Neuroscience of Mindfulness: How Do We Know What We Know

"Anatomy" Photo Credit: Untitled blue via Compfight cc

“Anatomy” Photo Credit: Untitled blue via Compfight cc

“To know what you know and what you do not know, that is true knowledge.” ~ Confucius

We have thus far examined The Neuroscience of Mindfulness & Anxiety and The Default Mode Network, Meditation, & Mindfulness in my Neuroscience of Mindfulness series. And until now you have graciously taken me at my word that what we know about the brain is the result of rigorous research. But there comes a time in any discussion that we must introduce the critical question of “How?” How do we know what we know? And how do we know what we do not know? We must remember the guidance of Confucius: true knowledge exists only when we are cognizant of both our ignorance and our competence.

The brain is a well whose bottom we may never appreciate; such is the complexity of the organ.

But the pace of our scientific understanding of the brain and mind continues to accelerate at a dizzying pace.

It is my hope that the following article will provide the reader with a brief introduction into the technology and experimental design that scientists have used to gather the knowledge that we now possess regarding the brain. This discussion will serve as an excellent reference going forward in my Neuroscience of Mindfulness series.

We will chart a course first into the technology we use to study the brain and then into the experimental design that employs the aforementioned technology. I have, as always, included the source reference material so that any interested reader can learn more at their own pace and to the depth that they desire. Additionally, I have included an interesting study or tidbit of information garnered from work with the technology or experimental design of interest.

There is a great deal of medical technology in use today, but for the purposes of our investigation we will examine two medical imaging techniques to understand how scientists have come to the conclusions that they have regarding neuroanatomy.

Computed tomography (CT) and magnetic resonance imaging (MRI) were both licensed for commercial use within one year of each other in the 1970s (CT in 1971 and MRI in 1972).

CT derives its name from the Greek tomos (“slice”) and graphein (“write”) because it uses X-ray radiation to “write” a three-dimensional representation of internal human anatomy from many two-dimensional slices.

CT technology was then combined with another scientific theory to create positron emission tomography (PET). PET uses the concept of radioactive decay to explore the human body in unprecedented ways. Radioactive decay is the process by which an unstable atom emits positrons (among other particles) in a random pattern. A PET scan can measure the decay and thus location of radioactively labeled glucose injected into the body (any chemical can be labeled – glucose just happens to the most commonly used). The PET scan utilizes the relationship between the brain and glucose to study neurological function. (1)

Glucose, or sugar, is virtually the only fuel that the brain consumes to maintain its high level of activity (when starving the brain can consume ketones but this is a discussion for another day). Exploiting the high dependence of brain metabolism (roughly equivalent to activity) on glucose, scientists can use injected radiolabeled glucose and a PET scan to examine which areas of the brain are active during different tasks and diseases.

"PET Scan" Photo Credit: Reigh LeBlanc via Compfight cc

“PET Scan” Photo Credit: Reigh LeBlanc via Compfight cc

So what have we used PET technology for?

A recent study using PET technology examined glucose metabolism in the brain of subjects during resting state. In particular, Hakamata et al. assessed two temperamental traits of healthy subjects and then measured glucose consumption as a rough approximation of grey matter (neurons – the basic cell of the brain) density. Let’s remember that the brain is like a muscle in that when we “exercise” a part of the brain it grows. In the case of the brain this growth takes on the form of increasing numbers of neurons (among other cells). Also, it is important to note that the increased size of a structure in the brain could either produce hyperactivity or be the result of hyperactivity.

Neuroscientists define personality as consisting of two different paradigms: temperament and character. Temperament is the reflexive emotional response to our environment while character utilizes higher brain processes to reinterpret temperamental reactions.

Temperament is the reason you do or do not enjoy crowds while character helps you recast yourself as a social creature despite your dislike.

The temperament trait of interest in Hakamata’s study was harm avoidance (depressive, anxious, vulnerable), and the character trait was self-transcendence (mindful, intuitive, judicious, spiritual). Investigators predicted and confirmed that those who scored highly on self-transcendence (mindfulness) would have increased glucose consumption (neuronal density) in the anterior cingulate cortex (ACC) and the prefrontal cortex (PFC). (2)

If we remember from my previous article, Default Mode Network, Meditation, & Mindfulness, the ACC/Attender facilitates our attentional focus on mental and emotional conflict. An additional task of the ACC/Attender is to orchestrate harm avoidance. This role will become important shortly.

