The Cortical Factor

I just finished viewing Lecture 18 in a 25-part video series by Robert Sapolsky of Stanford. Dr Sapolsky is to human behavior what Carl Sagan was to astronomy. There is no one better at explaining the topic to the general public than this man. It’s not even close. I first stumbled into Sapolsky in early 2003 and I’ve been something of a groupie ever since.

The video series I am watching is an actual undergraduate course in human behavior. I was looking forward to blogging on various highlights once I’d completed the series, but Lecture 18 represents the best exposition I’ve ever come across concerning how different parts of the brain talk to each other, so let’s get straight into it ...

Lower mammals have an olfactory hotline to the amygdala, the part of the brain in the limbic system that mediates fear and arousal and kickstarts fight or flight. Furry creatures are literally primed to react when they smell something funny. Mammalian limbic systems are standard issue for humans, except ours are wired to respond mainly to visual stimuli.

Ordinarily, the cortical areas of the brain are responsible for visual processing and sending info to the amygdala, but we don’t always have time to wait. There is a short-cut in the brain through the lateral geniculate (LG). The trade-off is that this information is less accurate. We’re more likely to make mistakes. As Dr Sapolsky explains, there is now strong evidence that this pathway is hyper-excitable in those with PTSD.

According to Dr Sapolsky, the frontal cortex should be regarded as part of the limbic system. Its role, essentially, “is getting you to do the harder thing when it’s the right thing to do,” as in behaving appropriately. Below is a screenshot of Dr Sapolsky illustrating in a very simple way two contrasting neural circuits. The circuit on the left has more axonal inputs going into its target neuron than the right. This makes it easier to activate this particular neural pathway.

But what if this pathway represents doing the wrong thing? To offset this, the frontal cortex essentially massages both circuits, inhibiting the left and biasing (rather than causing) excitation in the right. To accomplish enhanced excitation, the frontal cortex gets a boost from dopamine via projections shooting out of the ventral tegmental area and nucleus accumbens. Dopamine acts as the fuel in goal-directed behavior.

One illustration of doing the harder thing would involve reciting the months backward. The frontal cortex needs to be on its toes in processing the task, but those with damage in this area may have trouble over-riding the more habitual forward-recitation response.

Over time, learned behavior becomes automatic and gets stored elsewhere in the brain. Thus, someone with Alzheimer’s may not know what decade it is but still knows how to knit. This brings us to the famous example of Phineas Gage.

According to Dr Sapolsky, they take away your neurobiology license if you fail to mention this guy. In 1848, while tamping down blasting power during the construction of a railroad line, the powder exploded, sending the tamping rod through the side of Gage’s skull and out the top, taking out his left eye and emptying out most of his frontal cortex. (See top left image.) Amazingly, because the rod cauterized his blood vessels, Gage was able to get up and walk a mile-and-a-half to the nearest doctor.

Gage achieved a partial recovery, but experienced major problems controlling his behavior, leading his physician to conclude that this part of the brain “reins in our animal energies.” Interestingly enough, about a quarter of those on death row have a history of concussive trauma to the head.

Doing the harder and right thing tends to involve delaying gratification and not giving into temptation. Consider the m&m test. You hold five morsels in one hand and one in the other. The rule is you reach for five you get one, and vice-versa. People with cognitive impairments, even knowing the rule, may still reach for the five - they just can’t help it.

Lack of cortical input explains why our dreams make no sense. In REM sleep our frontal cortices are at their least active. That’s why in our dreams we do all sorts of things we would never want to do in real life. Thank heaven we're merely dreaming. Imagine, if we did some of that stuff in while awake. Oops - sometimes we mess up, and we find ourselves living with the consequences.

Much more to come ...

Rerun: Me, Captain Ahab, and the Anterior Cingulate Cortex

 From last last November ...

As I mentioned in a recent blog, someone very close to me is in a psych unit right now. In the old days, they simply would have referred to his condition as a nervous break-down. They got that right. His brain is indeed broken. But which part of the brain is broken? That’s what I want to know.

