The cerebral cortex, meninges, basal ganglia, and ventricular system

The cerebrum (telencephalon) is the largest part of the brain and comprises the cerebral cortex and subcortical structures (e.g., basal ganglia, hippocampus). The longitudinal fissure divides the brain into two hemispheres. The cortex represents the top-outer layer of the brain, which receives its convoluted appearance from a network of gyri and sulci. Sulci separate the cerebral cortex further into a frontal, temporal, parietal, and occipital lobe. The cerebrum is the key structure involved in perception, language, and coordination. The basal ganglia are situated beneath the cortex, and they are heavily involved in motor control. The cortical hemispheres contain one of the lateral ventricles each, with the smaller third and fourth ventricles being located between the two thalami in the diencephalon and between the cerebral aqueduct and obex respectively. The four ventricles form an interconnected system that produces, drains, and is filled with cerebrospinal fluid, which plays a role in waste removal and cushioning of the brain. The meninges comprise the three protective membranes that envelop the central nervous system, i.e. the brain and spinal cord.

Overview

• The cerebral cortex receives its convoluted appearance from a network of gyri (rounded ridges on the surface of the cortex) and sulci (furrows separating the gyri).
• The longitudinal fissure divides the brain into two hemispheres.
• Deep sulci divide each hemisphere further into a frontal, temporal, parietal, and occipital lobe.
• Deep sulci separate the cerebral cortex into different lobes: frontal, temporal, parietal, and occipital
• The main sulci
  • Central sulcus (of Rolando): separates the frontal and parietal lobes
  • Lateral sulcus (Sylvian fissure): separates the frontal and temporal lobes anteriorly and the parietal and temporal lobes posteriorly
  • Cingulate sulcus: separates the cingulate gyrus from the frontal and parietal lobes
  • Parieto-occipital sulcus: separates the parietal and occipital lobes
  • Calcarine sulcus: divides the occipital lobe horizontally into the cuneus (superior) and lingual (inferior) gyrus

Frontal lobe

The cortical regions responsible for processing the motor functions of the different regions of the body can be mapped using a motor homunculus.

Parietal lobe

Temporal lobe

Occipital lobe

Bilateral or large unilateral (esp. right-sided) lesions in the ventral occipitotemporal cortex may cause impairment of facial recognition (prosopagnosia).

Insular lobe

• Location
  • Small region of the cerebral cortex deep within the Sylvian fissure
  • Completely hidden below parts of the frontal, parietal, and temporal lobes
• Characteristics
  • Receives input from the thalamus (sensory thalamic nuclei) and the cerebral cortex
  • Reciprocally connected with the limbic system and frontal brain regions
• Function
  • Processing of emotions
  • Perception of body functions (interoception)
  • Integration and perception of somatosensory stimuli
  • Perception of gustatory and olfactory stimuli
  • Modulation of autonomic functions (e.g., blood pressure, gastrointestinal motility)

Internal capsule

• A deep subcortical structure that lies between the basal ganglia
• Largest collection of nerve fibers traveling to and from the cerebral cortex, forming the corona radiata (neuroanatomy), a collection of white matter fibers.
• Components: anterior limb, genu, and posterior limb
  • Anterior limb: contains the thalamocortical tract
  • Genu: contains the corticobulbar tract
  • Posterior limb: contains the corticospinal tract and thalamocortical and somatosensory fibers

Meninges

• Three layers of connective tissue that cover and protect the brain and the spinal cord
• Divided into (from outer to inner layer): dura mater, arachnoid mater, and pia mater

Falces of the brain

Spaces of the CNS

The Subarachnoid Space extends to the S2 vertebra.

Overview

• The basal ganglia are a group of nuclei that lie beneath the cortex.
• Distributed over the telencephalon, diencephalon, and mesencephalon (midbrain)

Cortico-basal ganglia-thalamo-cortical loop (CBGTC)

• A neuronal circuit between the cortices of the brain, the basal ganglia, and the thalamus
• Via this loop, the basal ganglia aid in the initiation of movement, control of skeletal muscles, and adjustment of posture.
• Two main pathways: the direct pathway and the indirect pathway.
• The balance of activity between the direct and indirect pathways is modulated by dopamine.

