fMRI research had implicated the limbic system with primitive behaviors."The data very strongly suggest that we do our believing with our gut. I think they tell us we are not going ahead and simply evaluating the facts," he said.The findings regarding limbic system involvement may explain why people hold on to beliefs long after demonstrable facts prove them wrong, he said.Dr. Richard Frackowiak, a professor of cognitive neurology at University College London in the U.K., was less surprised about the limbic system involvement. A judgment of the type used in the study also often elicits an emotional response, and the exercise may have resulted in cross-referencing to memories as well, he said.When the researchers contrasted belief and disbelief, across all stimulus categories, they identified a discrete region of MRI signal increase in the ventromedial prefrontal cortex, specifically in rostral regions of the gyrus rectus and the orbitomedial gyrus, predominantly in the left hemisphere."These results suggest that the differences among belief, disbelief, and uncertainty may one day be distinguished reliably, in real-time, by techniques of neuroimaging. This would have obvious implications for the detection of deception, for the control of the placebo effect during the process of drug design," the UCLA researchers wrote."The reasons you might want to have a belief or truth detector is that you might be able to avoid a lot of mess associated with extracting information from people by other means, say instead of torture. Wouldn't it be much more humane?" Cohen said. "For me personally, the notion of having a tool that goes and looks inside your head and interrogates its private thoughts is a scary possibility, and that's not what this work is about and that's not our intent in any way."For more information from the Diagnostic Imaging archives:

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Can functional MRI detect the anatomic point of origin of belief in a personal God? That profound physiological and philosophical question has been answered in the affirmative by Mark S. Cohen, Ph.D., and colleagues at the University of California, Los Angeles Center for Cognitive Neuroscience and the UCLA Brain Mapping Center.

fMRI maps anatomical origins of belief in God

Researchers have discovered a unique biomarker for neural progenitor and stem cells detectable with 3T proton MR spectroscopy. It noninvasively establishes the presence of the cells and their decreasing prominence with age in the brains of children, adolescents, and adult humans. 

Principal investigator Dr. Mirjana Maletic-Savatic and colleagues at the State University of New York at Stony Brook, Cold Spring Harbor Laboratory, and Brookhaven National Laboratory identified the presence of neural stem and progenitor cells (NPCs) by following an MR spectrum with a profile featuring a prominent peak at the frequency of 1.28 ppm that is unique to those cells. 

The biomarker was further validated using bromodeoxyuridine (BrdU) to label dividing cells in both ex vivo and in vivo mouse experiments. Neurogenesis was stimulated by electroconvulsive shock.

The 1.28 ppm biomarker most likely represents a mixture of lipids that includes saturated fatty acids and monounsaturated fatty acids, according to the authors. The precise relationship of the lipid mixture with neurogenesis has not yet been established.

The study was published in the Nov. 9 issue of 

"The implications are huge if reproduced independently," said Jeff W.M. Bulte, Ph.D., director of the Institute for Cell Engineering at Johns Hopkins University School of Medicine. "It looks like they have a peak that is fairly specific. I think this will generate a lot of interest." 

Bulte, who was not involved in the study, anticipates a rush of animal studies to explore the potential of the new biomarker for a wide range of questions - and possible drug therapies - in neurology and psychiatry, particularly depression and bipolar disorder.

The researchers have already made significant progress in human studies. Following the initial discovery and verification, Maletic-Savatic and her team demonstrated for the first time in vivo an age-related decrease in neurogenesis in the hippocampus of normal individuals from preadolescence to adulthood. 

Proton MRS was performed at 3T on three preadolescents (ages eight to 10), three adolescents (ages 14 to 16), and five adults (ages 30 to 35) to record any age-related changes in the density of endogenous NPCs in the hippocampus.

Maletic-Savatic found that declines in amplitude at 1.28 ppm correlated with the increasing age of the subjects.

For the preadolescents, the 1.28 ppm mean peak area was 50 x 10

). For the adolescents, the mean peak area was 26 x 10

). All the differences were highly statistically significant. 

"These are the first data from the living human brain that indicate a decrease in NPCs during brain development from childhood to adulthood," the authors wrote. 

The decrease in neurogenesis in humans was greater than expectations based on the results of animal studies, Maletic-Savatic said in an interview with 

 The effect of the decrease on the aging human brain is unknown. 

Maletic-Savatic said her work complements findings published earlier this year by Dr. Scott A. Small and colleagues at the Columbia University College of Physicians and Surgeons who reported another noninvasive in vivo correlate of neurogenesis - MRI measurements of cerebral blood volume (Proc Natl Acad Sci USA 104, 5638-5643). 

Small's correlate, which was applies to both rodents and humans, represents neural cell differentiation and integration.

"These are the two sides of the pathway," Maletic-Savatic said.

She is collaborating with Small and other researchers on studies to explore the role of NPCs in depression. 

 follows a 2006 report by Bulte and others, in which they reported using proton NMR spectroscopy to identify the major low-molecular-weight metabolites in murine embryonic stem cells and their neural stem cell derivatives - potential markers to study the effects of differentiation on cell metabolism (Magn Reson Med 2006;56:666-670).

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Researchers have discovered a unique biomarker for neural progenitor and stem cells detectable with 3T proton MR spectroscopy. It noninvasively establishes the presence of the cells and their decreasing prominence with age in the brains of children, adolescents, and adult humans.

Larry Schuster

Articles

Navigational MRI charts language map of brain

fMRI maps anatomical origins of belief in God

Proton MR spectroscopy monitors neural progenitor cells in human brain