The author is especially interested in consciousness - she wrote Journey to the Centers of the Mind: Toward a Science of Consciousness, 1995. She is interested in relations between consciousness, mind and brain… the “neural correlates” of consciousness

In the first three chapters she outlines anatomy, some typical mental functions and cellular structure and function

Chapter 1, Brains Within Brains, looks at the distinct anatomical divisions and concludes that they are not autonomous; rather they are a cohesive system. Asks whether each part has a different function. Concludes that the functions are not localized. Has some general comments on distribution and specificity of function, integration, and neuronal plasticity

Chapter 2, Systems of Systems, approaches the problem of localization of consciousness by looking at mental functions. She concludes again that the functions are not localized

Chapter 3, Pulse, Impulse, takes up the functioning of neural cells and neuro-transmission and neuro-modulation. She also considers the functions of the glial sells. She speculates that the complexity and large number of interconnections, the plasticity of the interconnections - to be taken up in the next chapter, and the variety and variation made possible by neurotransmission and neuro-modulation makes the computational model of the mind improbable

AM: The idea of Francis Crick that the 40Hz oscillations in the visual cortex are associated with visual consciousness is pertinent

The last two chapters consider development, integration of function, and mind-brain relations

In Chapter 4, Cells Upon Cells, she considers development - anatomy, mental function and cell - and considers what light this may shed on mind-brain relations. She reflects on the important topic of consciousness and its biological basis

She considers the question of whether consciousness begins at a specific point of development - conception, birth and so on - or whether the development of consciousness is a continuous process. She argues in favor of the seemingly more natural idea of continuous development - AM: any fixed point such as birth appears to be somewhat arbitrary and the fertilized egg is too simple. It is convenient to distinguish a general low level awareness from “higher” consciousness - clear and discrete, linguistic, self-consciousness. The development may be a continuous and gradual one with periods or bursts of rapid change corresponding the emergence of the higher elements established by the laying down of key brain structures and patterns - including loops - of neurotransmission

Chapter 5 - the final chapter - With Mind in Mind, considers in detail the gross physical and detailed neural structures and processes that are the correlates of memory, various kinds of memory - short and long term memory, explicit and implicit memory and how short term memory over time results over time in laying down of long term memories. The author’s psychological and biological descriptions are simplified

Since memory is “multi-staged and multifaceted” and “captures the individual’s resources for interpreting the world” she considers it to be a hallmark… perhaps the main hallmark of mind

AM: Since processing and memory are dynamically and anatomically integrated in the brain, the choice of memory is a revealing approach to mind and so to mind-brain relations. This relates to the idea that the forms of perception form the bases of the modalities of consciousness and of thought

Although the author cautions that a causal relation between the phenomenological and the physical in the human brain cannot yet be established, “… for the moment, it is sufficient to be aware of the correlation between these two levels… ”

AM: my impression is that she has shown how, in the minute details of function, modern neural science has begun to reveal a meeting ground – the places where mind meets brain

AM: In forming any such conclusion one may recall the processes of growth in other divisions of science that have conceptual content. The empirical - the facts, what is seen - is related to ideas or concepts. The ideas themselves are not seen. Rather they are organizing principles. They suggest new observations. When experiments and concepts are at odds the ideas and the observations come under review and a sufficient weight of disconfirming evidence occasions the reformulation of the concepts and or checking and reviewing the observations. The practical value to this use of concepts is the organizational and predictive efficiency. Further, since the origin of concepts is frequently anthropic in nature, there is also a centering of human being in nature. This in contrast to the view of science as alienating. The middle ground is that certain ways of doing and looking at science and certain uses of science are alienating

AM: Two Problems: Binding and Object Constancy

Note that the essence of this section has been absorbed to Journey in Being / related documents

The integration of memory and processing is the source of an outline to a solution to the binding problem. This is the problem of how the different attributes of an object - visual, tactile… and even the different visual aspects such as color, shape, size… are appear, in perception, as a single object rather than a number of separate sensations corresponding to the different aspects

In some ways this binding problem is a problem because of the one of the ways in which we may look at it: bottom-up in terms of sensations that we identify as components rather than top-down starting with the idea of a whole object. In the history of evolution life always interacted with objects. Still there is a problem because the bottom-up view is one approach to understanding - it is the “atomic” approach often used in science. The idea is reduce a complex object into simple components which can be understood. Build up understanding of the whole based on knowledge of the simple components. This is a key to understanding, to breakdown - psychosis etc. - and to development. I suppose I could get into a whole philosophy here of Holism-Atomism… but I shall not. Suffice it to say that in this example the integral view informs the atomic view

The solution idea is as follows. Initially, in development, a single sensation - a smell - may have no association. As memory is laid down the external stimuli are always of objects - even if extended ones - and so always come in bundles corresponding to objects rather than as isolated sensations. The different attributes are processed and so recorded in memory in different parts of the brain but, since the object is unitary, in association. Upon later encounters with the same object the diverse regions of the brain are stimulated in perception but are bound by prior association. This would be a problem if memory and processing centers were isolated from each other

I think there is a probable affinity between this solution and the form of the solution to the problem of the experience of object constancy. Object constancy is the adjustment of the perceptual [cognitive] system to see an object as having constant attributes such as size, shape, color regardless of the conditions - within limits - of perception such as distance, orientation, and lighting

Undoubtedly other forms of integration - perceptual-conceptual, conceptual-conceptual - are significant in binding… but I will take that up later

Chapter 1 Brains Within Brains

Begins with the experiments of Jean-Pierre-Marie Flourens [early eighteenth century] who found progressive global loss of function rather than selective impairment as he removed more and more of the brains of laboratory animals. He concluded that distinct functions could not be localized

