The Neuroscience Explosion

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999 Society

• The Neuroscience Explosion

Bennie Bub MD, FRCS Sep 5th, 2009
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Are human brains superior? Why?
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Actual Human Brain (right side)
Average adult brain weighs ? 3.3 lb (1300 -
1400 g) Volume Women ?1130 cc, Men ?1260 cc
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For intelligence, does SIZE matter?
What about complexity of convolutions?
3.3 lbs
10.5 lbs
Not to scale
3.5 lbs
Not to scale
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If not size, maybe Brain to Body ratio?
Mouse
.4
0.000012
3.2
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Maybe Encephalization Quotient? (Expected weights)
Ew(brain) 0.12w(body)2/3 or 3/4
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Perhaps its the neocortex?

• Newest evolution of 6-layered cerebral cortex
  (Area 2.5 ft2)
• Only in mammals
• Performs
• Higher functions like working memory, language,
  spatial-temporal reasoning, conscious thought,
  fine sensory-motor control.

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So its clearly the Neocortex to Brain ratio,
right?
Human Neocortex is 76 of total brain
mass Sperm Whale 87 Chimpanzee
72 Monkeys 55-60 Rodents
40-50 Platypus 48 Marsupials
20-30 Insectivores 10-20 (Reference
Nieuwenhuys, R., Ten Donkelaar, H.J. and
Nicholson, C., The Central nervous System of
Vertebrates, Vol. 3, Berlin Springer, 1998)
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Should we care about the brain at all?
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People think its important

• THE CACHALOT PROJECT (2002)
• To initiate a relationship with one specific pod
  of sperm whales.
• The team consists of
• an interspecies communication consultant
• bio-acoustician
• photo ID specialist
• a whale activist
• a ceremonialist
• an Azorean eco-tour entrepreneur

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Financial burden of central nervous disorders
2007 - USA Trillion
2006 - EU 400 Billion (35 of all diseases)
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Fascinating just one example

• THE PAOMNNEHAL PWEOR OF THE HMUAN MNID.
• I cdnuolt blveiee taht I cluod aulaclty
  uesdnatnrd waht I was raednig!
• It deosn't mttaer in waht oredr the ltteers in a
  wrod aepapr, the olny iprmoatnt tihng is taht the
  frist and lsat ltteers are in tiher rghit pclaes.
• Tihs is bcuseae the huamn mnid deos not raed
  ervey lteter by istlef, but teh wrod as a wlohe.

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So lets start at the beginning
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8000 - 7000 BCE 1st Neurosurgery
Healed Neolithic skulls
Trepanation Knife (Tumi) 1400 BCE
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1970 -- Self-trepanation!
Amanda Feilding aka Lady Amanda Neidpath,
Countess of Wemyss Produces a documentary "Hear
tbeat in the Brain
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4000 BCE - 1st known writing about the Mind
Sumerian tablets describe the mind altering,
euphoric effects by eating hul gil -
Plant of joy (Poppies) May have been used by
Neandertals (30,000 years ago) - fossilized
seeds found at burial sites.
Overdose
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3000 BCE Sumer (Specialization begins)

• Disease is due to Supernatural causes - Evil
  Gods or Spirits
• Body is compartmentalized!

A God creating Humans
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2500 BCE - Ancient Egypt (Good vs Evil)

• Heart is source of Life Good or Evil - Weighed
  against Feather of Goddess Maat (Truth Order)
  to check if the heart is heavier i.e. with guilt.
• Brain is minor and unimportant - teased out
  through the nose when embalming

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1600 BCE - Edwin Smith Papyrus (probably copied
from 2500 BCE)
1st true medical text - 15 ft. 77 lines in
Hieratic regarding 48 separate cases of
surgery.
Diagnosis concerning a gaping wound in his
head penetrating to the bone of his skull (and)
rending open the brain of his skull
Treatment Thou shouldst say concerning him, "An
ailment not to be treated
1536 BCE Ebers papyrus - The 110-page scroll,
about 20 meters long, contains some 700 magical
formulas, remedies incantations
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Ancient India

