What is Executive Function?

Executive function is a term that describes a wide range of cognitive behaviors and processes. It is broad enough of a term that some people simply describe it as, “what the frontal lobes do.” When asked what exactly the frontal lobes do do, some revert to the circular definition of “executive functions.” However, executive functions are distinct from – but related to – what the frontal lobes do. The frontal lobes are involved in motor functions (e.g., pre-motor and primary motor areas), eye movement (e.g., frontal eye fields), memory (e.g., acetylcholine-producing portions of the basal forebrain), and language (BA 44,45 or Broca’s area). In addition, some executive functions incorporate areas of the brain outside the frontal lobes – the parietal lobes or basal ganglia, for example. Like many cognitive domains, executive functions are part of a distributed network of brain structures and regions.

Most neuropsychologists however, would define (or at least accept the following definition of) executive function similar to this: Executive function is the ability to selectively attend to, work with, and plan for specific information. This means that executive function is deciding what information, cognitions, or stimuli are relevant, holding and working with that information, and then planning what to do with it. As such, executive function is largely the roles of planning and organization. It is also the ability to recognize and learn patterns (i.e., cognitive sets) but also have the cognitive flexibility to respond to set changes and make a shift in set. Executive function also involves being able to select the appropriate response or behavior while at the same time inhibiting inappropriate responses or behaviors.

Executive functions have been compared to the conductor of an orchestra who, in order to make sense of the disparate instruments, sounds, and parts, must coordinate the members and lead the efforts of all the components of the orchestra. Executive functions also have been compared to chief executive officers of companies. These comparisons demonstrate that executive functions are arguably the most complex and highest of all cognitive functions. However, just like most other cognitive functions, executive functions are comprised of relatively simple processes (e.g., attention and processing speed) – it is just the unique combination of these more basic processes that makes executive functions so powerful.

One potential problem with executive function as a cognitive domain is that it is large and loose. Many tests have been developed, or at least used, to assess executive function (e.g., Wisconsin Cart Sort Test, Stroop Color-Word Task, clock drawing, and so forth). Even though all such tests are used as measures of executive functioning, scores on them do not always correlate highly with each other. They do not always cluster together when subjected to principal components analysis or even structural equations modeling. This means that even though neuropsychologists have many purported tests of executive function, they all seem to measure different aspects of executive function. This might partially result from executive functioning tests being differentially affected by basic cognitive processes such as processing speed.

Even though, as previously mentioned, I do not believe executive functions and frontal lobe functions are synonymous terms, are we able to localize executive functions to the frontal lobes? Largely we can. The most evidence from neuroimaging studies and neurological injuries demonstrate that the prefrontal cortex – the area of the brain that is phylogenetically youngest and most advanced and as such, proportionately larger in humans than any animal – is necessary (but not necessarily sufficient) for executive functioning. When this area is disrupted in humans, they exhibit poor decision-making skills, including poor planning and poor maintenance or self-regulation of behavior. One area of the prefrontal cortex particularly involved in executive functions is the dorsolateral prefrontal cortex (area 46) – although both the orbitofrontal and anterior cingulate are involved in aspects of executive functions.

In 1986 Alexander, Delong, and Strick published their seminal work on five parallel and closed cortico-striato-thalamo-cortical loops. These frontal-subcortical circuits were hypothesized to be involved in a range of behaviors and cognitions based on the varying cortical connections of the loops. Previously, many researchers did not well-understand the role that the basal ganglia played in any sort of “higher” function; in fact, most viewed the basal ganglia as involved mainly in motor behaviors. Alexander, Delong, and Strick’s article set off a flurry of research into the functions of these frontal-subcortical circuits, which have been verified as existent in humans (Middleton & Strick, 2000). Over time different theories have modified these circuits, including that they are composed of direct, indirect, and hyperdirect pathways, which all function at different speeds or timings to allow the basal ganglia to regulate behavior. Mink (1996) proposed that actions (e.g., producing a specific word) are regulated by the direct and indirect pathways, which serve as large components of our ability to select and inhibit correct and incorrect responses, respectively. It is as if each individual fronto-cortical loop allows us to properly attend to the correct behavior or response and inhibit all other behaviors or responses, much like the DLPFC and orbitofrontal cortex and their associated loops are involved in the selection and inhibition of behavior, both major aspects of executive function.

