II. Brain Structure Brain, Mind, and Belief: The Quest for Truth If the brain were simple enough for us to understand,     we would be too simple-minded to understand it.                                                                          Anonymous

Brain Structure: Topics Components of the Brain The cerebral cortex Neurons, axons, dendrites Synapses Transmission of neural activity Left brain and right brain Front brain and back brain Layers of cortex Cortical columns The essence of cortical geography

The nervous system Central nervous system Spinal cord Brain Peripheral nervous system Motor and sensory neurons connected to the spinal cord

The brain Medulla oblongata – Myelencephalon Pons and Cerebellum – Metencephalon Midbrain – Mesencephalon Thalamus and hypothalamus – Diencephalon Cerebral hemispheres – Telencephalon Cerebral cortex Basal ganglia Basal forebrain nuclei Amygdaloid nucleus More..

The brain Medulla oblongata – Myelencephalon Pons and Cerebellum – Metencephalon Midbrain – Mesencephalon Thalamus and hypothalamus – Diencephalon Cerebral hemispheres – Telencephalon *Brain Stem Alternative partition: Brain stem* Cerebellum Thalamus & hypothalamus Cerebral hemispheres

The brain Medulla oblongata – Myelencephalon Pons and Cerebellum – Metencephalon Midbrain – Mesencephalon Thalamus and hypothalamus – Diencephalon Cerebral hemispheres – Telencephalon Cerebral cortex Basal ganglia Basal forebrain nuclei Amygdaloid nucleus

Thalamus and Cortex The cortex is the area for High-level information processing Language But the thalamus is also very important Timing and coordination of cortical activity Details not yet well understood Metaphor: The cortex is the orchestra A very large orchestra The thalamus is the conductor

Two hemispheres Right Left Interhemispheric fissure (a.k.a. longitudinal fissure)

Corpus Callosum Connects Hemispheres

Major Left Hemisphere landmarks Central Sulcus Sylvian fissure

The Sylvian Fissure opened up (it’s huge)

Major landmarks and the four lobes Central Sulcus Parietal Lobe Frontal Lobe Occipital Lobe Temporal Lobe Sylvian fissure

Primary motor and somatosensory areas Central Sulcus Primary Somato- sensory Area Primary Motor Area Sylvian fissure

Some terms.. Fissures and sulci (the “grooves”) Singular: sulcus – Plural: sulci The major sulci are usually called fissures Interhemispheric fissure Sylvian fissure Sometimes the term Rolandic fissure is used for the central sulcus Gyri Singular: gyrus – Plural: gyri

Alternatives terms for some fissures Interhemispheric fissure Also known as Longitudinal fissure Sylvian fissure Also known as Lateral sulcus Central sulcus Also known as Rolandic fissure

Primary Areas Primary Somato- sensory Area Primary Motor Area Primary Auditory Area Primary Visual Area

Divisions of Primary Motor and Somatic Areas Primary Somato- sensory Area Leg Primary Motor Area Trunk Arm Hand Fingers Mouth Primary Auditory Area Primary Visual Area

Higher level motor areas Primary Somato- sensory Area Actions per- Formed by leg Leg Actions performed by hand Trunk Arm Hand Actions performed by mouth Fingers Mouth Primary Auditory Area Primary Visual Area

Video of basic cortical anatomy http://www.youtube.com/watch?v=HVGlfcP3ATI&NR=1&feature=fvwp From Medical Legal Art (2009)

The brain operates by means of connections Neurons do not store information Rather they operate by emitting activation To other neurons to which they connect Via synapses Proportionate to activation being received From other neurons via synapses Therefore, a neuron does what it does by virtue of its connections to other neurons The first big secret to understanding how the brain operates

The cerebral cortex is a very large network Made up of interconnected neurons Very large Dynamic Changes take place in connection strengths Every neuron is connected (directly or indirectly) to every other neuron Therefore, all of the information in it has the form of a network The information is in the connectivity (stay tuned for further details)

Gray matter and white matter (coronal section)

Some brain quantities The cortex accounts for 60-65% of the volume of the brain But has only a minority of the total neurons of the brain Surface of the cortex – about 2600 sq cm That is, about 400 sq inches Weight of cortex – Range: 1,130 – 1,610 grams Average: 1,370 grams Brain mass nears adult size by age six yrs Female brain grows faster than male during 1st 4 yrs Thickness of cortex – (inf. from Mountcastle 1998) Range: 1.4 – 4.0 mm Average: 2.87 mm

Cortical Neurons Cells, but quite different from other cells Multiple fibers, branching in tree-like structures Input fibers: Dendrites Output fibers: Axons Great variation in length of fibers Short ones — less than one millimeter Long ones — several centimeters Only the pyramidal cells have such long ones

Cellular Communication: How to communicate with other cells Method One (Nervous System): Fibers projecting from cell body Branching into multiple fibers Input fibers – dendrites Allow cell to receive from multiple sources Output fiber – axon Allows cell to send to multiple destinations Method Two: Circulation Circulatory system Endocrine system Lymphatic system

