topics: |  brain | history | neuro-science

A readable introduction to the history, mechanics origins and functions of
the brain. Excellent coverage of the basics!

Chapter 1: Introduction

The opening chapter starts with a somewhat philosophical but engaging
discussion of your (the reader's) brain, discussing issues such as how you
are reading these very lines on this screen:

	as you read these words, your brain is commanding your eyes to make
	small but very rapid (about 500° per second) left-to-right movements
	called saccades...  You are not consciously aware of it, but these
	rapid movements are frequently interrupted by brief periods when the
	eyes are fixed in position.  Watch someone reading and you will see
	exactly what I mean. p.5

And goes on to discuss how the fovea is able to decipher just 7 or 8 letters of normal
print size at a time.  This leads to a discussion how the fact of this
move-stop-move manner of reading is completely undetected by your
consciousness, which constructs a "strong subjective
impression is that comprehension of the text flows uninterrupted".

Finally, considers the fact that we read words as a whole (possibly because
of the 8-character field of view of the fovea?) - which is why we can quite
easily read:

	   It deosn’t mttaer in waht oredr the ltteers in a wrod aer, the
	   olny iprmoatnt tihng is taht eth frist dan lsat ltteer be in the
	   rghit pclae. The rset cna be a taotl mses and yuo can still raed
	   it wouthit a porbelm. Tihs is bcuseae the huamn mnid deos not raed
	   ervey lteter by istlef, but the wrod as a wlohe. Amzanig huh?

Chapter 2: From humours to cells: components of mind

A good run through the history of the human endeavour to understand the
brain, from ancient thinking that associated mental processes with the
heart:

     The Egyptians for instance clearly did not hold the brain in
     particularly high esteem since in the process of mummification it was
     scooped out and discarded (a practice that stopped around the end of the
     2nd century ad). To the ancient Egyptians, it was the heart that was
     credited with intelligence and thought – probably for this reason it was
     carefully preserved when mummifying the deceased.

     Alcmaeon of Croton (b. 535 bc), a follower of Pythagoras [?], is among
     the first to have realized that the brain is the likely centre of the
     intellect. He is also the first known to have conducted human
     dissections and in doing so he noticed that the eye is connected to
     the brain by what we now know is the optic nerve. It was on the basis
     of his direct observations that Alcmaeon astutely speculated, a
     century before Hippocrates came to a similar conclusion, that the
     brain was the centre of mental activity.

And then going on to the Hipppocratic (d.370BC) "humours" theory that "the
four determinants of temperament were black bile (melancholy), yellow bile
(irascibility), phlegm (equanimity and sluggishness), and sanguine (passion
and cheerfulness). " This theory was widely influential for many centuries,
and influenced ideas in Jung and also the four types in tests such as
the w:Myers-Briggs Type Indicator].

After Hippocrates, Galen (d.201), who was a physician at a school for
gladiators, and gained an intimate understanding of the internal anatomy of
the human body, suggested that three fluid filled ventricles in the brain
were related to the rational brain, imagination, and memory.  Many
centuries later, in one of Leonardo da Vinci's (1452-1519) anatomical
sketches of the head, there are only three cavities marked O, M, and N
(image on p. 15).  In some of his later sketches, he marked these
ventricles as imprensiva (perceptual), sensus communis (binding of
senses into unified representation, term from aristotle), and memoria.

The humours idea also influenced Descartes, who held that the brain was
a centre for hydraulic control, as in the hydraulic machinery of the time.

In modern times, the major breakthrough was Golgi's (1843-1906) staining
approaches that highlighted the shape of an occasional neuron, but it was
not recognized as a individual cell or neuron - at the time the brain was
thought to be a vast continuous network (reticula) without any cellular
units as in the rest of the body.

Ramon y Cajal: A defining moment in neuroscience

It is Ramon y Cajal (1852-1934) who formulated the neuron doctrine,
revealing not only the cellular structure of the brain, but in what O'Shea
calls a "defining moment in neuroscience", his positing a polarized,
information processing role for these complex cells, with the dendrites
acting as inputs, and the long axon as output processes.

The reticular theory suggested that while other parts of the body
were constituted of cells, the structure of the brain was a single networked
mass; here cells had fused and become a vast interconnected network.

