Mar 22 2012

How Electroconvulsive Therapy Works

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144 Responses to “How Electroconvulsive Therapy Works”

  1. passionlessDroneon 22 Mar 2012 at 9:00 am

    Hi Stephen Novella –

    Two nice articles in as many days!

    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?

    Thanks.

    - pD

  2. Steven Novellaon 22 Mar 2012 at 10:47 am

    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

  3. SARAon 22 Mar 2012 at 11:09 am

    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.

  4. DevoutCatalyston 22 Mar 2012 at 12:21 pm

    Mayo says they were one of the first to offer TMS for depression, shortly after FDA gave approval in 2008. What’s the evidence look like for the current technology?

  5. DOYLEon 22 Mar 2012 at 1:51 pm

    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.

    Thank you

  6. Minon 22 Mar 2012 at 2:04 pm

    I don’t think I could ever forget that scene in Requiem for a Dream, no matter how much science is behind it.

  7. Rikki-Tikki-Tavion 22 Mar 2012 at 8:40 pm

    Thanks Steve, I’ve been wondering about that.

    “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.

  8. Davdoodleson 22 Mar 2012 at 10:25 pm

    “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.
    .

  9. Davdoodleson 22 Mar 2012 at 10:30 pm

    Sorry about the typos above – typing with a broken pinky…

    “ther” = the

    “tem” = term

    “posit-ictal” = post-ictal (or postictal, if you prefer)

  10. mdstudenton 22 Mar 2012 at 11:24 pm

    @ Rikki

    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.

  11. HHCon 22 Mar 2012 at 11:32 pm

    Does modern ECT create brain lesions or heart irregularities? Is dementia a result?

  12. Dirk Steeleon 23 Mar 2012 at 9:27 pm

    Having read the study in detail, it would appear that the researchers have successfully managed to record the brain damage that is caused by ECT.

  13. DarwynJacksonon 24 Mar 2012 at 3:23 pm

    @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.

  14. HHCon 24 Mar 2012 at 9:48 pm

    @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?

  15. Dirk Steeleon 25 Mar 2012 at 12:12 am

    DarwynJackson.

    You have no idea what ECT is doing to the brain except putting it into an abnormal state. You have even less understanding what it is doing to the mind of that individual.

    You assume that you can cure a condition like depression, which you assume has a proven neuroanatomical lesion, with a treatment that does not cause any neuroanatomical change?

    This is crazy.

  16. Dirk Steeleon 25 Mar 2012 at 12:30 am

    How Electroconvulsive Therapy Works.

    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’?

  17. Dirk Steeleon 25 Mar 2012 at 12:56 am

    Steven, you have provided a link to a study that shows that ECT can cause significant memory loss. The results of which say.

    ‘Evidence suggests that autobiographical memory impairment does occur as a result of ECT. Objective measures found memory loss to be relatively short term (6 months post-ECT).’

    Since I have not been able to find the full study I wonder if you can shed some light on how the ‘objective’ measures taken differ from the gathering of ‘subjective’ accounts.

    Thanks.

  18. sonicon 25 Mar 2012 at 11:24 am

    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?

    http://www.ncbi.nlm.nih.gov/pubmed/21322506
    RESULTS:
    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.
    CONCLUSIONS:
    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.

    (Full PDF available here–)
    http://www.power2u.org/downloads/1012-ReadBentallECT.pdf

    As this study was done in 2010, I’m thinking that there is a newer one? Perhaps this one is mistaken?

    (The study linked to claims ECT is ‘equally effective’ for bipolar and unipolar depression. But as far as I can tell that is to say ‘it doesn’t really work for either.’)

  19. Dirk Steeleon 25 Mar 2012 at 8:17 pm

    mdstudenton:

    ‘The level of depression that warrants ECT is far more extreme than simply being sad.’

    So having a profound debilitating sadness is much less extreme than merely being depressed?