Santiago Ramon y Cajal 1852-1934 Spanish neuroscientist “The father of modern neuroscience” Used microscope to examine brain tissue Was skilled at drawing Many of his drawings are still used today in teaching neuroscience Nobel Prize in Medicine, 1906

View of the cortex by Ramon y Cahal

Some quantities relating to neurons Number of neurons In cortex: ca. 27 billion (Mountcastle) Beneath 1 sq mm of cortical surface: 113,000 Synapses 440 million synaptic terminals/mm3 in visual area Each neuron receives avg 3,400 synaptic terminals

Formation of neurons in the fetus 500,000 neurons are formed per minute in the developing fetus (from a program on PBS, 2002) By 24 weeks, the brain has most of its neurons Checking: 500,000 per minute 30 million per hour 720 million per day 5 billion per week 96 billion in 24 weeks Checks!

Brains of the young and very young At about 7 months, a child can recognize most sound distinctions of the world’s languages By 11 months the child recognizes only those of the language of its environment At 20 months the left hemisphere is favored for most newly acquired linguistic information Brain mass nears adult size by age six yrs Female brain grows faster than male during 1st 4 yrs

Neuronal fibers Estimated average 10 cm of fibers per neuron A conservative estimate Times 27 billion neurons in cortex Amounts to 2.7 billion meters of neural fibers in cortex (27 billion times 10 cm) Or 2.7 million kilometers – about 1.68 million miles Enough to encircle the world 68 times Seven times the distance from the Earth to the moon Big lesson: Connectivity rules!

Types of cortical neurons Cells with excitatory output connections (spiny) Pyramidal cells (about 70% of all cortical neurons) Spiny stellate cells Cells with inhibitory output connections (non-spiny) Large basket cells (two subtypes) Columnar basket cells Double bouquet cells Chandelier cells Others

Types of cortical neurons

Pyramidal neurons About 70% of cortical neurons are of this type Microelectronic probe About 70% of cortical neurons are of this type

Structure of pyramidal neuron Apical dendrite Cell body Axon Myelin

Synapses The connections between neurons Neurotransmitters cross from pre-synaptic terminal to post-synaptic terminal Synaptic cleft – about 20 nanometers 40,000 synapses per neuron (4x104) And 27 billion neurons i.e., 27,000,000,000 = 27x109 1.1x1015 (over 1 quadrillion) synapses per cortex (4x104 x 2.7x1010 = 11x1014) (Big lesson: Connectivity rules!)

Diagram of synaptic structure

Release of neurotransmitter Presynaptic terminal releases neurotransmitter

Video of Synaptic Transmission http://www.youtube.com/watch?v=HXx9qlJetSU&feature=related By Jokerwe

Connections to other neurons Excitatory Pyramidal cells and spiny stellate cells Output terminals are on dendrites or cell bodies of other neurons Neurotransmitter: Glutamate Inhibitory All other cortical neurons Output terminals are on cell bodies or axons of other neurons Neurotransmitter: GABA GABA: gamma-aminobutyric acid

Inhibitory connections Axosomatic Axoaxonal

Myelin (and other features) Dendrite Axon terminal Node of Ranvier Soma Schwann cell Myelin sheath Nucleus

Integration of neural inputs Takes place at the axon hillock Excitatory inputs are summed Inhibitory inputs are subtracted Result of this summation is the amount of incoming activation Determines how much activation will be transmitted along the axon (and its branches), hence to other neurons Degree of activation is implemented as frequency of spikes

Transmission of activation (sensory neuron) Kandel 28

Spread of activation Activation moves across links At the small scale from neuron to neuron At larger scale, across multiple links In vision From retina to conceptual area of cortex In speech production, from meanings to their expression For a listener, From expression to meaning

Another kind of neurotransmitter Released into interneural space, has global effect – e.g. serotonin, dopamine

Events in short time periods Duration of one action potential: about 1 ms Frequency of action potentials: 1–100 per sec Rate of transmission of action potential: 1–100 mm per ms Faster for myelinated axons Faster for thicker axons Synaptic delay: ½ – 1 ms

Traveling the pathways of the brain Neuron-to-neuron time in a chain (rough estimate) Neuron 1 fires @ 100 Hz Time for activation to reach ends of axon 10 mm @ 10 mm/ms = 1 ms Time to activate post-synaptic receptor – 1 ms Neuron 2 Activation reaches firing threshold – 4 ms (??) Hence, overall neuron-to-neuron time – ca. 6 ms Time required for spoken identification of picture Subject is alert and attentive Instructions: say what animal you see as soon as you see the picture Picture of horse is shown to subject Subject says “horse” This process takes about 600 ms

Three views of the gray matter Different stains show different features

Layers of the Cortex From top to bottom, about 3 mm

Long-distance cortico-cortical connections White matter – Long-distance inter-column connections Example: the arcuate fasciculus A bundle of fibers very important for language Connects Wernicke’s area to Broca’s area

