The Instruments of Neuroscience17 Wolf,using Brookhaven National Labora E-labele ed (19 hasa half-life that nable for PET im sing MRI value tabolism in the brain.The ould be ombined with look for ogy germane to brain function ther using 2FDG.thev established a method for ima Functional Magnetic Resonance ing the tissue consum ption of glucose.Phelps,in a leap of insight.invented the block detector.a device that eventu- Imaging ally increased spatial resolution of PET from 3 centimeters When PET was introduced,the conventional wisdom to3 millimeters was that increased blood flow to differentially active parts of the brain was driven by the brain's need for Magnetic Resonance Imaging more oxygen.An increase in oxygen delivery permitted more glucose to be metabolized,and thus more energy Magnetic resonance imaging (MRI)is based on the principle of nuclear magnetic resonan which was hrs described and measured by Isidor Rabi in 1938.Dis- to back it up.In fact,if this proposal were true,then by Felix Bloch a increases in blood flow induced by functional demands should be equivalent to the increase in oxygen consump- tion.Ihis e to the pre e m er up( h tha in blo o in coil.The voltage char 6 on (Fox Raichle 1986).In additi on's ar infor was heing gused than ould be the a al 1988) In 1971 while Paul I aute W/hat was with that?Raichle (2008)relates tha sabhatical he was thinking hts as he ate oddly enough,a random scribble written in the margin of Michael Faraday's lab notes in 1845(Faraday,1933) napkin,and from these humble beginnings he developed brovided the hint that led to the solution of this puzzle the theoretical model that led to the invention of the first It was linus pauling and charles corvell who somehow magnetic resonance imaging scanner,located at The happened upon this clue. State University of New York at Stony Brook(Lauterbur Faraday had noted that dried blood was not mag- 1973).(Lauterbur won the 2003 Nobel Prize in Physi netic and in the margin of his notes had written that ology or Medicine,but his first attempt at publishing his he must try fluid blood.He was puzzled because he hindings was rejected by the moglobin contains iron.Ninety years later,Pauling and later Coryell (1936),after reading Faraday's notes,became could curious too ey found that indeed oxygenated anc deoxygenated noglobin behaved very ence magn in the no. n21 ribed by MR aliz Seiii o 1990 and his Bell Labo levels by administe 1000% with 1210% Hos ital dem to hu man subjects who were undergoing MRI following the iniection of They discovered that on room air,the structure of the
The Instruments of Neuroscience | 17 contrast material into the bloodstream, changes in the blood volume of a human brain, produced by physiological manipulation of blood fl ow, could be measured using MRI (Belliveau et al., 1990). Not only were excellent anatomical images produced, but they could be combined with physiology germane to brain function. Functional Magnetic Resonance Imaging When PET was introduced, the conventional wisdom was that increased blood fl ow to diff erentially active parts of the brain was driven by the brain’s nee d for more oxygen. An increase in oxygen delivery permitt ed more glucose to be metabolized, and thus more energy would be available for performing the task. Although this idea sounded reasonable, litt le data were available to back it up. In fact, if this proposal were true, then increases in blood fl ow induced by functional demands should be equivalent to the increase in oxygen consumption. Th is would mean that the ratio of oxygenated to deoxygenated hemoglobin should stay constant. PET data, however, did not back this up (Raichle, 2008). Instead, Peter Fox and Marc Raichle, at Washington University , found that although functional activity induced increases in blood fl ow, there was no corresponding increase in oxygen consumption (Fox & Raichle, 1986). In addition, more glucose was being used than would be predicted fr om the amount of oxygen consumed (Fox et al., 1988). What was up with that? Raichle (2008) relates that oddly enough, a random scribble writt en in the margin of Michael Faraday’s lab notes in 1845 (Faraday, 1933) provided the hint that led to the solution of this puzzle. It was Linus Pauling and Charles Coryell who somehow happened upon this clue. Faraday had noted that dried blood was not magnetic and in the margin of his notes had writt en that he must try fl uid blood. He was puzzled because hemoglobin contains iron. Ninety years later, Pauling and Coryell (1936), aft er reading Faraday’s notes, became curious too. Th ey found that indee d oxygenated and deoxygenated hemoglobin behaved very diff erently in a magnetic fi eld. Deoxygenated hemoglobin is weakly magnetic due to the exposed iron in the hemoglobin molecule. Years later, Kerith Th ulborn (1982) remembered and capitalized on this property described by Pauling and Coryell, realizing that it was feasible to measure the state of oxygenation in vivo. Seiji Ogawa (1990) and his colleagues at AT&T Bell Laboratories tried manipulating oxygen levels by administering 100 % oxygen alternated with room air (21 % oxygen) to human subjects who were undergoing MRI. Th ey discovered that on room air, the structure of the Wolf, using Brookhaven National Laboratory’s powerful cyclotron, 18 F-labeled 2-fl uorodeoxy-D-glucose (2FDG) was created (Ido et al., 1978). 