The PFC/Decision-Maker decides where to direct our attentional awareness and willpower. Additionally we should remember that the ACC/Attender and PFC/Decision-Maker are two members of the task-positive network: the network responsible for our cultivation of mindfulness.

All of this is to say that it was no surprise that high glucose consumption (activity) of the ACC/Attender and PFC/Decision-Maker correlated with high scores on the self-transcendence (mindfulness) character trait. Also of no surprise was the discovery that those who scored highly on the harm avoidance measure had decreased activity in the ACC/Attender and PFC/Decision-Maker regions of the brain. The surprise came in the finding that high scores on self-transcendence (mindfulness) showed a protective effect even if the same subject scored highly on the harm avoidance measure.

Thus, Hakamata et al. hypothesized that the cultivation of mindfulness may protect against, without having to eliminate, negative temperamental traits.

PET technology is truly astounding but contains two significant drawbacks that will explain why MRI technology is becoming the new standard for studying the function of the brain. First, PET scans require that the patient be exposed to ionizing radiation, which is not without risk. Second, by definition radioactive compounds decay, and so a PET scan can only study relatively brief mental activities.

On that note, let’s introduce the MRI. MRIs use strong magnetic fields to excite hydrogen atoms within the body. The body is approximately 65% water (some variation between sexes) and water is made up of 2 hydrogen atoms and 1 oxygen atom (H20) so there is no shortage of hydrogen atoms to excite. The excited hydrogen atoms emit a radio frequency that is detectable by the MRI. Thus, the MRI is able to produce amazingly detailed images of the human body without exposing the patient to ionizing radiation.

MRI technology took a quantum leap forward in 1992 with the development of the functional MRI (fMRI). The fMRI is capable of measuring blood flow and thus glucose and oxygen delivery to different parts of the brain. (3)

Recalling from our earlier discussion, the brain uses glucose as an almost exclusive fuel source. Thus, the fMRI, like the PET scan, can reveal activity within the brain while a patient executes certain mental tasks.

"fMRI" Photo Credit: pennstatenews via Compfight cc

“fMRI” Photo Credit: pennstatenews via Compfight cc

For an example of the fMRI in action, let’s return to my previous article on the default mode network (DMN). In this article we learned that the medial prefrontal cortex (mPFC)/Emotional Sensor processed the personal meaning of social and emotional information. But how do we know this?

Well, one study recruited patients with social anxiety disorder and used an fMRI to examine their brains while they entertained a negative self-view for 12 seconds. For example, if a patient was embarrassed by his shyness he was encouraged to think, “I am ashamed of my shyness” for 12 seconds. The self-recriminating thought process correlated to an activation of the mPFC/Emotional Sensor (among other structures).

After 12 seconds the patient was instructed to focus on his breath (the patients had been trained in mindful breathing). Lo and behold the simple act of refocusing on the breath deactivated the mPFC/Emotional Sensor and engaged the structures involved in the task-positive network. (4)

Because of the limited generalizability of any single study many additional studies have been used as data points to confirm the mPFC’s role as the “Emotional Sensor.”

Technology would be meaningless without a methodological approach to its use. With that in mind let’s review the methods utilized to study the brain.

There are many ways that neuroanatomical function is determined, but we will briefly discuss the most important methods: animal studies and human studies.

In animal studies scientists are able to insert electrodes, create lesions, inject dangerous chemicals, and generally tinker with the brain in a way that is ethically unimaginable in humans. I will not discuss the ethics of animal experimentation except to say that I did not pursue a PhD in neuroscience because of, among other factors, the personal inability to experiment on animals. That being said, the sacrifices made by animal subjects have led to tremendous advances in science and medicine.

Scientists have learned a great deal from examining the brains of our animal colleagues, utilizing the close evolutionary proximity of monkeys and the great apes to make approximations for the human brain. Furthermore, mammals as a group share a surprising amount of overlap in brain structure making rats and mice useful test subjects despite their seemingly vast evolutionary separation.

For an example of how animal studies have informed our neuroscientific understanding of the brain let’s examine the amygdala. In my previous article we referred to the amygdala as the “Emoter” because it generates the substrate of our raw emotions. The amygdala/Emoter is responsible for the immediate and unconscious processing of fearful stimuli before the higher cortical regions have gotten conscious control of the situation.

There has been a great deal of research into the amygdala/Emoter and we will briefly discuss one of the leading contributors as an example of how we came to our current understanding of this important structure.