Continues with long discredited phrenology of Franz Gall a doctor born in Vienna in 1758. AM: Why consider long discarded ideas that later became the subject of ridicule? Because [1] they contain hidden assumptions that later more sophisticated theories continued to make… even up to today, [2] despite the parts of older theories that seem obviously ridiculous today they may have contained ideas that, at least in historical context, are interesting and useful. For example, although the measurement of bumps on the skull appear to be totally misconceived, Gall’s list of thirty-two character traits is interesting as history and as insight into the fashion of the era. The traits, supposed to be the building blocks of character, were associated with specific locations in the brain as revealed by the craniology. The ontological assumption is that of essences that form a hierarchy. That Gall’s ideas appear to be so misconceived to us and yet were once the rage somewhere in the borderline between science, fad and fashion can be a lesson for any time

Some main themes of the book

These two approaches set the stage for one of the main themes - localization vs. distribution of function in the brain. AM: The anticipated resolution, that it is a variegated combination of localization and distribution, will also remain inadequate as long as the idea of function is essentialist [1] and static. This latter point is a second though implicit theme

The experiments of Paul Broca [1861] and Carl Wernicke helped discredit phrenology and also show that function is not completely localized - Broca’s and Wernicke’s distinct areas in the brain are two major locations associated with language function

John Hughlings-Jackson [1835-1911], a British neurologist, viewed the brain as organized in a hierarchy… with the higher, most recently developed functions, the human ones, at the top of the hierarchy - in control. The influence of this kind of thinking was seen in psychiatry [superego of Freud] and escape from a higher controlling force in crowd behavior

Next: Paul MacLean’s hierarchical triune brain concept developed in the 1940s and 1950s. The “primitive reptilian brain”, the brain stem, is responsible for instinct; the “old mammalian brain”, the limbic system, responsible for emotion including aggression and sex; and the “new mammalian brain”, the cortex - Latin for “bark”, responsible for rational thought. Does not discredit the triune brain concept. But adds that MacLean’s does not explain how functions are localized

Material on brain size and weight, ration of brain to body weight, differential size of the cerebellum [little brain], differential size of the cortex and its convolutions [surface area. Relations of these factors to intelligence. Does not consider surface area to body size. Development of the cortex related to ability to think. Dolphins are about as intelligent as dogs

Notes on the cortex. About 2mm thick. Divisible, according to different conventions, into functions that belong to fifty to a hundred separate areas - this makes sense up to a point. Some brain areas with “single” function: the motor cortex for conscious motor control; the visual and auditory cortexes for visual and auditory processing respectively; the somatosensory cortex for touch. Multiple and integrated functions: the parietal cortex [top] receives signals from the visual, auditory and somatosensory systems and is involved in a range of motor functions. The function appears to association and coordination of the different sensory modalities and of different motor function; and of sensory with motor function; and more generally with cognitive processes and that includes thought. Hence the alternative names integration or association for the parietal cortex

Interesting Details and Issues

The substantia nigra and is normally black - its cells produce dopamine… and melanin is the end product of dopamine metabolism. In Parkinson’s patients - difficulty walking, stiffness of limbs, hand tremors at rest - the substantia nigra is pink: its cells have died

The target region of the dopamine is primarily the striatum - more on this in the next chapter - that is implicated in movement

But: the same chemical is distributed over many brain regions while each brain region makes and uses many different chemicals. So what is more important when considering brain damage: the brain region concerned or the change in chemical balance in the brain

Another reason that it is difficult to associate functions with particular regions: the neuronal plasticity observed in partial recovery after stroke

Measurement Techniques

X-Ray

CAT-computerized axial tomography

PET- positron emission tomography

MRI- magnetic resonance imaging

MEG-magnetoencephelography

The importance of different techniques

[1] Revealing physiological function: X-Ray reveals altered anatomy; CAT resolution, though based on X-Rays has higher resolution and, through computer imaging, provides 3-D information; PET shows differential and altered metabolism - radioactive glucose or water is inject IV and in the brain positrons emitted collide with electrons and gamma rays emitted form the image; [2] Space and time resolution: MRI measures oxygen concentration but does not require injection - the oxygen alters the magnetic properties of hemoglobin - and can pinpoint areas as small as 1 to 2 mm and measure events over seconds; MEG measures the magnetic field generated by differential electrical activity has superior time resolution but is currently accurate only for the outer regions of the brain

Overall Conclusions for Brain Function

Distributed function and specificity

Neuronal plasticity

Integration

Chapter 2 Systems of Systems

Motion and Sensation in Evolutionary Development of Nervous Systems

Brains are found in multicellular organisms with locomotion -animals… this is the key that makes a “centralized processing” necessary and adaptive. Plants can move in response to light but do not generate moment to moment environmentally aware movements as animals do. Of course environmental awareness requires [is] perception and requires a responsive sensory apparatus and processing

The Reflex Arc Involves Only the Spinal Cord

The reflex arc involves only the spinal cord. However, the normal repertoire of human movement are not fixed responses

Rhythmic, Semireflex Movements Originating in the Brain Stem

Rhythmic movements such as walking and running involve more complex coordination of muscle groups but even these are semiautomatic. The signals for these repetitive movements come the spinal cord and originate in the brain stem. There are four such “motorways” coming down the spinal cord from the brain stem. The first is responsible for semiautomatic and semireflex rhythmic kind of motion just mentioned; a second coordinates movement with visual and sensory information; a third is important for balance and the fourth mediates the motion of individual limbs

Fine Movement Originates in the Motor Cortex

The motor cortex is a strip-like region of the cortex fitting across the brain like a hair-band. Controls motion by signals to the individual digits. Different parts of the body are controlled by different parts of the motor cortex… and the amount of the motor allocated to a given part of the body corresponds to the precision of movement needed. Thus the hands and the lips have an enormous allocation

The motor cortex also exerts a hierarchical influence over the other four movement motorways. And is central in control of movement

Does the Brain Have a Single “Movement Center”?

