Jonathan C. Horton
Boundary disputes
Nature 406: 565 (10 Aug 2000)

Discussion and Abstract by Science News

ON LOCALIZATION OF FUNCTION IN THE HUMAN BRAIN

For more than 200 years, neurobiologists have been concerned with the general problem of what is called "localization of function" in the human brain. That there is considerable localization of function is indisputable: there are brain regions involved with specific primary inputs such as vision, audition, taste, etc., brain regions for specific primary outputs to various muscle systems, and brain regions for speech and the understanding of language. The still unclear aspects concern anatomical localization of other so-called "higher faculties", e.g., learning, memory, perceptual analysis, motivations, various other cognitive abilities, etc.

Classical studies of localization of function in the human brain essentially began with Franz Joseph Gall (1758-1828), who postulated that the shape of the human brain, especially its convolutions, was related to "mental capacity", and that different parts of the brain were involved with different parts of the human body. This latter proposal concerning the relation between different parts of the brain and different parts of the body was essentially a correct view. But Gall also believed he could correlate the shape of the human brain with various emotional and temperamental qualities, and that the shape of the brain, particularly its convolutions, could be deduced from the irregularities existing in the topology of the overlying skull. Thus began the 19th century pseudoscience of "phrenology", a quackery that postulated that various human character traits could be identified by literally feeling bumps on the head. The public adored the idea, and so-called "phrenologists" continued to bamboozle the public long after Gall was dead. What started as a useful view that correlated brain anatomy with function, ended in a popular pseudoscience that still had the public confused and misled 100 years later.

The next most important figure in this field was Pierre Paul Broca (1824-1880), a neurosurgeon who in 1861 discovered the motor area of the brain responsible for speech, and who studied a series of patients with traumatic injuries in this area. As a result of Broca's work, the idea that at least certain brain functions are localized was put on a firm scientific footing, and a long history of research by clinical neurologists attempting to correlate traumatic brain injury to loss of specific brain function began. Beginning in the 1950s, evidence from localized electrophysiological studies was added to the data resulting from studies of traumatic brain injury, and in the 1990s an entirely new set of data from *functional magnetic resonance imaging of the human brain in action became available to researchers studying localization of brain function. This field is now intensely active and of signal importance in neurology and cognitive science. But the human brain is profoundly complex, and there are still more questions than answers about how things get done in this 1400-gram mass of tissue that makes us what we are. The term "cortex" (cerebral cortex), in this context, refers to the thin surface layering of nerve cells of the brain, the region only several millimeters thick but covering all of the brain surface. This is the part of the central nervous system most intimately involved with the so-called "higher faculties", although the cortex generally operates in concert with other parts of the brain. The structure is primitive in lower mammals, and is found progressively more pronounced and with greater surface area in primates and man. Many contemporary neurobiologists who study the brain emphasize precise "mapping" of the cerebral cortex into "areas" associated with specific functions.

Jonathan C. Horton (University of California San Francisco, US) presents an essay on localization of function in the human brain, the author making the following points:

1. Given the limitations of histology, researchers often designate areas in brain cortex by topography. For example, any region that contains its own representation of the visual world qualifies for "area" status. Unfortunately, topographic order in other than primary visual areas ("higher" visual areas) is often too crude to provide a reliable definition of boundaries. Another limitation is that topography may not be meaningful outside sensory and motor cortices. The author asks: "What constitutes topography in regions concerned with language, motivation, or personality?"
   
   
2. The author points out that relentless experimental efforts and a battery of technical advances have provided us with better maps of the brain. But much of the cortex stubbornly refuses to be mapped, and the author suggests it is worth questioning the assumption that the cerebral cortex consists of a finite number of areas with sharp borders. An alternative is that only certain regions -- mostly motor and sensory cortex -- are organized in this way. Other regions might be diffuse fields separated by gradual transitions in function, properties, and connections. As Broca said in 1861: "Although I believe in the principle of localization, I have asked and still ask myself within what limits this principle can be applied." The author (Horton) concludes: "For brain cartographers, the last frontier is in their heads."
   

