Lennart Heimer: concepts of the ventral striatum and extended amygdala

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Dr. Lennart Heimer, the famous neuroanatomist of Swedish descent, died last year but left a legacy that will impact the neurosciences and potentially psychosurgery for years to come. He developed an anatomical technique for demonstrating the terminal boutons that helped to delineate basal forebrain anatomy. During these studies, he realized the relationship of basal forebrain structures to the limbic system, thus initiating the concept of the ventral striatum and parallel basal ganglia circuitry.

Heimer excelled as a teacher as well and honed his brain dissection technique to one of the most effective tools for understanding neuroanatomy. His legendary sessions with neurosurgical residents resulted in his recognition as one of the world’s leading fiber tract dissectors. His gentle, engaging manner has been documented in several media formats.

Abstract

Dr. Lennart Heimer, the famous neuroanatomist of Swedish descent, died last year but left a legacy that will impact the neurosciences and potentially psychosurgery for years to come. He developed an anatomical technique for demonstrating the terminal boutons that helped to delineate basal forebrain anatomy. During these studies, he realized the relationship of basal forebrain structures to the limbic system, thus initiating the concept of the ventral striatum and parallel basal ganglia circuitry.

Heimer excelled as a teacher as well and honed his brain dissection technique to one of the most effective tools for understanding neuroanatomy. His legendary sessions with neurosurgical residents resulted in his recognition as one of the world’s leading fiber tract dissectors. His gentle, engaging manner has been documented in several media formats.

One of the world’s great neuroanatomists died last year, but his legacy will impact neuroscience and psychiatry for years to come. Dr. Lennart Heimer (Fig. 1), an American scientist of Swedish origin, developed a fiber tract and terminal bouton tracing technique and utilized it over the course of a long and prolific scientific career to delineate the basal forebrain structures. From his early pioneering studies came the concepts of the ventral striatum and the extended amygdala—a neuroanatomical framework of the utmost interest to psychiatrists involved in schizophrenia and addiction and now to neurosurgeons as they again enter the field of psychosurgery.

Fig. 1
Fig. 1

Photograph of Dr. Lennart Heimer, the American neuroanatomist of Swedish descent, who developed a silver impregnation stain for tracing terminal boutons throughout the brain. He used this technique to delineate the human basal forebrain anatomy, and he proposed the concept of the ventral striatum.

Dr. Heimer shaped the lives of many scientists, both young and old, from his laboratory at the University of Virginia; however, he had an equal passion for teaching. Scores of medical students, residents, and faculty physicians learned neuroanatomy from his famous brain dissections. Retiring from the research laboratory just a few years ago, he continued to teach, publish, and speak until the last year of his life. With a full national and international lecture schedule planned for the year, Dr. Heimer died of pancreatic cancer on March 12, 2007, at the age of 77 years. He was surrounded by his family at his farm in Trevilians, Virginia, where he was working on his last book.27

The Development of a Neuroanatomist

Lennart Heimer was born in Östersund City, the capital of Jämtland county in central Sweden, on March 11, 1930, to Gösta and Rakel (Karlstedt) Heimer. As a young man, he had a passion for sports, excelling in soccer and track and field. He was most gifted in alpine skiing, however; twice he was the Swedish junior slalom champion and later qualified for the Swedish Olympic team in 1952 (Fig. 2). As a native to a city traditionally considered a “Vinterstaden” (winter city), it is said that Lennart was never late in putting on his skis when an opportunity arose, and it was also on the ski slopes that he met his Norwegian wife, Hanne-Björg, with whom he spent the remainder of his 51 years. Had it not been for his wife and his burning interest in medicine, Heimer might have stayed on the ski slopes for the rest of his life.

Fig. 2
Fig. 2

Photograph of Heimer, a gifted athlete who excelled in numerous sports, although downhill skiing was his passion. In 1952 he qualified for the Swedish Olympic team.

