5 posts tagged “brain”

This is a book mostly about the human pre-frontal cortex by a leading psychological neurologist who escaped from the Soviet Union. So not only will you get some brain information but also the story of the author's professional life.

To hear an podcast interview with Elkhonon Goldberg by fellow Voxer Ginger Campbell go here.

The prefrontal cortex has two functions. A motivation defining function in which basic internal motivations (goals) are modified and refined to conform with the external environment and an executive function in which a coordinated set of actions and thoughts are defined and maintained. Like all cortex regions the prefrontal cortex extends the abilities of  certain sub-cortical regions.

In the case of the executive function the reticular formation in the brain stem is its sub-cortical analog. The hypothalamus feeds fundamental motivation signals (food search, flee, mate, security search, etc) into the reticular formation which based upon environmental conditions regulates the expression of various actions. For example, slowly increasing electrical stimulation of the Hypothalamic region in birds that initiates the flee response will first trigger a walk, then a run, then a flight. If the bird is trapped then it will fight. These actions are all part of a coordinated set belonging to the response.

The conformance of motivation signals to the environment has their subcortical analogs as well. These subcortical regions include the amygdala, septum, and others. This is discussed in my review of The Emotional Brain.

The prefrontal cortex accounts for 29% of the total cortex in humans, 17% in the chimpanzee, 11.5% in the gibbon, 8.5% in the lemur, 7% in the dog, and 3.5% in the cat. (page 33)

For me the most significant new idea was Goldberg's suggestion that the underlying difference between the two brain hemispheres is based upon their learning rate in response to novelty (page 40). In all learning, a system has to make a trade-off between the speed of learning and the accuracy of learning. Those associations, as formed by conditioned learning, formed after only one or a few observed event correlations have a high probability of being wrong (the correlation could just be a coincidence) compared to associations formed after a longer observation time. It would be advantageous for any animal to be able to work with either the uncertain or certain associations depending on the task at hand. This pre-adaptation of the hemispheres is why language is most often found on the left side because of the tight context rules for grammar. Setting up a context involves making many more associations that cannot be contradictory if context control is to work. In contrast the right side of the brain would tend to be the more intuitive  since it works with uncertain associations but these are associations that would not yet exist on the left side. Brain scan observations show that the right hemisphere is more active when a task is novel while the left hemisphere is more active when the task is practiced (page 49).

Interestingly males (40% to 22%) exhibit more context dependent decision making than females (15% to 12%) in a test called the Cognitive Bias Task (page 90). In this test a "target" object was shown along with 2 choice objects. The subjects had to choose the object they liked the most. The choice strategies tended to be consistent for each individual subject with the context dependent types choosing the object most similar to the target object. In contrast the context independent types would choose objects based upon color, shape, or some other parameter. Still context types are a minority in both genders.

Males with damaged right frontal lobes behaved in an extremely context dependent fashion while those with damaged left frontal lobes behaved in an extremely context independent fashion. In contrast damage to either lobe in females produced extremely context dependent behaviors (page 95).

The two major syndromes (or end points in a damage continuum) that arise from damage to the prefrontal cortex correspond to deficits in one of the two prefrontal cortex functions. The dorsolateral syndrome (chapter 8) comes from damage to the medial areas of the prefrontal cortex and it produces pseudo-depression. Like depression this patient has an inability to initiate behaviors. Yet when behaviors can be induced after much effort they tend to persist without stopping.  In severe cases the patient will lie passively in bed, neither eating nor drinking. Patients with this syndrome are no longer bothered by pain even though they can describe the pain they feel just like normal people. Most of these patients will also have Anosognosia in which they are unable to recognize their limitations with the result that they have no motivation to undergo rehabilitation excercises. Minor or slowly developing dorsolateral syndromes can be very hard to recognize since people assume that the person is becoming lazy or simply disinterested in things due to age.

The orbitofrontal syndrome (chapter 9) is a condition in which the patient is emotionally disinhibited and impulsive. They are not able to defer immediate gratification and cannot see the consequences of their actions. They will say what is on their minds without regard to the social consequences as well. If these actions seem childish, well, they are. The prefrontal cortex is the last brain region to mature and it does not become mature until around age 18 (page 144). The author also discusses the consequences of this sort of pre-frontal cortex damage in regards to criminal responsibility.