Gray matter and white matter (coronal section) Grey matter White

The White Matter Provides long-distance connections between cortical columns Consists of axons of pyramidal neurons The cell bodies of those neurons are in the gray matter Each such axon is surrounded by a myelin sheath, which.. Provides insulation Enhances conduction of nerve impulses The white matter is white because that is the color of myelin

Functional layout of the gray matter Primary areas: Visual (occipital) Auditory (temporal) Somatosensory (parietal) Motor (frontal) Secondary areas Association areas Executive area, in prefrontal lobe

Primary and other areas Primary Somato- sensory Area Primary Motor Area All other areas are secondary, association, or executive areas Primary Auditory Area Primary Visual Area

The cortical network has a hierarchical structure At ‘bottom’, the primary systems Somatosensory, visual, auditory, motor In ‘middle layers’ the association areas and ‘higher-level’ motor areas At ‘top’ (prefrontal cortex) the supra-modal association area Frontal lobe comprises 1/3 of the area of the cortex Prefrontal cortex is nearly 1/4 of the whole cortex Prefrontal functions Planning, anticipation, mental rehearsal, prediction, judgment, problem solving

Sequence of development in the cortex

Major anatomical-functional dichotomies Left hemisphere vs. Right hemisphere Left Analytical, linguistic, digital Maintains existing beliefs Right Metaphorical, artistic, analog Open to new data and ideas Front (anterior) vs. Back (posterior) Front Action and planning of action Process oriented Back Perception Perceptual integration Object oriented

Left hemisphere vs. right hemisphere Analytical thinking Exact Digital Heightened contrast Proof Right Hemisphere Holistic thinking Metaphorical Analog Fuzzy boundaries Hunches, intuition

Corpus Callosum (revealed by excision of top of RH)

Cerebral dominance for language Linguistic abilities are subserved by the left hemisphere in about 97% of people 99% of right-handed people A majority of left-handers But this is just a first approximation

The Role of RH in semantics Conceptual information, even for a single item, is complex Therefore, widely distributed A network Occupies both hemispheres RH information is more connotative LH information more exact

Faulty thinking in cognitive science (among some but not all practioners) The brain (likewise the mind) is like the computer An example of the misapplied metaphor

The Cortex is a Network Entirely different structure than that of computers Connectivity as key property of brain structure Symbol-manipulation is the key property of computers The cortex operates by means of connections Transmission of activation along neural pathways Changes in connection strengths

Computers and Brains: Different Structures, Different Skills Flexible, fault tolerant Slow processing Association Intuition Adaptability, plasticity Self-driven activity Unpredictable Self-driven learning Computers Exact, literal Rapid calculation Rapid sorting Rapid searching Faultless memory Do what they are told Predictable

Things that brains but not computers can do Acquire information to varying degrees “Entrenchment” How does it work? Variable connection strength Connections get stronger with repeated use Perform at varying skill levels Degrees of alertness, attentiveness Variation in reaction time Mechanisms: Global neurotransmitters (next slide) Variation in blood flow Variation in available nutrients Presence or absence of fatigue Presence or absence of intoxication

Global neurotransmitters Released into interneural space, has global effect – e.g. serotonin, dopamine

Neuronal Structure and Function: Connectivity White matter: it’s all connections Far more voluminous than gray matter Cortico-cortical connections The fibers are axons of pyramidal neurons They are all excitatory White since the fibers are coated with myelin Myelin: glial cells There are also grey matter connections Unmyelinated Local Horizontal, through gray matter Excitatory and inhibitory

Pyramidal neurons and their connections Connecting fibers Dendrites (input): length 2mm or less Axons (output): length up to 10 cm Synapses Afferent synapses: up to 50,000 From distant and nearby sources Distant – to apical dendrite Local – to basal dendrites or cell body Efferent synapses: up to 50,000 On distant and nearby destinations Distant – main axon, through white matter Local – collateral axons, through gray matter

Connecting fibers of pyramidal neurons Apical dendrite Basal dendrites Axon

Interconnections of pyramidal neurons Input from distant cells Input from neighboring columns Output to distant cells

Neuronal Structure and Function: Connectivity Synapses of a typical pyramidal neuron: Incoming (afferent) – 50,000 (5 x 104) Outgoing (efferent) – 50,000 Number of synapses in cortex: 28 billion neurons (Mountcastle’s estimate) i.e., 28 x 109 Synapses in the cortex (do the math) 5 x 104 x 28 x 109 = 140 x 1013 = 1.4 x 1015 Approximately 1,400,000,000,000,000 i.e., over 1 quadrillion

How does all this complex structure work? A structure sui generis – quite unlike computers and in fact unlike anything else we have ever known Extraordinarily complex Billions of neurons Trillions of interconnections How can we make sense of it? Stay tuned: Next week: Brain function

T h a n k s f o r y o u r a t t e n t i o n !