QY: Jonathan C. Horton, Univ. of Calif. San Francisco 415-476- 4044.

Summary by SCIENCE-WEEK http://scienceweek.com 1Sep00
For more information: http://scienceweek.com/swfr.htm

Related articles

IMAGING THE FUNCTIONING HUMAN BRAIN

For most of this century, research on the human brain concerned with relating structure to function depended in general on clinical studies (both postmortem and in living patients), investigations that correlated specific brain traumas to specific behaviors and behavioral defects. In addition to these studies, there were related studies in animal models in which various surgical and pharmacological interventions were correlated with animal behavior, but animal models have limited utility when the so-called "higher functions" in humans are the focus of investigation. Then, approximately 20 years ago, new "imaging" technology became available, methods that allow non-invasive identification of those parts of the human brain activated by specific behaviors. These new technologies have revolutionized the field of brain physiology, and neurobiologists now anticipate a near-future acceleration of our understanding of the relation between the brain and behavior.

... ... X. Weng et al (3 authors at 3 installations, CN US) present a short review of recent work on imaging the functioning human brain, the authors making the following points: 1) Functional brain imaging techniques have made significant advances during the past decade. These techniques allow the identification of the functional anatomy of cognitive processes, the characterization of temporal correlations of brain activity identification of the functional anatomy of cognitive processes, the characterization of temporal correlations of brain activity and behavior, and the examination of regional changes of physiological and biochemical processes. Among various imaging modalities, *functional magnetic resonance imaging (fMRI) and *positron-emission tomography (PET) have seen the most technical advances.

2) Functional magnetic resonance imaging measures oxygenation-level-dependent activity. Recently, thanks to advances in fast imaging techniques and a refinement in our understanding of the relationship between neuronal activity and associated cerebrovascular hemodynamics, a new method -- event- related fMRI -- has been developed. This new method is significant because the procedure allows for selective averaging of individual trials in mixed task paradigms, which permits exploration of brain function with experimental paradigms similar to those used in traditional behavioral and electrophysiological studies. Event-relate fMRI has quickly led to a number of applications in cognitive neuroscience.

3) Positron-emission tomography is a sensitive imaging method that uses radiotracers labeled with short-lived positron- emitting isotopes to track chemical transformation in a living system. The technique measures radioisotope concentrations in the nanomolar-picomolar range. Another unique feature of PET is its biochemical selectivity to molecular targets such as cell receptors, transporters, or enzymes involved in the synthesis or metabolism of neurotransmitters. PET has thus been extensively receptors, transporters, or enzymes involved in the synthesis or metabolism of neurotransmitters. PET has thus been extensively used for biochemical and pharmacological imaging of the human brain, in addition to its wide use to identify the anatomical correlates of cognitive processes. -----------

X. Weng et al: Imaging the functioning human brain. (Proc. Natl. Acad. Sci. US 28 Sep 99 96:11073) QY: Xuchu Weng wengxc@psych.ac.cn -----------

Text Notes:

