Once way to interpret this result is that some patients with major depression have overactive connectivity between that part of the brain that generates the emotion of depression and the part of the brain involved in cognition and concentration. In these patients, therefore, their depressed mood has a significant effect on their thoughts and ability to concentrate. ECT appears to reduce this hyperconnectivity, which should significantly reduce the symptoms of depression.
Much of the time hyper/hypo connectivity findings invoke the concept of a ‘hardwired’ brain differences; here is seems to mean something different, at least my assumption is that we don’t think that ECT is physically changing the structural components of the brain usually discussed within a context of brain connectivity. (?)
Can you, or anyone, help me with a little insight onto this?
the “hardware” analogy is problematic, because the brain is really wetware – a dynamic combination of hardware and software.
It is possible that there are more and more robust connections, and it is possible that the number of connections are within the normal range but their activity is simply increased, or both may be true. The fMRI findings just show increased activity, and don’t really distinguish underlying cause.
ECT decreases the activity in that region (and elsewhere, but may have a disproportionate effect on hyperactive regions), but probably does not change the underlying hardwiring (at least not right away). Perhaps it is just a compensation for the dysfunctional wriing, or perhaps it resets the increased activity. These are all good questions to explore.
Because the brain is wetware, function alters wiring, so that is another variable to consider
Its encouraging to hear that there may be a more targeted research. I have major depression and do not respond to meds. I have an overwhelming fear of ECT. But as I get more desperate, it becomes more acceptable.
Its a hard thing to do – choose between losing everything in your life because you are no longer able to function enough to support daily life, or have ECT and lose portions of yourself, however temporarily, as result.
I wish there were a less terrifying (to me) option.
Is it possible that major depression has anything to do with hyper connected multi-sensory neurons,so that the experience is immersive,exponential and “super present”.Also is there a possibility that depression is prone to a kind of kindling.Does one depressive bout lead to others with greater frequency and lead to a cycle of feedback,difficult to interrupt.
“For example, implantable computer chips that alter brain activity.”
I have to point out though, that I’m not too sure about the moral implication of this. You’re sad? Just zap this connection. Worried? Zap that one and you’re fine. My worry is that, once you have such an implant, it will become too convenient for you to just manipulate the brain out of uncomfortable thoughts. Thus keeping you from living them out in art, creativity or, if needed, revolution.
“The major side effect is memory loss, which can be significant.”
When I was a mental health nurse in Australia in the 1980s and early 90s, the procedure was always performed unilaterally (ie small pads about three inches apart, applied to one side of ther head, around the temporal lobe), subsequent to muscle relaxants and a general anaesthetic.
At that time the thinking was that, in unilateral ECT, the electrical impulse skipped across the surface of the brain, just sufficient to induce a “quasi epileptic” seizure, ie involving the brain itself releasing a flood of neural activity.
The impulse itself was fairly unremarkable (I’m not an electrician), not a massive jolt when applied to my hand – something like a TENS machine, enough to cause a muscle to spasm mildly when activated.
In contrast, a bi-lateral ECT was thought to send electricity through the brain, causing more confusion and memory loss etc.
Other factors that were thought to be at play included the effect of the the general anaesthetic itself which, even absent ECT, results in short tem memory loss; the effects of the underlying depression on memory; and the results of the posit-ictal phase of the seizure itself.
Not saying any of it’s right or wrong, but more to illustrate that, even in those dark days, minds were pondering it.
The level of depression that warrants ECT is far more extreme than simply being sad. Assuming brain activity altering computer chips are made that are shown to work better and with fewer side effects than ECT, I would imagine that, like ECT, they would only be used in the most extreme cases after all other less invasive therapies have failed to show any meaningful results.
@DevoutCatalyst: I’ve been working in ECT/TMS studies for the past year and I’m fairly certain that the evidence demonstrates a substantially lower effect size for TMS as compared to ECT. TMS is efficacious in 9-14% of the population (correcting for placebo) as opposed to RUL ECT, which has been shown to alleviate vegetative symptoms of MDD in over 70% of patients
@HHC: ECT has not been demonstrated to cause any gross neuroanatomical lesions in human or primate models. Although sympathetic outflow may cause some cardiac changes, modern drugs eliminate any risk of cardiac irregularities/damage resulting from ECT.