No, because there are two other “centers”, the basal ganglia and the cerebellum. The cerebellum is important for movements where there is a continuous feedback from the senses which in turn influence the next movement… and could be called the “auto-pilot” of the brain. The basal ganglia, a group of interconnected regions that includes the striatum and the substantia nigra, is associated with “ballistic” movement - motion in a predetermined trajectory. When the striatum is impaired there can be wild involuntary movements [Huntington’s chorea] whereas death of the dopamine producing cells of the substantia nigra results in Parkinson’s disease in which there is difficulty moving at all combined with muscle rigidity and tremor. In normal movement the effects of the striatum and the substantia nigra operate in a balance

There Are Multiple Centers for Movement… that are in Dialog

The cerebellum has strong interconnections with the lateral premotor area that is distinct from and is in front of the motor cortex. The basal ganglia connect to a part of the motor cortex called the supplemental motor area. Damage to the supplemental motor area results in symptoms like those of Parkinson’s disease

The generation of movement is the net result of many brain regions acting together and in interaction

The Somatosensory System… Does it Have a Single Center?

There are two major “motorways” up the spinal cord leading up the spinal cord to the Somatosensory cortex… an area just behind the motor cortex that is responsible for registering touch, temperature… and pain. The first, the evolutionary system, is mainly related to pain and temperature… and the newer system carries precise systems for touch again with disproportionate allocation of cortical regions to hands and lips

May be making the point that there is no single somatosensory center

But sensation has additional, specialized organs for specialized sensation - seeing, hearing, taste, smell… whose inputs to the brain are not passed up the spinal cord

Vision

Considers this in detail. Here I will just note the main points. AM: Vision is the most completely researched of the sensory systems

Compound eye - up to 30,000 facets in some insects. These eyes can be large in relation to body size with more processing in the peripheral organ… than in sophisticated where the input will not already have been heavily biased. The advantages of the compound eye: large visual field, very sensitive to change and to planes of polarization

The human eye - an example of the camera eye - provides high resolution. Light absorbed by cells on the retina and a signal relayed to the optic nerve. The exit of the optic nerve is the blind spot - to the middle of the eye near the nose. Also near the middle but toward the ear is the fovea a small indent densely packed with cones [associated with color vision and perception of fine detail] where the inner layers of the retina are absent, there are no blood vessels, and light has an almost unrestricted passage to the light-sensitive cells. Birds of prey have up to five times more concentrated cells in the fovea than humans. Eagles have two foveas - the search fovea for side vision whereas the pursuit fovea judges depth which is done with both eyes

The human [mammal?] eye can move back and forth in the socket while birds’ eyes are fixed

Two types of photoreceptive cells - rods for vision in low light and cones for color and contrast in normal light. Perception by rods is associated with rhodopsin, which breaks down into retinal and opsin when it absorbs light in the visual range of the electromagnetic spectrum… rhodopsin is continuously regenerated and builds up in the dark. The maximum sensitivity of a completely dark adapted eye is at 5000 angstroms and at this wavelength the threshold for vision is a single quantum and there is a chemical amplification in the rod itself before providing the electrical visual signal from the rod. There are three types of cones corresponding to primary colors: red, green or blue. Other colors are registered by exciting different combinations of the cones in different proportions. The changes that take place in the three cone pigments have not been analyzed, simply because, so far, they have defied isolation, because their concentrations are so much less than that of the rod pigment

The retina does not signal everything in the visual field uniformly. There is an enormous bias toward contrast and motion

Visual Processing

From the retina, cells send signals via the optic nerve to the thalamus - in the diencephalon or middle brain - that relays the signals to the visual cortex

Various integrative functions revealed by different damage to the visual cortex in different individuals. Example: woman in forties with highly localized damage experienced loss of motion perception. Other examples: loss of shape or color or low light perception. Loss of color could be due to damage to the retina or, bilaterally, to critical brain regions; if latter is unilateral half the world appears in black and white and half in color

Agnosia is inability to perceive form… severity varies among patients and for a given patient from time to time… and may be due to hierarchic assembly in perception of complex forms which could be arrested at different stages. Understanding and seeing may be inextricably linked… ”form blindness” may be due [in some cases?] due to loss of integrative processes

Vision of color, form, movement can be independent… with processing in parallel… this raises the binding problem for vision [2] - where and how do the parallel visual signals converge into a single entity. The connectivity and processing responsible for the binding is not centralized but, likely, a balanced dialogue - and staged or hierarchic - among key brain regions

The “Mystery” of Consciousness

“… How do we actually see?” She is asking: AM: How - and where - does the subjectivity, the feeling of awareness itself… how does this arise?… and “the riddle is compounded” by blindsight which apparently involves awareness but not consciousness - in blindsight subjects report not seeing an object but their behavior indicates awareness of it. One idea toward an explanation of this - and of cognitive processing in general - is that the cortex also sends signals to intercept and modify incoming signals from sense organs. Blindsight is perhaps due to rupture in the balanced hierarchic circuitry

… but blindsight also depends on motion: if the object begins to move the subject, in some cases, reports seeing it. In terms of the idea, to be presented later, that processing for different facets of vision [3] - or perception generally - occurs in different brain regions, this makes sense

Prosopagnosia - the failure to recognize faces - is a reverse of blindsight: awareness without recognition. associations can also - idiosyncratically - reverse prosopagnosia

The enigma of consciousness… the first person, subjective conscious element: this is the same as the point above - the mystery of consciousness

A related mystery: why [how] are electrical signals arriving in the cortex experienced as vision, while exactly the same kind of signals arriving in the auditory cortex experienced as hearing? And what of synethsesia… where the distinctions between the senses breakdown - most commonly sound is experienced as color though “virtually any combination of the two plus senses is possible.” Synesthesia may be due to aberrations in the association cortex… or to physiological malfunction at the neuronal level

Arousal and sleep

Level of arousal, as the degree of perceptual intensity of the environment, is a “parameter” of consciousness… and varies from coma to deep sleep to being awake to extreme excitement, fear… One measure of arousal can be monitored as electrical activity averaged over large areas of the cortex

The EEG records activity from cells just beneath the surface of the brain. Scientific application of the EEG is studying electrical activity in the brain and its relation to various mental activities, states and disorders. Clinical application includes diagnosis of disorders such as epilepsy including location of the damaged tissue. Slow waves generated mainly at the back of the head, the alpha waves, correspond to being relaxed and conscious… this is one way to provide “bio-feedback.”