Chapter 10 describes the groundbreaking investigation of "Kevin" who because of a horse fall damaged his reticular formation and the temperoparietal brain regions (thus his reduction in ability to form new memories). After Keven had recovered physically from the event he still had the following mental deficits (Page 158).

"Keven was perseverative: that is, his behavior invariably fell into repetative stereotypes. Every evening he would arrange his clothes for the following day and the clothes were always the same.... Despite his superficial flair, any conversation with Kevin rapidly deteriorated into a rather vacuous activity such as simple card games. He had a small repertoire of rehearsed stock topics, and the conversation would predictably and quickly drift toward one of them, say, a discussion of some of his friends.

"In the restaurant he tended to order every item on the menu, 10 or 20 items in all .... He spent most of his time though, languishing in his apartment, occasionally asking people to play simple card games .... His behavior during the games was childlike. He would clap his hands with joy after winning and throw temper tantrums after losing. He was not above cheating.

"Keven's affect (mood) was constantly oscillating between euphoria and superficial rage. These mood swings were abrupt, extreme, and could be precipitated by the most trivial events - like a waitress in a restaurant asking him if he wanted more coffee"

"Kevin had no insight into his condition"

"Kevin's mind was astoundingly concrete. When I once said that it was time to repeat the AT scan, this was meant with genuine puzzlement. Why the CAT scan, Keven marveled, if after all he had been hurt by a horse, not a cat?"

Second generation CAT scans showed Kevin's ventral tegmental region of the reticular formation was completely destroyed. This region sends massive amounts of dopomine neurons to the prefrontal cortex (page 161) probably for the purpose of defining the top level motivational contexts which the frontal cortex then refines.

Overall another great book for one's neuroscience collection.

 

I have been following this new line of treatment for depression using electrodes to stimulate certain regions of the brain with much interest. The results of the first trial experiments are starting to be published. Popular Science Magazine this month has an up close and personal report on this entitled "Happiness is a Warm Electrode" which describes the result for a severely depressed patient named Diane Hire.

On the operating table this happens:

At his (the doctor's) signal two volts of electricity .. radiate outward from the tip a few millimeters in every direction. ... Hire feels warm at first, a bit flushed.

And then it happens. The room looks brighter to her. The faces, the big circular lights overhead, the cieling, they all seem clearer. Malone asks her how she feels. "I'm really happy" she replies, clearly surprised. "I feel like I could get up and do all sorts of things." But even more telling than her words is the look on her face. For the first time in 20 years, with a halo bolted to her head and two freshly drilled holes in her skull, Hire smiles.

This trail is taking place at Cleveland Clinic in collaboration with Brown University. Others are occurring at Emery University and the University of Toronto. All told perhaps 50 patients are enrolled.

This article also reports:

Scientists are just starting to identify a class of what they call vulnerability genes. In essence they come in two forms: lucky and unlucky. "If you have one version, you are relatively resilient in the face of stress.," says Brown University Psychiatrist Ben Greenburg, who is collaborating with the Cleveland Clinic group. "But if you have another, the more severe the stress you have in your life, the more likely you are to develop depression."

Recent studies show that pills (anti-depressants) work only 50 percent of the time.

Time is dangerous in depression, with suicide --- the eleventh leading cause of death in the U.S. --- claiming more than 32,400 lives every year.

Depression started controlling Hire's life in her early 30's. At 36, after 12 years of service in the Navy, she was medically discharged because of the disease. She went back to school to become a physical therapist. She worked and worked, trying to ignore her growing unease and inability to relate to family and friends, let alone strangers.... In 1999 she stopped working for good. She started semi-regular courses of ECT. The treatment failed to improve her mood and affected her short term memory, a common side effect. ... By 2006 Hire rarely left her sofa, spent most days in sweatpants, and watched television from morning to night. It took her weeks to work up the motivation to clean the house. ... "It was a really black, dismal existence." Hire recalls. "I just couldn't function."

The day after the electrodes are put in testing takes place.

Baker turns the voltage on and off as the machine (fMRI) scans her brain. For 30 seconds, she's happy. Then Baker turns off the electrodes. Hire's smile fades, and the machine maps how her brain reacts. Another 30 seconds pass, and the happiness returns. Cowan later marvels at the effect of the stimulation on Hire and other depression patients, "They're always laughing, and I'm wondering how can you be laughing like this so soon after surgery?"