Cajal suggested that even brains were made of cells, but these were
specialized for information processing.
Key ideas of his neuronal theory:
  a. neurons are separate cells connected at synaptic junctions
  b. neurons are directional : polarized w.r.t. function; information flows in
   one direction, from input region (dendrites) to output (axon temrinals)

It is instructive to read about Cajal's surprise on encountering insect
neurons that "are as complex and display as much diversity as neurons in
the human cortex":

	the quality of the psychic machine does not increase with the
	zoological hierarchy. It is as if we are attempting to equate the
	qualities of a great wall clock with those of a miniature watch.

honey bees: 10^6 neurons
snails: 2x 10^4
primitive worms (nematodes) ~ 300
humans - 10^11 or so  [on average, x 7.10^3 synapses = 10^14 connections,
			max as a child; age 3 ~ 10^15]

In 1906 Cajal shared the Nobel Prize for Physiology and Medicine
with Golgi, ‘in recognition of their work on the structure of the
nervous system’,  It was the first jointly shared Nobel Prize,
and it was controversial because of Golgi's conviction that
Cajal was wrong to reject the reticular theory.

 
variety of motor neurons.  the neurons are not identified in the text. 
a is a purkinje cell, and b most likely a pyramidal cell.

Ends with an aside on phrenology, the discredited "science" of measuring
the strength of an individual's various "faculties" by measuring bumps on
the skull.

Chapter 3: Signalling in the brain: getting connected

A quick run through the physiology of the neuron and neurochemistry of its
connections.  Action
potentials, synapses, nerve impulse speeds (up to 120 m/s),
neurotransmitters, ion channels, membrane voltages, polarization, all
summarized in  14 terse pages.

conduction velocities of impulses in the brain are slow, about 120 metres
per second in the fastest conducting axons. p.28

Much was learned about the neuron from experiments on the squid - has a
giant axon - 1mm dia - basis of our knowledge of sodium and potassium
flows, and the ionic theory of action potentials (Alan Lloyd Hodgkin and
Andrew Fielding Huxley, 1940s, Nobel 1963)

Chapter 4: From the Big Bang to the big brain

SINGLE CELLED ORGANISMS developed in water. could move with flagella or
shorter hairs, cilia, or foot-like extensors, pseudopodia.  ability to
move, coupled w ability to sense gives evolutionary advantage.

Paramecium - swims towards decaying organic matter.  Obstacle avoidance
in the Paramecium with primitive touch sensors:
     involves reversing the direction of swimming and turning away from the
     obstacle before proceeding in the forward direction. 44
[much like today's bumper-sensing electric cars]

MULTI-CELLULAR: capability for specialization
initially nerve-nets --> radial bodies

In early creatures the neurons would have been connected in a diffuse net
(e.g. hydra); but with the emergence of animals with "bilaterally symmetric
body plans" which gave these creatures a "head" where the mouth, and hence
more sensors, were located.

The embryonic developmental process of the brain echoes its evolutionary
origins. What we know as the cortex is the frontmost part or the
telencephalon.  The forebrain is very minor in fish amphibians and reptiles,
and is larger in mammals, but in primates it enlarges disproportionately, and
comes to completely surround the rest of the forebrain and the midbrain.

In hominid evolution, the pre-frontal cortex more than tripled in size in
the last 2mn years. 54

Neuro-anatomy

Quick descriptions of the function and anatomy of the different main parts in
terms of the three main (historical) segments - the forebrain (all of the
cortex, as well as the basal ganglia and the diencephalon), the midbrain,
and the hindbrain (together the brainstem).

hindbrain : medulla, pons, and cerebellum
midbrain: substantia nigra, inferior colliculus, superior colliculus, and
	  the reticular formation (extending into the medulla)
forebrain
   - telencephalon --> two cortical hemispheres and basal ganglia -
   	evolutionarily new;
   - diencephalon part of limbic system, the thalamus, and hypothalamus
     hypothalamus, is very small in size yet controls important functions
      such as sex, emotion, the interpretation of smells, the regulation of
	body temperature, hunger, and thirst. Also controls body’s hormonal
	system.