    Or is this just rhetorical rubbish?

  20. DarwynJacksonon 26 Mar 2012 at 4:24 am

    @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.

  21. Dirk Steeleon 26 Mar 2012 at 10:56 am

    DarwynJackson:

    ‘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?

  22. HHCon 26 Mar 2012 at 12:49 pm

    @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?

  23. Dirk Steeleon 26 Mar 2012 at 1:11 pm

    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.

  24. cwfongon 26 Mar 2012 at 2:10 pm

    Dirk, re wetware. You don’t have google?

  25. mdstudenton 26 Mar 2012 at 2:13 pm

    @ Dirk Steele

    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??

  26. Dirk Steeleon 26 Mar 2012 at 3:35 pm

    cwfong:

    I even read the wikipedia article. I wondered what scientific definition Steven was using. Perhaps you could help?

  27. Dirk Steeleon 26 Mar 2012 at 3:37 pm

    mdstudent:

    ‘Do you really want to play the my anecdote is better than your’s game??’

    Well that is all psychiatry consists of isn’t it?

  28. DarwynJacksonon 26 Mar 2012 at 4:09 pm

    @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.

    @HCC: Sorry, I’m not familiar with exactly which meds Anesthesiologists gave for ECT prior to this decade. I’ve only learned the procedure in the last few years. If you’re interested, here’s a brief TED Talk on the history behind ECT: http://www.ted.com/talks/sherwin_nuland_on_electroshock_therapy.html

  29. Dirk Steeleon 26 Mar 2012 at 5:33 pm

    DarwynJackson:

    ‘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.

    http://neuroskeptic.blogspot.co.uk/2012/03/brain-scanning-just-tip-of-iceberg.html

    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!

  30. Dirk Steeleon 26 Mar 2012 at 5:52 pm

    @DarwynJackson

    ‘Although ECT has historically had significant side effects from amnesia,’

    Are you disagreeing with Steven and the paper referenced?

  31. DarwynJacksonon 26 Mar 2012 at 5:58 pm

    @Dirk: No.
    I am however, drawing a contrast between the frequency & degree of retrograde amnesia caused by sine wave ECT & brief pulse.

    Please see the remainder of the sentence you’ve quoted-
    “modern practices have reduced or eliminated most of these concerns.”

  32. Dirk Steeleon 26 Mar 2012 at 5:58 pm

    @DarwynJackson

    ‘Several psychometric tests, psychiatric interviews, fMRIs, and observations of behavior are utilized to quantify efficacy of modern treatments.’

    Well I have been reading Neuroskeptic’s blog on fMRI so I may be biased.

    Are the other tests scientific or anecdotal?

    Sherwin Nuland explains how he escaped from the depression of a disasterous marriage by the use of ECT, narrowly avoiding a lobotomy. I chose a different path.

  33. DarwynJacksonon 26 Mar 2012 at 6:25 pm

    @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.”

  34. Davdoodleson 26 Mar 2012 at 6:43 pm

    “Well [anecdote] is all psychiatry consists of isn’t it?”

    Thetans told me so.
    .

  35. cwfongon 26 Mar 2012 at 6:56 pm

    “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.’

  36. Dirk Steeleon 26 Mar 2012 at 7:06 pm

    @cwfong.

    Wetware. There are many other definitions on wiki. Too many to repeat here. Which one does Steven mean?

  37. cwfongon 26 Mar 2012 at 7:08 pm

    Ask him nicely this time, he usually prefers that approach.

  38. Dirk Steeleon 26 Mar 2012 at 7:12 pm

    @Davdoodles

    ‘Thetans told me so.’

    Pathetic. For the record I am not, nor have I ever been, swayed by Scientology or any other religious dogma.

  39. Dirk Steeleon 26 Mar 2012 at 7:28 pm

    @DarwynJackson
    Please see the remainder of the sentence you’ve quoted-

    ok.