Electrical activity has been recorded as early as the third fetal month but only in the sixth fetal month do slow regular waves emerge. Until age 10 there are two very slow: the theta of 4 - 7 Hz, and the delta of 1 - 4 Hz never seen in healthy awake adults

The EEG reveals four stages of sleep plus rapid eye movement or REM sleep. Humans descend rapidly through stages 1 through 4 after falling asleep… and gradually surface and descend through the four stages throughout the night. REM is dream sleep. In normal sleep one may toss and turn but in dream sleep, when the EEG is the same as when awake, the muscles become paralyzed. In an average night’s sleep of seven and a half hours humans can have two and a half hours of dreams. The longest recorded continuous period of REM is two and a half hours

Reptiles do not display REM, birds do occasionally, all mammals - according to their EEG - appear capable of dreaming

Why do we dream? Is there a value to dreaming? One theory [4] is that, no longer tied down to the reality of the world, the brain begins to freewheel… but it seems to be more than just that since subjects deprived of REM sleep overcompensate on subsequent nights and enter REM more often, and presumably, for a longer total period of time. A second idea is that dreams help adjust to and consolidate recent events. This, too, is probably partial at most since at 26 weeks the fetus spends all its time in REM sleep. REM sleep time gradually decreases during childhood so dreams may be a function of a brain in the process of maturing, of forming connections, when association among brain regions is less

Comments on possible relation to schizophrenia in which waking consciousness is said to be similar to normal - real but illogical - dreaming and brain association is - a possible hypothesis - less

What is the function of normal sleep? Since animals are vulnerable during sleep it must have a benefit. Synthesis in the brain of proteins required for conscious and autonomous brain function is much higher in sleep. Deprived of sleep, energy storage becomes inefficient. Rats deprived of sleep require more food and finally die, underweight and exhausted, despite huge food intake

Brain / body “knows” when sleep is needed. The pineal gland secretes melatonin that is associated with sleep / wake. In humans sleep / wake cycle is controlled in a circadian [bio-]rhythm that is fine tuned by external cues

Pain

… sensitivity to pain also varies over the day. This reminds us that pain is a subjective phenomenon. Nerve conduction apparently does not vary over the day. When arrows were removed from the wounds of injured soldiers, they were often twisted in the wound as are acupuncture needles, and the soldiers sometimes had relief from pain. Similarly acupuncture also relieves pain - sometimes enough to allow surgery. The effect occurs about 20 minutes after insertion of the needles and lasts for about an hour. Applying local anesthetic before applying the needles blocks the analgesic effect of acupuncture - this suggests that transmission or brain reception of pain signals is necessary. The delayed effect suggests that the needles are not directly responsible for the effect of acupuncture but that some natural chemical may be released in the brain. Enkephalin [endorphins], discovered in the early 1970s, are the brains own morphinelike chemical substance. Narcotic antagonists block the effects of narcotics including enkephalin and reduce the effectiveness of acupuncture

Enkephalin are found in a variety of locations in the brain and spinal cord [CNS]

This a particular example of the general point of this chapter that for particular functions - motion, perception… - a number of brain areas are active in parallel. Functions are distributed and the corresponding brain activity is associative

Now begin to look at brain-mind in a “bottom-up” approach… at the cell level where the details of the signal and memory processes lie… so as to understand, in detail, the underlying mechanisms

Chapter 3 Pulse, Impulse

A typical body [non-neural] cell is 20 - 100 m m in dia

Electrical [nerve] signals are transmitted at some 220 miles per hour

Early experiments: Golgi Stain

Camillo Golgi 1843 - 1926, a medical graduate of Padua University discovered that silver nitrate stains one in ten to a hundred neurons black… and so the stained neurons appear black on a pale background

The soma or body of a neuron comes in a variety of shapes: round, oval, triangular, fusiform - spindle like… Like other cells, the soma contains the “life support” organs for the neuron

The neuron has many dendrites or branches - that receive electrical signals from other cells, a soma and an axon, a long fiber that transmits signals when fired by the cell, many times longer than the rest of the neuron - up to a meter in the spinal cord. Relative to the thin axon, hard to see even under a microscope, the dendrites are short and stubby. According to the density of the dendrites there appearance of neurons varies enormously - there are at least 50 basic shapes

Incoming signals are not transmitted directly - individually or in combination. If some combination of incoming signals is strong enough the neuron is “triggered” and generates a signal

Channels and Action Potentials

Luigi Galvani 1737 - 1798 showed nerves from the spinal cord generate electricity and thought all electricity lay in living tissue… but Michael Faraday 1791 - 1867 showed the fundamental and universal nature of electricity

In neurons flow of electricity is due to one of four ions potassium on the inside and sodium, calcium, or chloride on the outside. The membrane of a neuron has two layers with a non-conducting fatty middle that prevents ions from moving in or out. There also negatively charged proteins inside the cell and normally the inside of the neuron is -70 to -80 mV relative to the outside. This state of disequilibrium is maintained by the sodium-potassium pump

The membrane barrier can breached through protein pathways or “channels” across the membrane… these conduct the ions

The Action Potential of 1 - 2 ms

As a consequence of the trigger described above the following occurs:

Depolarization: Sodium ions [Na⁺] briefly enter the cell through sodium channels making the potential +20 mV relative to the outside

Hyper-polarization: K⁺ ions leave the cell resulting in overshoot of the normal -70 to -80 mV in which the inside potential becomes -90 mV