Functional anatomy of the basal ganglia

Direct pathway of the basal ganglia (excitatory)

• Function: increase in motor activity
• Pathway
  • Motor cortex activation → glutamate release → striatum stimulation → GABA release → inhibition of Gpi → inhibition of GABA release → thalamus disinhibition → premotor cortex stimulation → muscle activation → ↑ movement
  • In addition, the subthalamic nucleus stimulates the substantia nigra (pars compacta) → dopamine release → stimulation of D1 receptor in striatum → further inhibition of Gpi → inhibition of GABA release → thalamus disinhibition → premotor cortex stimulation → muscle activation → ↑ movement

Binding of dopamine to D1 Receptors stimulates the excitatory D1Rect pathway.

Indirect pathway of the basal ganglia (inhibitory)

• Function
  • Decrease in motor activity
  • Modulation of the disinhibitory effect of the direct pathway
• Pathway
  • Motor cortex activation → glutamate release → stimulation of striatum → GABA release → inhibition of Gpe → inhibition of GABA release → ↓ inhibition (activation) of subthalamic nucleus → glutamate release → stimulation of substantia nigra (pars reticularis) and Gpi → GABA release → inhibition of thalamus → inhibition of premotor cortex → deactivation of muscles → ↓ movement
  • The striatum also stimulates the substantia nigra (pars compacta) → dopamine release → stimulation of D2 receptor in striatum → inhibition of GABA release → disinhibition of Gpe → GABA release → inhibition of subthalamic nucleus → ↓ stimulation of GPi → disinhibition of thalamus → ↑ movement

The indirect pathway is inhibitory.

Dopaminergic pathways

• Dopaminergic pathways are collections of neurons that release dopamine.
• Dysfunction of dopaminergic pathways is involved in some psychiatric diseases (e.g., schizophrenia), addiction disorders, and movement disorders (e.g., Parkinson disease).
• Antipsychotic drugs target dopaminergic pathways.

Overview

• Consists of four interconnected cavities within the brain: the two lateral ventricles; the third ventricle, located in the diencephalon; and the fourth ventricle, located dorsal to the pons
• Involved in the production and circulation of cerebrospinal fluid (CSF)
• CSF serves as a fluid cushion and removes waste products from the brain

The foramina of Luschka are the Lateral apertures and the foramen of Magendie is the Medial aperture of the fourth ventricle.

Cerebrospinal fluid

• Description: a clear and colorless fluid derived from blood plasma that provides mechanical support to the CNS and transports biochemical compounds (e.g., neuromodulators) and waste products
• CSF production: produced by choroid plexuses in the lateral, third, and fourth ventricles by filtration of plasma
• CSF flow: lateral ventricles → third ventricle (via interventricular foramina) → fourth ventricle (via cerebral aqueduct) → diffusion and active transfer into the subarachnoid space (via foramina of Luschka and Magendie) → reabsorption in the arachnoid granulations (a group of projections of the arachnoid mater into the dural sinuses) → drainage into the dural venous sinuses

Basal cisterns (subarachnoid cisterns)

• Description
  • Numerous compartments within the subarachnoid space formed by a separation of the pia mater and arachnoid membrane, filled with cerebrospinal fluid
  • Contain arteries, veins, and nerves
  • Interconnected and essential for CSF circulation
  • Cisterna magna
    • Largest of the basal cisterns
    • Located posterior to the medulla
    • The median aperture and the lateral apertures drain CSF into the cisterna magna.
• Clinical relevance
  • Subarachnoid hemorrhage
  • Mass effect in accumulation of cerebrospinal fluid
  • Arachnoid cyst: common, benign, and usually asymptomatic cystic lesion containing cerebrospinal fluid

