Front Cover

The Cerebral Cortex in Neurodegenerative and Neuropsychiatric Disorders

The Cerebral Cortex in Neurodegenerative and Neuropsychiatric Disorders: Experimental Approaches to Clinical Issues

Copyright

Contents

List of Contributors

Foreword

Introduction

I - Introductory ChaptersPart

1 - Anatomy of the Cerebral Cortex

INTRODUCTION

CORTICAL AREAS

Frontal Cortex

Parietal Cortex

Temporal Cortex

CORTICAL LAYERS

Layers and Outputs (Fig. 1.8)

Layers and Inputs

CORTICAL VERTICALITY (COLUMNS)

CELL TYPES

Pyramidal Neurons

Neurochemical Features

Interneurons

Parvalbumin-Positive Interneurons

Calretinin-Positive Interneurons

Layer 1 Interneurons

Nitric Oxide Producing γ-Aminobutyric Acid Transmitting Interneurons

CONNECTIONS

CONCLUDING REMARKS

REFERENCES

2 - Cortical Plasticity in Response to Injury and Disease

PLASTICITY: A MAJOR PLAYER IN RECOVERY FROM CENTRAL NERVOUS SYSTEM INJURY AND DISEASE

SYSTEMS LEVEL PLASTICITY

Experience-Based Plasticity

Plasticity After Brain Trauma

Plasticity in Neurodegeneration

Systems Level Plasticity in Therapeutic Approaches

Methodology: Imaging and Electrophysiology

PLASTICITY AT THE MICROANATOMICAL LEVEL

Dendritic and Axonal Changes

Axonal Plasticity of Injured Corticospinal Axons

Methodology: Neuronal Tracing and Histological Techniques

Synaptic Plasticity

Methodology: In Vitro and In Vivo Electrophysiology

HOW CAN WE PROMOTE AND MODIFY PLASTICITY?

BEWARE THE DARK SIDE OF PLASTICITY

CHALLENGES AND HOPES FOR THE INVESTIGATION OF CENTRAL NERVOUS SYSTEM PLASTICITY

REFERENCES

3 - Imaging Approaches to Cerebral Cortex Pathology

INTRODUCTION

MAGNETIC RESONANCE IMAGING

Brain Volumetry (T1-Weighted Magnetic Resonance Imaging)

Brain Metabolite Levels (1H Magnetic Resonance Spectroscopy)

White Matter Lesions (T2-Weighted Imaging and Fluid-Attenuated Inversion Recovery)

Cerebral Microbleeds (T2*-Weighted Imaging and Susceptibility Weighted Imaging)

Diffusion Tensor Imaging

Resting State Brain Network Function

POSITRON EMISSION TOMOGRAPHY

Cerebral Perfusion, Glucose Metabolism and Oxidative Stress

Blood–Brain Barrier Dysfunction

Inflammatory Cells

β-Amyloidosis

Tau Protein Aggregation

FUTURE DIRECTION AND EXPERT OPINION

REFERENCES

II - The Cerebral Cortex in Neurodegenerative Disorders

4 - Alzheimer’s Disease

CLINICAL MANIFESTATIONS

Tau and Neurofibrillary Tangles

Amyloid and Plaques

CEREBRAL CORTEX PATTERN OF ALZHEIMER’S DISEASE PROGRESSION

Tauopathy in Clinical Alzheimer’s Disease

Clinical Evidence for Interneuronal Spreading of Tauopathy in Alzheimer’s Disease

Transsynaptic Spreading? In Vitro and Animal Models

Soluble β-Amyloid and Alzheimer’s Disease Pathology

Are Soluble Aggregates of β-Amyloid the Answer?

Evidence From Patients With Alzheimer’s Disease

In Vitro Models and Animal Models of Soluble β-Amyloid Toxicity

Are Lysosomes the Source of Soluble β-Amyloid?

IMAGING ALZHEIMER’S DISEASE PATHOLOGY

ALZHEIMER’S DISEASE THERAPEUTICS

FUTURE DIRECTIONS

REFERENCES

5 - Vascular Dementia

INTRODUCTION: THE CHALLENGE OF VASCULAR DEMENTIA

RISK FACTORS FOR VASCULAR COGNITIVE IMPAIRMENT

CORTICAL VASCULAR LESIONS OFTEN ASSOCIATED WITH DEMENTIA

VASCULAR ALTERATIONS LEADING TO CEREBRAL DAMAGE

CEREBRAL LESIONS RESULTING FROM VASCULAR MECHANISMS

Infarcts

Hemorrhages

Diffuse Leukoencephalopathy

VASCULAR CONTRIBUTIONS TO COGNITIVE IMPAIRMENT AND DEMENTIA

POTENTIAL MECHANISMS OF INTERACTION BETWEEN VASCULAR CONDITIONS AND DEMENTIA

EXPERIMENTAL MODELS OF VASCULAR DEMENTIA

Ischemic Models

Hypertensive Models

Diabetic Models

CADASIL Models

PREVENTION AND TREATMENT

REFERENCES

6 - Frontotemporal Dementia

INTRODUCTION

CLINICAL MANIFESTATIONS

Frontotemporal Dementia Clinical Syndromes

Frontotemporal Dementia Pathology

IMAGING STUDIES OF FRONTOTEMPORAL DEMENTIA

FRONTOTEMPORAL DEMENTIA GENETICS

EXPERIMENTAL MODELS

C9ORF72

Tau (MAPT)

Progranulin (GRN)