As it turned out, I couldn’t get anterior cingulate cortex (ACC) out of my head. It’s as if my own ACC couldn’t filter out my own speculative obsessions about this individual’s ACC. Screw this psychiatry bullshit, I wanted to scream. Open up the hood, poke around inside, find out what’s wrong, and fix the goddamn thing.

So here I am, late Thanksgiving evening, burping up my afternoon prandial over-indulgences, when I come across a New York Times front page story on psychiatric brain surgery. I’ve previously written stories on this. Guess which part of the brain we’re talking about?

Now my ACC is lighting up like a Christmas tree.

I wake up the next morning only to discover that my fellow blogger Willa Goodfellow has just published a piece on Prozac Monologues, entitled: Thanksgiving and the Anterior Cingulate Cortex.

That’s not the end of the story. Last August, I cited Willa as one of my top six bloggers. In my review, I said: “Let's put it this way: Until I encountered Prozac Monologues, I thought I was the only one who had ever mentioned, anterior cingulate, in a blog.”

Now my ACC is in Captain Ahab Moby Dick mode:

All that most maddens and torments; all that stirs up the lees of things; all truth with malice in it; all that cracks the sinews and cakes the brain; all the subtle demonisms of life and thought ...

Okay, some basics:

The ACC is part of the cingulate cortex, which snakes beneath the brain’s outer cortices. The region has more specialized functions across different areas than a world religion has schisms and heresies and sects, but the simple version is that the ACC plays a major role in modulating the two-way traffic between the brain’s limbic and cortical regions. It is also wired into other circuits known as "cortico-striatal-thalamic-cortical loops," which has to do with filtering out irrelevant thoughts and emotions and sensory inputs, thus allowing us to focus on the relevant ones.

Significantly, anterior cingulate malfunction has been implicated in all manner of mental illnesses, from depression and bipolar to ADD to OCD to schizophrenia. On a most elemental level, when the brain is unable to filter out the overload, the “I” that is supposed to be in charge is overwhelmed and can’t cope. For instance, in OCD the brain literally locks onto one thought and can’t let it go.

So here was the person close to me, obsessed on fearful end-of-the-world thoughts, depressively ruminating to the point of psychosis or near psychosis, and totally lacking the ability to make a rational assessment of his present and plan his future. It had to be the ACC.

Ha! If only life were so simple. In a review article in “Psychiatry,” Dhwani Shah MD of the University of Pennsylvania et al point out that “psychiatric syndromes cannot be localized in a single, so-called ‘abnormal’ brain region.” Rather, “mood and anxiety disorders involve immensely complex interconnected systems or networks of organization within the brain.”

Take my depression - please! The authors are quick to point out that the causes of depression are complex and only partly understood. Nevertheless, a picture is beginning to emerge of interconnecting brain systems in a state of stress-induced collapse. The technical term is allostatic overload, which is what happens when a highly complex and self-regulating system such as the brain fails to maintain homeostasis (equilibrium).

As Shah et al describe it, the brain circuitry involved in depression is grouped into three main components: cortical (appearing to give rise to the psychomotor and cognitive aspects of depression), subcortical (involving the affective aspect of depression, including anhedonia and sadness), and modulatory (regulating two-way cortical-limbic traffic, including stress and hormonal pathways).

Okay, here’s where it gets interesting. Brain systems may be infinitely and infernally complex, but we are beginning to see the merit in zeroing in on specific strategic targets (or “nodes”) in experimental surgical interventions. Significantly, for OCD and depression, that target is the ACC (more specifically for depression, the subgenual anterior cingulate corresponding to Brodmann area 25).

Lest we create a false impression, psychosurgery is almost certainly not the future of psychiatry. But it is simply impossible to imagine a different tomorrow without coming to grips with how a surgical technique of last resort is changing how we look at mental illness.

Trust me, things are changing.

To be continued ...