The decision to pursue medical research was not an obvious choice for the grandson of a stationmaster and the son of a “häradsskrivare” (government executive) from central Sweden. Heimer initially studied land and water resources engineering for a career in civil engineering. However, well into his 2nd year at Chalmers University of Technology at Göteborg on the Swedish west coast, he regretted the decision and realized that medicine would be a more interesting and appropriate choice. Because Heimer lacked the necessary biology classes, he traveled to Freies University in West Berlin to complete his premedical training. It was at this time that he pursued another talent—art—which he would utilize throughout his career. In fact, in 1959 as a 1st-year medical student at the University of Göteborg (now Gothenburg), the largest university in Scandinavia, Heimer wrote and illustrated his first textbook of neuroanatomy with a little help from his father, who corrected his misspellings.16 The ambitious student requested that the legendary Alf Brodal write a foreword for the book, although this request was refused given Heimer’s youth and inexperience.

As a medical student in the Department of Anatomy, Lennart was asked by his professor to research the spinal column and sitting. His refusal, because of his intense interest in brain anatomy, left him somewhat ostracized within the department. Fortunately, he found success with the behavioral psychologist Knut Larsson, who not only established him as an avid cigar enthusiast, but also influenced the remainder of his scientific career. Heimer, Larsson, and a skilled laboratory technician constructed a stereotactic apparatus to access all regions of the rodent brain, including its basal surface.22 Through serendipity, two important findings resulted from their early studies: 1) lesions localized to the medial preopticoanterior hypothalamic region abolished sexual behavior in rats and 2) extensive lesions at the junction of the mesencephalon and diencephalon were followed by a drastic increase in sexual behavior.31 Later they discovered that the destruction of the main olfactory system eliminated mating in nonexperienced animals for the entire lifespan.23,24 The studies on the sexual behavior of rats seemed limited without more detailed knowledge of the neuronal circuits in the basal forebrain, and Heimer became curious as to whether new axonal tracing techniques utilizing silver impregnation could be used to delineate functional brain anatomy.

The success of these early studies with Larsson by the time Heimer was 35 years of age resulted in an offer to work with Dr. Walle J. H. Nauta in the Department of Psychology and Brain Science at the Massachusetts Institute of Technology (Fig. 3). The premier neuroanatomy labs at the time were located in Boston with Nauta, Scandinavia with Brodal, and Hungary with Szentágothai. Heimer had graduated in 1963 with an M.D. degree and never continued toward a Ph.D., believing that his publications spoke for themselves.

Fig. 3
Fig. 3

Photograph of the young neuroanatomist (far right) and his wife, Hanne-Bjorg (second to the right). After medical school, Heimer was invited to study with Dr. Walle Nauta (left), one of the preeminent neuroanatomists of the era.

Nauta had distinguished himself as one of the world’s eminent neuroanatomists with his silver technique for tracing degenerating axons.35,36 The Nauta stain revolutionized the study of brain anatomy so that projection fibers and targets of deep nuclei could be traced and identified. Nauta’s laboratory attracted brilliant young scientists like Heimer, and the atmosphere surrounding these pioneering studies was energetic and exciting. It was during this time with the gifted technician Robert Fink that Heimer developed methods for selective silver staining of degenerating axonal boutons.9 Although considered a modification of Nauta’s method for staining degenerating axons, the Fink-Heimer stain had the advantage of tracing degenerating nerve fibers and visualizing their terminal boutons (Fig. 4). Initial doubts centered on whether the Fink-Heimer method actually identified axonal projections, but electron microscopy studies of the terminal boutons with Alan Peters soon validated the technique.25 In fact, Heimer also demonstrated that electron microscopy could reveal the function of terminal boutons: symmetric, flat boutons were inhibitory and asymmetric, round boutons were excitatory. By the age of 40 years, Heimer had accomplished much and was recognized in Scientific American as a pioneering neuroanatomist.20 The Fink-Heimer stain represented the primary tool for tracing central nervous system pathways such as the fine neural connections of the basal forebrain.