Just as damage to the dorsolateral prefrontal cortex (DLPFC) produces deficits in executive function, damage to any part of the DLPFC loop also results in executive dysfunction. Benke, Delazer, Bartha, and Auer (2003) presented two clinical cases of patients with left caudate lesions (the lesions also affected part of the anterior limb of the internal capsule as well as portions of the putamen and pallidum; however, the infarcts affected the caudate the most). Among other deficits, both patients had executive function impairments, including problem-solving deficits, many perseverative errors, and set-shifting problems. Even though the patients had no direct DLPFC damage, they exhibited similar deficits to patients with DLPFC lesions. These executive deficits persisted over time.

As a cognitive domain, and even as broad as it might be, executive functioning has ecological validity. Price and colleagues (2008) found that executive dysfunction was related to greater difficulty performing IADLs. Specifically, patients with executive dysfunction had more difficulty performing IADLs than patients with memory deficits did. Thus, how quickly, flexibly, and accurately people can organize, solve, plan, or attend to specific neuropsychological tasks seems to correlate with their accomplishment of everyday tasks of life, such as finances, driving, and shopping.

References

Alexander, G. E., DeLong, M. R., & Strick, P. L. (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annual Review of Neuroscience, 9, 357-381.

Benke, T., Delazer, M., Bartha, L., Auer, A. (2003). Basal ganglia lesions and the theory of fronto-subcortical loops: Neuropsychological findings in two patients with left caudate lesions. Neurocase, 9, 70-85.

Middleton FA, & Strick PL. (2001). Basal ganglia output and cognition: evidence from anatomical, behavioral, and clinical studies. Brain Cogn., 42, 183-200.

Mink, J. W. (1996). The basal ganglia: Focused selection and inhibition of competing motor programs. Prog Neurobiol, 50, 381-425.

Price, C.C., Garvan, C., and Monk, T. (2008). Type and severity of cognitive impairment in older adults after non-cardiac surgery. Anesthesiology, 108, 8-17.

Video of my brain

I posted a video of my brain on YouTube just to show the quality of MRI scans we have now (and the fun things we can do with post-processing). The scans were done on a 3T Philips Achieva MR scanner. We acquired 2 T1 scans of my brain (160 1mm slices – 1 mm cubed voxel size) then post-processed the DICOMs using FreeSurfer. The skull-stripped output files (in NIFTI format) were then rendered in 3D in OsiriX. I created a fly-through movie of the brain and exported it as an MP4 movie. If you have any questions about the process, feel free to ask.

Revisiting Clive

Yesterday I posted a video clip about Clive Wearing. Here is the first part of a different documentary about Clive. This video goes more in-depth about his condition. Clive is sometimes referred to as the man with the shortest memory. Not only were his two hippocampi destroyed, but also surrounding areas of the his temporal lobes as well as portions of his left frontal lobe. He also remembers very little from before his illness, which is quite rare; this condition is called retrograde amnesia. Clive lives in an ever-present now, without connection to past or future. Other parts to this video can be found on YouTube.

The Unusual Case of Clive Wearing

Clive Wearing is a 70 year old British man who contracted herpes simplex encephalitis in 1985. The virus destroyed his hippocampi bilaterally (as well as surrounding areas). He has complete anterograde amnesia and can only remember up to about 20 seconds. He retained the ability to play the piano and conduct a choir (which he did previously to his illness); this is because this procedural memory involves different areas of the brain, including the basal ganglia and the cerebellum. I’ll revisit this case over the coming days. Meanwhile, here is a clip from a BBC production that presents part of Clive’s story.

Banjo Pickin’ Brain Surgery

Mo at Neurophilosophy posted a great video of Deep Brain Stimulation (DBS) surgery being performed on a man with essential tremor, while he plays the banjo. As with most brain surgeries, the patient was awake, alert, and talking. The doctors had him play the banjo so they could fine tune (pun intended) the electrode placement in order to have the best response.

