May 21 2020

Localizing Executive Function

Where in the brain is a specific ability located? This is a more complex question than it may at first seem, mainly because we first have to define each specific ability. Some are obvious, like the ability to voluntarily move your right hand. The motor strip in the cortex physically maps to the body, and it is relatively easy to correlate a specific part of the brain to weakness of any specific body part. But even something as simple as motor control has many layers – other parts of the brain that modify control, allowing for smooth coordinated movement, for example.

Arguably the most difficult functions to localize in the brain are the more abstract ones, like executive function. This is extremely challenging partly because we don’t really know what those functions are at their most fundamental level. We can learn what behaviors they allow, but how? What is actually happening in the brain when you make a decision, for example?

Some of these more abstract functions are also difficult to study because they may be bilateral, meaning that the same structure on both sides of the brain contribute to the function. Therefore a lesion taking out one side won’t necessarily cause any deficits. Motor control, by contrast, is unilateral, so one single lesion causes an obvious deficit. This is important because studying lesions is one major way neuroscientists localize brain function – wait for it to break and than see what doesn’t work. Historically such lesion studies have been the most important method for mapping the brain.

Today we have other methods, such as imaging the brain functioning (fMRI), mapping electrical activity with EEG, and even temporarily influencing brain function with electrical or magnetic stimulation. This data (the first two methods, anyway), however, is mostly correlational. It can still be powerful, but a lesion is helpful in confirming causation.

This background brings us to a recent study in which the authors review a patient with rare bilateral lesions in a particular brain region causing deficits of executive function. They also do a meta-analysis of imaging studies correlating executive functions to this same region. The region is the inferior frontal junction (IFJ), located at the junction of the inferior frontal sulcus and the inferior precentral sulcus. The patient is a 56 year old woman with multiple small strokes from a heart condition that led to blood clots going to the brain. The IFJ in both hemispheres suffered strokes, giving a rare opportunity to do a lesion study of the IFJ.

First lets explore a bit further what is meant by “executive function.” This is defined partly as the ability to adapt to a changing context, either internal or environmental.  But again neuroscientists struggle to figure out what the most fundamental components of this ability are. There are many behaviors that fall under the concept of executive function, such as strategic planning, understanding and applying rules, the ability to change strategies, and to inhibit one’s own behavior. One researcher boils this down to what they think are the fundamental components of executive function – working memory (a specific type of memory in which bits of data can be manipulated), task switching, and inhibitory control.

These functions are studied with specific testing paradigms. One example is the Stroop test – in this test the subject is shown cards that have the names of colors spelled out in ink of a different color (so the word “red” may appear in blue ink). The task is to name the color of the ink, not the word. This involves inhibiting the reading of the word, which requires inhibitory control. This is a surprisingly difficult task and always causes some slowing. The question is, how much does it slow down an individual, and how many mistakes do they make? Someone with executive function impairment has difficulty stopping themselves from reading the words, and trying to do so causes extreme slowing.

Another example is task switching, give a single task with alternating rules, or switching the rules in the middle of a task. An example of the latter would be trail making in which you have a page with letters and numbers, and you have to connect them with a single line. The task is to go from 1 to a to 2 to b, etc. Switching from numbers to letters requires executive function. Or you can have cards with different features, like different numbers of different objects of different colors. The subject may have to sort the cards by color, then are told to switch to sorting by object type. Those with executive function disorder will continue to follow the original rules, making more mistakes after the rule change.

The subject in this study was given extensive testing of this type, collectively called neuropsychological testing. She demonstrated profound deficits in the executive function domain across the board, and these deficits were not explained by other deficits, such as language or memory. The authors conclude that their metaanalysis of prior studies points to the IFJ as a key region for executive function, and that this new lesion study confirms that the IFJ has a causational relationship to executive function.

This does not mean that the IFJ is the one location for all executive function, just that it is a critical junction for it. This gets back to the old “modules vs networks” discussion – is the brain comprised mainly of modules with specific functions or networks with specific functions. The answer is – yes. The brain consists of networks of modules. Modules seem to do a specific type of processing, but can serve different functions when networking with different other brain regions. The IFJ, therefore, is likely a module that performs a critical type of processing and networks with other regions involved in executive function. Take out the IFJ on both sides and the executive function networks are largely broken.

The authors also hope to apply their method of metaanalysis to other brain regions to help further the task of mapping the more esoteric parts of the brain.

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