Overview

• The nervous system is primarily composed of:
  • Neurons: polarized cells with the ability of transmitting signals from one cell to another
    • Pyramidal cell: principal neurons of the cerebral cortex required for motor control and cognition
    • Stellate cells (brain): star-shaped interneurons whose axons do not extend beyond the cortex
  • Supporting glial cells
  • For more information on the microscopic anatomy of the neurological tissue, see “Nerve tissue.”
• Cortical neuroanatomy
  • The cerebral cortex can be divided into the neocortex and allocortex.
  • Can also be divided into 47 Brodmann areas, defined by their cytoarchitecture.
• The blood-brain barrier separates the brain tissue from circulating blood and provides protection (e.g., from microorganisms, drugs)
• The blood-cerebrospinal fluid barrier separates the cerebrospinal fluid from the blood circulation.

Cortical neuroanatomy

Neocortex

• Makes up the majority of the cerebral cortex
• Responsible for high-level processes (e.g., sensory perception, cognition, language skills)
• Layers:
  • Molecular layer: nerve fibers
  • External granular layer
    • Densely packed, small nonpyramidal cells (e.g., stellate cells)
    • Small pyramidal cells that project axons to other cortical areas
  • External pyramidal layer: small to medium-sized pyramidal cells that project axons to other cortical areas
  • Internal granular layer
    • Termination area of thalamocortical projections (form lines of Gennari in the primary visual cortex)
    • Filled with densely packed, medium-sized pyramidal and nonpyramidal cells
  • Internal pyramidal layer: large pyramidal cells give rise to the axons that form the corticospinal tracts and corticobulbar tracts (pyramidal tracts to the brainstem and spinal cord)
  • Multiform layer: composed of pyramidal and nonpyramidal cells of various size

Allocortex

• Composed of three layers
• Consists of the hippocampus and the olfactory cortex

Blood-brain barrier

• Description: a barrier of CNS blood vessels separating the brain from circulating blood
• Function: protects the central nervous system from microorganisms, cells, proteins, and drugs that can cause damage to the brain and other structures
• Components
  • Capillary endothelial cells → have tight junctions
  • The basal lamina
  • Astrocytes
  • Pericytes
• Transport mechanisms across the blood-brain barrier
  • Ion channels (e.g., sodium, potassium)
  • Selective transport (slow): amino acids, glucose, vitamin K, vitamin D
  • Diffusion (fast): nonpolar and lipid-soluble substances (e.g., oxygen and carbon dioxide)
• Structures with no blood-brain barrier
  • Structures located around the brain ventricles (circumventricular location), including:
    • Area postrema: vomiting center (contains the chemoreceptor trigger zone)
    • Organum vasculosum lamina terminalis (OVLT): osmoreceptors
    • Neurohypophysis: oxytocin and ADH release directly into the blood
  • Allow certain molecules to affect brain function (e.g., blood-borne drugs and hormones)
• Damage mechanisms
  • Brain infarction and tumors break endothelial cell tight junctions, thereby causing vasogenic edema.
  • Hyperosmolar solutions (e.g., mannitol) cause vasodilatation and shrinkage of endothelial cells, thereby disrupting the blood-brain barrier and increasing its permeability to other drugs.

Blood-cerebrospinal fluid barrier (BCSFB)

• Function: separates cerebrospinal fluid from the blood circulation
  • Impermeable to cells, almost all proteins, and toxins (e.g., hydrophilic medications, bacteria)
  • Selectively permeable to substances required for regulation and production of CSF, e.g., glucose and electrolytes
• Structure: formed by the choroid plexus
  • Modified ependymal cells (choroid epithelial cells) held by tight junctions
  • Capillary endothelial cells have fenestrations
  • Basal membrane
  • Choroid plexus carcinoma: a rare malignant neoplasm of the choroid plexus (∼ 1% of pediatric intracranial malignancies)
    • Primarily occurs in children < 5 years
    • Typically associated with signs of hydrocephalus, which can be caused by both increased CSF production and CSF outflow obstruction.