An Introduction to and Overview of the Brain

bi sang by seung ji baek

The human brain is a wondrous thing. It is the single most complex organ on the planet. It sits atop the spinal cord. Gazing upon the brain, one sees four main distinct areas – two roughly symmetrical hemispheres, a cerebellum stuck up underneath the posterior part of the brain, and a brainstem sticking out and down from the middle of the brain. Each cerebral hemisphere is divided into four visible lobes: frontal, temporal, parietal, and occipital. The frontal lobes jut out at nearly a 90 degree angle from the spinal cord and are the largest part of the human brain. The temporal lobes stick out the sides of the brain, like thumbs pointing forward at the side of a fist. The parietal lobes are harder to distinguish. They are just posterior to the frontal lobes and dorsal to (above) the temporal lobes. The occipital lobes are at the very back of the brain, like a caboose on a train.

The outside of the brain is covered with a series of bumps and grooves. The bumps are called gyri (sing. gyrus) whereas the grooves are called sulci (sing. sulcus). This outside part of the brain is filled with tiny cell bodies of neurons, the main functional cell of the brain. Some people estimate that there are 100 billion neurons in the central nervous system (brain + spinal cord). This outer layer of the brain is called the cortex (which means “bark”). The cortex is only about 5mm thick, or about the thickness of a stack of 50 sheets of copy paper, yet it is responsible for much of the processing of information in the brain.

At room temperature the brain is the consistency of warm cream cheese. If removed from the skull and placed on a table, it would flatten and widen out a bit, like jello that is warming up. The brain is encased in a series of protective sheaths called meninges. The outermost encasing is called the dura mater (L. “tough mother”), which is thick and tough and is attached to the skull. The next layer in is softer. It is called the arachnoid layer; it adheres to the brain. Just underneath this layer is where cerebrospinal fluid (CSF) flows. This fluid is produced in holes in the middle of the brain called ventricles. CSF helps cushion the brain as well as remove waste products from the brain. Underneath this is a very thin and fine layer called the pia mater (L. “soft mother”), which adheres directly to the cortex and is difficult or impossible to remove without damaging the cortex. These three layers of meninges serve to protect the brain.

The brain can be roughly split into three functional areas, each one more “advanced” than the previous. The brainstem (and midbrain), which includes such structures as the medulla, pons, and thalamus, activates and regulates the general arousal of the cortex. Damage to the brainstem often results in coma or death. The next rough functional area is the posterior portion of the brain (parietal and occipital lobes and portions of the temporal lobes). This area is heavily involved in sensory processing – touch, vision, hearing. It sends information to other parts of the brain largely through the midbrain structures. The last functional area includes the frontal lobes. This area can regulate all other parts of the brain but is essential for goal-setting, behavior inhibition, motor movements, and language. The frontal lobes are the most advanced area of the brain and arguably the most important for human functioning – for what makes us human. In summary the three areas roughly are responsible for:

  1. Overall arousal and regulation
  2. Sensory input
  3. Output, control, and planning

Underneath the cortex is a large area of the brain that looks white. This area is comprised of the axons of the neurons of the cortex and subcortical structures. These axons are the pathways between neurons – like superhighways connecting cities. The axons look white because the majority are covered with a fatty tissue called myelin. Myelin helps axons work more efficiently and transmit more quickly. The white matter of the brain is as important for normal brain functioning as the gray (neurons) matter is.

The brain is energy-hungry. It cannot store energy so it needs a constant supply of nutrients from blood. However, blood can be toxic* to neurons so the brain has to protect itself from the blood and other toxic materials through what is called the blood-brain barrier. This barrier keeps blood cells out of the brain but allows molecules of nutrients (e.g., glucose) to pass into or feed the cells. The entire surface of the brain is covered with blood vessels, with many smaller vessels penetrating deep into the brain to feed the subcortical structures. Deoxygenated blood must be removed from the brain. Veins take the blood out of the brain and drain into venous sinuses, which are part of the dura matter.

The brain works as a whole to help us sense, perceive, interact with, and understand our world around us. It is beautiful in its form and function.

*”Today, we accept the view that the BBB limits the entry of plasma components, red blood cells, and leukocytes into the brain. If they cross the BBB due to an ischemic injury, intracerebral hemorrhage, trauma, neurodegenerative process, inflammation, or vascular disorder, this typically generates neurotoxic products that can compromise synaptic and neuronal functions (Zlokovic, 2005Hawkins and Davis, 2005 and Abbott et al., 2006).” From Zlokovic, B. V. (2008). The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron57(2), 178-201.