Me, Captain Ahab, and the Anterior Cingulate Cortex

As I mentioned in a recent blog, someone very close to me is in a psych unit right now. In the old days, they simply would have referred to his condition as a nervous break-down. They got that right. His brain is indeed broken. But which part of the brain is broken? That’s what I want to know.

As it turned out, I couldn’t get anterior cingulate cortex (ACC) out of my head. It’s as if my own ACC couldn’t filter out my own speculative obsessions about this individual’s ACC. Screw this psychiatry bullshit, I wanted to scream. Open up the hood, poke around inside, find out what’s wrong, and fix the goddamn thing.

So here I am, late Thanksgiving evening, burping up my afternoon prandial over-indulgences, when I come across a New York Times front page story on psychiatric brain surgery. I’ve previously written stories on this. Guess which part of the brain we’re talking about?

Now my ACC is lighting up like a Christmas tree.

I wake up the next morning only to discover that my fellow blogger Willa Goodfellow has just published a piece on Prozac Monologues, entitled: Thanksgiving and the Anterior Cingulate Cortex.

That’s not the end of the story. Last August, I cited Willa as one of my top six bloggers. In my review, I said: “Let's put it this way: Until I encountered Prozac Monologues, I thought I was the only one who had ever mentioned, anterior cingulate, in a blog.”

Now my ACC is in Captain Ahab Moby Dick mode:

All that most maddens and torments; all that stirs up the lees of things; all truth with malice in it; all that cracks the sinews and cakes the brain; all the subtle demonisms of life and thought ...

Okay, some basics:

The ACC is part of the cingulate cortex, which snakes beneath the brain’s outer cortices. The region has more specialized functions across different areas than a world religion has schisms and heresies and sects, but the simple version is that the ACC plays a major role in modulating the two-way traffic between the brain’s limbic and cortical regions. It is also wired into other circuits known as "cortico-striatal-thalamic-cortical loops," which has to do with filtering out irrelevant thoughts and emotions and sensory inputs, thus allowing us to focus on the relevant ones.

Significantly, anterior cingulate malfunction has been implicated in all manner of mental illnesses, from depression and bipolar to ADD to OCD to schizophrenia. On a most elemental level, when the brain is unable to filter out the overload, the “I” that is supposed to be in charge is overwhelmed and can’t cope. For instance, in OCD the brain literally locks onto one thought and can’t let it go.

So here was the person close to me, obsessed on fearful end-of-the-world thoughts, depressively ruminating to the point of psychosis or near psychosis, and totally lacking the ability to make a rational assessment of his present and plan his future. It had to be the ACC.

Ha! If only life were so simple. In a review article in “Psychiatry,” Dhwani Shah MD of the University of Pennsylvania et al point out that “psychiatric syndromes cannot be localized in a single, so-called ‘abnormal’ brain region.” Rather, “mood and anxiety disorders involve immensely complex interconnected systems or networks of organization within the brain.”

Take my depression - please! The authors are quick to point out that the causes of depression are complex and only partly understood. Nevertheless, a picture is beginning to emerge of interconnecting brain systems in a state of stress-induced collapse. The technical term is allostatic overload, which is what happens when a highly complex and self-regulating system such as the brain fails to maintain homeostasis (equilibrium).

As Shah et al describe it, the brain circuitry involved in depression is grouped into three main components: cortical (appearing to give rise to the psychomotor and cognitive aspects of depression), subcortical (involving the affective aspect of depression, including anhedonia and sadness), and modulatory (regulating two-way cortical-limbic traffic, including stress and hormonal pathways).

Okay, here’s where it gets interesting. Brain systems may be infinitely and infernally complex, but we are beginning to see the merit in zeroing in on specific strategic targets (or “nodes”) in experimental surgical interventions. Significantly, for OCD and depression, that target is the ACC (more specifically for depression, the subgenual anterior cingulate corresponding to Brodmann area 25).

Lest we create a false impression, psychosurgery is almost certainly not the future of psychiatry. But it is simply impossible to imagine a different tomorrow without coming to grips with how a surgical technique of last resort is changing how we look at mental illness.

Trust me, things are changing.

To be continued ...