... ... *functional magnetic resonance imaging (fMRI): We must first distinguish between magnetic resonance imaging (MRI) and "functional" magnetic resonance imaging (fMRI) as applied to the brain. The former is essentially a technique for examining morphology, while the latter is a technique for examining activity of brain tissue. Both techniques involve computerized analysis of data. In general, MRI involves magnetic coils producing a static magnetic field parallel to the long axis of the patient or subject, combined with inner concentric magnetic coils producing a static magnetic field perpendicular to the long axis. A radio-frequency coil specifically designed for the head perturbs the static fields to generate a magnetic resonance image. The interaction physics in this technique is that between the magnetic fields and atomic nuclei in brain tissue. "Sliced" views can be obtained from any angle, and the resolution is quite high and on the order of millimeters for current magnetic field views can be obtained from any angle, and the resolution is quite high and on the order of millimeters for current magnetic field strengths of 1.5 tesla. Functional magnetic resonance imaging (fMRI), the variant of MRI discussed here, is based on the fact that oxyhemoglobin, the oxygen-carrying form of hemoglobin, has a different magnetic resonance signal than deoxyhemoglobin, the oxygen-depleted form of hemoglobin. Activated brain areas utilize more oxygen, which transiently decreases the levels of oxyhemoglobin and increases the levels of deoxyhemoglobin, and within seconds the brain microvasculature responds to the local change by increasing the flow of oxygen-rich blood into the active area. This local response thus leads to an increase in the oxyhemoglobin-deoxyhemoglobin ratio, which forms the basis for the fMRI signal in this technique. Because of its high spatial resolution (millimeters) and high temporal resolution (seconds) compared to other imaging techniques, fMRI is now the technology of choice for studies of the functional architecture of the human brain.

... ... *positron-emission tomography (PET): This is a technique for producing cross-sectional images of the body after ingestion and systemic distribution of safely metabolized positron-emitting agents. The images are essentially functional or metabolic, since the ingested agents are metabolized in various tissues. Fluorodeoxyglucose and H(sub2)O(sup15) are common agents used for cerebral applications, and in cerebral applications of central importance to the technique is the fact that changes in the cellular activity of the brains of normal, awake humans and importance to the technique is the fact that changes in the cellular activity of the brains of normal, awake humans and unanesthetized laboratory animals are invariably accompanied by changes in local blood flow and also changes in oxygen consumption.

Summary & Notes by SCIENCE-WEEK http://scienceweek.com 26Nov99
For more information: http://scienceweek.com/swfr.htm -------------------

Related Background:
BRAIN ACTIVITY CORRELATES OF VISUAL AND VERBAL MEMORY

In contemporary human neurobiology, memory is categorized into two types: declarative memory (available to consciousness) and procedural memory (generally not available to consciousness). Declarative memory includes memory for such things as daily episodes, words and their meanings, and history. Procedural memory includes motor skills, associations, puzzle solving skills, and so on. Identification of the neurological correlates of memory in humans has until recently been based on slow advances produced primarily by clinical evidence resulting from localized traumatic injuries and localized tissue damage caused by various diseases (all termed "lesions").

But the pace of research in this field has now markedly increased due to several new imaging techniques that allow identification of brain regions activated in normal conscious subjects during various mental tasks. The technique called "*functional magnetic resonance imaging" (fMRI) is now an ascendant methodology, and this is the tasks. The technique called "*functional magnetic resonance imaging" (fMRI) is now an ascendant methodology, and this is the technique that forms the basis for this report. (fMRI technical details are provided in the notes below.) From clinical data involving brain damage, it has long been known that one region essential for declarative memory is the *medial temporal lobe of the brain: bilateral damage to this brain region produces global amnesia, a pervasive memory deficit for all new events and new facts. There is additional brain damage evidence that regions of the frontal lobes also contribute to declarative memory. Memory deficits resulting from unilateral medial temporal lobe or frontal lobe damage are often specific, with left-side lesions impairing verbal memory, and right-side lesions impairing nonverbal memory. Brain lesion studies, however, cannot distinguish whether a given brain region normally participates in the encoding of ongoing experiences into memories, or the storage of the memories over time, or the later retrieval of those memories. In contrast, the newer methods of functional neuroimaging can indeed make such distinctions.

... ... J.B. Brewer et al report the use of event-related functional magnetic resonance imaging to identify specific brain activations that differentiated between visual experiences that were later remembered well, remembered less well, or forgotten. During fMRI scanning of medial temporal lobe and frontal lobe regions, subjects viewed complex color photographs, and subjects later received a test of memory for the photographs. The authors report their results indicate that the degree of activation in right received a test of memory for the photographs. The authors report their results indicate that the degree of activation in right frontal lobe and bilateral *parahippocampal regions measures how well a particular visual experience is encoded, and that the degree of activation therefore predicts whether the visual experience will be remembered well, remembered less well, or forgotten by the individual.