    “modern practices have reduced or eliminated most of these concerns.”

    Steven refers to a paper the results of which claim ‘Evidence suggests that autobiographical memory impairment does occur as a result of ECT.’

    So do you disagree with this?

  40. Dirk Steeleon 26 Mar 2012 at 7:32 pm

    @cwfong

    Are you playing games?

    ‘Ask him nicely this time, he usually prefers that approach.’

    Where did I not ask nicely?

  41. Dirk Steeleon 26 Mar 2012 at 7:37 pm

    @DarwynJackson

    ‘I’m not sure I understand the question.’

    You mentioned a number of tests that can objectively measure depression. I asked if you could supply the specific detail of those tests so I could read them. Thanks.

  42. DarwynJacksonon 26 Mar 2012 at 7:42 pm

    @Dirk:
    “Steven refers to a paper the results of which claim ‘Evidence suggests that autobiographical memory impairment does occur as a result of ECT.’ So do you disagree with this?”

    No, not at all.

  43. cwfongon 26 Mar 2012 at 7:48 pm

    “Where did I not ask nicely?”

    Perhaps it was the reference to science fiction?

  44. DarwynJacksonon 26 Mar 2012 at 7:58 pm

    @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.

  45. Dirk Steeleon 26 Mar 2012 at 8:14 pm

    @DarwynJackson

    Thanks. I am familiar with Ham-D, Montgomery Asberg Depression Rating Scale and such. I will read up on the AMI.

  46. Dirk Steeleon 26 Mar 2012 at 8:21 pm

    @DarwynJackson

    Bimey! The AMI kit costs £120! 50 quid for the manual and over 70 for 25 scoring sheets! Have you an illegal download or website I could refer to?

  47. Dirk Steeleon 26 Mar 2012 at 8:32 pm

    @cwfong

    ‘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 [3] in their technical terminology. Wetware refers to “that aspect of any living system that can be treated as an information system”.
    [edit] 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.
    [edit] Scholarly usage

    Theorist[clarification needed] Richard Doyle uses the plural, “wetwares” [4] 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.

  48. cwfongon 26 Mar 2012 at 8:54 pm

    Sorry, but that wasn’t what I’d call a nice approach.

  49. DarwynJacksonon 26 Mar 2012 at 8:57 pm

    @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.

  50. Dirk Steeleon 26 Mar 2012 at 9:30 pm

    @cwfongon

    ‘Sorry, but that wasn’t what I’d call a nice approach.’

    Why? Please explain. Thanks.

  51. Dirk Steeleon 26 Mar 2012 at 9:35 pm

    @DarwynJackson

    ‘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?

  52. cwfongon 26 Mar 2012 at 10:27 pm

    Because it’s whys all the way down.

  53. ccbowerson 26 Mar 2012 at 10:43 pm

    “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.

  54. ccbowerson 26 Mar 2012 at 10:45 pm

    … or at least thats how I see it.

  55. Dirk Steeleon 26 Mar 2012 at 10:46 pm

    @cwfong

    ‘Because it’s whys all the way down.’

    My mistake. I thought it was turtles….

  56. cwfongon 26 Mar 2012 at 10:50 pm

    Why?

  57. Dirk Steeleon 26 Mar 2012 at 11:01 pm

    @ccbowers

    .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?

    I will need to think about this.

  58. Dirk Steeleon 26 Mar 2012 at 11:06 pm

    @cwfongon

    ‘Why?’

    Why not?

  59. cwfongon 26 Mar 2012 at 11:10 pm

    Etc.

  60. Dirk Steeleon 26 Mar 2012 at 11:11 pm

    Ect.

  61. cwfongon 26 Mar 2012 at 11:22 pm

    I win.

  62. ccbowerson 26 Mar 2012 at 11:38 pm

    “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)

  63. Dirk Steeleon 26 Mar 2012 at 11:39 pm

    If you want. I have no interest in winning or losing. I will let others be the judge of your behaviour.