The transient positive-negative wave is the action potential

Re-polarization: K⁺ ions leave through potassium channels

The actual process is more complex involving a calcium channel, hypothesized anion [Cl^-] for which there is some evidence

Output reflects “net input” not through intensity [-90 mV] but by frequency of the action potentials. 1 - 2 Hz is slow, 30 - 100 Hz is normal, and some neurons achieve 500 Hz

Francis Crick thinks that the 40 Hz oscillations in the visual cortex and elsewhere are associated with consciousness primarily because this frequency is associated with binding

Neuron to neuron transmission - the Synaptic Gap

Golgi thought neurons were joined together somewhat like a hair net… but was opposed by the Spanish anatomist Ramon y Cajal who held that there was a gap between neurons

Experimental study became possible with the advent of the electron microscope capable of x 10,000 - the first true electron microscope was built in 1933 but it was a while before the x1,500 magnification of the light microscope was surpassed and the problem of heating and destruction of specimens was solved

In the 1950s the electron microscope showed Cajal was right. However, it turns out that while transmission across a synaptic gap is the primary mode some neurons are fused at “gap junctions” where transmission is more rapid and requires less energy

One objective of the next topic is to see what advantage neurotransmission across a synaptic gap may have over the faster and more efficient - with respect to time and energy - gap junction process

Neurotransmission and neurotransmitters

In the 19^th Claud Barnard, a Frenchman, suggested curare works by interfering with transmission of nerve signals. Beginning early in the 20^th century it was shown that curare works by blocking the neurotransmitter acetylcholine or ACH

Neurotransmitters - are released from nerves and neurons in the brain. AM: Some neurotransmitters are acetylcholine - the first chemical occurring in the nervous system shown to be a neurotransmitter, epinephrine and norepinephrine, dopamine, serotonin [5-hydroxytryptamine]. It is, apparently, hard to show that a chemical found in the brain is - or is not - in fact a neurotransmitter. The following are some probable neurotransmitter [neuromodulator] amino acids - excitatory such as glutamic acid and aspartic acid and inhibitory such as gamma-aminobutyric acid [GABA] and glycine, histamine, adenosine triphosphate and neuroactive peptides. There is evidence that the stated amino acids act as excitatory or inhibitory neurotransmitters. The neuroactive peptides are sequences of amino acids usually longer than amino acid transmitters but shorter than proteins and hormones and are different from the classic neurotransmitters in a number of ways including synthesis, duration of action - several seconds to days in contrast to milliseconds for, e.g., acetylcholine. The peptides are associated with neuromodulation. This is scratching on the surface with respect to mechanisms and modes of action and detail of a system of information that is in flux

ACH is stored in vesicles at the end of the axon. The number of vesicles emptying their contents is proportional to the number of action potentials… and in this way the electrical signal is converted into a chemical one… the synaptic gap is crossed with thousandths of a second or milliseconds = 0.001s. At the outside of a dendrite of a receptor neuron the transmitter binds to a matching protein called a receptor and the combined complex molecule triggers the opening of a channel and so sets up a transient potential difference that is one of many signals transmitted down the dendrites to the body of the cell… and the cycle is set to repeat

Once the transmission is done the transmitters must be removed and the vesicles replenished… and this takes additional energy

What are the advantages of chemical transmission? There are 10¹¹ neurons in the human brain each with ten to a hundred thousand neurons connecting to it. Transmission with neurotransmitters adds versatility. The input to a neuron is summed over the 10 to 100 thousand inputs of varying intensity; neurotransmission adds to this complexity by having many different neurotransmitters each with its own target and different effect on the final voltage; this is further enhanced by modulation. The variety and amounts of the neurotransmitters released depends on the different inputs and their degrees of activity. Additionally, due to the interaction between the limbic system and the endocrine / hormonal / neurotransmitter system this points to a mechanism for an effect of emotion and mood upon cognition and thought

Drugs

Nicotine docks at one type of ACH receptor and so mimics the action of ACH. Alteration of neurotransmission is the basis of action of many nervous system drugs including those that alter mental states and processes. In addictive drugs the normal action of neurotransmission is severely altered and thus the basis of use and, at the same time by de-sensitization, of physiological habituation and addiction

Morphine, and derivatives and analogs - the opiate narcotics, bind to opiate receptors and provide relief from pain… and, also, relaxation and pleasure… and, in the case of heroin which passes into the brain quickly, a “rush.” The opiate narcotics bind to the same receptors as the neurotransmitters produced by the body - enkephalin, endorphin, and dynorphin. Narcotic antagonists naloxone [narcan], naltrexone, nalorphine… block and reverse the action of opiates - both naturally occurring in and foreign to the body

Cocaine increases availability of noradrenaline by blocking its re-uptake… and so simulates stress… and hence one of its dangers. Amphetamine causes excessive release of and blocks re-uptake of noradrenaline and its precursor dopamine

Neurotransmitters dopamine, noradrenaline and ACH are normally released from the brain stem in a fountain-like arrangement onto more sophisticated cortical and sub-cortical structures. Arousal levels, sleep, wakefulness are affected. The primitive structures has a controlling effect on the more recently evolved mental functions

AM: I presume that there is a reverse process… and that no single level is completely in control

Ecstasy targets the 5-HT or serotonin neurotransmitter system

Repeated use of ecstasy in rats causes death of the raphe nuclei - the neurons that send a fountain-like structure of axons into the higher brain regions… and is also the target for much anti-depressant medication

Questions:

Effect, relation and integration of the endocrine system

How do opiates affect pain and its perception… detailed mechanisms

How does naloxone block opiates without producing their effects

Chapter 4 Cells Upon Cells

Development

Details of fetal development emphasizing the nervous system are given… and omitted here. A key point of interest is the differentiation and choreography

At maximum rates 250,000 new neurons are formed a minute

The first recognizable neural development is at about 12 days after fertilization - the “embryonic disk” is three layers thick… the middle layer appears to send chemical signals to the upper layer called the neural plate to diversify again to become neurons. At 9 weeks there are recognizable brain regions. Around 11 weeks the cerebellum is recognizable

