>> Frontal Lobe Function

	Interview with Robert T. Knight, University of California, Berkeley From Studying The Mind, VHS © 2003, W. W. Norton

What are some of the main functional distinctions between different subregions of the prefrontal cortex?

Well, the frontal lobe is a big part of the cortical mantle—it’s a very big territory—so when you try to subdivide it you have to be respectful of the fact that you're probably encompassing multiple regions.

We can break the frontal lobe down into three broad regions. The first is the area that was reported by Harlow in the terms of Phinneas Gage back in 1848, the orbital frontal cortex. It sits above the orbits of the eye and is related to your control over your social behavior and your emotional world and emotional interactions. The other broad area is the lateral frontal cortex, which is most involved in executive control of cognitive activities. The third area is the medial part of the frontal lobe, which is between the hemispheres. In general a large part of this cortex, including the areas such as supplementary motor cortex and parts of the premotor cortex, is related more to motor planning, motor control, and motor sequencing.

If you now step back and use those three broad divisions, the neurological and neurosurgical data that's been acquired over many years by many investigators fits with that split. So for instance, if you take patients who've had damage to their orbital frontal cortex, they will score normally in tests that assess cognitive functions such as working memory, general intelligence or mental flexibility. But if you look at things that assess their ability to socially interact properly–such as their ability to read other people's feelings or modulate their own emotional state—they have a lot of problems. This is a serious health problem around the world, particularly since the advent of the automobile, because that part of your frontal lobe is very susceptible to damage from traumatic head injury. The orbital frontal cortex is likely to get bruised, contused like you had a bruise on your arm, often with permanent damage. For instance, in the United States there probably were about 100,000 cases last year who damaged that area.

Are there differences in function between the left and right hemispheres of the frontal lobe?

If you look at the lateral frontal cortex, the first big laterality in that part of the brain is the fact that about 98 percent of right-handed people have language in their left hemisphere. The next big lateralization is probably related to attention capacity. Whereas the left hemisphere has subsumed language function, there is a tendency for the right hemisphere to be more involved in attention control: how you allocate your mind's eye to this, that, or the other thing. That lateralization is not as strong as the lateralization for language, but it is certainly there in humans, and interestingly, if you measured the frontal lobes of babies, you'd actually see that the right frontal lobe is slightly bigger then the left, so it's probably hard-wired just like some of language is hard-wired to the left hemisphere. Once you get past those two broad separations, language and attention, it gets a little bit murky. And it probably gets murky because there's redundant function between areas of your left and right frontal cortex.

Now, in terms of the orbital frontal cortex we know a whole lot less in terms of lateralization and whether the left and the right frontal cortex are asymmetrically organized. There's some information from gunshot wounds–penetrating gunshot wounds to the frontal lobe from Vietnam vets. And there’s some information from the Iowa group which has done a lot of the really excellent work on orbital frontal function indicating some degree of laterality in the orbital frontal cortex in the affective domain. So that if you lesion the left orbital frontal cortex you're more likely to get a depressive type, anxious depressive response in the patient. If you lesion the right orbital frontal cortex, you're more likely to get a character deficit, a personality disorder. That may be a bit overstated but there probably is some asymmetry. It's an area where there's much less research than has been done in lateral prefrontal cortex function.

How do changes in the frontal lobes over the course of a lifetime correspond to behavior?

Well, the issue of the frontal lobe in development, both the development of function and then the attempt to maintain it and then probably the slight dwindling of it, is really a very, very interesting area. It again brings out this idea that longitudinal research gives you big insights into how the brain functions. One important thing that's happened is the ability to scan and to get developmental information on children. We know for instance, that there are clear bursts of development in the frontal lobe with normal development, including things that we have gleaned from the animal literature that probably are related to neural pruning. The thickness of the frontal lobe actually decreases during certain stages of the development, with probably one big window between ages of four and seven. Another window occurs in the early teenage period, and associated with this decrease in the thickness of the frontal lobe is an increase in the white matter conductivity of the frontal lobe. So the idea is that you're getting competition for neuronal conductivity, some neurons win, and the ones that win have better and more robust connections to the other parts of the brain—that would be the simple interpretation. And some of these changes appear to correlate with certain classic developmental phases that have been developed or studied in the cognitive development literature, Piagetan concepts and things like that.

In terms of late life, one thing that we know is that the idea that the brain is static is probably not true; it's constantly growing, reshaping. There is evidence in the literature that with aging, when you get over the age of about 70, there are decreases in the number of cells in the frontal cortex. Yet, at the same time, the cells that remain seem to try harder. So when a young person first learns a task they show lots of frontal lobe activity, but once the task becomes automatic, frontal lobe activity drops. But when an older person performs that same task, there's evidence of more frontal lobe activation. And my lab has found that in several different cognitive tasks, using electrophysiological measures where we see increased voltage from frontal electrode sites, and functional brain imaging, we see more frontal activation in older adults. I'd say that this is a wide open area for research, and the best is probably yet to come. And I would say that the best is probably also going to include neuropharmacology at some point. That's one of the missing puzzle pieces that we're not interleaving into our cognitive neuroscience research enough—the effects of drug manipulations on various physiological and behavioral measures.