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 ...

OCD - Why Science Has Rendered Antipsychiatry Irrelevant

Antipsychiatry dogma contends that because science has failed to show any link between underlying brain dysfunction and psychiatric symptoms that mental illness is a myth and psychiatry is a fraud.

Antipsychiatrists have been getting away with this for years. Mental illness, after all, is highly complex, which doesn't lend itself to gift-wrapped causes and effects the way a simpler brain illness - say Huntington's - does.

Wait - I take that back. Last night, at my local NAMI here in San Diego, I heard Neal Swerdlow MD, PhD of UCSD talk about obsessive-compulsive disorder (OCD).

OCD is a failure in the brain to screen out certain thoughts. People with OCD, for instance, may drive themselves (and others) crazy obsessing over whether one's pet poodle has succeeded in picking three sets of door locks and is now being carved up for lab experiments.

The thought is ridiculous, but the consequence is deadly serious. Literally, the victim cannot stop the thought. The thought takes over to the point where the victim may feel compelled to leave work and drive home. Should that happen enough times, the victim becomes both unemployable and a social leper.

Dr Swerdlow opened with a short clip of a Huntington's patient. Individuals with Huntington's experience uncontrollable movement. The brain, literally, fails to screen out certain movement impulses. The area of the brain responsible, the cingulate, is the same area of the brain most implicated in OCD.

With Huntington's, of course, the symptoms are obvious (uncontrollable movements). Of course something mechanical in the brain has to be wrong. Uncontrollable thoughts and inner torment, on the other hand, are invisible. Of course psychiatry is at fault for creating a mythical illness out of thin air in order that Big Pharma can sell more drugs.

Forget about the victim.

The problem with OCD, Dr Swerdlow explained, lies in "gating." I have discussed gating on this blog numerous times in relation to schizophrenia. The victim is overwhelmed - too much sensory input, too much thought, too much emotion. The brain can't filter out the irrelevant stuff, cannot focus, cannot function, cannot cope.

In a normal brain, on a cellular level, the neuron essentially makes a "yes-no"decision in response to a neurotransmitter message from another neuron. Air conditioner noise? "No." Not relevant. Tune it out. Instructions from your doctor? "Yes." Very relevant. Pay attention.

On a systems level, the thinking and reacting areas of the brain - and areas in between - are organized around processing and prioritizing all the "incoming." These circuits are referred to as "cortico-striatal-thalamic-cortical loops" and similar-sounding names. Self-correcting feedback is both top-down and bottom up and exists in interdependent relationships with parallel loops.

Neurons that specialize in gating tend to exist in the mid-brain regions, such as the cingulate. In a famous set of experiments performed two decades or so ago, OCD subjects (ones obsessed with cleanliness) shared a brain scan machine with a "dirty" sweat sock. Their respective brain loops lit up like a Christmas tree (much like the image on the right). When exposed to a "clean" sock, their brains quieted down (much like the image on the left).

We know that with Huntington's the neurons in the cingulate die off. There is no gating function to regulate excess dopamine signaling related to movement, and the brain fails to compensate by recruiting gating neurons from other areas of the brain.

Similarly, with OCD, we know that the cingulate is operating below capacity, with about 15 percent less neurons. In some cases, serotonin antidepressants may enhance cingulate function. Or the brain may be successful in recruiting gating neurons from other areas of the brain. This is why CBT and other talking therapies can work so well for OCD and other mental illnesses - often, we can literally train our brains to lay down new roadwork.

Because of our knowledge of cause and effect and our ability to pinpoint an exact location, brain surgery to treat OCD is not only feasible, it is being performed, albeit very rarely and only as a last resort for severe cases on treatment-refractory individuals. Capsulotomies and cingulotomies essentially compensate for lack of gating by surgically turning off the flow of certain brain circuits.

In February this year, the FDA approved deep brain stimulation (DBS) for OCD. DBS has a history of use in Parkinson's and is showing promise for depression. A lead is inserted near the affected brain area. Electrical pulses travel up wiring from a pacemaker device implanted below the brain. For OCD, the signaling from the lead has the effect of interrupting the thoughts that the cingulate is supposed to be screening out.

Brain surgery for psychiatric illness, of course, raises a whole host of ethical and other issues, and you can expect antipsychiatry to add its unmodulated voice to this conversation. But in the context of this blog piece, think of surgery for OCD as the icing on the cake.

Mental illness is indeed, unequivocally real. We can point to the brain systems. We can link breakdowns in these systems to behavior. We have treatments based on this knowledge.

In the face of such overwhelming evidence, why would antipsychiatry think otherwise? Hmm ... defective thought gating?