The results of these limited tests are impressive so far. In 2005 the Toronto group found that four our of six patients showed significant improvements. ... The Cleveland Brown collaboration reports improvements in 70 percent of their patients, half of who are in complete remission.

Medtronic, a company in Minneapolis that manufacturers the hardware for DBS, is working with the Food and Drug Administration to plan the largest study yet of depression and DBS - a 100 patient trial.

Six months after the operation:

She (Hire) is energetic. She shakes my hand firmly and looks me straight in the eye --- something she says she simply wouldn't have been able to do before. She laughs often. She now walks 50 miles a week, talks to her family constantly, chats with strangers in the post office. And her smile is a regular, everyday thing, not a freakish, fleeting appearance in a crowded operating room.

The location of the electrodes is probably important for the success of this operation. A German Study put it in the Nucleus Accumbens. The wikipdia article mentions Brodman area 25 which is close to the Nucleus Accumbens.

 

Despite being over 10 years old now this book by a leading researcher in the field gives some good information on the fear generating system of the brain.

The first two chapters review the various psychological movements of the 20th century with the third chapter narrowing that down to how they dealt with emotion. By the mid 1980's (page 53) the experimental evidence was in showing that affective (emotional) reactions could take place in the absence of conscious awareness. The key figure was Robert Zajonc who first demonstrated the phenomena known as the exposure effect in which emotionally neutral things one has previously seen are preferred over novel objects. After this discovery, in another experiment, he presented pictures to people so fast that they had no conscious recollection of what they saw yet they still exhibited this exposure effect. Today we call this subliminal suggestion. The main point here is that some unconscious brain mechanism is a work here and this is what the author, Joseph LeDoux investigated from a neuroscience perspective (this exposure effect is also the main reason why we must endure advertising).

Zajonc took this further. By subliminally presenting an emotionally charged picture (a smiling or frowning face) just before a normally presented emotionally neutral picture and doing this for a whole set of pictures the test subjects had a tendency to later either like or dislike the neutral images according to what emotionally charged images was associated with them (page 59).

Chapter 4 gives a brief history of the localization of different functions within the brain as related to emotion. In 1929 Philip Bard showed that following the removal of the entire cerebral cortex in cats that they will still exhibit a full range of coordinated emotional rage reactions. This only stops when the hypothalamus is also disconnected from the rest of the brain (page 81). Yet these cats are hyper-reactive such that full rage responses are provoked from the most minor stimuli. This suggested that the neural signals diverged in the thalamus with one set going to the cerebral cortex and the other going to the hypothalamus.

Chapter 5 examines the history of whether human emotions are mostly biologically based or psychologically (culturally) based. The general conclusion is that all emotions must have some biological root even though they are expressed via the filter of culture. Yet no consensus exists on what exactly those root emotions might be. To me the biological roots of emotion are obvious and based upon the two active behavioral strategies of any organism: avoidance and acquisition. The first strategy is to avoid danger. The second strategy is to acquire food, water, sex, and habitat.  Emotions enter in different ways depending on the strategy. With avoidance the presence of danger generates the emotion of fear while the presence of water, food, sex, and habitat give the emotion of contentment, peace, and security (emotions signaling inactivity). The lack of water, food, sex generate their specific emotions. The lack of habitat also generates a specific emotional signal relating to temperature, shade, and enclosure, etc (however a normal habitat is defined for that species). Yet the lack of these desired qualities also generates a general discomfort signal commonly called anxiety in humans and if unresolved (or if the involved neural circuits are out of tune) leads to depression which can be seen as an overactive defense mechanism protecting the body from the steroids and other effects of long lasting anxiety (similar to how fever can sometimes become overly extreme). This differentiation into specific and general emotion is what is lacking in present theory.

Chapter 6 gets into learning phenomena of conditioning (Pavlov's dog), especially fear conditioning in which a tone is paired with an electrical shock. This chapter finally gets into some neuroscience by describing the pathway of an auditory triggered fear conditioning. The key brain center involved in producing fear responses in all vertebrate animals turned out to be the central nucleus of the amygdala. It receives neuronal inputs direct from the auditory thalamus thus its inputs do not depend on the cerebral cortex. Electrical stimulation increases the heart rate (blood pressure increase), induced animal freezing responses, stress hormone release, and reflex potentiation (they get faster and stronger). Lesions eliminate these responses in fear conditioning experiments. Joseph LeDoux himself further refined these results by showing that the central amygdala's projection to the periaqueductal grey of the brain stem was responsible for the freezing reflex, that its projection to the lateral hypothalamus was responsible for the blood pressure rise. Others showed that its projection to the bed nucleus of the stria terminalis (in the hypothalamic region) was responsible for the stress hormone release.

