The Human Hypothalamus

The Human Hypothalamus

Anterior Region

1st Edition - June 15, 2021

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  • Editors: Dick Swaab, Felix Kreier, Paul Lucassen, Ahmad Salehi, Ruud Buijs
  • eBook ISBN: 9780128199763
  • Hardcover ISBN: 9780128199756

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The Hypothalamus is an important area of the brain for understanding a variety of neurological disorders. This volume summarizes for readers the anatomy and physiology of the anterior hypothalamus, to better understand pathology and treatment of hypothalamus related disorders. In addition to anatomy and physiology in humans, cytoarchitecture and chemoarchitecture in rodents is provided. The volume explores the role of the hypothalamus in disorders of eating, sleeping, anxiety, and mood, as well as its role in sexual behavior and gender identity. Coverage includes how Parkinson’s, Alzheimer’s and other neurological disorders relate to the hypothalamus.

Key Features

  • Reviews the anatomy and physiology of the anterior hypothalamus
  • Provides cytoarchitecture and chemoarchitecture from rodents
  • Discusses hypothalamic related disorders of eating, sleeping, anxiety, and mood
  • Covers how Parkinson’s, Alzheimer’s and other neurological disorders relate to the hypothalamus
  • Explores the role of the hypothalamus in sexual behavior and gender identity