@DarwynJackson: ECT does not cause gross lesions, but does it create micro-lesions? What if a patient has an untreated or diagnosed heart problem prior to ECT, can the he/she have a significant heart problem after ECT?
I have read through your blog but have been unable to find where you explain how ECT works. The nearest I could get is;
‘It has not been know exactly how ECT works. It is known that ECT reduces brain activity and raises seizure threshold (makes it less likely to have a seizure). This implies that overall neuronal activity is reduced, so perhaps ECT is inhibiting overactivity in a part of the brain that is driving the depression.’
Or perhaps not. If ECT does reduce brain activity then maybe it implies that it is causing damage to the brain. Are there not other actions that can be taken to reduce brain activity? A hard blow to the head with a baseball bat? Perhaps this could also inhibit the alleged ‘overactivity’?
My grandfather got ECT some years ago.
He suggested that I never, under any circumstance get the treatment or allow someone I cared for to get it.
This experience no doubt clouds my judgement on this– but I have looked into a number of times and–
Isn’t it true that the studies that are placebo controlled show no efficacy for this procedure?
These placebo controlled studies show minimal support for effectiveness with either depression or ‘schizophrenia’ during the course of treatment (i.e., only for some patients, on some measures, sometimes perceived only by psychiatrists but not by other raters), and no evidence, for either diagnostic group, of any benefits beyond the treatment period. There are no placebo-controlled studies evaluating the hypothesis that ECT prevents suicide, and no robust evidence from other kinds of studies to support the hypothesis.
Given the strong evidence (summarised here) of persistent and, for some, permanent brain dysfunction, primarily evidenced in the form of retrograde and anterograde amnesia, and the evidence of a slight but significant increased risk of death, the cost-benefit analysis for ECT is so poor that its use cannot be scientifically justified.
@HCC: Electroconvulsive Therapy has not been shown to cause gross of microscopic lesions in neural tissues. (Sorry for not clarifying that earlier.) ECT does require some cardiological clearance for patients recovering from recent myocardial infarction, but there are no absolute contraindications for the use of ECT. In some retrospective studies looking at 74,000 ECTs performed in VA hospitals over the past 10 years, there were no incidences of death (cardiac or other cause) related to ECT. It has not been shown to cause any form of cardiac damage since the introduction of modern cardiac drugs (mostly labetalol/nifedipine) used during the procedure.
It has been regarded as the safest procedure currently performed under general anesthesia & is considered the most highly efficacious treatment of mood disorders in the history of Psychiatry. It has persisted for over 70 years, despite the wide availability of psychotropic medications, because it is so dramatically effective for treatment resistant depression/ acute suicidality.
‘because it is so dramatically effective for treatment resistant depression/ acute suicidality.’
There are thousands of people writing of their experiences on the internet who would vehemently disagree with you. I personally know of two people who have felt this treatment has ruined their memories and life, a view which is denied by their psychiatrist that performed the procedure. From where do you obtain such confidence in your assertion?
@DarwynJackson: Labetalol was FDA approved May 24, 1985; Nifedipine was FDA approved September 6, 1989. Prior to the FDA approval of these drugs, were other drugs used in conjunction with ECT? In the early years of ECT use in 1940s, was there any drugs or protocols for use other than levels of shock treatment?
Steven, I am interested in your use of the word ‘wetware’. I cannot find any reference outside of the field of science fiction. Apart from on wiki stating that wetware is a computer comprised of organic materials like the brain. Thanks.
For a clinical definition of depression, major depressive episodes, and other mood disorders see the DSM-IV.
It is well known that ECT is highly invasive and can have significant side effects which is why it’s only recommended as a treatment of last resort. Think chronically depressed and suicidal patients for whom all other treatment modalities (pharm, talk therapy, etc) have been exhausted without showing any meaningful benefits.
And what about the thousands of people writing of their experiences on the internet who would vehemently disagree with you? I personally know of two people who have felt this treatment has had little effect on their memories and saved their lives, a view which is supported by their psychiatrist that performed the procedure…
Do you really want to play the my anecdote is better than your’s game??
@Dirk Steele: “Well that [anecdote] is all psychiatry consists of isn’t it?” I would have to say that this is a rather dated view of psychiatry. Current research in neurostimulation psychiatry, as well as psychopharmacology, are certainly rooted in substantially more than anecdotes. Several psychometric tests, psychiatric interviews, fMRIs, and observations of behavior are utilized to quantify efficacy of modern treatments. I think your perception of psychiatric medicine may be predicated on an earlier psychoanalytic approach to mental health.