Brain metabolism ^[2][3][4]

• Energy demand
  • The brain requires 15% of the cardiac output and ∼ 20% of the body's oxygen to function properly. ^[2]
  • Main energy-demanding functions of the brain:
    • Active transportation of ions
    • Maintenance and restoration of membrane potentials
    • Synthesis and metabolism of neurotransmitters
  • Metabolic requirements vary according to regional neuronal activity and are directly related to changes in cerebral blood flow and energy substrate utilization (see “Cerebral autoregulation”).
• Energy sources
  • Energy is mainly derived from the aerobic oxidation of glucose.
  • The uptake of glucose by neurons is provided by the insulin-independent GLUT3 transporter.
  • Under particular circumstances, the brain has the capacity to use other energy substrates:
    • Ketone bodies during prolonged fasting
    • Lactate during periods of intense physical activity

Brain homeostasis ^[5]

• Interactions between the brain and peripheral organs such as the liver, pancreas, adipose tissue, gut, and muscle are critical for the maintenance of energy and glucose homeostasis.
• The blood-brain barrier plays a key role by: ^[6]
  • Exchanging substances between the blood and brain parenchyma
  • Modulating the response to extrinsic environmental factors and physiological changes (e.g., sleep/wake cycles, aging, diet) by adjusting its permeability
  • The choroid plexus contributes by maintaining a constant diffusion of nutrients to the CNS through the CSF
  • For more information, see “Blood-brain barrier” and “Blood-cerebrospinal fluid barrier” in “The cerebral cortex, meninges, basal ganglia, and ventricular system.”
• The hypothalamus plays a key role in homeostasis by:
  • Modulating energy intake and expenditure
  • Modulating hepatic glucose production, insulin and glucagon secretion, and skeletal muscle glucose uptake, therefore maintaining glucose homeostasis
  • Peripheral metabolic hormones and nutrients target hypothalamic neuronal circuits, providing feedback signals that help maintain this balance. (See “Regulation of appetite and satiety” in “General endocrinology”)
    • Cholecystokinin, peptide YY, and GLP-1 provide information on energy intake with meals.
    • Leptin stimulates locomotor activity, skeletal muscle fatty acid oxidation, and brown adipose tissue thermogenesis, regulating energy expenditure.
    • Neuropeptide Y and POMC-producing neurons, located in the arcuate hypothalamic nucleus, respond to neuroendocrine dysregulation.
    • Insulin acts as an adipose signal, modulating energy metabolism.
    • IL-6 provides information on muscle mass and exercise and stimulates energy expenditure for active muscles.

Impaired ability of the brain to maintain homeostasis may result in weight gain, obesity, and diabetes mellitus type 2.

Overview

• The brain is derived from 3 primary vesicles.
  • Prosencephalon (forebrain)
  • Mesencephalon (midbrain)
  • Rhombencephalon (hindbrain)
• These vesicles develop into 5 subdivisions (secondary brain vesicles)
  • Prosencephalon → telencephalon and diencephalon
  • Rhombencephalon → metencephalon and myelencephalon
  • Mesencephalon

Embryology of the brain

• Migration of neurons from the ventricular zone to the cortical zone during weeks 12–24 of gestation leads to the folding of the cerebral cortex. ^[7][8]
• Lissencephaly: failure of neuronal migration → lack of cortical sulci and gyri (smooth brain)
  • Etiology: genetic mutations (e.g., of the reelin gene) or intrauterine viral infections during the first trimester of pregnancy (esp. CMV)
  • Clinical features
    • Typically manifests with microcephaly, ventriculomegaly, and craniofacial abnormalities
    • Neurological deficits include developmental delay, seizures, and abnormalities of muscle tone (e.g., dysphagia, muscle spams).
• For more information on the embryology of the nervous system see “Neurulation” and “Spinal cord tracts and reflexes.”

Tell Di, Mes met My: The 1^st vesicle is telencephalon, 2^nd is diencephalon, 3^rd is mesencephalon, 4^th is metencephalon, and 5^th is myelencephalon (the order of the secondary brain vesicles).