Clinical neurologists, researchers in neurology

Table of Contents

  • Cover image
  • Title page
  • Table of Contents
  • Copyright
  • Handbook of Clinical Neurology 3rd Series
  • Foreword
  • Preface
  • The HCN volumes on the Human Hypothalamus
  • Contributors
  • Contents of related volumes
  • Section 1: Introduction
  • Chapter 1: Introduction: The anterior hypothalamus
  • Section 1: Introduction
  • Section 2: The Basal Forebrain Cholinergic System
  • Section 3: The Circadian System
  • Section 4: Bed Nucleus of the Stria Terminalis and the Fear Circuit
  • Section 5: Preoptic Area
  • Chapter 2: History of hypothalamic research: “The spring of primitive existence”
  • Abstract
  • Discipline of Neuroendocrinology: Current Definitions
  • Neurosecretion and central effects of neuropeptides
  • Portal system
  • Early Ideas About Pituitary and Pineal Gland Function
  • Neurosecretion and the Neurohypophysis
  • Blood Supply to the Hypothalamus and Pituitary
  • Releasing Factors
  • Neuropeptides as Neurotransmitters or Neuromodulators: The Central Pathways Involved
  • Control of Autonomic Functions by the Hypothalamus
  • Future Directions
  • Chapter 3: Anatomy and cytoarchitectonics of the human hypothalamus
  • Abstract
  • Gross Anatomy
  • Vascular Supply
  • Cytoarchitecture
  • Hypothalamic Pathways
  • Chapter 4: Morphology and distribution of hypothalamic peptidergic systems
  • Abstract
  • Introduction
  • Hypothalamic Peptidergic Systems in Human
  • Concluding Remarks
  • Chapter 5: MRI maps, segregation, and white matter connectivity of the human hypothalamus in health
  • Abstract
  • Introduction
  • MRI Mapping and Fiber Tracking of the Hypothalamus
  • 3D and 2D Hypothalamic Architecture
  • Macroconnectivity
  • Conclusion
  • Chapter 6: Magnetic resonance imaging of the hypothalamo–pituitary region
  • Abstract
  • Introduction
  • History of Pituitary and Hypothalamic Imaging
  • Technique and Methodology of Magnetic Resonance Imaging
  • Normal MRI of the Pituitary Gland and Hypothalamic Region
  • Indications for Pituitary MRI
  • Imaging of Sellar, Parasellar, and Hypothalamic Lesions
  • Benign Lesions (Macroadenomas, Microadenomas, Craniopharyngiomas, Meningiomas, Pituicytomas, Schwannomas)
  • Cystic Lesions (Rathke's Cleft Cysts, Epidermoid Cysts, Dermoid Cysts, Arachnoid Cysts)
  • Malignant Tumors (Chordomas, Chondrosarcomas, Primary Germ Cell Tumors, Gliomas, Metastases and Lymphomas)
  • Vascular, Inflammatory, and Infectious Lesions (Aneurysms, Hypophysitides, Abscesses)
  • Empty Sella
  • Congenital Abnormalities (Pituitary Stalk Interruption Syndrome, Hamartomas)
  • Surgical Indications
  • Summary
  • Chapter 7: Resting-state functional connectivity of the human hypothalamus
  • Abstract
  • Introduction
  • Resting States Functional Connectivity
  • Analyzing Resting-State Functional Connectivity
  • Imaging of the Hypothalamus Using MRI
  • Functional Imaging of the Hypothalamus
  • Hypothalamus RSFC
  • Hypothalamus RSFC in Metabolism and Eating Behavior
  • Hypothalamus RSFC in Persons of Normal and Excessive Weight
  • Effect of Hunger and Satiety on the Hypothalamic Functional Connectivity Network
  • Effect of Nutritional Modulation on Hypothalamus RSFC
  • Hormonal Modulation of the Hypothalamic Resting-State Network
  • Hypothalamus RSFC in Neurological and Psychiatric Diseases
  • Hypothalamus RSFC in Addiction and Depression
  • Hypothalamus RSFC in Neurological Diseases
  • Hypothalamus RSFC in Patients with Migraine
  • Concluding Comments
  • Chapter 8: Neurogenesis in the adult hypothalamus: A distinct form of structural plasticity involved in metabolic and circadian regulation, with potential relevance for human pathophysiology
  • Abstract
  • Introduction
  • The Hypothalamic Neurogenic Niche: A Brief Overview of the Experimental Models
  • Does the Adult Human Hypothalamus Contain a Neurogenic Niche?
  • Comparative Assessment of the Hypothalamic Niche between Rodents and Humans
  • Pathophysiologic Implications of Hypothalamic Neurogenesis in Humans
  • How to Move Forward?
  • Acknowledgments
  • Chapter 9: Matching of the postmortem hypothalamus from patients and controls
  • Abstract
  • Introduction
  • Potential Confounding Factors
  • Conclusion
  • Acknowledgments
  • Section 2: The basal forebrain cholinergic system