  64. cwfongon 26 Mar 2012 at 11:42 pm

    That’s why.

  65. DarwynJacksonon 26 Mar 2012 at 11:42 pm

    @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.

  66. Dirk Steeleon 26 Mar 2012 at 11:47 pm

    @ccbowers

    ‘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.

  67. PhysiPhileon 26 Mar 2012 at 11:48 pm

    Dirk:

    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.

  68. Dirk Steeleon 26 Mar 2012 at 11:56 pm

    @DarwynJackson

    ‘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.

  69. Dirk Steeleon 27 Mar 2012 at 12:08 am

    @PhysiPhile

    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.

  70. HHCon 27 Mar 2012 at 12:31 am

    @DarwynJackson: Thanks for the informative TED talk link!

  71. DarwynJacksonon 27 Mar 2012 at 12:46 am

    @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. :)

  72. PhysiPhileon 27 Mar 2012 at 1:18 am

    dirk: good questions.

    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).

  73. cwfongon 27 Mar 2012 at 2:48 am

    Epiphenomena, byproduct, accidental and not selected with intent or purpose? Otherwise that was quite a tour de force.

  74. PhysiPhileon 27 Mar 2012 at 10:07 am

    cwfong,

    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.

  75. cwfongon 27 Mar 2012 at 1:49 pm

    @PhysiPhile:
    “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.

  76. PhysiPhileon 27 Mar 2012 at 4:47 pm

    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:

    Atomic physics -> chemistry -> biochemistry -> biology -> us.

    You see how those arrows can’t be reversed? How would a quark change its properties according to an organism? Can you tell me how top down control would work?

  77. PhysiPhileon 27 Mar 2012 at 4:48 pm

    “Yet you’re rather certain…”

    I’m certain of nothing. I’m just trying to figure things out like you.

  78. cwfongon 27 Mar 2012 at 5:21 pm

    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 that in turn activated biological systems.

  79. PhysiPhileon 27 Mar 2012 at 6:52 pm

    I know that it’s not linear. I am working on a paper dealing with how we can apply nonlinear models (eg graph theory, choas theory) to neurons (via their nonlinear differential equations that describe the voltage across their membrane), can potentially explain how emergence of these properties works.

    Think about an ant colony. Each ant follows simple chemical signals that are laid by other ants that have no idea why they are laying that trail down. The ants end up building a moat around their colony just in time to protect it from monsoon season.

    My question to you is where did the idea to build a moat come from in this scenerio?

  80. cwfongon 27 Mar 2012 at 7:28 pm

    Life forms are essentially optional choice assessors and anticipate results based on trial and error strategies and continual reassessment of the results of efforts. In that sense they are all intelligent learners and collectively have developed intelligent strategies. Of course a number of biologists such as Dawkins don’t believe this and a yet growing number that I’ve previously referred to here do.

    At this point however, the naysayers will enter this conversation and it’s off to the races – but I’ll not race again on this track unless it’s for a newer purpose.
    But if you want my opinion as to where trial and error strategies originated in the universe, you could ask me and I’ll try to answer. But better than that, start by reading Whitehead and his writings on Process Philosophy.

  81. cwfongon 27 Mar 2012 at 7:33 pm

    I didn’t mean to duck your question about the moat, but I’d rather you think about what might be the answer based on the proposition that ants are group problem solvers, as well as individual learners that contribute to what their cultures learn and remember.

  82. ccbowerson 27 Mar 2012 at 8:32 pm

    “Intent and purpose are biological qualities”

    More specifically in this case, human constructs. Not to be just a “naysayer” to cwfong, because I enjoyed the exchanges on this topic more than I usually do when this topic comes up (and it comes up quite often).

  83. cwfongon 27 Mar 2012 at 8:52 pm

    Well, I’m not going to argue anymore with those here who believe there are any biological entities at all that act without some element of intent and purpose. Been there here and done that.