Touches the ontogeny recapitulates phylogeny idea… and notes that there is partial recapitulation in the development of the cortex. The convolutions in the cortex, which are significantly more in humans than any other species, occurred late in evolution and also appear relatively late in development of the human brain at about seven months’ gestation. The advantage of the convolutions or folds is there is more surface area

AM: Implies that the bush or tree-like pattern of evolution, a metaphor due to Darwin, implies that ontogeny recapitulates phylogeny is wrong. This is not the claim being made therefore the author’s implication is not correct

The cortex and adaptability

Surface area of the cortex is one factor in adaptability. Thickness of the cortex and complexity of the pattern of organization of neurons are other factors

The Regions of the Brain and Development of Specialized Neurons

Neuronal replication is followed by differentiation, specialization and migration of the neurons from the primitive location of their formation to the final place in the developed brain

Inter-neurons connect other neurons in small local circuits

Glial cells have numerous functions:

Structure

Energy source for neurons

Remove toxins

Making a path followed in neural migrations

When glial cells do not develop properly, problems develop… including that neurons do not migrate to the right place

How do neurons “know” when to stop migration?

The brain develops in a layered structure that is something like an onion. Outer layers develop later. The cortex develops last. The mature cortex has six layers that assemble from a thin initial layer - the cortical plate. The inner layers of the cortex form first and neurons travel through the inner layers as they form the outer layers

What makes a cell become a cortical neuron? Little is known. There are molecules known as cell adhesion molecules that may act like “sticky badges.” It is likely that the neurotransmitter a cell will use is determined as soon as neurons have stopped proliferating

By birth most neurons are in place… but connections, myelin sheathing, and glial cells continue to develop. The myelin sheathing is important in keeping nerves insulated and thus maintaining the integrity of transmission

The brain is 350 cc at birth, about the size as that of an adult chimpanzee. The adult human brain is about 1400 cc

Behavior and mind

Reflexes develop first… some are present within the first month. This is followed by voluntary movement [within months?] which is paralleled by myelination [for efficient conduction]. There is massive myelination in the first months of life; this continues up to 15 years and beyond; myelin can increase in density as late in life as 60 years

Fine finger movement including independent control of digits begins at the end of the first year

The Babinski reflex or sign

In an infant the toes fan out and up when the balls of the feet are stroked but in an adult they curl inward. This is a test for integrity, in the adult. of the spinal cord and certain parts of the brain: in certain kinds of damage the “positive” Babinski will re-emerge

The autonomic nervous system

The parasympathetic system - default control of autonomic function… in relaxed states

The sympathetic system - corresponding to arousal… including “flight or flight”… the adrenal medulla releases adrenaline to circulate the body heart rate and blood pressure go up; airways are dilated to enhance breathing and oxygen supply

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Propanolol - a beta blocker - slows the heart rate that registers the action of the parasympathetic system… and so has a calming or anti-anxiety effect

Development of consciousness

Abruptly… or continuously?

Or… does consciousness require a nonlinear effect such as a feedback looping?

Post natal growth of the brain

Repeat: by birth - 9 months after conception - most neurons are in place at the appropriate brain region. The developments are:

Development of connections

Compared to age two, the connections at birth are sparse

As seen on time lapse video axons are sent out by web-like endings called growth cones. Author asks how the brain could be a computer or even compared with one

How do the axons know where to go? Possibly genetics, fine tuned by local factors - a common theme in development. Local factors include guiding chemicals such as nerve growth factor or NGF - one of many such chemicals - released by the target cell for the axons… and, perhaps, transferred back to the original cell and switches off a genetically programmed self-destruct mechanism… and so, cells that do not make correct connections self-destruct. Another possibility that explains the very long distances that some axons travel is that in early development when brain structures are still close, there a few pioneer fibers that then become stretched out during growth along which other axons are able to follow

Topographical development: In a frog’s eye each axon leaving the eye has a target territory within the relevant target structure - the tectum. This is the fixed aspect of a type of organization that is known as topographical. There is also an adaptable aspect. If half of the outgrowing neurons are destroyed the remaining neurons invade the entire tectum; and if half of the tectum is destroyed the outgrowing neurons crowd into half the space… and all this is done in a topographical manner

Activity and growth

There is a “use it or lose it” rule that is normally beneficial because it means that neuronal circuits are established according to which cells are working and this reflects the particular environmental conditions in which the individual lives. In some cases, however, deprivation of experience in development leads to retarded growth

The selectivity in connection means that experience conditions individuality including memory. Unused neuronal interconnections die off but, quantitatively, this is offset by interconnections that are formed normally and as a result of experience and use

At sixteen the brain is considered to be mature but this just means that adaptability and formation of interconnections lessens at maturity but does not cease

Raises the question of what is an enriched environment and cautions that environmental richness does not equate to wealth or formal education

Concludes that you can teach an old dog new tricks… ”Politicians, heads of business… are very often in their sixties and seventies when presumably at the peak of their powers.”

Chapter 5 With Mind in Mind

This chapter deals with two questions:

What is the hallmark of mind?

Where, how and when does mind and consciousness arise in the brain?

AM: The author is going to conclude - not without good reason - that memory is a “cornerstone” of mind. I think she is really saying - this is her agenda - that memory is the hallmark of mind. This is, in fact, one current view. This is not as severe distortion as it might seem to be since, in the brain, memory and processing appear to be well integrated. I think a general principle of cognition and mental function is the integration of the different aspects with one another through evolution, genetics, and development… and this is what makes the relatively ad hoc approaches of artificial intelligence [viewed as machine replication of human or animal intelligence] so unproductive of any significant duplication of natural intelligence

Experience and neural development

Experience conditions the micro-circuitry

Experiences never had cannot shape personality… this is empiricism!