18 F has a half-life that is amenable for PET imaging and can give precise values of energy metabolism in the brain. Th e fi rst work using PET to look for neural correlates of human behavior began when Phelps joined Kuhl at the University of Pennsylvania and together, using 2FDG, they established a method for imaging the tissue consumption of glucose. Phelps, in a leap of insight, invented the block detector, a device that eventually increased spatial resolution of PET fr om 3 centimeters to 3 millimeters. Magnetic Resonance Imaging Magnetic resonance imaging (MRI) is based on the principle of nuclear magnetic resonance, which was fi rst described and measured by Isidor Rabi in 1938. Discoveries made independently in 1946 by Felix Bloch at Harvard University and Edward Purcell at Stanford University expanded the understanding of nuclear magnetic resonance to liquids and solids. For example, the protons in a water molecule line up like litt le bar magnets when placed in a magnetic fi eld. If the equilibrium of these protons is disturbed by zapping them with radio fr equency pulses, then a measurable voltage is induced in a receiver coil. Th e voltage changes over time as a function of the proton’s environment. By analyzing the voltages, information about the examined tissue can be deduced. In 1971, while Paul Lauterbur (Figure 1.29) was on sabbatical, he was thinking grand thoughts as he ate a fast-food hamburger. He scribbled his ideas on a nearby napkin, and fr om these humble beginnings he developed the theoretical model that led to the invention of the fi rst magnetic resonance imaging scanner, located at Th e State University of New York at Stony Brook (Lauterbur, 1973). (Lauterbur won the 2003 Nobel Prize in Physiology or Medicine, but his fi rst att empt at publishing his fi ndings was rejected by the journal Nature . He later quipped, “You could write the entire history of science in the last 50 years in terms of papers rejected by Science or Nature ” [Wade, 2003]). It was another 20 years, however, before MRI was used to investigate brain function. Th is happened when researchers at Massachusett s General Hospital demonstrated that following the injection of FIGURE 1.29 Paul Lauterbur (1929–2007). 002_021_CogNeu_4e_Ch01.indd 17 7/17/13 9:27 AM
18|CHAPTER I A Brief History of Cognitive Neuroscience Air 0 Raichle understood the potential of these scanning methods, some sic pr gene s h dif ren pe ng the ce hane tas pr cisely data wa is vielding mishmash of results that varied in anatomical location from FIGURE 1.30 Images of a mouse br under varying oxygen cond person to person.Eric Reiman,a psychia- trist working with raichle sugg ted that venous system was visible due to the contrast provid- ging blood flow across subjects might solve this ed by the deoxygenated hemoglobin that was present problem.The results of this approach were clear and un- On 100%O,,however,the venous system completely ambiguous(Fox,1988).This landmark paper presented disappeared(Figure 1.30).Thus contrast depended on the first integrated approach for the design.execution. the blood oxygen level.BOLD (blood oxygen level- and interpretation of functional brain images. dependent)contrast was born.This technique led to But what can be learned about the brain and the the development of functional magnetic resonance im- behavior of a human when a person is lying prone in aging(fMRI).MRI does not use ionizing radiation,it scanner?Cognitive psychologists Michael Posner, combines beautifully detailed images of the body with Steve Petersen,and Gordon Shulman,at Washington tive MRIth all RI to b digms, ng the c n me not ta long for an dopted by resear resulting in explosive growtho me gnier to fMRI.Th expermen you know nd n mapping Baseline 30 50g OFE 130 70 MRI Visual Cortex Response 6000 ON 5900 1908 250 2708 5700 5600 0306090120150180210240 OFF ON ON FIGURE 1.31 An early set of fMRI images showing activation of the human visual cortex