Fig. 4
Fig. 4

Photomicrograph of terminal boutons surrounding a neuron, as demonstrated by the Fink-Heimer stain. This modification of prior tract tracing techniques enabled scientists to visualize terminal boutons instead of degenerating axons. It became the primary tract-tracing method of the time.

After 7 years at the Massachusetts Institute of Technology, the young Heimer was recruited to the University of Virginia by Dr. Jan Langman, chairman of the Department of Anatomy, and by Drs. John Jane and Sven Ebbesson of the Department of Neurosurgery to develop a strong neuroscience research program. An older, distinguished neuroanatomist was passed over for the position as Heimer demonstrated youth, vigor, and expertise with the new electron microscopy and fiber-tracing techniques (Fig. 5). In essence, he was viewed as the future of neuroanatomy—which eventually proved true. His texts on experimental neuroanatomical techniques became basic references for neuroscientists.26,29 There was a single year in 1979–1980 when Dr. Heimer helped to establish a neuroscience center at the University of Aarhus, Denmark, but he returned to a joint appointment in the Departments of Neurosurgery and Otolaryngology—Head and Neck Surgery at the University of Virginia, the position that he would maintain for the rest of his career.

Fig. 5
Fig. 5

Heimer used electron microscopy in addition to tract-tracing methods in his studies of neural connectivity. He was able to demonstrate neuronal function with ultrastructural analysis of axonal boutons.

In the 1970s funding for research in neuroanatomy and connectivity waned as molecular biology assumed the major interest of neuroscientists to understand brain function; however, Heimer persevered with his tract-tracing techniques and electron microscopy studies. He preached the concept that anatomy is critical to understanding brain organization, which in turn reveals brain function. Indeed he demonstrated this principle as he used neuroanatomy to understand the anatomical associations and chemical relationships of the limbic brain.

Teaching by Brain Dissection

While uncovering the basic anatomical structures in his laboratory in Cobb Hall at the University of Virginia, Dr. Heimer developed an equal passion for teaching. He utilized brain dissection much like he used fiber-tracing techniques in research—to elucidate the basic concepts of neuroanatomy to medical students, residents, and any enthusiast of the neurosciences. These legendary brain dissections grew from Saturday neurosurgery conferences to other departments of the medical school and then to other universities. Soon Heimer was recognized not only for his many accomplishments in the lab but also as an expert teacher and dissector of the brain. He believed brain dissection to be fundamental to any student of neuroscience as “no book, plastic model, or high-tech computer simulation can replace gross dissections as a vehicle for the study of the human brain.”15 Only a few basic instruments and simple tissue fixation were required to provide lasting knowledge of the body’s most complex organ. Armed with only a brain knife and a formalin-fixed brain, he captivated audiences for hours and effectively imparted his vast knowledge of brain structure with a gentle and concise manner. In 1983 he organized his teaching thoughts into the classic medical school text, The Human Brain and Spinal Cord: Functional Neuroanatomy and Dissection Guide,13 which has since been republished in its current second edition.14 Because of the high demand for his live dissections, Heimer produced a digital video disc sponsored by the American Association of Neurological Surgeons that captures his method, lilting accent, and gentle mannerisms in a timeless work.12 These dissections are also available on the internet from the online journal Neurosurgical Focus of June 2005.15 Fortunately, his technique for brain dissection has been recorded in several formats for all to enjoy and to ascertain a sense of the man so dedicated to his students and his subject.

Concepts of the Ventral Striatum and Extended Amygdala

The fundamental concept of the ventral striatopallidal system is that the allocortex (olfactory cortex and hippocampus) is related to the basal ganglia in a manner similar to the neocortex with its corticostriatopallidal circuit. Thus, parallel circuits exist in the basal ganglia whereby the ventral striatum projects to limbic regions (Fig. 6). This notion was first demonstrated in rodents by using cytoarchitectural, histochemical, and tract tracing experiments.18 The discovery of new fiber tract tracing methods in the 1960s allowed the discovery of new forebrain circuitry, namely, the ventral striatum and extended amygdala. At the forefront of these techniques were the Fink-Heimer modification of the Nauta-Gygax method9 and the cupric-silver method of de Olmos.6 Both silver impregnations allowed the study of these long, circuitous fiber tracts in the human basal forebrain.