  84. PhysiPhileon 27 Mar 2012 at 8:58 pm

    That’s a loaded proposition because I do not accept ants are group problem solvers. I don’t think have the brain to be anything that we would consider problem solvers. As with you comment about life be choice makers…Are you saying that a bacterium makes choices? To make that claim you and I must have different understandings of what “choice” means.

  85. PhysiPhileon 27 Mar 2012 at 9:05 pm

    In what way do life forms anticipate results? As with the ant example, I don’t believe the ants anticipated monsoon season – I think monsoon season coincides with the higher order patterns that emerge for laying down trace hormones that they replicate for reasons that are unknown to the ant. If they didn’t have some mechanism to accommodate monsoons they wouldn’t be here for us to study.

  86. PhysiPhileon 27 Mar 2012 at 9:10 pm

    “Well, I’m not going to argue anymore with those here who believe there are any biological entities at all that act without some element of intent and purpose. Been there here and done that.”

    I’ll infer from this that you do adhere to the same mechanism of developing beliefs as I do, ergo, discussion is futile.

    As an aside, sometimes I will develop intense anxiety because I know most people are like you and I am very alone in how I reason and most conversations I have end in a similar fashion.

    Let us continue on our previous paths…

  87. cwfongon 27 Mar 2012 at 9:14 pm

    OK by me.

  88. ccbowerson 28 Mar 2012 at 12:06 am

    “I’ll infer from this that you do adhere to the same mechanism of developing beliefs as I do, ergo, discussion is futile.”

    Really, is this true? I thought this was a skeptical blog followed by skeptics. I guess not all of us are, unless this was written tongue-in-cheek.

  89. cwfongon 28 Mar 2012 at 1:41 am

    We both had the sense to know we were at an impasse, so agreed it was time to stop disagreeing. So why not let the guy alone. When it comes to rattling off the details of our physical processes, this guy is phenomenal. It would take me days to write what he did off the top of his head. I just recognized an area where we likely disagreed, and he confirmed that it was an honest disagreement. Why pick a nit for no other reason than to pick it.

  90. Dirk Steeleon 28 Mar 2012 at 7:35 am

    @DarwynJackson

    ‘If you are considering any neurostimulation/intervention for yourself or a loved one, I hope you’ll approach the matter with healthy skepticism’

    I think it has been proven that the efficacy of ECT is improved when performed on someone you don’t like much.

    @PhysiPhile

    You seem a clued up clever chappie. What is your take on the paper Steven uses to show how ECT works? To me it is full of flaws and an example of really bad science. What do you reckon?

  91. Dirk Steeleon 28 Mar 2012 at 8:02 am

    @@PhysiPhile

    ‘In what way do life forms anticipate results? As with the ant example, I don’t believe the ants anticipated monsoon season – I think monsoon season coincides with the higher order patterns that emerge for laying down trace hormones that they replicate for reasons that are unknown to the ant.’

    Funnily enough I was having this conversation down the pub last night with some guy who kept colonies. I must read some more E O Wilson and Hamilton. So although ants act unknowingly, aren’t their genes encoded with knowledge of the higher order patterns of the environment. So is it possible that this unconscious information can anticipate seasons. Is it possible for us to still make choices even tho our consciousness doesn’t realise it until half a second later? Or is that me being ignorant again? This free will marlarky does my head in.

  92. ccbowerson 28 Mar 2012 at 10:07 am

    cwfong-

    In retrospect I assume that PhysiPhile was being a bit tongue in cheek, but taken literally I don’t believe I was nitpicking. If discussion is truly futile and we hold onto our beliefs despite what we can learn from others, why are we here at this blog “talking” to strangers? The reason, I hope is that we want different perspective than our own to further understanding.