LIMBIC SYSTEM: forming the rim or limbus between the two hemispheres.
   includes the amygdala and the hippocampus that are, in an evolutionary
   sense, the oldest parts of the forebrain.  In reptiles backwards,
   hippocampus involved in decision responses to olfactory sense; in mammals
   and man - major role in memory.  also includes hypothalamus.

Chapter 5 Sensing, perceiving, and acting

Details of the visual system - the eye, and cross-cranial lines leading to
the occipetal lobes.

cones are highly concentrated at the fovea, an area of just one square
millimetre. p.67
The fovea could be rightly regarded as the most important square millimetre
in your body.

Optical fiber - about 10^6 ganglion cells.  [Retina: 10^8]
fovea: mostly cones
rest of retina: rods outnumber cones 10:1

adaptation: photoreceptor sensitivity is adapted to avg bkgd light
intensity.  rods report changes wrt avg bkgd level, and not absolute
intensity.
perception: based on relative differences of brightness.
	    TV screen seems quite black

Each ganglion cell has a unique view on the visual world, called its
receptive field.

two types of response to light in the receptive fields of retinal ganglion
cells: centre-ON, centre-OFF.

about 60% of ganglion cells crossing the chiasm.  most of the ganglion
cells terminate in the LGN in the thalamus.  the majority of post-synaptic
neurons from the LGN project to the primary visual cortex or striate cortex
or V1.

At these stages, receptive fields from R and L eyes are separate, so
information processing is still monocular.  Later binocular neurons report on
two receptive fields, either when the same region is activated in both, or
when different regions are activated in both.

ganglion cells : respond to bright center or dark center
LGN : combines these inputs
primary cortex: neurons do not respond to points, but to edges or bars with
	high contrast
    neurons in nearby positions on the surface of the visual cortex have
    neighbouring receptive fields

functional organization: V1 is organied in layers (I-VI).  neurons excited by
	the same optimal orientation are organized in vertical columns across
	layers.

Distributed vs Sparse models of recognition

Most neuroscientists today believe that perceptions are dispersed over
populations of neurons that require near simultaneous activation for the
generation of visual percepts.  no "grandmother cells".

However, a minority of neuroscientists claim that at the level of
individual neurons the encoding system is explicit and highly
selective. According to this idea the activity of visual recognition neurons
is not distributed but ‘sparse’ – becoming increasingly so as the deciphering
of an object proceeds. Thus for the sparseness camp, encoding involves the
activation of fewer and fewer neurons as neuronal activity represents more
and more selective combinations of object features.

evidence for sparseness: responses from individual neurons in the medial
temporal lobe (MTL).  patients undergoing treatment for intractable epilepsy
were shown pictures of movie stars and famous buildings while the activity of
single neurons in the MTL was recorded. One of the neurons responded when
seven quite different pictures of the same actress, Jennifer Aniston, were
shown. In an extraordinary display of selectivity and discrimination,
however, the same neuron did not respond to pictures of Jennifer with her
then husband Brad Pitt.

In some instances a neuron would respond to the object and to the word
representing the object. For example, one neuron responded selectively to
different pictures of the Sydney Opera House and to the letter string ‘Sydney
Opera’ but not to the letter string ‘Eiffel Tower’.
[study by Quiroga etal] 75-76

ganglionic targets other than LGN

bilateral pupillary reflex: Some retinal ganglion cell axons leave the optic
	tract before the LGN and goes to the region called pretectum.  This
	pathway activates a reflex response to bright light that causes the
	constrictor muscles of the iris to contract, reducing the diameter of
	the pupil. The reflex is bilateral so both pupils are constricted at
	the same time, even if the bright light enters one eye only.

hypothalamic region: important in bodily functions that show a day/night or
circadian rhythm.

superior colliculus: Layered structure - involved in changing the direction
of gaze from one object the brain finds interesting to another.  Outer layer
has a 2D map of the visual world.  Deeper layers encode a motor map for the
oculomotor system that can direct the ballistic saccade to that part of the
visual field.  intermediate layers constitute a visual motor map or a
guidance system that for generating a rapid saccadic eye movement precisely
to the point in visual space that activated the visual map.
The (final) motor layers are responsible for initiating the
bursts of nerve impulses in the motor neurons causing the direction
of gaze to move very rapidly from one fixed point to another.

when a potentially interesting object appears in the peripheral visual field,
it will activate neurons in the corresponding visual map.  This can then
activate the motor map that can bring the new object onto the fovea.

