Monday, November 30, 2009

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 ...


megs said...

This was on PBS last night. Facinating.

"Brain Fitness Frontiers"

Do a search to see if it's on again.

Willa Goodfellow said...

I keep pondering that same NYT article. But I am not convinced of "the merit in zeroing in on specific strategic targets." As you note, mental illness is experienced in a highly complex and interconnected system. These single shot interventions have NOT been that successful, if you are measuring long term improvement in the patient's total quality of life. Destroying part of the ACC, the ACC for heaven's sake, is bound to have wide ranging effects, not all of them intended, not withstanding the 60% success rate at improving one particular OCD score.

Some of my musings:

It didn't surprise me that it was a Swedish institute that reported finding "apathy and poor self-control for years after..." these procedures. I have come to expect that US research articles will fail to report quality of life issues or long term results.

I have been thinking about the implications of homeostasis and neuroplasticity, which work both for and against the single target interventions, such as the current crop of antidepressants. Prozac increases plasticity, so that the brain actually repairs itself. But then homeostasis takes over, and Prozac "poops out." What's that about?

I wonder if given enough time, the ACC might repair itself after this brain insult, like some stroke victims' brains. The hope might be that the patient regains self-control functions, and not the fixation functions. But who can predict?

Where was I reading that "The normal brain maintains homeostasis" but that things go out of whack in less normal brains? It seems to me that each brain maintains homeostasis with reference to itself. Which is why it's just so damn hard for us to get better. The brain keeps trying to return to its original whacked out state.

And which is why your insistence on a multi-pronged approach is so important: meds, therapy, support and life-style. It takes a lot of work to change these neural pathways, and keep them changed. No, I am sorry, my friend, for your friend, that you can't just open the hood and fix it.

Which reminds me... no, I will hold that thought for my own blog!

And then what about the complexities of the ethical issues? Do people who are truly desperate have the right to desperate measures that seem stupid to others who are not so desperate? Maybe. I guess people have a right to cut, if that's the only way they can experience a break in their pain. I sure have considered it. On the other hand, does the surgeon ("first do no harm") have the right to do the cutting?

This sure is fun. I hope we keep meeting like this! -- Willa

John McManamy said...

Hi, Willa. Fascinating points. Let's see if I can address them one by one:

1. DBS would be an improvement on the older gamma knife surgeries, as no lesions are done and nothing is destroyed, and the surgery is reversible. Nevertheless, DBS is experimental, as a last resort.

2. Like you said, research studies are suspect, even those executed in good faith. It's always good to have an outside source checking the same data. In the US, with mood disorders, the atmosphere is far too clubby, insiders refereeing fellow insiders. Maybe that's why we need outsiders like the Swedes to keep us honest.

3. Re homeostasis taking over: Bingo! In an earlier blog I reported on a talk by Robert Cloninger, who argued psych treatment is all about getting us back to our "Stable State A" when we really need to find a new "Stable State B," which tends to involve us going through a trail of tears.

4. I hadn't considered the above in terms of Prozac poop-out, but this explains everything. Homeostasis presumes everything is okay, but your saying what if our baseline homeostasis is messed up? Then, no matter what, we're pushing it uphill, which explains why we get frustrated.

5. But my guess is that those who have a healthy baseline homeostasis have a good prognosis. I've seen this in support groups - high functioning individuals who have a setback, get back to feeling better, then are back to work, and you never see them again.

6. Re desperate measures and ethical issues - Yep, I would say the desperate patients have the right to choose. Otherwise, we are condemning them to lives of unmitigated desperation.

7. One point I missed: Yes, a select intervention at a specific target in what appears to be a total system breakdown is indeed worth questioning. Last year, I heard Helen Mayberg explain at a conference that one reason Brodmann area 25 was chosen was because of all the connections to many other brain regions. My understanding is that the ACC is like a bottleneck or a hub, though this is an oversimplification.

Pleasure meeting up like this. Let's do it again. :)