THERAPEUTIC APPROACHES

Therapies of General Relevance

Therapies for Frontotemporal Dementia Genetic Subtypes

FUTURE DIRECTIONS

REFERENCES

7 - Parkinson’s Disease and the Cerebral Cortex

INTRODUCTION

PATHOPHYSIOLOGY OF PARKINSON’S DISEASE

ANIMAL MODELS OF PARKINSON’S DISEASE

TREMORS AND THE CEREBRAL CORTEX

AKINESIA AND BRADYKINESIA AND THE CEREBRAL CORTEX

COGNITIVE IMPAIRMENT AND THE CEREBRAL CORTEX

NEUROTRANSMITTERS AND GENE EXPRESSION IN THE CORTEX

CONCLUSION

REFERENCES

8 - Huntington Disease

INTRODUCTION

CLINICAL FEATURES AND SYMPTOMS OF HUNTINGTON DISEASE

CEREBRAL CORTEX IN HUNTINGTON DISEASE: POSTMORTEM STUDIES

CEREBRAL CORTEX IN HUNTINGTON DISEASE: BRAIN IMAGING FINDINGS

CEREBRAL CORTEX AND SYMPTOM HETEROGENEITY FROM HUMAN STUDIES

DYSFUNCTIONAL CORTICOSTRIATAL NETWORK IN HUNTINGTON DISEASE ANIMAL MODELS

HUNTINGTON DISEASE PATHOGENESIS: MECHANISMS AND PATHWAYS IN RELATION TO CORTEX

THERAPEUTIC ASPECTS AND FUTURE DIRECTIONS

CONCLUSION

REFERENCES

9 - Cortical Manifestations in Amyotrophic Lateral Sclerosis

BACKGROUND

NEUROPSYCHOLOGICAL MANIFESTATIONS OF FRONTOTEMPORAL DYSFUNCTION IN AMYOTROPHIC LATERAL SCLEROSIS

MOLECULAR, CLINICAL, AND NEUROPATHOLOGICAL CORRELATES OF FRONTOTEMPORAL DYSFUNCTION IN AMYOTROPHIC LATERAL SCLEROSIS

NEUROIMAGING CORRELATES OF IMPAIRED NEURAL NETWORK FUNCTION AS THE BASIS OF FRONTOTEMPORAL DYSFUNCTION IN AMYOTROPHIC LATERAL SCLEROSIS

MODELS OF NEUROPSYCHOLOGICAL DYSFUNCTION IN AMYOTROPHIC LATERAL SCLEROSIS

THERAPEUTIC STRATEGIES

CONCLUSIONS AND FUTURE DIRECTIONS

REFERENCES

10 - Cortical Involvement in Multiple Sclerosis

INTRODUCTION

RELEVANCE OF CORTICAL PATHOLOGY TO MULTIPLE SCLEROSIS

CORTICAL STUDIES IN HUMAN MULTIPLE SCLEROSIS

IN VIVO MODELS OF MULTIPLE SCLEROSIS CORTICAL PATHOLOGY

IN VITRO STUDIES RELEVANT TO CORTICAL PATHOLOGY

CORTICAL PATHOLOGY AND THERAPEUTICS

FUTURE PERSPECTIVES

REFERENCES

III - The Cerebral Cortex in Neuropsychiatric Disorders

11 - Prefrontal Cortical Abnormalities in Cognitive Deficits of Schizophrenia

INTRODUCTION

COGNITIVE DEFICITS REPRESENT CORE SYMPTOMS OF SCHIZOPHRENIA

THE PREFRONTAL CORTEX: A NODAL POINT MEDIATING COGNITIVE DEFICITS

ABNORMALITIES INVOLVE BOTH PYRAMIDAL AND NONPYRAMIDAL NEURONS

PYRAMIDAL NEURONAL ABNORMALITIES MAY LOWER THEIR EXCITABILITY

Γ-AMINOBUTYRIC ACID NEURONAL CHANGES REDUCE INHIBITORY TONE IN THE PFC

PRECLINICAL ANIMAL MODELS OF SCHIZOPHRENIA WITH PREFRONTAL CORTEX ABNORMALITIES

CONCLUSIONS

REFERENCES

12 - Role of the Prefrontal Cortex in Addictive Disorders

INTRODUCTION

CLINICAL EVIDENCE FOR PREFRONTAL CORTICAL PATHOLOGY IN ADDICTION

EFFECTS OF ACUTE DRUG EXPOSURE AND DRUG-RELATED CUE EXPOSURE ON HUMAN PREFRONTAL CORTEX ACTIVITY PATTERNS

HUMAN PREFRONTAL CORTEX REGULATION OF INHIBITORY CONTROL MECHANISMS: RELEVANCE TO ADDICTION

THE PREFRONTAL CORTEX IN ADDICTION-RELATED NEURAL CIRCUITS

MODULATION OF PREFRONTAL CORTICAL NEUROTRANSMITTER RELEASE BY DRUGS OF ABUSE: EVIDENCE FROM ANIMAL MODELS

ROLE OF THE PREFRONTAL CORTEX IN ADDICTION-RELATED BEHAVIORAL PHENOMENA: EVIDENCE FROM ANIMAL BEHAVIORAL PHARMACOLOGY RESEARCH

NEUROCHEMICAL CONTROL OF DRUG-RELATED REWARD PROCESSING IN THE PREFRONTAL CORTEX: ROLE OF DOPAMINE–GLUTAMATE INTERACTIONS IN ANIMAL MODELS

CANNABINOID MODULATION OF DRUG-RELATED REWARD PROCESSING IN THE ANIMAL PREFRONTAL CORTEX–MESOLIMBIC CIRCUITRY CIRCUITRY

SUMMARY

REFERENCES

List of Acronyms and Abbreviations

Index

A

B

C

D

E

F

G

H

I

L

M

N

P

R

S

T

V

W

Y

Back Cover