Integrating sound with vision

how do we turn the gaze to the source of sound?  - the diff in time in the
two ears is no more than a few hundred microseconds - in fact we can
discriminate upto 10 microseconds.

audio system - Medial Superior Olive - MSO - uses a coincidence detector.
a series of neurons arranged anatomically so the signal reaches in
opposite times from the two ears to gauge the disparity in the two signals.
The neuron which gets both signals simultaneously determines the
coincidence; its offset from the center of the array is indicative of
direction.

For higher frequencies (above 2khz), the acoustic shadow of the head itself
is used - sound from the left is louder in the left ear.  this amplitudes
difference is mapped to sound source location in the midbrain.

internal sensing and feedback

many tasks executed with ease are more complex than appears at first sight.
e.g. holding a glass under water to fill it.  glass is getting heavier
constantly yet we hold it.  are the muscle tensions adjusted based on visual
feedback of how much water there is?

but actually controlled by feedback from the muscles themselves.  as the
biceps (agonistic muscle) lengthen a little w
load, this is sensed by sensory neurons in the muscle spindles; these have
excitatory synapses with the motor neurons, which then increase the force.
very rapid and sensitive system.  simultaneously, the activity of the motor
neurons innervating the antagonistic triceps muscle is inhibited.  83

Chapter 6: Memories are made of this

Types of memory- short and long term memory.  How are LT memories formed?
Not the case that over time, memories get faded progressively; far from
it, certain memories are formed actively, and are represented by "robust
alterations in the brain’s chemical and physical make-up."
In comparison,
short-term and working memory is relatively unstable.

What gets converted?  Emotion plays a big role - for example,

	the vivid memory we have of precisely what we were doing when for
	instance we first saw the news of the 9/11 attack ... we remember the
	important details of that grave event, but we also remember many
	trivial facts associated with what we were doing at the time. These
	are memories that in normal circumstances would certainly have been
	quickly forgotten. Flash bulb memory shows that emotional association
	is a powerful facilitator of long-term memory formation.

These processes of course are completely our image of ourselves as conscious
creatures, aware of our world, and altering who we think we are,
(see How the mind forgets and remembers: The Seven Sins of Memory).

Some memories - e.g. motor tasks like riding a bicycle - are never forgotten
- so they are more robustly encoded.  Complex motor skills acquisition
involves the basal ganglia and the cerebellum; but these memories are
implicit.  [Unconscious?]

Episodic Memory

Episodic Memory, on the other hand, consists of memories of events or
episodes.  These differ from memory for facts in several ways:

     First, we can acquire a memory for a fact [by repetition], but a
     remembered episode, a childhood visit to the zoo, only happened once and
     there is no opportunity for learning the event by rehearsal. Secondly, a
     fact is a fact, our semantic memory for a new telephone number is
     therefore either true or false. ... Episodic memories are not so easily
     verified. My sister and I may have very different memories of that visit
     to the zoo. So episodic memories are personal, highly selective,
     idiosyncratic, and possibly false, but they may also be richly complex
     and movie-like in character. They constitute the stories we tell
     ourselves about our past, they are the things we would write about in
     our autobiography. 88

UNCONSCIOUS / REPRESSED MEMORIES: In the 1940s US neurosurgeon Wilder
   Penfield performed operations on conscious epileptic patients -
   electrically stim small regions of cerebral cortex ==> patients reported
   very detailed memories of long past events, which were not conscious other
   wise.  Repeated stimulation ==> same memory.

Hippocampus as locus of memory - detailed mental maps (MRI).
London taxi drivers - only the hippocampi are significantly larger.

    my genes and yours use the same genetic code as worms, flies,
    chrysanthemums, brewers’ yeast, and even slime mould ... 91

How memories form : Eric Kandel and the Sea Slug

How do we know about our learning processes?  Relates the interesting story of
Eric R. Kandel who in the 1960s worked on the giant sea slug
Aplysia californica.