Fig. 6
Fig. 6

Drawings showing the ventral striatum of the human basal forebrain. A. Coronal schematic at the level of the nucleus accumbens. B. The ventral pallidum (VP) extends downward into the region recognized as the substantia innominata. C. The sublenticular portion of the substantia innominata is associated with the extended amygdala. In this concept of the substantia innominata, the basal nucleus of Meynert (B) is a relatively small third component. D. Central (Ce) and medial (Me) nuclei of the amygdala are apparent with their corresponding projections along the stria terminalis and the superior component of the bed nucleus of the stria terminalis. ac = anterior commissure; BL = basolateral nucleus of amygdala; BM = basomedial nucleus of amygdala; BSTL = bed nucleus of stria terminalis, lateral division; BSTM = BST, medial division; BSTS = BST, superior division; Cd = caudate; Cl = claustrum; EGP = external segment of the globus pallidum; Ent = entorhinal cortex; f = fornix; HDB = diagonal band; Hy = hypothalamus; IGP = internal segment of GP; La = lateral nucleus of the amygdala; opt = optic track; ox = optic chiasm; Pir = piriform cortex; Pu = putamen; SLEA = sublenticular component of extended amygdala; st = stria terminalis; Th = thalamus; VDB = diagonal band; VS = ventral striatum. This figure was published in Handbook of Chemical Neuroanatomy, Vol 15, Heimer L, de Olmos J, Alheid G, et al, p 58, Copyright Elsevier, 1999.

In some early rodent experiments utilizing his modified silver staining technique, Dr. Heimer lesioned the prepiriform cortex and olfactory tubercle to demonstrate that subsequent degeneration occurred in the mediobasal fore-brain—the substantia innominata. This observation contradicted the commonly accepted belief that the olfactory cortex projects substantially to hypothalamic regions.18 He remarked, “that the olfactory tubercle represents a striatal structure rather than a cortical olfactory structure could hardly be dismissed.” The fact that there are no reciprocal projections between the two, as would normally be expected with association cortex, further supported this notion. Lesions in the nucleus accumbens and olfactory tubercle resulted in neuronal degeneration along the continuum of the ventral globus pallidum,29 and thus the terms “ventral striatum” and “ventral pallidum” were introduced to describe this apparent extension of the basal ganglia.

Just as the dorsal basal ganglia projects through the thalamus or more specifically through ventral anterior and ventrolateral nuclei as part of its cortical circuit, it was later suggested that the ventral striatalpallidal system projected through the medial dorsal nucleus of the thalamus, heralding the idea of parallel corticostriatalthalamic circuits from dorsal and ventral basal ganglia.19

In this concept of the basal forebrain, which contains ventral striatum and extended amygdala, the substantia innominata no longer represents an independent structure in the region but instead is divided into its 3 component parts. The anterior portion represents the subcommissural substantia innominata, which is the ventral extension of the pallidum. The posterior portion involves the sublenticular substantia innominata and is associated with the extended amygdala. “This two part division of the substantia innominata is one of the corner stones of [the] conceptualization of the basal forebrain.”33 For completeness, it should be mentioned that the third component of the substantia innominata is the cholinergic basal nucleus of Meynert, which occupies a relatively small volume compared with the anterior and posterior divisions (Fig. 6).

In the 1920s Johnston30 suggested an association between the bed nucleus of stria terminalis and the centromedial amygdaloid nuclei because he observed a continuum of these structures during human and nonhuman vertebrate embryonic development. Decades later a similar relationship was noted in mammals when de Olmos,5 a close friend of and collaborator with Heimer, observed columns of gray matter in the sublenticular substantia innominata (Figs. 7 and 8). Using his cupric-silver technique, de Olmos demonstrated a continuum of central amygdala around the internal capsule to the lateral bed nucleus of the stria terminalis, and he later corroborated this circuit as well as its association connections by performing retrograde fluorescent tracer studies.