    I’m sure that the intent was to conclude that you were at “an impasse,” but I was just checking. Tone is hard to gauge in typed text, and emoticons are insufficient and often annoying

  93. Dirk Steeleon 28 Mar 2012 at 12:43 pm

    For anyone who wants to approach ECT with a healthy skepticism I suggest a read of Doctors of deception: what they don’t want you to know about shock treatment. By Linda André.

    (I have not had the pleasure of ECT so at least I know that I don’t know.)

  94. cwfongon 28 Mar 2012 at 2:09 pm

    @ccbowers,
    “If discussion is truly futile and we hold onto our beliefs despite what we can learn from others, why are we here at this blog “talking” to strangers?”
    You tell me. I learned from talking to PhysiPhile, who asked positive questions. You on the other hand struck me as positively negative.

  95. ccbowerson 28 Mar 2012 at 3:05 pm

    “You on the other hand struck me as positively negative.”

    Really? I never said discussion is futile, in fact just the opposite. And I don’t develop “beliefs” impervious to discussion. Perhaps you consider that negative

  96. cwfongon 28 Mar 2012 at 4:10 pm

    *“Intent and purpose are biological qualities”
    More specifically in this case, human constructs.*

    Negative.

  97. PhysiPhileon 28 Mar 2012 at 5:35 pm

    “What is your take on the paper Steven uses to show how ECT works?”

    I have issues as far as I don’t think it adds much to the current research but I wouldn’t call it bad science. However, I only read their abstract and conclusion and skimmed the article.

    They actually address my main complaint but then they basically say they controlled for it but completely missed why this data is so limited. Here’s the except:

    “In a large number of functional connectivity
    studies that are typically referred to as “resting-state fMRI,” subjects are
    instructed “to just relax and not to think about anything specific.” However,
    as pointed out by Morcom and Fletcher (27), the concept of a resting state or
    baseline in the human brain is somewhat elusive. In the absence of a specific
    task, we anticipate that brain activity will exhibit a wider variance because
    different subjects will be thinking about different things and some may even
    fall asleep. In this study, we used a simple virtual ball-passing task to keep
    the subjects’ attention focused. Based on the theoretical arguments put
    forward by Morcom and Fletcher (27), we anticipate that such a task will
    reduce the within-group variance, and therefore improve the sensitivity of
    the between-group comparison.”

    The problem is that the normal brain state is highly dynamic. fMRI data is limited but has uses: eg retrospectively to monitor an established brain-function connection. I want to see more anatomical-functional relationships demonstrated before this paper really catches my interest. A brain in aa fMRI machine is very different (on the cognition level) than a brain doing other tasks. They attempted to isolate this by having the subjects have a similar experience but I am saying that it’s not inter-subject variability that I want to see isolated it’s intra-subject variability in time and environment.

    Brain properties are much like the uncertainty principle where the more you try to confine an electron in space the more uncertainty you are about its velocity…the more you confine a brain property in space the more the property fades

  98. PhysiPhileon 28 Mar 2012 at 5:39 pm

    Sorry ignore the last paragraph – I thought I deleted it. I started to type that but realized it wasn’t relevant.

  99. Mlemaon 28 Mar 2012 at 8:30 pm

    I’m glad you failed to delete it.

  100. ccbowerson 28 Mar 2012 at 8:33 pm

    *“Intent and purpose are biological qualities”
    More specifically in this case, human constructs.
    -Negative.*

    Actually, I was intending to be literal here, and not a dig at you specifically (although now I see how it can be easily seen as both). I am saying that intent and purpose are human constructs, but I realize they are not necessarily restricted to humans. You like to apply intent and purpose to organisms in ways that I think are unjustified, but…we don’t really need to retread this topic. We have also previously had the same impasse.

  101. cwfongon 28 Mar 2012 at 8:44 pm

    Still you brought it up as a known fact with no need of explanation.

    Whereas Damasio writes, for example: “The survival intention of the eukaryotic cell and the survival intention implicit in human consciousness are one and the same.”