      The Aplysia brain has about 20,000 neurons, some of which are large
      enough to be visible to the naked eye. ... Kandel and co-workers
      studied [the habituation response to] a reflex in which the sea slug
      withdraws its gill protectively in response to a mild touch stimulus to
      a body-part called siphon. If the stimulus to the siphon is repeated a
      number of times, the gill withdrawal reflex becomes weaker until
      finally the animal ignores the touch stimulus. The waning of
      sensitivity to repeated stimulation is known as habituation and is a
      very simple form of learning found in all animals incl humans. 92

After habituation (e.g. to a clock chiming), one can be re-sensitized
(e.g. if it suddenly chimes more loudly than usual) and then we can again
perceive that signal.  Kandel showed that long-term sensitization involved
new protein synthesis (new brain structures) but short-term did not.
Analyzing the circuit of the Aplysia, Kandel+ were able to show that the
synapses between the sensory nerves and a set of
"modulatory neurons" were getting strengthened by repeated activation.

	Moreover they showed that the neurotransmitter of the modulating
	neuron is serotonin (a neurotransmitter found in all animals), and
	that when a single puff of serotonin is directed at the sensory to
	motor neuron synapse, the synapse was strengthened for a few
	minutes... If four or five puffs of serotonin are delivered in
	succession, the result is a long-term strengthening of the synapse.

But this is short-term memory.  LT memory involves protein creation which
requires the activation of a suitable gene. This happens after repeated
activation through the enzyme "kinase" which enters the cell body and
interacts with other proteins which eventually turn on some genes (some
early, and some late).  These new proteins are transported back to the cell
boundary where they strengthen the existing synapse, and also help form new
synapses.

Kandel: 2000 Nobel in medicine

Chapter 7 Broken brain: invention and intervention

The penultimate chapter discusses computational algorithms that simulate
brains (neural nets). and the possibility of merging machines with biological
brains.   For example, a cochlear implant may directly excite some sensory
neurons where the auditory hair in the inner ear (cochlea) may have been
damaged.  Other more direct interactions with the cortical areas (monkeys
controlling robot arms) are discussed.  Ends with a section on chemicals for
treating brain pathologies, particularly antidepressants.

   Strongly implicated in depressive disorders are the slow monoamine
   transmitters serotonin, noradrenalin, and dopamine.  In the brain of a
   depressed person there is an insufficiency of these transmitters.

Antidepressants, the first of which were discovered more than
50 years ago, are now the most widely prescribed drugs.

... there is growing concern that the monoamine hypothesis is wrong and that
some antidepressants may increase the likelihood of suicide. The fact we know
very little about the fundamental neurobiology of depression.

Epilogue

The epilogue discusses future brain research, the role of FMRI etc.

On the whole, I found the book an excellent introduction, covering much
material and reasonably up to date.  However, for a book meant for a general
audience the language can get quite technical, e.g.

	neurons are hugely diverse in morphology. They have exceedingly fine
	and profusely branched processes ramifying from the cell’s body and
	intermingling among the branches of other neurons. The complexity and
	diversity of their physical appearance easily exceeds that of all
	other cell types found in any other part of the body.

Other reviews

PD Smith, in the Guardian

I think, therefore I am. But what am I? A brain, perhaps? Neuroscientist
Michael O'Shea's very short guide to a very complex organ takes us on the
ultimate ego-trip: a journey into our own brains. The brain is "the most
exquisitely complex and extraordinary machine in the known universe". It
weighs just 1.2kg yet contains 100bn nerve cells. But it is not "simply
performing computational algorithms". Brains are in a different league even
from today's computers: "even the most complex artificial brains do not
approach the efficiency or capability of a fly's brain", which is no bigger
than a full-stop. Biological brains are so much more interesting and subtle
than silicon. Take what you're doing now - reading. Yuo cna raed tihs wouthit
a porbelm. "Tihs is bcuseae the huamn mnid deos not raed ervey lteter by
istlef, but the wrod as a wlohe. Amzanig huh?" O'Shea writes with real
enthusiasm, taking us through the origins of brain science, the evolution of
nervous systems, the mechanics of memory and on into the future, when
computers and brains will be increasingly integrated.