  • Chapter 10: Spatial topography of the basal forebrain cholinergic projections: Organization and vulnerability to degeneration
  • Abstract
  • Introduction
  • Topographic Projections of the BF in Rodents and Nonhuman Primates
  • Topographic Projections of the Basal Forebrain in Humans
  • Spatial Topography of Basal Forebrain Vulnerability to Neurodegeneration
  • Acknowledgments
  • Chapter 11: The diagonal band of Broca in health and disease
  • Abstract
  • Introduction
  • Locating the “Diagonal Band”
  • Defining the “Nucleus” and the “Limbs” of the Diagonal Band
  • Rostro-Caudal Mapping of the DBB
  • The Neurochemical Profile of Neurons in the nvlDBB
  • The Often Neglected nhlDBB
  • Delineation of the Boundaries of the nvlDBB
  • Neuropathology of the nvlDBB
  • Alzheimer's Disease (AD)
  • Parkinson's Disease (PD) and Lewy Body Dementias (LBD)
  • Other Neurological Conditions and Aging
  • Functional Correlates of nvlDBB Cell Loss
  • Conclusion
  • Chapter 12: Nucleus basalis of Meynert degeneration predicts cognitive impairment in Parkinson's disease
  • Abstract
  • Introduction
  • Cognitive Impairment in Parkinson's Disease
  • The Nucleus Basalis of Meynert
  • Neuroimaging Techniques to Study Cognitive Impairment and the Role of the Nucleus Basalis of Meynert in Parkinson's Disease
  • Therapeutic Interventions
  • Conclusion and Future Directions
  • Chapter 13: Enlargement of early endosomes and traffic jam in basal forebrain cholinergic neurons in Alzheimer's disease
  • Abstract
  • Introduction
  • Basal Forebrain Cholinergic Neurons Degeneration
  • Possible Iatrogenic Mechanisms of Cholinergic Degeneration
  • Intrinsic Mechanism: Failed NGF Signaling
  • Therapeutic Strategies Targeting the Cholinergic System
  • Conclusions
  • Acknowledgment
  • Chapter 14: Gene and cell therapy for the nucleus basalis of Meynert with NGF in Alzheimer's disease
  • Abstract
  • Introduction
  • The Cholinergic System and the Basal Forebrain
  • Treatment with ChEIs in Alzheimer's Disease
  • Rationale for Nerve Growth Factor in Alzheimer's Disease
  • Intracerebroventricular Infusion of NGF
  • Local Delivery of NGF
  • Conclusion
  • Section 3: The circadian system
  • Chapter 15: The circadian system: From clocks to physiology
  • Abstract
  • Introduction
  • Clock Genes: The Driving Force Behind the Rhythm in the SCN and of the Metabolism in Peripheral Cells
  • Circadian Rhythms in Physiology: Continuously Changing Homeostasis
  • Rhythmic Secretion ofHormones: A Reflection of SCN Activity
  • The SCN Controls the Rhythmic Physiology of All the Organs in the Body
  • Disturbances in SCN Activity Trigger Pathologies
  • Desynchrony of Behavior With the Light–Dark Cycle: A Deviation in Modern Life Leads to a Wide Variation of Pathologies
  • Conclusion
  • Chapter 16: Development of the circadian system and relevance of periodic signals for neonatal development
  • Abstract
  • Introduction
  • Final comments
  • Acknowledgment
  • Chapter 17: Disrupted circadian rhythms and mental health
  • Abstract
  • Introduction
  • Circadian System
  • Disruption of Circadian Rhythms and Anxiety
  • Disruption of Circadian Rhythms and Major Depressive Disorder
  • Circadian Rhythm Disruption and Bipolar Disorder
  • Circadian Rhythm Disruption and Schizophrenia
  • Conclusions and Future Directions
  • Acknowledgments
  • Chapter 18: Diurnal and seasonal molecular rhythms in the human brain and their relation to Alzheimer disease
  • Abstract
  • Diurnal Rhythms and Dementia in Older Adults
  • Seasonal Rhythms and Dementia in Older Adults
  • Diurnal Brain Molecular Rhythms in Model Organisms
  • Seasonal Brain Molecular Rhythms in Model Organisms
  • Diurnal and Seasonal Molecular Rhythms in the Human Neocortex
  • Chapter 19: Circadian changes in Alzheimer's disease: Neurobiology, clinical problems, and therapeutic opportunities
  • Abstract
  • Introduction
  • Pathogenesis of AD: Beaten Tracks and Novel Emerging Concepts
  • Hypothalamus at the Crossroads of Early Circadian and Metabolic Disruptions in AD: Evidence From Animal Models
  • Functional Consequences of an Early Hypothalamic Involvement in AD Pathogenesis
  • Clinical Challenges: From Bench to Bedside
  • Therapeutic Opportunities
  • Conclusion/Summary
  • Chapter 20: The circadian system in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy
  • Abstract
  • Introduction
  • Circadian Alterations in PD, MAS, and PSP
  • Neuropathologic and Functional Dissection of the Neuronal Circuitry Governing Circadian Rhythms in PD, MSA, and PSP
  • Pathologic Status of the Afferent Pathways to the Clock
  • Pathologic Status of the Central SCN Clock
  • Pathologic Status of the Efferent Pathways of the Clock
  • Conclusions
  • Chapter 21: Retina and melanopsin neurons
  • Abstract
  • Melanopsin Retinal Ganglion Cells: Anatomy, Physiology, and Functions
  • Melanopsin Retinal Ganglion Cells: Resistance to Neurodegeneration in Mitochondrial Optic Neuropathies
  • Melanopsin Retinal Ganglion Cells in Age-Related Neurodegenerative Disorders
  • Melanopsin Retinal Ganglion Cells in Aging
  • Conclusions
  • Chapter 22: Melatonin and the circadian system: Keys for health with a focus on sleep
  • Abstract
  • Introduction
  • Melatonin: Identification and Synthesis
  • Melatonin: Role, Mechanisms of Action, and Clinical Perspectives
  • Conclusions
  • Acknowledgments
  • Chapter 23: Melatonin receptors, brain functions, and therapies
  • Abstract
  • Introduction
  • Expression of Melatonin Receptors in the Human Hypothalamus
  • Function of Melatonin Receptors in Hypothalamus
  • Drugs Targeting Melatonin Receptors
  • Future Drug Developments
  • Chapter 24: Chronotherapy
  • Abstract
  • Introduction
  • Biological Rhythms: An Overview Relevant for Chronotherapy
  • The Sleep/Wake Cycle, A Target for Chronotherapy
  • Some Basic Concepts About Chronopharmacology
  • Melatonin, A Chronobiotic Prototype
  • Future of Chronotherapy
  • Concluding Remarks
  • Chapter 25: The use of melatonin to mitigate the adverse metabolic side effects of antipsychotics
  • Abstract
  • Introduction
  • Antipsychotics and Their Side Effects: A Bad Name
  • Melatonin Use in Antipsychotic-Induced Adverse Metabolic Effects: Clinical Studies
  • Why Melatonin? The Circadian System and Metabolic Regulation
  • Mechanisms Implicated in Antipsychotic-Induced AMEs and Their Prevention With Melatonin
  • Clinical Implications
  • Conclusions
  • Section 4: Bed nucleus of the stria terminalis and the fear circuit
  • Chapter 26: Chemoarchitecture of the bed nucleus of the stria terminalis: Neurophenotypic diversity and function
  • Abstract
  • Introduction
  • Neurotransmitters
  • Neuropeptides
  • BNST Sexual Dimorphism and Control of Sexual Behaviors
  • Human BNST
  • Overview and Conclusions
  • Chapter 27: Functional anatomy of the bed nucleus of the stria terminalis–hypothalamus neural circuitry: Implications for valence surveillance, addiction, feeding, and social behaviors
  • Abstract
  • Introduction
  • Anterior BNST Circuitry
  • Posterior BNST Circuitry
  • BNST–Hypothalamus Circuitry
  • BNST–Hypothalamus Circuitry in Valence Surveillance
  • The BNST in Addiction
  • BNST–Hypothalamus Circuitry in Feeding
  • BNST–Hypothalamus Circuitry in Social Behavior
  • Sex Differences in the BNST
  • Concluding Comments
  • Chapter 28: Roles of the bed nucleus of the stria terminalis and amygdala in fear reactions
  • Abstract
  • Overview
  • Defining Fear
  • The Bed Nucleus of the Stria Terminalis
  • The Amygdala
  • Differences between the amygdala and BNST in contributions to fear
  • Section 5: Preoptic area
  • Chapter 29: The median preoptic nucleus: A major regulator of fluid, temperature, sleep, and cardiovascular homeostasis
  • Abstract
  • Introduction
  • Neurochemical Properties of MnPO Neurons
  • Neural Connectivity
  • Body Fluid Homeostasis
  • Body Temperature Homeostasis
  • Sleep Homeostasis
  • Cardiovascular Homeostasis
  • Concluding Remarks
  • Chapter 30: The neuroendocrinology of the preoptic area in menopause: Symptoms and therapeutic strategies
  • Abstract
  • Introduction to the Preoptic Area and Thermoregulation
  • Estrogen and Dysfunctional Thermoregulation
  • The Importance of KNDy Neurons in Menopause and Thermoregulation
  • Neurokinin B and Hot Flushes
  • Antagonism of NKB/NK3R Signaling as a Therapy for Hot Flushes
  • Conclusion
  • Acknowledgments
  • Chapter 31: The intermediate nucleus in humans: Cytoarchitecture, chemoarchitecture, and relation to sleep, sex, and Alzheimer disease
  • Abstract
  • Chemoarchitecture of the Intermediate Nucleus
  • Conclusion
  • Index