Joseph Ledoux is a neuroscientist with a PhD from State University of New York at Stony Brook. He is perhaps the best-known researcher on the neurocircuitry of fear.

"Rat" Photo Credit: Jessica Florence via Compfight cc

“Rat” Photo Credit: Jessica Florence via Compfight cc

In 2000 Ledoux et al. published a review of the current state of knowledge about the amygdala/Emoter. Within this study Ledoux cites single neuron experiments in which a rat was exposed to a fearful stimulus and the activity of an individual neuron was measured. The single neuron experimental design allows researches a precise method of targeting brain regions of interest. Using this method, scientists were able to confirm that the amygdala/Emoter is responsible for core processing of fear, fear extinction, and reflexive fear processing. (5)

Next up: humans.

Human studies come in roughly two flavors: lesion studies and functional studies.

Functional studies employ medical imaging technology to study the brain during specific tasks. An example of a functional study was examined earlier in our reference to the study of negative self-view in patients with social anxiety disorder.

Lesion studies (lesion means a damaged area of tissue) exploit a lesion from a stroke, tumor, surgery, or traumatic event to study the behavioral and neurological deficits incurred. One of the most famous lesion studies was of a patient with the initials HM.

HM had intractable epilepsy and after exhausting all medical treatments underwent a surgical procedure in the 1950s that would not only alter his life but also the course of medical history for years to come.

HM’s seizures were determined to originate in his temporal lobes. Surgeons operated to remove parts of both temporal lobes, containing the hippocampi among other structures. We referred to the hippocampus as the “Memorizer” in my previous article because of its relationship to memory.

The hippocampus is known to generate and modulate memory while its role in memory retrieval and storage is a bit more controversial. In fact, there may not be a single location of storage instead memory may be the summation of many different neural networks working together. At this point we just don’t know. We will see why the memory retrieval and storage are not as clear-cut as we progress in HM’s story.

First, let’s examine memory in more detail. Memory can be roughly split into implicit (non-declarative) and explicit (declarative) memory. And each of these can be further subdivided again.

Implicit memory is largely unconscious and relatively immune to hippocampal lesions, suggesting an alternative site of storage. Implicit memory consists of procedural and emotional components. The procedural component of implicit memory allows you tie your shoe without thinking about it. The emotional component of implicit memory triggers your sense of fear when you hear a dental drill because of a long ago emotional association between the sound and pain.

Explicit memory is conscious and can be broken down into episodic and semantic components. Semantic memory stores your knowledge of words, numbers, and concepts while episodic memory records autobiographical information about your life. Explicit-episodic memory is the most sensitive to hippocampal lesions while explicit-semantic memory is relatively immune. This again suggests an alternate location for semantic memory. (6)

One final note involves short-term memory and the regions of the brain responsible for its function.

Short-term memory is a halfway station between longer-term storage and present moment awareness.

Short-term memory has often been suggested to be capable of storing 7 plus or minus 2 concepts at a time (in fact there is a famous and highly influential book by the psychologist George Miller titled The Magical Number Seven, Plus or Minus Two). There is a great deal of disagreement about this number, but we can use it as a rough approximation of the capacity of short-term memory. The duration of short-term memory recall is also far from clear but a rough estimate may be around 30 seconds. However, the duration of short-term memory can be greatly extended through rehearsal (repeating the given set of information over and over in one’s head).

Short-term memory provides the ability to remember a new phone number long enough to unlock your phone and place the call or remember a brief list of directions for an upcoming turn on a road.

Short-term memory seems to involve activation of the lateral prefrontal cortex (lPFC) and the anterior cingulate cortex (ACC) among other structures. In my previous article, Default Mode Network, Meditation, & Mindfulness, we learned that the lPFC is responsible for our ability to juggle short-term concepts in our conscious arena while the ACC/Attender plays an important role in maintaining conscious attentional awareness of a concept. (7)

So we have implicit-procedural/Shoe-tying, implicit-emotional/Fear-tying, explicit-semantic/Conceptual, explicit-episodic/Autobiographical, and short-term/Active Memory.

Now we can return to the hippocampal hardship of HM.

"Memory Loss" Photo Credit: _annamo via Compfight cc

“Memory Loss” Photo Credit: _annamo via Compfight cc

The surgical removal of both temporal lobe regions that house the hippocampus/Memorizer cured HM of his epilepsy but very soon after awakening from surgery HM’s doctors and family noticed profound deficits in memory. Interestingly, the removal of one of the two hippocampi does not produce the same deficits we will discuss in the proceeding paragraphs.