A similar, medial circuit was later identified when retrograde fluorescent tracers were injected into the rodent accessory olfactory bulb and labeled cells in a continuous column were observed from the medial amygdala to the posterior ventral region of the sublenticular region to the medial bed nucleus of the stria terminalis.7 Thus, the central division of the extended amygdala is associated with projections to the lateral hypothalamus, whereas the medial division projects to the medial hypothalamus.

Fig. 7
Fig. 7

Drawing illustrating the extended amygdala. The central division of the amygdala (Ce) is associated with projections via the stria terminalis to the lateral hypothalamus, and the medial division (Me) projects to the medial hypothalamus. Notice that the laterobasal nuclei of the amygdala are not included in the extended amygdala. The supracapsular component of the extended amygdala is depicted in Fig. 6B, whereas the sublenticular component is most visible in Fig. 6C. Amg = amygdala; Co = cortical amygdaloid nuclei. This figure was published in Handbook of Chemical Neuroanatomy, Vol 15, Heimer L, de Olmos J, Alheid G, et al, p 59, Copyright Elsevier, 1999.

Fig. 8
Fig. 8

Photograph of Dr. Heimer and his long-time friend and collaborator José de Olmos of Argentina. The two worked together to pioneer the concepts of the ventral striatum and extended amygdala. Sadly, de Olmos died the year following Heimer’s death.

Implications for Psychosurgery

The ventral striatopallidal system and the extended amygdala are thus major components of the limbic system and have been implicated in schizophrenia, addiction, depression, and obsessive–compulsive disorders.17 It has been proposed that the development of schizophrenia is related to excessive inhibition in these pathways,38 and morphometric studies have revealed volume loss in the amygdala and/or hippocampus in 54% of patients with schizophrenia.4 Findings of Kluver and Bucy, as well as more recent evidence from intracranial limbic electrodes8 and patients undergoing temporal lobectomy, have indicated that the amygdala is associated with aggression and emotion.39 In fact, bilateral stereotactic amygdalotomy has been performed for severe aggressive behavior34 and self-mutilation disorders.10 Perhaps extended amygdala structures will be targeted for future psychiatric interventions.27

Neurosurgeons have long been interested in treating psychiatric disease by targeting the limbic system. Early lesioning procedures included capsulotomy and subcaudate tractotomy—targets remarkably close to ventral striatal structures. More contemporary neurosurgical interest in psychiatric disease has been focused on these regions in the context of deep brain stimulation, including the subgenual cingulate and Brodmann area25 for treatment-resistant major depression32 and obsessive-compulsive disorder treatments targeting the anterior capsule1,2,11,37 and nucleus accumbens shell.

Note, however, that the exact targets for deep brain stimulation electrodes in the ventral striatum regions remain unclear.3

The Ultimate Tribute

Very few people earn during their lifetime a level of status and respect that garners recognition from colleagues and peers from around the world. Lennart Heimer was one such man. In October 1998, neuroscientists from across the globe convened in Charlottesville for a 3-day symposium addressing the ventral striatum and honoring in particular the man who conceived of it. Conference organizer, Jacqueline McGinty, described the event: “To hear such outstanding presentations and passionate discussion intermingled with overwhelming camaraderie and admiration for Lennart Heimer was a rare and unique opportunity.”33 The quality of scientific work presented was superb and was catalogued by the New York Academy of Sciences as the text Advancing from the Ventral Striatum to the Extended Amygdala.33 No one was more deserving of such a high-quality conference than Heimer, and Dr. John Jane Sr. very appropriately summarized this acknowledgment with an evening toast from the poet W. H. Auden: “Let us honor if we can the vertical man, though we value none but the horizontal one.”

Lennart Heimer’s influence on neuroanatomy is profound and permanent. In a similar way, his colleagues and coworkers influenced him and in turn were changed by the relationship. José de Olmos, George Alheid, Robert Switzer, Scott Zahm, and Laszlo Zaborszky are devoted basic scientists and friends who carry forward the concepts and teachings of Lennart Heimer. His clinical colleagues in the Department of Neurosurgery at the University of Virginia Health System are forever grateful and have dedicated their new library to him.