    And at least PhysiPhile explains his objections. So if you can, explain how microbes avoid other microbes without the purpose of avoiding them, or how they decide which way to move without any intent to choose a direction to move.

  102. ccbowerson 28 Mar 2012 at 9:32 pm

    “So if you can, explain how microbes avoid other microbes without the purpose of avoiding them, or how they decide which way to move without any intent to choose a direction to move.”

    Intent and purpose are higher functions than you are describing in this sentence. To me, having intent and purpose to an action imply a big picture understanding of behavior, of which bacteria are incapable of, and it is not simply reacting to stimuli (regardless of if this behavior is advantageous).

    Besides, how would we determine the “intent” or “purpose” of a given behavior of bacteria? In this sense it becomes a human construct, because any attribution becomes our interpretation of their behavior. Adding this extra layer all seems unnecessary, and does not appear to add any understanding.

    In your view, do viruses or prions also have intent and purpose?

  103. cwfongon 28 Mar 2012 at 9:56 pm

    So of course you haven’t answered my question of how microbes avoid things or choose directions, etc. Or found a way to counter Damasio. As to prions, if they are living (and that’s debatable), they have the implicit intention to survive, and viruses especially have intentions to use our human cells metabolic machinery to replicate, and carry out their particular purposes in the bargain.
    My point being, and demonstrated by your answers, that you are indeed a negative skeptic, with no positive contribution to this discussion so far.

  104. ccbowerson 28 Mar 2012 at 10:16 pm

    “My point being, and demonstrated by your answers, that you are indeed a negative skeptic, with no positive contribution to this discussion so far.”

    Not at all. As far as I am concerned the items you want me to address/counter are unsubstantiated claims, and there is no way to address them other than the way I have (which is very similar to how other people have addressed this issue). I am not burdened to disprove your unsubstantiated claims, and that doesn’t make me negative.

    The quote you posted: “The survival intention of the eukaryotic cell and the survival intention implicit in human consciousness are one and the same” is simply an unsupported assertion. At best it is the continuum fallacy, but I actually think he is comparing two different things. …but I thought we were at an impasse?

  105. cwfongon 28 Mar 2012 at 10:26 pm

    An impasse means you stop interrupting me with the same argument that we were supposedly at an impasse on.
    And now you claim that Damasio makes unsupported assertions. Get real.
    And it’s an unsubstantiated claim that bacteria for example move to avoid predators, or change directions in pursuit of an immediate or even longer term goal? Baloney.

    Substantiate this recent article on the subject: Gambling on Bacteria
    http://www.aftau.org/site/News2?page=NewsArticle&id=13085

  106. BillyJoe7on 29 Mar 2012 at 6:17 am

    I am happy to read that article as metaphor.
    And I would be surprised if the author inputes consciousness and emotion to bacteria.
    But I’m not going to rehash the argument.
    Except to wonder again if quantum mind and universal consciousness could be far behind.

  107. ccbowerson 29 Mar 2012 at 9:02 am

    “And it’s an unsubstantiated claim that bacteria for example move to avoid predators, or change directions in pursuit of an immediate or even longer term goal? Baloney.”

    That is not what I’m saying at all. I thought it was obvious by my comments, but perhaps not. The unsubstantiated claim is that the apparent intent is a single cell’s actions = “the intention implicit in human consciousness.” I am not questioning the actual behavior of bacteria in this case.

    I do not want to be stuck in a cwfong vs BJ7 battle though.