HM’s implicit and short-term memory systems were largely intact while his explicit memory system was devastated. There is some debate among scholars whether HM was able to form new explicit-semantic/Conceptual memories but for our purposes we will examine just the explicit-episodic/Autobiographical memory system.

HM suffered from profound anterograde (from the Latin antero “in front of”) amnesia. This meant that he could not form new memories of events he experienced. Additionally he suffered from retrograde (from the Latin retro “backward”) amnesia for events that had occurred up to 11 years prior to the surgery.

Because HM’s implicit and short-term memory systems were intact, he felt a sense of warmth towards family and was able to remember approximately 30 seconds worth of experience. But if HM met someone and that person subsequently left the room, upon returning 30 seconds later HM would have no recollection of having ever met them.

HM could still tie his shoes and learn new tasks demonstrated by his increasing speed in solving maze problems but could never remember the simplest conversation or whether he had eaten lunch ten minutes before. (8)

There are probably more questions than answers generated by the case of HM but the information gathered was invaluable to our knowledge of memory.

So what was the point of all this information?

The point is to realize that our knowledge of the brain (and the rest of the body) is a result of many individual experiments that all point in a similar direction.

Maybe an analogy will help clarify my meaning.  Let’s imagine that an advanced race were able to write the definitive textbook on the inner workings of the brain, explaining every minutiae and detail of its function.  The only catch of this hypothetical textbook is that it is written in a completely new language: Futurese.

Now let’s imagine that this future race were able to harness their time-traveling abilities (here’s hoping) to send a copy of this textbook along with a Futurese-to-English dictionary back in time to arrive at your doorstep.  The scientists of the world would join in a collectively held breath as you began your translation process.

You begin your translation with the very first word of the first chapter.  You thumb through the immensely thick Futurese-to-English dictionary to find the corresponding English word, and, “Ah hah!” you find it.  Each Futurese-to-English word you translate represents a single scientific study of the brain.

Maybe you’re able to translate enough Futurese words to create a sentence (if they even still have those).  You raise your arms triumphantly and shout the sentence out loud.  But the meaning falls flat and incomplete on your ears.  And who’s to say that the meaning of the sentence was not lost in translation all together.

So you keep plugging along and you put together a paragraph and then a page.  But each page begets a larger question, and you scratch your head at the sentences that don’t translate well into English.

This analogy parallels our current state of knowledge about the brain.  We know a tremendous amount and our knowledge is accelerating at a very rapid pace, but whether we are on chapter 2 or 10 remains to be seen.

The full complexity of the human brain awaits a complete translation, but I am hopeful that we will one day provide the storyline for just such a futuristic textbook.

References

1. Townsend, D. W., Valk, P. E., & Maisey, M. N. (2005). Positron emission tomography. Springer-Verlag London Limited.

2. Hakamata, Y., Iwase, M., Kato, T., Senda, K., & Inada, T. (2013). The neural correlates of mindful awareness: a possible buffering effect on anxiety-related reduction in subgenual anterior cingulate cortex activity. PloS one, 8(10), e75526.

3. Huettel, S. A., Song, A. W., & McCarthy, G. (2004). Functional magnetic resonance imaging (Vol. 1). Sunderland, MA: Sinauer Associates.

4. Goldin, P. R., & Gross, J. J. (2010). Effects of mindfulness-based stress reduction (MBSR) on emotion regulation in social anxiety disorder. Emotion, 10(1), 83.

5. LeDoux, J. E. (2000). Emotion circuits in the brain. Annu. Rev. Neurosci, 23, 155-184.

6. Wood, R., Baxter, P., & Belpaeme, T. (2011). A review of long-term memory in natural and synthetic systems. Adaptive Behavior.

7. Jonides, J., Lewis, R. L., Nee, D. E., Lustig, C. A., Berman, M. G., & Moore, K. S. (2008). The mind and brain of short-term memory. Annual review of psychology, 59, 193.

8. Corkin, S. (1984, January). Lasting consequences of bilateral medial temporal lobectomy: Clinical course and experimental findings in HM. In Seminars in Neurology (Vol. 4, No. 2, pp. 249-259).

 

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1 Response

  1. Thanks for the great MRI photo :-). We used it in a piece on how the mind impacts our everyday reality. Hope you enjoy 🙂 http://www.thegoyslife.com/2012/12/16/thoughteality/

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