Memory is [therefore] a or the basic key to personality

Types or modes of memory

Short and long term memory

Individuals with global amnesia can have short term memory

Long term memory has many aspects and each has a respective short term form

Short and long term memory work in series and not in parallel. In other words, short term memory is involved through repetition and emphasis in the laying down of long term memory… And the ability to have long term memory?

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Explicit and implicit memory

Explicit memory is memory that is recalled in consciousness or awareness

Implicit memory refers to ingrained behavior patterns

These differences go toward explaining differential loss of function in memory impairments including the memory loss seen in stroke

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The basis of memory

HM [a classic study in amnesia] is a case of complete loss of explicit memory. The middle part of temporal lobe including the hippocampus was removed in an attempt to epileptic seizures that were so frequent that it was impossible to live a normal life. The results:

Anteretrograde amnesia for explicit memory starting from 2 years before the surgery

No corresponding STM loss

Retained implicit LTM

Conclusion: damage to the hippocampus results in impairment to laying down of explicit memories. The medial thalamus is often implicated in anteretrograde amnesia for explicit events but this effect is often temporary

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Source amnesia is loss of memory for when and where an event occurred. This affects, primarily, memory for events which are unique - “I saw a pink elephant on the hill at sunset” is an event, while knowledge that there are pink elephants is knowledge of a fact. The medial temporal lobe and hippocampus affect memory for facts and events while the prefrontal cortex affects only memory for events. Because the prefrontal cortex is disproportionately large in humans, the author speculates, memory for events is highly enhanced… whereas, say, a cat may not have the ability to remember a particular spring day on which it caught a mouse, it probably has the vaguer and more general recall of catching mice. The general conclusion for humans was sort of confirmed by the mid-1900s experiments of Wilder Penfield who stimulated the medial temporal lobe but not the prefrontal cortex or other regions of individuals who would sometimes report very vivid dreamlike scenes without particular time and space points of reference

Lacking a large prefrontal cortex, “episodic” memories for events would almost become “semantic” memory for facts… And - the inner resources of he prefrontal cortex balance the torrent of sensory data. Damage to the prefrontal cortex has been compared to and implicated in schizophrenia

So… the hippocampus and the medial thalamus play a role in the laying down of explicit long term memories in the medial temporal lobe in a process that takes about two years

To what extent is memory for events tied up with language?

Mechanisms of memory: How are long term memories for facts or events stored?

By progressively removing more of the cortex in rats, Karl Lashley found that there is no specific part of the brain matches retention of memory. Rather, as more cortex was removed, the rats became progressively worse at memory tasks

Penfield found a many-many relation between the site of stimulation and the specific memory recalled

An explanation of these facts is that memory is associated with overlapping circuits… and on neuron could be a member of number of different circuits. The specific combination of neurons stimulated would determine which circuit becomes activated

Biochemist Stephen Rose found, from experiments with chicks - guess what kind - that different parts of the brain are involved in processing and memory for different features such as size, color, motion… of the same fact. This would explain Lashley’s conclusion of how no specific part or parts of the brain appear match memory retention despite the fact that this conclusion was mistaken

STM lasts about half and hour… laying down of long term memories takes about two years and this is done by the hippocampus and the medial thalamus but it is not known exactly how… [it seems that this is a simplification in that the periods are not that definite, and there may also be some intermediate mechanisms]

One idea, obvious after the fact, is that a memory is or equals a connection of otherwise unconnected elements brought together for the first time in the fact or event to be remembered

AM: Right here, in the nitty gritty, one begins to see the intimate relation between memory and processing: processing lays down memory and memory conditions processing in the same or overlapping locations… this paragraph entered to Journey in Being

As the network becomes established, the hippocampus and medial thalamus become less and less important in terms of the specific memory until, when the LTM is established its existence is, now, independent of the hippocampus and the medial thalamus

Perhaps implicit memory also depends, like explicit memory as described immediately above, on a dialog between the cortex and sub-cortical structures

Individuals with Parkinson’s disease and Huntington’s chorea have damage or disease to parts of the basal ganglia. Perhaps these are both lapses in the implicit memory system, faults in different aspects of the habit of generating movements - individuals with Huntington’s chorea can no longer generate a movement in appropriate context… and in Parkinson’s disease the individual can no longer sequence a movement

AM: two interesting things to note. There is a fair amount of theorizing going on. Memory is a hallmark of mind… these movement disorders are a form of [implicit] memory deficit… specification of the type of deficit. The theorizing is not necessarily correct and even if it is correct in a general sense it may be mistaken in the specifics. Why do it at all? First note that there is no harm. It does not in any way impair the medical process of diagnosis and treatment… and in the long run may help. Second, if concepts are important then they must be discovered or created by a process of trial and error. It is this trial and error process to which we are being exposed. That is good in itself. So why are the concepts important? Scientifically, we get a better handle on the diseases - what is a mess of large amounts of information becomes coordinated and organized by the concepts into a small dose information contained in a small number of concepts. We are then ready to proceed to higher levels. It is a most efficient use of our cognitive resources to maintain a balance between information and concepts. Philosophically, concepts give us understanding of what is going on… what is mind… what is consciousness… what are the essences of mind and so on… what is the relation between mental processing and the underlying biological / material processes?

The basal ganglia are not the only brain regions involved in implicit memory. The cerebellum is involved in conditioning of movement

A crucial difference from explicit memory is that the sub-cortical structures involved in implicit memory have a looser connection with the cortex. For example, the striatum - pivotal in Huntington’s chorea - receives an input from the cortex but does not send one directly back. Hence [speculates] these brain regions freewheel more autonomously than the corresponding regions for explicit memory. This might be expected of activities that are performed without attention or conscious effort. these activities would not need constant referral to the cortex which plays a key role in conscious attention. The cortex is left free for other functions such as explicit memory

Memory at the neural level

How do neurons register the changes involved in memory - short and long term? What is happening at the neuronal level when memory is laid down?