To clarify- I’m not asserting hat Psychiatry is perfect & without need for improvement. Rather, I think that meaningful critiques of modern medical practice cannot be predicated on antiquated views of mental health from films like One Flew Over the Cuckoo’s Nest. Although ECT has historically had significant side effects from amnesia, to fractures & even death, modern practices have reduced or eliminated most of these concerns. Right Unilateral, Ultra-brief Pulse ECT coupled with anesthesia & paralytics is a very different procedure from what you may be envisioning.
‘Several psychometric tests, psychiatric interviews, fMRIs, and observations of behavior are utilized to quantify efficacy of modern treatments.’
Are you refering to tests such as the Ham-D or Montgomery Asberg Depression Rating Scale (which were created in the 1960s). In my mind these checklists are little more than anecdotal and have little scientific credence.
I must admit my views on fMRIs have changed since I started reading Neuroskeptic’s blog.
The TED talk by Sherwin Nuland tells of his escape from depression, caused by a disasterous marriage, by the use of ECT, narrowly escaping a lobotomy in the process. And then discovering the efficacy of using the word ‘Basingstoke’. (I do not want to use bad language here). I myself chose a different path!
@Dirk: “Are the other tests scientific or anecdotal?”- I’m not sure I understand the question. Some measures, such as patient’s reports, are useful, but subjective as compared with standard tests of memory or cognition. I’m not sure any measures are “anecdotal.”
“I even read the wikipedia article. I wondered what scientific definition Steven was using. Perhaps you could help?”
Read it again. The part that doesn’t say that ‘wetware is a computer comprised of organic materials like the brain.’
@Dirk: Ah, I’m sorry I misunderstood your query. When you asked “Are the other tests scientific or anecdotal?” I failed to interpret that as “…if you could supply the specific detail of those tests so I could read them.”
If you’re asking specifically about the testing of autobiographical memory, the most common test is called AMI (autobiographical memory interview). There are too many measures of various subsets of memory to include an exhaustive list here.
If you are referring for the metrics to quantify the symptoms of MDD, the most common is the HAM-D.
Again the inclusion of every psychometric test currently used isn’t possible in the margins of this brief post, but most studies explain the specific metric used in the ‘methods’ section.
Hope that is at least somewhat helpful to get you started.
‘Perhaps it was the reference to science fiction?’
Well I am aware of the term being used by Orson Scott Card, Rudy Ruckner, Peter Hamilton, William Gibson, Neal Stephenson, and many other science fiction authors. Even Timothy Leary has got into the act. According to wiki, Technical usage…
International standards have been completed for telebiometrics that include  in their technical terminology. Wetware refers to “that aspect of any living system that can be treated as an information system”.
 Computer jargon
The term Wetware is used in conversation, notably USENET and in hacker culture. Also known as liveware, meatware or the abbreviation PEBKAC (Problem Exists Between Keyboard And Chair), it is a term generally used to refer to a person operating a computer. It refers to human beings (programmers, operators, administrators) attached to a computer system. In this context the term is often intended for humorous effect; for example, in the frequently wry humor of technical support staff, a wetware-related problem is a euphemism for user error.
 Scholarly usage
Theorist[clarification needed] Richard Doyle uses the plural, “wetwares”  to describe the shifting experience and nature of embodiment in the context of proliferating information technologies.
I was asking for a scientific explanation…. or just what Steven meant.
Since you seem to be an expert, perhaps you can enlighten me. Thanks.
@Dirk: Yes, I’m aware. These test are copyrighted & highly protected. The reason I didn’t bother naming the test(s) earlier is because they’re nearly impossible to access outside of a research clinical setting. I don’t own a copy of any of the metrics. Sorry
If it helps, the test is basically a series of questions about life events. The questions are repeated months after the ECT procedure & the answers are compared to see if the recall of autobiographical data is impaired by neuromodulatory interventions. I know that’s a horrible oversimplification, but the details of administering these metrics take years to learn. (Hence the length of a PhD program or medical residency.)
But my endpoint earlier was simply that objective measures of cognitive function and mood do exist. Therefore, there is substantially more to modern Psych than simple anecdotes & subjective patient reports.