18 | CHAPTER 1 A Brief History of Cognitive Neuroscience Raichle understood the potential of these new scanning methods, but he also realized that some basic problems had to be solved. If generalized information about brain function and anatomy were to be obtained, then the scans fr om diff erent individuals performing the same tasks under the same circumstances had to be comparable. Th is was proving diffi cult, however, since no tw o brains are precisely the same size and shape. Furthermore, early data was yielding a mishmash of results that varied in anatomical location fr om person to person. Eric Reiman, a psychiatrist working with Raichle, suggested that averaging blood fl ow across subjects might solve this problem. Th e results of this approach were clear and unambiguous (Fox, 1988). Th is landmark paper presented the fi rst integrated approach for the design, execution, and interpretation of functional brain images. But what can be learned about the brain and the behavior of a human when a person is lying prone in a scanner? Cognitive psychologists Michael Posner, Steve Petersen, and Gordon Shulman, at Washington University , developed innovative experimental paradigms, including the cognitive subtraction method (fi rst proposed by Donders), for use while PET scanning. Th e methodology was soon applied to fMRI. Th is joining together of cognitive psychology’s experimental methods with brain imaging was the beginning of human functional brain mapping. Th roughout this book, we will venous system was visible due to the contrast provided by the deoxygenated hemoglobin that was present. On 100 % O 2 , however, the venous system completely disappeared (Figure 1.30). Th us contrast depended on the blood oxygen level. BOLD (blood oxygen level– dependent) contrast was born. Th is technique led to the development of functional magnetic resonance imaging (fMRI). MRI does not use ionizing radiation, it combines beautifully detailed images of the body with physiology related to brain function, and it is sensitive (Figure 1.31). With all of these advantages, it did not take long for MRI and fMRI to be adopted by the research community , resulting in explosive growth of functional brain imaging. Machines are useful, however, only if you know what to do with them and what their limitations are. Time (s) 0 30 60 90 120 150 180 210 240 6000 5800 5700 5900 5600 Signal intensity MRI Visual Cortex Response off on off on b FIGURE 1.31 An early set of fMRI images showing activation of the human visual cortex. a FIGURE 1.30 Images of a mouse brain under varying oxygen conditions. Air O2 002_021_CogNeu_4e_Ch01.indd 18 7/17/13 9:27 AM
The Book in Your Hands |19 draw from the wealth of brain imaging data that has been on, to the cor ntrol of l age,devoting a chap ach.The foll The Book in ol.s new chapter for this edition on consciousness.free wil Your Hands and the law. Each chapter begins with a story that illustrates and Our goals in this book are to introduce you to the big introduces the chapter's main topic.Beginning with questions and discussions in cognitive neuroscience and Chapter 4.the story is followed by an anatomical orien- to teach you how to think,ask questions,and approach tation highlighting the portions of the brain that we know those questions like a cognitive neuroscientist.In the are involved in these processes,and a description of what next chapter,we introduce the biological foundations of a deficit of that process would result in.Next.the heart of the brain by presenting an overview of its cellular mecha- the chapter focuses on a discussion of the cognitive pro nisms and neuroanatomy.In Chapter 3 we discuss the cess and what is known about how it functions,followed methods that are available to us for observing mind- by a summary and suggestions for further reading for brain relationships,and we introduce how scientists go those whose curiosity has been aroused
The Book in Your Hands | 19 about interpreting and questioning those observations. Building on this foundation, we launch into the core processes of cognition: hemispheric specialization, sensation and perception, object recognition, att ention, the control of action, learning and memory, emotion, and language, devoting a chapter to each. Th ese are followed by chapters on cognition control, social cognition, and a new chapter for this edition on consciousness, fr ee will, and the law. Each chapter begins with a story that illustrates and introduces the chapter’s main topic. Beginning with Chapter 4, the story is followed by an anatomical orientation highlighting the portions of the brain that we know are involved in these processes, and a description of what a defi cit of that process would result in. Next, the heart of the chapter focuses on a discussion of the cognitive process and what is known about how it functions, followed by a summary and suggestions for further reading for those whose curiosity has bee n aroused. draw fr om the wealth of brain imaging data that has bee n amassed in the last 30 years in our quest to learn about how the brain enables the mind. The Book in Your Hands Our goals in this book are to introduce you to the big questions and discussions in cognitive neuroscience and to teach you how to think, ask questions, and approach those questions like a cognitive neuroscientist. In the next chapter, we introduce the biological foundations of the brain by presenting an overview of its cellular mechanisms and neuroanatomy. In Chapter 3 we discuss the methods that are available to us for observing mind– brain relationships, and we introduce how scientists go 002_021_CogNeu_4e_Ch01.indd 19 7/17/13 9:27 AM