Dr. Heimer is survived by his wife, Hanne-Bjorg; sons, Hakon, Mikael, Gösta, and Knut; 4 grandchildren; and sisters Gudrun Strandberg and Bodil Karlén of Sweden. He left an enormous legacy of students and colleagues in all fields of neuroscience and psychiatry. His ideas and scientific contributions will last for generations.

Acknowledgments

We thank the Heimer family for kindly allowing us to prepare this article. We also thank Drs. Robert Switzer, Alan Peters, Laszlo Zaborszky, and Scott Zahm for providing information. Mrs. Cindy Roberson assisted with manuscript preparation.

Sources of support: none reported.

References

  • 1

    Abelson JLCurtis GCSagher OAlbucher RCHarrigan MTaylor SF: Deep brain stimulation for refractory obsessive-compulsive disorder. Biol Psychiatry 57:

  • 2

    Anderson DAhmed A: Treatment of patients with intractable obsessive-compulsive disorder with anterior capsular stimulation. Case report. J Neurosurg 98:

  • 3

    Aouizerate BCuny EMartin-Guehl CGuehl CAmieva HBenazzouz A: Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report. J Neurosurg 101:

  • 4

    Bogerts BMeertz ESchönfeldt-Bausch R: Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage. Arch Gen Psychiatry 42:

  • 5

    de Olmos J: The Neurobiology of the Amygdala.

  • 6

    de Olmos JS: A cupric-silver method for impregnation of terminal axon degeneration and its further use in staining granular argyrophilic neurons. Brain Behav Evol 2:

  • 7

    de Olmos JSAlheid GFBeltramino CA: The Rat Nervous System.

  • 8

    Fenwick P: Aspects of Epilepsy in Psychiatry.

  • 9

    Fink RPHeimer L: Two methods for selective silver impregnation of degenerating axons and their synaptic endings in the central nervous system. Brain Res 4:

  • 10

    Fountas KNSmith JRLee GP: Bilateral stereotactic amygdalotomy for self-mutilation disorder. Case report and review of the literature. Stereotact Funct Neurosurg 85:

  • 11

    Greenberg BDMalone DAFriehs GMRezai ARKubu CSMalloy PF: Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology 31:

  • 12

    Heimer L:

  • 13

    Heimer L: Human Brain and Spinal Cord: Functional Neuroanatomy and Dissection Guide.

  • 14

    Heimer L:

  • 15

    Heimer L: Instructional video. Dissection of the human brain. Neurosurg Focus 18(6B):

  • 16

    Heimer L:

  • 17

    Heimer L: A new anatomical framework for neuropsychiatric disorders and drug abuse. Am J Psychiatry 160:

  • 18

    Heimer L: The olfactory connections of the diencephalon in the rat. An experimental light-and electron-microscopic study with special emphasis on the problem of terminal degeneration. Brain Behav Evol 6:

  • 19

    Heimer L: Limbic Mechanisms. The Continuing Evolution of the Limbic System Concept.

  • 20

    Heimer L: Pathways in the brain. Scientific American 225:

  • 21

    Heimer Lde Olmos JSAlheid GFPearson JSakamoto N: Handbook of Chemical Neuroanatomy.

  • 22

    Heimer LKuikka VLarsson KNordstrom E: A headholder for stereotaxic operations of small laboratory animals. Physiol Behav 7:

  • 23

    Heimer LLarsson K: Mating behavior of male rats after olfactory bulb lesions. Physiol Behav 2:

  • 24

    Heimer LLarsson K: Mating behavior in male rats after destruction of the mamillary bodies. Acta Neurol Scand 40:

  • 25

    Heimer LPeters A: An electron microscope study of a silver stain for degenerating boutons. Brain Res 8:

  • 26

    Heimer LRobards MJ: Neuroanatomical Tract-Tracing Methods.