For simplicity consider memory in its simplest form: association between two previously unassociated elements which, for simplicity, will be two single cells

AM: what is the theoretical scoop here. Looking ahead, the author is going to talk about the association theory of memory and memorization… at the level of ideas. This idea is older than the neurology of memory. Some people, including professionals and scientists, proceed by saying “Oh, here is a idea - mind etc. - to be explained by the nuts and bolts level of reality. Let’s just jump in and explain. I’m so practical and smart, not like those eggheads with their heads in the clouds.” The problem is the question of what actually are we explaining. This is why it is important to have a description of how mind works at a mental level so we know we are talking about a significant idea and, also, so we have something real to explain: mechanism at mind-level corresponds to mechanism at neural level. It’s a fact of life that humankind is a concept forming animal, that this is the result of evolution and adaptation, and that if an individual does not want to think or rethink ideas and concepts then he / she is letting other people do this for them… accepting someone else’s ideas as so obvious as to think of them as concrete. It’s a type of rigidity though recognized as something else

In the 1940’s the :visionary psychologist Donald Hebb proposed that when a cell X excited a target cell Y the synaptic connection X ® Y would be strengthened, i.e. it would become more effective in chemical signaling

An alternate mechanism: a third cell Z impinges the transmitting cell X… only if Z and X are active at same time would X release more transmitter molecules onto Y. This has been demonstrated in the sea slug Aplysia whose nervous system is so simple that even single neurons have names

Mechanisms for sustained strengthening [STM] are called long term potentiation or LTP. These may underlie STM but probably not LTM

Mechanisms for long term memory

The STM mechanisms may activate genes and the resulting products alter the neuron - transmitter efficiency, number of receptors, efficiency with which a receptor opens an ion channel and so on - for very long periods

Another possible mechanism of [STM --> LTM] neural change by gene expression is even more radical. It is based in the idea that experience modifies, not so much the numbers of the neurons, but the connections. In general terms, the more the experience the more the connections. Within an hour of training on a task certain proteins are deployed. Two examples:

1. A “growth-associated protein” GAP-43. It is contained in growth cones of neurons and its synthesis occurs at a high rate when neurons are extending their axons. GAP-43 is activated during LTP or long term potentiation. Thus certain proteins are associated with growth of connections and its relation to experience

2. The cell adhesion molecules or sticky badges referred to earlier. While GAP-43 lays down the memory as growth of interconnections, the cell adhesion molecules stabilize the interconnections and so make the memories long term

The neural logic of memory

How do increased interconnections underpin memory? AM: What is really being asked is the following. We saw above the connection between experience and laying down of permanent connections and so of memory… but we need to be more specific. Memory has a structure and a process - the process of recall of relevant information - and how does interconnectivity underpin the structure and the process. This is the question of the neural logic of memory

In principle an answer is simple. AM: By similarity between memory and brain. By correspondence between the structure and processing of memory on the one hand and the structure and processing of neural signaling on the other hand. In terms of the association mechanism of memory there is a similarity, correspondence, analogy between the neural interconnections [the structure] and the associations [memory.]

AM: The logic is simple but profound and extends to all functions of mind and the relation to brain structure and process. One must first find correspondences. Then, of course, establish it firmly by showing causality, predictive power, necessity, economy…

Five month babies show explicit memory which in turn means that their hippocampus and medial thalamus must be operational… but, despite this, adults do not generally recollect events that occurred before the age of three or so. Why? This would be explained by the formation in children up to the age of three of interconnections that are not as rich or as robust as the interconnections formed later

An alternative, complementary or co-factor explanation relates to different form of memory… which is, of course complementary at least to some extent to the interconnections not being as rich or otherwise qualitatively different

This brings the authors account to an end. She says “As such, memory is a good place to end our brief glimpse of he brain, for it is a cornerstone of the mind.” AM: This is an analogy and not an established relation. We are still on the shores of the ocean of understanding

Looking Forward… some problems

Complexity of actions of neurotransmitters, inhibitors, exciters, modulators…

How neurons grow, differentiate, and go to the correct location in the brain

Origin of individuality and consciousness. Of what might a fetus be conscious?

The relation of brain to mind and the riddle of the physical basis of consciousness. “This is the ultimate puzzle”

Latest Revision, Copyright and Document Status

Written Fall 1999, revised February 13, 2013

No claim to copyright by Anil Mitra

For the writers work, see his current Website and essay, Journey in Being

No further action for Journey in Being™

The document may be useful if I return to study and write in the area of mind / brain

The interest: The topic itself and biopsychology, consciousness, mind, neurobiology - with endocrine and immune function

The purpose: Understanding mind-brain; an overview of concepts and ideas for use in further research. This is not intended to be my work or for publication… therefore most of the summary consists of paraphrases and some verbatim quotes. I have made some comments on the text itself added a few reflections; these are labeled “AM ”

[1] The idea of essentialism, in this context, is that a named function - say vision - is unitary. However “vision” is not unitary. Objects have visual attributes - size, shape, color, motion… We perceive these attributes and others. In some species, corresponding to different adaptations, the set of perceived attributes is different. It follows that vision is not unitary… and that perception of the different attributes may be distribute in different regions of the brain. This is in fact the case and explains the gradual and global degradation of performance in the laboratory experiments of Flourens. Ask, also: are there any unitary functions or attributes? What does it mean that the functions are not static? Two types of dynamics can be identified: developmental dynamics in which perception of objects as unitary is not given at [say] birth but requires experience and associated neural development; and process dynamics in which the actual perception requires an integration and perhaps association and feedback in the instant to instant production in perception of objects. These features of integration, feedback and association may be opaque to the perceiver under normal and usual conditions

[2] Not, of course, limited to vision. Binding occurs with other senses, among senses; between perception and recognition and conception…

[3] Shape, size, color, motion…

[4] The sense of the word “theory” here - related to “mechanism” - there can be more than one theory [1] at different levels of explanation and [2] as contributing factors at the same level of explanation