• Vedas Sacred Literature (Veda means
  Knowledge).
• Samhitas The oldest Indian documents devoted to
  medicine.
• 1500 2000 BCE Atharvaveda (1st written
  reference to medical arts)
• Describes epilepsy, insanity, neuralgia,
  headaches, blindness.
• Treatment Prayers, charms and incantations
• 800 - 400 BCE (Susruta Samhita Mainly about
  surgery)
• The most prestigious of the healing arts.
• 78 to 162 CE (Charaka Samhita Mainly about
  anatomy)
• There are three major body parts)
• 1 Heart - most important
• 2 Urinary bladder
• 3 Head - crooked face, confusion, lockjaw,
  muteness, etc

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525 BCE - Alcmaeon of Croton

• Health is equilibrium of Opposing Humors -
  proved by animal dissection
• Brain (not heart!) is central organ of sensation
  and thought
• Illnesses were caused by problems in
  environment, nutrition and lifestyle
• Eye itself contains light

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460 370 BCE Hippocrates of Cos

• Father of Medicine
• Rejected superstition in favor of science
• Classified diseases
• Set moral and professional standards
• Wrote the original Hippocratic oath

? Dr. Benjamin Rush bled Washington (4 qts. in 24
hrs) for excess circulation
? Schumanns Humoresque
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The Brain according to Hippocrates
Men ought to know that from the brain and from
the brain only, arise our pleasures, joys,
laughter and jests, as well as our sorrows,
pains, griefs and tears But when the brain is
still, a man can think properly.
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Ancient China
475 - 221 BCE Zang Fu Doctrine (Period of
Contending States)
Chinese medicine concerns Tao, the World Spirit.
Disease is an imbalance between Yin (female)
Yang (male), its contrasting components.
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335 BCE - Plato Aristotle
Socrates c. 469 - 399 BCE Plato (428 - 347
BCE) Aristotle (384 - 322 BCE) Overlapped by
20 adult years
Plato Soul survives death (vide Descartes
1649) Aristotle Heart is organ of thought
sensation Brain is merely a radiator
designed for cooling
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The School of Athens
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300 BCE - Herophilus of Chalcedon
Discovers nervous system Differentiates motor
and sensory nerves First detailed account of
structure of Brain, Heart.
Human dissection banned in Rome but not in
Alexandria.

• Introduces scientific (experimental) method.
• Founder of Anatomy - Public human vivisection
  (600).
• Concludes intelligence lies in the ventricles of
  the brain
• His works were lost but were much quoted later
  by Galen

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150 CE - Galen (Claudius Galinus) of Pergamum
Human Physiological System

• Massive dose of teleology accepts brain humors.
• Dissects only animals. Coined the word
  autopsy.
• First Sports Medicine doctor - Physician to
  gladiators.
• First introduced the notion of experimentation
  to medicine.

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From Galen Until 16th Century - 1200 years!
Jeroen Anthonissen van Aken a.k.a.
Hieronymus Bosch Extraction of the Stone of
Madness
Caption reads "Meester snyt die Keye ras - myne
name is Lubbert Das"
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Millennia of Surgical Instruments
And 2000 years later
Ancient Egypt
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Andreas Vesalius 1543 - New anatomy
Andreas van Wesel - Brussels

• Starts the neuroscientific revolution at age 28
  by human dissection - correcting Galen - and
  publishing
• De Humani Corporis Fabrica libri septum
• (Some of earliest neuroscience textbooks)
• Higher functions not in ventricles

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Rene Descartes 1649 - Brain mind

• Brain functions like a machine
• Nerves are filled with animal spirits
• Brain is separate from Mind, which is immaterial
  and they intersect at pineal gland which acts
  like a valve controlling the flow of information.

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Thus from Renatus Cartesius

• What is Mind? No matter.
• What is Matter? Never mind!

Just kidding
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Thomas Willis 1664 - Brain monograph

• First Monograph on Brain - determines thought is
  separate from basic motor functions (e.g.
  walking)
• Introduces Neurology, Hemisphere, Lobe

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Luigi Galvani 1791- bioelectricity
Animal Electricity workshop.