Image: Bi Sang by Seung Ji Baek

Building a Better Brain

Let’s look forward a number of years. Bioengineering is at the point where replacing people’s organs with lab-grown ones is standard procedure. Gone are the days of transplant patients taking anti-rejection medications for the rest of their lives. Transplanted organs are all manufactured using stem cells from their own body, from bone marrow or from skin or any number of different sources. New organs are rapidly grown using modified growth hormones to speed up their development. A complete new organ is grown within a few weeks, a surgery performed, and the transplant patient home within days. Because of the relative low cost of such procedures, all have access to transplants. Replacing hearts, livers, lungs, kidneys, and other organs increased the life expectancy dramatically with most people living well over 100 years. Scientists are on the verge of transplanting the first manufactured brain. Knowledge of neural networks and cognition is at the point where a person’s entire knowledge system and all memories can be downloaded and stored as a backup. Scientists are working on manufacturing an entire replica human body as a “clone” in case a person is seriously injured. While individual organs come fairly cheap, a whole body is prohibitively expensive. A large portion of the cost is the brain. Even though scientists have created working brains, their success rate is still only about 5% (but always getting better). They go through a lot of brains.

Some people use this new biotechnology for creating backups of their bodies. Other people have started using it to enhance the performance of their existing body. In laboratory situations scientists are able to create organs that are effectually perfect. They are created in well-controlled situations and don’t have to go through the gauntlet of normal development, with exposure to teratogens, fluctuations in nutrition, and all the other things that can affect development. Popular organs to replace are hearts and lungs. People are able to run faster than ever before due to more efficient hearts and lungs. Other people get new legs or arms with well-sculpted muscles. Still other receive nanotech implants to enhance normal biological performance. None of this is being done in the United States or in the United Kingdom but there are plenty of countries that don’t outlaw the procedures

With the common body enhancing going on many people want to enhance their brains. They want a new brain created with certain gyri a little bit bigger and cortex a little bit thicker. Some researchers are working on improving the speed and efficiency of neurotransmitting. Most of the improvements in brain design come from turning on and off certain genes at different time points in development and providing the lab-grown brains optimal nutrients and stimulation. These enhancements can create brains that can learn 1000 times more in 1000 times less time.

I’ve taken a bit of liberty in my hypothetical treatment of bioengineering and biotechnology in the unspecified future. There is little, scientifically-speaking, that stands in the way of us as humans eventually reaching this point. The question is, should we? Should we seek to create immortal and essentially all-knowing humans through science. Supposing humans can build better brains and bodies, should they control and manipulate natural biological processes to the extent that they can create “superbeings”? I’m not going to answer any of the questions; I just want to raise them. With our great advances in bioengineering, technology, and neuroscience, where do we draw the line, assuming we do draw a line? Do we eradicate all developmental, genetic, and environmental diseases and disorders. Do we cure epilepsy, cancer, Autism, Alzheimer’s Disease, and ever other disorder? Do we enhance some functioning, such as hearts or muscles but not the brain?

With all advances in science, we have to always be mindful of the underlying morality and ethics of the advances. we need to make sure that our advances do not out-pace our morals.

Moral Development and the Brain

Moral reasoning is the ability a person has to reason in and through social, ethical, and emotional situations. One component of moral reasoning is moral behavior, which is the intentional and voluntary acting in a prosocial manner (Walker, 2004). Moral behavior and reasoning are the foundation for “many human social and cultural institutions such as family structures, legal and political government systems that affect the lives of virtually every person” (Eslinger, Flaherty-Craig, & Benton, 2004, p. 100). Often situations in life are morally ambiguous and involve a choice between two actions that both have consequences that may or may not be in opposition to each other. Some researchers, such as Lawrence Kohlberg, believe that people will reason through these situations at varying levels or stages, with some in a very concrete and egotistic manner and others in an abstract and universal manner.

Lawrence Kohlberg was the first researcher to come up with a major testable theory of moral development. He formulated six stages of development, with most adults reaching stage four, a few five, and very few stage six. The first two stages are at the pre-conventional level (typically self-centered and concrete reasoning), stages three and four are at the conventional level (recognition of social norms and laws), and the last two stages at the post-conventional level (recognition of universal rights and responsibilities). While Kohlberg’s theory of moral development is a stage model, the progression through the stages is not necessarily viewed as invariant. This means that people reach them at different rates and do not always reason at a particular stage with any given dilemma. There is significant variability within and between people in moral reasoning abilities. Most research focuses on between-person variability.

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