Significantly, this central nucleus does not receive the neural projections from the auditory thalamus, instead its neighbor, the lateral nucleus, is the region that gets the inputs. Lesion here also disrupt fear conditioning responses. At the time this book was written which of the several possible intra-amygdala pathways is responsible for the fear conditioning responses was not known.

Electrical stimulation of the amygdala in humans most often produces the conscious sensation of fear (page 172). Damage localized to the amygdala in humans is very rare but one such patient was studied by Antonio Damasio. This patient was unable to recognize a fear facial expression even though she could identify all the other major classes of facial expression (page 173).

Chapter 7 compares the unconscious learning involved in fear conditioning with the conscious episodic learning (what we humans consider memory) that involves the hippocampus. Learning in this fear brain circuit is independent of conscious learning in that one can learn to fear something without remembering when or where that fear originated. Also discussed is the novelty detection function of the cortical region (perirhinal and parahippocampal areas) that acts as the way station between the hippocampus and the rest of the cerebral cortex. Not very well explained in this book is the role of the hippocampus. Memory in the brain is the correctly activated pathway between a stimulus and a response. This pathway is selected an extensive network of overlapping context control circuits. The hippocampus provides the commands to form the circuits for spatial and temporal context based upon if the space and time of an event is sufficiently different from previously triggered context forming commands.

Chapter 8 is a very good discussion mental illness emphasizing the role that unconscious fear conditioning might play. This is rather obvious for various phobias and stress disorders but this also has a role in producing anxiety and thus depression. The author suggests that panic attacks could be a fear conditioning that improperly treats the body's own autonomic fear responses as a fear producing stimulus (page 258). In learning theory this is known as the "assignment of credit" problem. This is the problem of determining which prior event should be associated with a fear event.

Chapter 9 is a discussion of consciousness. What is new for me is the consideration of working memory in conscious sensations. Working memory is a more comprehensive idea about short term memory which allows one to remember temporarily up to 7 things at a time for up to a few minutes. Working memory also involves the active mental processing involving the quick comparison of these 7 things. I have long wondered about the different strengths of conscious sensations between thoughts and immediate experiences (including dreams). The difference seem to be due to working memory indicating that either more neurons in the amygdala are recruited into the event or the neural activation in the amygdala lasts longer than would be normal. Working memory seems to be controlled by the lateral prefrontal cortex at the very front of the brain which exists only in primates (page 274) so presumably it is able to keep amygdala neurons active longer. Below the prefrontal region is the orbital cortex which seems to be responsible for evaluating an emotional stimulus in terms of longer term goals.  In college my roommate was givin laughing gas (Nitrous oxide) during a tooth drilling and he reported it "hurt like hell" but that he didn't care. Perhaps the orbital cortex is responsible for that phenomena. The medial prefrontal cortex seems to be involved in the extinction of fear associations.

The involvement of working memory in conscious sensations begs the question of whether the amygdala would produce the conscious sensation of fear in non-primates if the neurons were artificially stimulated.

So overall a good and thought provoking book.
 

"Hordes of giant mice are devouring endangered seabird chicks on a remote South Atlantic island and may be pushing some of the birds to extinction, scientists report." This is the lead-in to a news report by National Geographic.

For me what is amazing is that these bird chicks which are still a lot larger than the mice let the mice attack and eat them without fighting back. Their brains just are not wired to give a defensive response to animals that are small and non-bird like.

These mice are also in the process of evolving larger sizes in order to become better preditors. So we see early stage evolution at work.

Here is a news article describing a recent finding about a human pre-frontal cortex region which intergrates some deep emotional centers with goal directed social behavior. The deep emotional center called the Amygdala mentioned in the article, when electrically stimulated, produces the conscious sensation of fear. This is another among many in recent years indicating that the wiring of our biological brain is responsible for our personality leaving conscious sensations (collectively the soul) with some other evolutionary purpose.

New York Times Article