• Brain secretes animal electricity into the
  tissues i.e. inherent in animal tissues.
• Volta Frogs leg serves as both conductor
  (electrolyte) and detector of electricity.
• Galvani stimulated study of peripheral nerve
  physiology Volta (?battery)

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Young Galvani
Luigi, stop playing with those batteries and eat
your frogs legs!
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Franz Joseph Gall 1808 - Phrenology
Cranioscopy (or Phrenology ) 31 (6 later)
Personality Organs each with a specific mental
function
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James Parkinson - 1817
Essay on Shaking Palsy
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Pierre Flourens 1825 - Brain divisions

• Founder of Experimental Brain Science
• Debunked Galls phrenology
• First to demonstrate that the Main Divisions of
  brain are indeed responsible for different
  functions.

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Phineas Gage 1848 - Frontal personality
Aha! So personality is in the Frontal
Lobes! This indirectly leads to frontal lobotomy
for depression
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Paul Broca 1862 - Speech expression
Syphilitic lesion in Brocas Area

• 1st Localization of a Speech Center
• Expressive aphasia - patient could only say
  Tan

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Hermann von Helmholtz 1863

• Invented Ophthalmoscope. Major contributions to
  acoustics, mathematics, electricity, magnetism,
  etc., etc
• Measured speed of nerve impulses - 27 m/s (1000
  X slower than electricity in a wire)

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1864 - Warrens Household Physicianby Ira Warren
A.M., M.D.Pub. Bradley Dayton CO, Boston

• Tumors of the Brain
• (Complete text)
• Tumors infect the brain occasionally, growing
  around it, on all sides, pressing themselves into
  its substance, and causing many disturbances.
  Cancers and Hydatids are found there.
• The signs which these irritating bodies produce
  are like those of other diseases of the brain,
  and
• therefore cannot be distinguished during life.

Clinical neurology was not keeping up
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Carl Wernicke - 1874
Receptive Aphasia Speaks fluently but language
content is word salad.
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Emil Kraepelin - 1887- Schizophrenia

• Founder of modern scientific psychiatry
• Shows mood swings in Manic Depression now
• called Bipolar Spectrum Disorders.
• Differentiates this from Dementia Praecox now
  Schizophrenia (1887)
• Introduced the terms Neurosis, Psychosis.

Opposed Freud. Proposed naming of Alzheimers
Disease
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Louis Wain 1860 - 1939 (late onset Schizophrenia
age 50)
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Louis Wain - Realistic cat
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Louis Wain - Stage 1
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Louis Wain - Stage 2
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Louis Wain - Stage 3
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Louis Wain - Stage 4
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Louis Wain - Stage 5
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Henry Head - 1903
49 days later (Surgery 4/25/1903)
At age 42 he had cutaneous nerves of his own
forearm cut, to accurately map their regeneration
(patients werent reliable enough!)
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Camillo Golgi (1843 - 1926) - Nobel 1906
Hippocampus 1st time anyone has actually seen an
entire neuron! Says Nerve cords are a
continuous mass devoid of constructive units
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Santiago Ramón y Cajal - Nobel 1906

• Formulated
• The Neuron Doctrine
• metabolic independence of neurons
• Neurons change during functioning of the nervous
  system.

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The Household Physician(now by Multiple authors
(including Ira Warren)Woodruff Pub. Co. 1910

• Tumors of the Brain
• (Complete text)
• Tumors infect the brain occasionally, growing
  around it, on all sides, pressing themselves into
  its substance, and causing many disturbances.
  Cancers and Hydatids are found there. The signs
  which these irritating bodies produce are like
  those of other diseases of the brain, and
  therefore cannot be distinguished during life.
• Syphilis is often the cause of them, and, when
  due to this, may be cured

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Otto Loewi - 1921 The first neurotransmitter
Literally dreams this experiment which settles
whether signaling across synapse is chemical or
electrical
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Hans Berger - The first EEG - 1924

• First recording of brain waves in man,
  Elektroenkephalogram .
• Described different waves and rhythms, normal
  abnormal - including epilepsy

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Charles Sherrington - 1932

• Law of Reciprocal Innervation
• Coined the word Synapse
• Said neural activity increases regional blood
  flow (basis of todays fMRI)