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    Heimer LTrimble MVan Hoesen GWZahm DS: Anatomy of Neuropsychiatry: the New Anatomy of the Basal Forebrain and its Implications for Neuropsychiatric Illness.

  • 28

    Heimer LWilson RD: Golgi Centennial Symposium Proceedings.

  • 29

    Heimer LZaborszky L: Neuroanatomical Tract-tracing Methods 2: Recent Progress.

  • 30

    Johnston JB: Further contribution to the study of the evolution of the forebrain. J Comp Neurol 35:

  • 31

    Larsson KHeimer L: Mating behavior of male rats after lesions in the preoptic area. Nature 202:

  • 32

    Mayberg HSLozano AMVoon VMcNeely HESeminowicz DHamani C: Deep brain stimulation for treatment-resistant depression. Neuron 45:

  • 33

    McGinty JF (ed): Advancing from the Ventral Striatum to the Extended Amygdala.

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    Narabayashi HNagao TSaito YYoshida MNagahata M: Stereotaxic amydalotomy for behavior disorders. Arch Neurol 9:

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    Nauta WJGygax PA: Silver impregnation of degenerating axon terminals in the central nervous system: (1) Technic. (2) Chemical notes. Stain Technol 26:

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    Nauta WJGygax PA: Silver impregnation of degenerating axons in the central nervous system: a modified technic. Stain Technol 29:

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    Nuttin BJGabriëls LACosyns PRMeyerson BAAndréewitch SSunaert SG: Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder. Neurosurgery 52:

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    Stevens JR: Ann N Y Acad Sci 877:

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    Trimble MRVan Elst LT: On some clinical implications of the ventral striatum and the extended amygdala: investigations of aggression. Ann N Y Acad Sci 877:

Article Information

Address correspondence to: W. Jeffrey Elias, M.D., Department of Neurosurgery, University of Virginia Health System, Box 800212, Charlottesville, Virginia 22908. email: wje4r@virginia.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Photograph of Dr. Lennart Heimer, the American neuroanatomist of Swedish descent, who developed a silver impregnation stain for tracing terminal boutons throughout the brain. He used this technique to delineate the human basal forebrain anatomy, and he proposed the concept of the ventral striatum.

  • View in gallery

    Photograph of Heimer, a gifted athlete who excelled in numerous sports, although downhill skiing was his passion. In 1952 he qualified for the Swedish Olympic team.

  • View in gallery

    Photograph of the young neuroanatomist (far right) and his wife, Hanne-Bjorg (second to the right). After medical school, Heimer was invited to study with Dr. Walle Nauta (left), one of the preeminent neuroanatomists of the era.

  • View in gallery

    Photomicrograph of terminal boutons surrounding a neuron, as demonstrated by the Fink-Heimer stain. This modification of prior tract tracing techniques enabled scientists to visualize terminal boutons instead of degenerating axons. It became the primary tract-tracing method of the time.

  • View in gallery

    Heimer used electron microscopy in addition to tract-tracing methods in his studies of neural connectivity. He was able to demonstrate neuronal function with ultrastructural analysis of axonal boutons.

  • View in gallery

    Drawings showing the ventral striatum of the human basal forebrain. A. Coronal schematic at the level of the nucleus accumbens. B. The ventral pallidum (VP) extends downward into the region recognized as the substantia innominata. C. The sublenticular portion of the substantia innominata is associated with the extended amygdala. In this concept of the substantia innominata, the basal nucleus of Meynert (B) is a relatively small third component. D. Central (Ce) and medial (Me) nuclei of the amygdala are apparent with their corresponding projections along the stria terminalis and the superior component of the bed nucleus of the stria terminalis. ac = anterior commissure; BL = basolateral nucleus of amygdala; BM = basomedial nucleus of amygdala; BSTL = bed nucleus of stria terminalis, lateral division; BSTM = BST, medial division; BSTS = BST, superior division; Cd = caudate; Cl = claustrum; EGP = external segment of the globus pallidum; Ent = entorhinal cortex; f = fornix; HDB = diagonal band; Hy = hypothalamus; IGP = internal segment of GP; La = lateral nucleus of the amygdala; opt = optic track; ox = optic chiasm; Pir = piriform cortex; Pu = putamen; SLEA = sublenticular component of extended amygdala; st = stria terminalis; Th = thalamus; VDB = diagonal band; VS = ventral striatum. This figure was published in Handbook of Chemical Neuroanatomy, Vol 15, Heimer L, de Olmos J, Alheid G, et al, p 58, Copyright Elsevier, 1999.