Product details

  • No. of pages: 542
  • Language: English
  • Copyright: © Elsevier 2021
  • Published: June 15, 2021
  • Imprint: Elsevier
  • eBook ISBN: 9780128199763
  • Hardcover ISBN: 9780128199756

About the Editors

Dick Swaab

Dick Swaab (1944) earned his medical and doctoral degrees at the University of Amsterdam, where he became involved in brain research during his third year of medical school. He was Director of the Netherlands Institute for Brain Research from 1978 to 2005. Since 1979 he is Professor of Neurobiology at the Medical Faculty, University of Amsterdam.

In 1985, Dr. Swaab founded the Netherlands Brain Bank (NBB) to serve as a source of clinically and neuropathologically well-documented research tissue. Since its founding, the Brain Bank has provided samples from more than 4,000 autopsies to 500 research groups in 25 countries. He was director of the NBB until 2005.

He is Leader Research team Neuropsychiatric Disorders, Neth. Inst for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences (KNAW). Swaab is also appointed for 2011-2017 Chao Kuang Piu Chair of Zhejiang University, Hangzhou, P.R. China.

His major research interests focus on, sexual differentiation of the human brain in relation to gender identity and sexual orientation, aging of the brain, Alzheimer’s disease, the neurobiological basis of depression, suicide and eating disorders. He has published over 540 papers in SCI journals, authored more than 200 chapters in books, and edited more than 60 books. Swaab mentored 84 PhD students from which 16 are now full professor. He is “Companion in the Order of the Dutch Lion”, bestowed by her Royal Majesty Queen Beatrix of the Netherlands. In 2008 Swaab obtained the Academy medal for his role in national and international neuroscience.

Dick Swaab is author of the 2 volume monograph The Human Hypothalamus that appeared in the Handbook of Clinical Neurology series, Elsevier, Amsterdam (1000 pp) and the Dutch best seller We are our Brains (450.000 copies sold), that is translated in 14 languages. A children's version of the book (You are your brains) has also appeared in Dutch in 2013 and Russian (2014). Swaab's H-factor is 76.

Affiliations and Expertise

Netherlands Institute for Brain Research, University of Amsterdam, Amsterdam, The Netherlands

Felix Kreier

Felix Kreier is a pediatrician and affiliated with OLVG Hospitals in Amsterdam, The Netherlands.

Affiliations and Expertise

OLVG Hospitals, Amsterdam, The Netherlands

Paul Lucassen

Paul J. Lucassen did his PhD in 1995 on Alzheimer’s Disease at the Netherlands Institute for Brain Research in Amsterdam. After a.o. a postdoc in Leiden, he became Full Professor of Brain Plasticity in 2011 at the Swammerdam Institute for Life Sciences (SILS) of the University of Amsterdam, The Netherlands. His group studies molecular, nutritional, pharmacological and environmental regulation of brain plasticity. They combine molecular tools, in vitro/vivo model systems, human brain tissue, cohort studies and brain imaging. A major focus is on adult neurogenesis and cognition in relation to; (early life) stress, exercise, enrichment, depression, brain insults and dementia.

Affiliations and Expertise

Swammerdam Institute for Life Sciences (SILS) - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands

Ahmad Salehi

Ahmad Salehi is affiliated with Stanford Medical School, Department of Psychiatry & Behavioral Sciences, in Palo Alto, CA, United States.

Affiliations and Expertise

Stanford Medical School, Department of Psychiatry and Behavioral Sciences, Palo Alto, CA, United States

Ruud Buijs

Dr. Ruud M. Buijs is head of the Physiology department of the I.I.Biomedicas at the UNAM university and leader of the group Hypothalamic Integration Mechanisms. In that group, the scientists study how the brain and body interact with each other, and hereby the attention is focussed on autonomic and hormonal regulation of body functions under the influence of the biological clock of the brain.

Affiliations and Expertise

Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, Mexico D.F.

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