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Antonio Caetano de Abreu Freire (Egas) Moniz -
1935

• Developed
• Angiography
• Psychosurgery Nobel
• Prefrontal leucotomy 27 patients
• (precursor to lobotomy)

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Walter Freeman - Frontal Lobotomy1936-1967
Psychiatry gone Crazy
3500 Personal cases in 23 states (including
Rosemary Kennedy)
From 1936 to late 1950s 40,000 - 50,000
Americans are lobotomized ? 100,000 worldwide!
Psychiatrist with NO surgical training though he
initially worked with several surgeons, including
James W. Watts. Anesthesia is
ECT! Leucotomes break so he invents ice-pick
for transorbital lobotomy - takes few minutes. On
national campaign, he drives Lobotomobile to
state institutions.
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Julius Axelrod - 1946

• Rejected by medical schools during great
  depression.
• Synthesized Tylenol (aspirin-phenacetin-caffeine)
  
• Not one penny of royalties!
• Nobel Prize for Storage, Release and
  Inactivation of neurotransmitters

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Wilder Penfield (1891-1976) 1951
Motor Cortex

• The greatest living Canadian!
• (born in Spokane, Washington, USA)
• Constructs brain maps in awake epileptics

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Penfield - Cortical Representation
Sensory Homunculus
Motor Homunculus
Movement
Sensation
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Penfield - Cortex Homunculi
Motor
Sensory
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Michael E. Phelps - PET Scan 1973

• 1975 the first commercial PET scanner
• 70s 80s PET was mainly used for research
• PET shows that the brain changes while learning a
  new language task.
• The map shows regions activated by this task.
• PET Shows the increased metabolism by glucose
  uptake in cells that work harder than in their
  resting state.
• (using more energy and thus more blood flow).

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First human MRI - Paul C. Lauterbur 1973
(1929-2007) Nobel 2003
MRI came from brainstorm at a Pittsburgh diner
and was scribbled on table napkin. Introduced
gradients in the magnetic field to determine the
origin of radio waves emitted from nuclei of the
object of study. Demonstrated 2D images on test
tube samples.
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Roger Guillemin Andrew Schally 1977

• Peptide hormones are produced in the Brain
• Relationship of Hypothalamus Pituitary
• The Nobel Duel by Nicholas Wade

Understanding Glandular Diseases
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David Hubel Torsten Wiesel - 1981
Nobel Shared with Roger Sperry
How visual information is transmitted from retina
to brain building from simple stimuli to complex
images.
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Stanley PrusinerPrion 1982 Single
Nobel 1997
Normal
Creutzfeld-Jacob Human Mad Cow)

• New infective agent of - kuru, CJD, scrapie,
  BSE.
• Mutant PRION - makes normally harmless cellular
  prion proteins fold abnormally thus causing
  non-function or abnormally functioning proteins.
• Studies provide insights into other types of
  dementia.

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Functional MRI (fMRI) - Seiji Ogawa 1990
Increase in local blood flow accompanies neural
activity (Sherrington 1932)
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Diffusion Spectrum Imaging
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Diffusion Spectrum Imaging
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Decade of the Brain 1990-2000proclamation by
President George Bush and Congress
Sponsors Library of Congress National
Institute of Mental Health
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Decade of Behavior project (2000 - 2010)

• Sponsor American Psychological Association
• Multidisciplinary initiative http//www.decadeofb
  ehavior.org
• Goals
• Improve education and health care
• Enhance safety in homes and communities
• Actively address the needs of an aging
  population
• Help to curb drug abuse, crime, high risk
  behaviors, poverty, racism, and cynicism
  towards government

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Decade of the Mind - proposal for 2010 - 2020

• George Mason Universitys Krasnow Institute for
  Advanced Study
• Project begun in 2007
• Trans-disciplinary and multi-agency - 4 billion
  dollar goal for research

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Some Allied Neuroscience Fields
At Amherst College a neuroscience degree requires
14 courses, which is the largest number required
for any major .
In 2005, MIT officially opened the new Brain and
Cognitive Sciences Complex the largest
neuroscience research center in the world, to
address one of the great scientific challenges of
the 21st century the understanding of the human
brain and mind.