  • View in gallery

    Drawing illustrating the extended amygdala. The central division of the amygdala (Ce) is associated with projections via the stria terminalis to the lateral hypothalamus, and the medial division (Me) projects to the medial hypothalamus. Notice that the laterobasal nuclei of the amygdala are not included in the extended amygdala. The supracapsular component of the extended amygdala is depicted in Fig. 6B, whereas the sublenticular component is most visible in Fig. 6C. Amg = amygdala; Co = cortical amygdaloid nuclei. This figure was published in Handbook of Chemical Neuroanatomy, Vol 15, Heimer L, de Olmos J, Alheid G, et al, p 59, Copyright Elsevier, 1999.

  • View in gallery

    Photograph of Dr. Heimer and his long-time friend and collaborator José de Olmos of Argentina. The two worked together to pioneer the concepts of the ventral striatum and extended amygdala. Sadly, de Olmos died the year following Heimer’s death.

References

1

Abelson JLCurtis GCSagher OAlbucher RCHarrigan MTaylor SF: Deep brain stimulation for refractory obsessive-compulsive disorder. Biol Psychiatry 57:

2

Anderson DAhmed A: Treatment of patients with intractable obsessive-compulsive disorder with anterior capsular stimulation. Case report. J Neurosurg 98:

3

Aouizerate BCuny EMartin-Guehl CGuehl CAmieva HBenazzouz A: Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report. J Neurosurg 101:

4

Bogerts BMeertz ESchönfeldt-Bausch R: Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage. Arch Gen Psychiatry 42:

5

de Olmos J: The Neurobiology of the Amygdala.

6

de Olmos JS: A cupric-silver method for impregnation of terminal axon degeneration and its further use in staining granular argyrophilic neurons. Brain Behav Evol 2:

7

de Olmos JSAlheid GFBeltramino CA: The Rat Nervous System.

8

Fenwick P: Aspects of Epilepsy in Psychiatry.

9

Fink RPHeimer L: Two methods for selective silver impregnation of degenerating axons and their synaptic endings in the central nervous system. Brain Res 4:

10

Fountas KNSmith JRLee GP: Bilateral stereotactic amygdalotomy for self-mutilation disorder. Case report and review of the literature. Stereotact Funct Neurosurg 85:

11

Greenberg BDMalone DAFriehs GMRezai ARKubu CSMalloy PF: Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology 31:

12

Heimer L:

13

Heimer L: Human Brain and Spinal Cord: Functional Neuroanatomy and Dissection Guide.

14

Heimer L:

15

Heimer L: Instructional video. Dissection of the human brain. Neurosurg Focus 18(6B):

16

Heimer L:

17

Heimer L: A new anatomical framework for neuropsychiatric disorders and drug abuse. Am J Psychiatry 160:

18

Heimer L: The olfactory connections of the diencephalon in the rat. An experimental light-and electron-microscopic study with special emphasis on the problem of terminal degeneration. Brain Behav Evol 6:

19

Heimer L: Limbic Mechanisms. The Continuing Evolution of the Limbic System Concept.

20

Heimer L: Pathways in the brain. Scientific American 225:

21

Heimer Lde Olmos JSAlheid GFPearson JSakamoto N: Handbook of Chemical Neuroanatomy.

22

Heimer LKuikka VLarsson KNordstrom E: A headholder for stereotaxic operations of small laboratory animals. Physiol Behav 7:

23

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