‘the details of administering these metrics take years to learn. (Hence the length of a PhD program or medical residency.)’
Are they really so difficult? Can’t you give me a little clue as to the questions asked?
‘But my endpoint earlier was simply that objective measures of cognitive function and mood do exist. Therefore, there is substantially more to modern Psych than simple anecdotes & subjective patient reports.’
I am sure they do exist. I am just trying to find evidence of them. Can you help?
“I was asking for a scientific explanation…. or just what Steven meant.”
Well, the original quote seems pretty clear to me. Perhaps you want an elaboration? In the above comments he wrote: “…because the brain is really wetware – a dynamic combination of hardware and software. ”
I think the point he is making here is that the hardware/software analogy taken from computer technology is problematic when it comes to biological nervous systems, since there is no meaningful distinction between the concepts of hardware and software in this context. In biological systems the hardware and software functions are performed by the same ‘components’ and these components are constantly changing because they are the cells of a living organism.
.Well, the original quote seems pretty clear to me. Perhaps you want an elaboration? In the above comments he wrote: “…because the brain is really wetware – a dynamic combination of hardware and software. ”’
Thanks for the explanation. If I understand you correctly then it means that the software and hardware are the same. There is no meaningful distinction. The hardware is the software. And the software is the hardware. Or a ‘dynamic’ combination? How do you define the word dynamic? Is this science or mere conjecture?
“If I understand you correctly then it means that the software and hardware are the same.”
Well, I think part of the point is that it is problematic to think in terms of hardware and software at all when in comes to the brain. It becomes confusing when you do that because they don’t really apply. (Those terms are already a bit vague in computing, but at least the term has some applicality there)
@Dirk: Can’t give much specifics as the Psychology students usually do the testing for us as their practice, but basically the questions are things like “What did you do on New Years?” “Who was with you?” ect… Changes in the answer 3 mos later indicate a deficit in autobiographical recall.
Understanding not the questions, but rather the fine points of administering the test & scoring are the difficult parts. The metrics are only scientifically validated for a specific type of administration, so variation reduce the validity. The reason things like the DSM-IV are not practical tools for laypersons is that the fine points actually do take years to understand. I’m not sure it’s realistic to fully understand the mechanics of all the testing batteries without some background education in the field.
‘Well, I think part of the point is that it is problematic to think in terms of hardware and software at all when in comes to the brain.’
I agree. But Steven introduced the term ‘wetware’. I was just trying to understand what he meant. Trying to find a valid definition. But thanks for your input. Others have just tried to ridicule me for asking the question.
To understand this you must understand how biology works in time.
There are processes that are regulated at different time intervals. For example, the availability of substrates (eg ATP hormones neuropeptides) that can fall down their energy gradients or inhibit/activate another substrates by getting close and distorting its electron density function. This works on the order of immediate to minutes. Then you have modification of these materials (like a breaking or making of a covalent bond) which works from minutes to hours. Then you have You have synthesis of new ezymes which is at the hours to days range. Finally you can actually grow new membrane (this would be the growth of the connections between neurons). This takes even longer because membranes have metabolically expensive molecules and you need to synthesis a lot of substrates.
You see how there’s a gradient to which the materials of our brain can change? The distinction is arbitrary but not meaningless as you say because there are processes far enough apart that you can safely call them hardware vs software if you’d like. I see it as a false spectrum to say there isn’t. Of course its fuzzy…it’s biology – but you can still use the analogy if you understand that there are overlaps in time intervals.
I must say though that I haven’t given this topic justice because there are other process that are much more interesting to me like feed back loops that can change the brain, ergo, mind. Realize the mind is just an epiphenomenon of these basic processes.
‘The reason things like the DSM-IV are not practical tools for laypersons is that the fine points actually do take years to understand.’
Well I have spent years trying to understand the DSM. (Version II was my initial introduction). I have a degree in maths but maybe because I am so old I must be out of date, and therefore these new ideas must be beyond my comprehension.
I see what you mean. But what I do not understand is how ATP neuropeptides are affected by ECT. How are the substrates measured with accuracy? Are you sure that energy gradients effect our thought processes? I do not think that electron density functions are fully understood. Well not in the scientific literature. Maybe you can point me to the relevant study.
But thanks for your input. I shall certainly follow this up further. Cheers.