... ... In a contiguous paper, A.D. Wagner et al report a study of human brain activation during word encoding, the study involving two different experimental designs and the use of functional magnetic resonance imaging to examine how brain activation differs for subsequently remembered and subsequently forgotten verbal experiences. The authors report their results indicate the ability to later remember a verbal experience is predicted by the magnitude of activation in left *prefrontal and temporal cortices during the experience. The authors suggest these findings provide direct evidence that left prefrontal and temporal regions jointly promote memory formation for verbal experiences.

J.B. Brewer et al (5 authors at Stanford University, US): Making memories: Brain activity that predicts how well visual experience will be remembered. (Science 21 Aug 98 281:1185)

QY: James B. Brewer <brewer@psych.stanford.edu>

A.D. Wagner et al (8 authors at Harvard University, US): Building memories: Remembering and forgetting of verbal experiences as predicted by brain activity. (Science 21 Aug 98 281:1188)

QY: Anthony D. Wagner adwagner@nmr.mgh.harvard.edu

Text Notes:

... ... *functional magnetic resonance imaging: See notes in reports above.

... ... *medial temporal lobe: The temporal lobes are roughly the lower sides of the brain, above the ears and behind the temporal bones of the skull, but when the human brain is viewed from the side, as it usually is in common gross depictions, the large and functionally important ventral and infolded parts of the temporal lobes are not visible. In general, the larger anatomical regions of the human brain are best visualized as highly corrugated lobular structures extensively folded and densely packed to fit inside the volume-limiting protective skull. But isolated verbal descriptions of the architecture are of limited use: anatomical graphics are the best sources for visualization of gross brain structures.

... ... *parahippocampal regions: These are parts of the temporal lobes, visible only when the temporal lobes are unfolded away from the main brain mass.

... ... *prefrontal: The portion of the frontal lobes anterior to the motor region.

Summary & Notes by SCIENCE-WEEK http://scienceweek.com 2Oct98
For more information: http://scienceweek.com/swfr.htm

Related Background:

FUNCTIONAL ANATOMY OF HUMAN MUSIC PROCESSING

The existence of special perceptuo-motor skills in certain individuals presents many puzzling questions for the cognitive neurosciences. One such ability whose cerebral substrate remains essentially unknown is absolute pitch (also called "perfect pitch"), a relatively rare ability that refers to a long-term internal representation for the pitch of tones in the musical scale, typically manifested behaviorally by the ability to identify by the name of the musical note the pitch of any sound without reference to another sound, or by the ability to produce a given musical tone on demand. In contrast, relative pitch, which is well-developed among most trained musicians, refers to the ability to make pitch judgments about the relation between notes, such as within a musical interval.

The term "functional brain imaging" refers to a number of different techniques for mapping activity in the brain in response to external stimuli or during sensory, perceptual, or cognitive events. Positron emission tomography is a technique for producing cross-sectional images of the body after ingestion and systemic distribution of safely metabolized positron-emitting agents. The images are essentially functional or metabolic, since the ingested agents are metabolized in various tissues. Fluorodeoxyglucose and essentially functional or metabolic, since the ingested agents are metabolized in various tissues. Fluorodeoxyglucose and H(sub2)O(sup15) are common agents used for cerebral applications, and in cerebral applications of central importance to the technique is the fact that changes in the cellular activity of the brains of normal, awake humans and unanesthetized laboratory animals are invariably accompanied by changes in local blood flow and also changes in oxygen consumption. Magnetic resonance imaging is a technique involving images produced by mobile protons of a tissue excited by the application of a magnetic field, and when used in functional cerebral imaging, the basis of the technique is that it images very small metabolic, blood-flow, and perfusion-diffusion changes in vivo, in real time, and with no risk to the subject.