Summary Thomas Willis first introduced us,in the mid 1600s,to the theory for many vears until Hebb emphasized the hiolog idea that dama to the brain could influence behavior and cal basis of leamning and chomsky and miller realized tha that the cerebral cortex might indeed be the seat of what associationism couldn't explain all learning or all actions of the mind. a loca scientist and both language).Ramon y Cajal,Sherrington,and Brodmann, brain rgions coul support a loc once aga ng toge was in n Soon scientists began to realize that the in tion of the vas ready for a g of the brain's neural networks might be what enables the mind. brain.The resulting marriage is cognitive neuroscience. At the same t a blossoming of in teci5earc iationism that a nse followed hy a reward woul be maintained and that these associations were the basis of So welcome to cognitive neuroscience.It doesn't matter how the mind learned.Associationism was the prevailing what your background is,you're welcome here. Key Terms aggregate field theory(p.7) cytoarchitectonics(p.8) phrenology (p.6) rationalism(p.10) syncytium (p.9) cognitive neuros nce (p.4) 品
20 Key Terms aggregate fi eld theory (p. 7) associationism (p. 12) behaviorism (p. 13) cognitive neuroscience (p. 4) cytoarchitectonics (p. 8) empiricism (p. 10) Montreal procedure (p. 13) neuron doctrine (p. 9) phrenology (p. 6) rationalism (p. 10) syncytium (p. 9) Summary Th omas Willis fi rst introduced us, in the mid 1600s, to the idea that damage to the brain could infl uence behavior and that the cerebral cortex might indee d be the seat of what makes us human. Phrenologists expanded on this idea and developed a localizationist view of the brain. Patients like those of Broca and Wernicke later supported the importance of specifi c brain locations on human behavior (like language). Ramón y Cajal, Sherrington, and Brodmann, among others, provided evidence that although the microarchitecture of distinct brain regions could support a localizationist view of the brain, these areas are interconnected. Soon scientists began to realize that the integration of the brain’s neural netw orks might be what enables the mind. At the same time that neuroscientists were researching the brain, psychologists were studying the mind. Out of the philosophical theory of empiricism came the idea of associationism, that any response followed by a reward would be maintained and that these associations were the basis of how the mind learned. Associationism was the prevailing theory for many years, until Hebb emphasized the biological basis of learning, and Chomsky and Miller realized that associationism couldn’t explain all learning or all actions of the mind. Neuroscientists and psychologists both reached the conclusion that there is more to the brain than just the sum of its parts, that the brain must enable the mind—but how? Th e term cognitive neuroscience was coined in the late 1970s because fi elds of neuroscience and psychology were once again coming together. Neuroscience was in nee d of the theories of the psychology of the mind, and psychology was ready for a greater understanding of the working of the brain. Th e resulting marriage is cognitive neuroscience. Th e last half of the 20th century saw a blossoming of interdisciplinary research that produced both new approaches and new technologies resulting in noninvasive methods of imaging brain structure, metabolism, and function. So welcome to cognitive neuroscience. It doesn’t matt er what your background is, you’re welcome here. 002_021_CogNeu_4e_Ch01.indd 20 8/1/13 1:25 PM
Thought Questions 木女hov the md k时e 3.How do you think the brain might be studied in the future? 2.Will modemn brain-imaging experiments become the 4.Why do good ideas and theories occasionally get lost new phrenology? over the passage of time?How do they often get redis covered: Suggested Reading K6 Raichle,M.E.(1998).Behind the scenes of functional maging:A 21
21 Suggested Reading K ass -S imon , G., & F arnes , P. (1990). Women of science: Righting the record. Bloomington: Indiana University Press. L indzey , G. (Ed.). (1936). His tory of psychology in autobiography (Vol. 3). Worcester, MA: Clark University Press. M iller , G. (2003). Th e cognitive revolution: A historical perspective. Trends in Cognitive Sciences, 7, 141–144. R aichle , M. E. (1998). Behind the scenes of functional brain imaging: A historical and physiological perspective. Procee dings of the National Academy of Sciences, USA, 95, 765–772. S hepherd , G. M. (1991). Foundations of the neuron doctrine. New York: Oxford University Press. Z immer , C. (2004). Soul made fl esh: Th e dis covery of the brain—and how it changed the world. New York: Free Press. Thought Questions 1. Can we study how the mind works without studying the brain? 2. Will modern brain-imaging experiments become the new phrenology? 3. How do you think the brain might be studied in the future? 4. Why do good ideas and theories occasionally get lost over the passage of time? How do they oft en get rediscovered? 002_021_CogNeu_4e_Ch01.indd 21 8/1/13 1:25 PM