@HHC: You’re most welcome! If you are considering any neurostimulation/intervention for yourself or a loved one, I hope you’ll approach the matter with healthy skepticism & not be dismayed by the overabundance of misinformation on this topic.
I’ll tackle this first: “Are you sure that energy gradients effect our thought processes?”
YES! Simple example. When you’re fasting and the rate that you’re fat cells are releasing their fatty acids is greater than the rate that you can use those fats for energy then you generate a molecule called beta-hydroxybutyate. This molecule is used by the brain instead of it’s usual substrate and it gives you euphoria. This whole fasting process works by low amounts of ATP making the potential energy at the beginning high than the end (favorable http://en.wikipedia.org/wiki/Gibbs_free_energy). This is the most basic example I can think of that is within the scope of a blog post.
Now on to your question about electroshock and the brain:
it’s well established that neurons communicate via synapses. The environment at the synapse is modulated by action potentials. Action potentials are cell membrane phenomena that work by separating ions across a membrane. It is the electric field that is developed between these ions that control the firing of the synapse. This was first described by Hodkin-Huxley in the 50′s (http://en.wikipedia.org/wiki/Hodgkin%E2%80%93Huxley_model). This electric field across the membrane can be controlled by simply transcribing channels that have properties that allow ions to move through them (thus changing the electric field). Using electrodes, you’re just manually setting the membrane voltage. Anytime you separate something in biology it requires energy. The brain uses most its energy separating ions. The energy to do this comes from ATP. So that’s how ATP relates.
“I do not think that electron density functions are fully understood.”
If you can describe something in terms of the particles wave distrubution which we know (well described by Erwin Schrodinger a long time ago) then that is the most fundamental way of knowing something in science. Everything else. Newtonian mechanics. Water. Biology. Life. is just epiphenomena.
I don’t know what you mean by: how are the measured with accuracy? They are measured with various techniques depending on the resolution that is required to support or refute a hypothesis. If we’re talking about neuropeptides we’d use an ELISA (Enzyme-linked immunosorbent assay: google it for more info) or if we’re looking for ATP we can stick atoms on the ATP molecule that glow and then count the photons to infer the concentrations (http://pubs.rsc.org/en/Content/ArticleLanding/2012/CC/C2CC17629G).
If you want to anthropomorphize the universe and ask about intent or purpose I would say the purpose is to fit into the limits of the sum probability density functions of energy and because the universe is expanding and energy is ~constant, the energy density of the universe must decrease (entropy). This means that all the biochemistry that shows us pulling away electrons from high energy molecules (eg glucose amino acids) to lower energy substrates (eg CO2, water) and feeling like I am an active interpreter of reality by emergent brain properties fits with ends of the universe – the universe is only ends, no means.
I don’t like using words like intent or purpose because as I have learned from Dr Feynman, you shouldn’t explain things with ideas that are more abstract than the one you’re explaining. Intent and purpose are biological qualities that have bubbled up from the satisfying of these equations and energies of the universe so using those words to describe the universe is like using my brain to assess my brain state – kinda like what steve talked about last week on the podcast.
“you shouldn’t explain things with ideas that are more abstract than the one you’re explaining”
Fine, but in effect you did just that by gratuitously stating: “Everything else. Newtonian mechanics. Water. Biology. Life. is just epiphenomena.”
Feynman also reminded us that there is no certainty. Yet you’re rather certain that intent and purpose are limited to “biological qualities” and (I assume) that otherwise there are no such qualities in the universe that biological forms evolved from.
In any case, it’s clear we won’t agree on this. So otherwise keep up the good work.
Fine, but in effect you did just that by gratuitously stating: “Everything else. Newtonian mechanics. Water. Biology. Life. is just epiphenomena.”
You misunderstand. Those things fall out of the laws of energy (like how matter/energy exist in space) and constants/facts (like potential energy goes from high to low). You can’t understand matter waves from biology but you can theoretically understand biology, although not practically, matter wave to biology if you accounted for the wave equations of all the particles:
The arrows that represent causative sequence can’t be reversed. But if causes are the results of evolving strategies, I don’t know why they’d have to be reversed to assert their commonality in that respect. And remember that causation is not linear, it’s multi directional.
Biological intelligence causes chemicals to react for productive purposes – unless of course it was an elementary intelligent universal process that created the chemicals t