... ... Zatorre et al (5 authors at McGill University, CA) report a study of the neural basis of human absolute pitch using both structural and functional brain imaging techniques (magnetic resonance imaging and positron emission tomography). Although there were some localization differences between absolute pitch possessors and control non- absolute-pitch musicians when responding to musical tones, the results as a whole bring the authors to suggest that absolute pitch may not be associated with a unique pattern of cerebral activity, but rather may depend on the recruitment of a specialized network involved in the retrieval and manipulation of verbal-tonal associations. -----------

QY: Robert J. Zatorre md37@musica.mcgill.ca
(Proc. Natl. Acad. Sci. US 17 Mar 98 v95:p3172)

(Science-Week 24 Apr 98)

Related Background:

ON DYSLEXIA AND FUNCTIONAL DISRUPTION IN BRAIN ORGANIZATION

Dyslexia is impaired reading ability when the reading competence is below that expected from the individual's general intelligence and there is no impairment of vision. It has been proposed that dyslexic children and adults lack phonologic awareness, an awareness that strings of letters (orthography) are connected to corresponding units of speech (phonologic constituents) that they represent. In biology, magnetic resonance imaging is a technique involving images produced by mobile protons of a tissue excited by the application of a magnetic field, and when used in functional cerebral imaging, the basis of the technique is that it images very small metabolic, blood-flow, and perfusion-diffusion changes in vivo, in real time, and with no risk to the subject, with the essential idea of mapping activity in the brain in response to external stimuli or during sensory, perceptual, or cognitive events.

... ... Now Shaywitz et al (15 authors at 2 installations, US) report a study to find the location and extent of the functional disruption in neural systems that underlies dyslexia. Functional magnetic resonance imaging was used to compare brain activation patterns in dyslexic and nonimpaired subjects as they performed tasks that made imaging was used to compare brain activation patterns in dyslexic and nonimpaired subjects as they performed tasks that made progressively greater demands on phonologic analysis. Brain activation patterns differed significantly between the groups, with dyslexic readers showing underactivation in certain specific brain areas and overactivation in other specific brain areas. The authors suggest their results support a conclusion that the impairment in dyslexia is phonologic and that brain activation patterns may provide a neural signature for this impairment.

QY: Sally E. Shaywitz sally.shaywitz@yale.edu (Proc. Natl. Acad. Sci. US 3 Mar 98)
(Science-Week 10 Apr 98)

Related Background:

SPATIAL WORKING MEMORY LOCALIZED IN HUMAN FRONTAL CORTEX

Magnetic resonance imaging is a technique involving images produced by mobile protons of a tissue excited by the application of a magnetic field, and when used in functional cerebral imaging, the basis of the technique is that it images very small metabolic, blood-flow, and perfusion-diffusion changes in vivo, in real time, and with no risk to the subject, with the essential idea of mapping activity in the brain in response to external stimuli or during sensory, perceptual, or cognitive events. The brain-anatomical term "superior frontal sulcus" refers to a fissure on the superior frontal surface of each frontal lobe. In this report, "working memory" is the process of maintaining an active representation of information so that it is available for this report, "working memory" is the process of maintaining an active representation of information so that it is available for use, and "spatial working memory" refers to working memory involved with spatial memory tasks (remembering locations of briefly displayed objects or images).

... ... Courtney et al (5 authors at National Institutes of Health, US), using functional magnetic resonance imaging in humans, report an area in the superior frontal sulcus specialized for spatial working memory. The authors suggest that localization of the area in a more superior and posterior region in the human brain than in the monkey brain may explain why it has not been recognized previously.

QY: Susan M. Courtney Susan_Courtney@nih.gov (Science 27 Feb 98)
(Science-Week 13 Mar 98)
For more information: http://scienceweek.com/swfr.htm

top