  108. cwfongon 29 Mar 2012 at 1:29 pm

    BillyJoe7 is an ignorant liar who is trying to get back some credibility after failing miserably to understand a book on physics whose author explained his meaning in various interviews, and book reviewers all over cyberspace quoted and elaborated upon its contents. And the author told Steven Novella personally what he meant – who then told BillyJoe7, who then said Steven must have got it wrong.
    Now this ignoramus implies that I’ve granted consciousness and emotion to bacteria, so he can set up a straw-man argument against it. Which he’d likely fail to do even then as all his arguments reflect a lack of logical ability, even when he’s presenting a case for the obvious. If he doesn’t like the conclusions of a scientific article, he calls its findings metaphorical. Ask him to explain what that word means and he can’t. He relies on what he learned and didn’t learn in high school last century, and has been fighting to maintain that level of his ignorance ever since.
    His father wanted him to be a Creationist priest but since he would have had to preach on it in the bargain, he became an atheist to avoid the complications of persuasive discourse.
    Watch now while he replies in his usual stumbling and bumbling fashion. Pettifoggery, some call it, but he’s not even good at that.

  109. cwfongon 29 Mar 2012 at 1:34 pm

    And at least ccbowers is not questioning the behavior of bacteria, which may or may not mean he now agrees that they move with some measure of intent and purpose. BillyJoe7, of course, thinks they dance to a metaphor or something.

  110. daedalus2uon 29 Mar 2012 at 5:30 pm

    I just saw this yesterday and haven’t had a chance to put my $0.02 in until now.

    Depression and fMRI are things I happen to be well informed on.

    There are a number of problems with the paper Dr Novella discussed. First, fMRI doesn’t actually measure “connectivity”, what it measures is purely a hemodynamic effect, a sudden decrease in the quantity of deoxyhemoglobin in that volume element of the brain. This reduction is caused by local vasodilation which relaxes the local vessels and causes fresh oxygenated blood to enter that region, displacing deoxyhemoglobin. Oxyhemoglobin is diamagnetic, deoxyhemoglobin is paramagnetic, fMRI measures that magnetic susceptibility differences in different volume elements and imputes the relative vasodilation of those volume elements compared to the average of the whole brain.

    Second (and this relates directly to my research), there are two types of connectivity. There is actual physical connections, where cells touch and where an action potential can propagate from one cell to another. There are far more actual connections than can actually be used at one time. Each nerve cell has about 10,000 actual connections to other cells and some back to itself. On average, for each cell that fires, one downstream cell also fires. We know this is approximately correct because if the average was different than one, the number of cells that were firing would increase exponentially until they all were and there would be a seizure. If the number is less than one, there would be exponential decreases in firing until all firing would be extinguished. Neither happens, so on average the number must be one.

    The other type of connectivity is functional connectivity. That describes (in principle) which downstream nerve cell fires for each upstream nerve that fires. Since on average only one out of 10,000 connections is triggered, the functional connectivity is ~1/10,000 the actual connectivity.

    It is not possible to measure functional connectivity without electrode implants. MEG (measuring of electrical activity via magnetic fields) can be used, but that cannot be done in conjunction with MRI. The blood flow changes that are observed in fMRI correlate very well with functional connectivity, but that is only correlation.

    The volume elements that are being looked at (few mm x few mm) actually contain millions of nerve cells with many billions of connections. The response of that neural network is highly non-linear and depends on the minutia details of how the nerves are connected and how they fire in sequence. With millions of cells and billions of connections, there are a lot of details. Approximating the activity of that complex network with a single scalar magnitude of “activity” is of very small fidelity. It isn’t even an absolute hemodynamic activity, it is blood flow relative to the average of the rest of the brain.

    The vasodilation observed in fMRI is caused by neurogenic release of nitric oxide in the sub-nanomolar region. The vasodilation precedes neuronal activation (when the action potentials propagate into that volume element) and the NO release precedes the vasodilation. My hypothesis is that the prompt neurogenic NO that triggers the vasodilation also changes the sensitivity of neurons in that volume element to firing, and so modulates the number of downstream neurons that fire. A little more NO, then the number becomes greater than one, the local activation increases exponentially until the NO level goes back down (due to the increased oxyhemoglobin level but also due to superoxide from MAO, mitochondria and other things. The number goes below one and the activity exponentially declines.

    For the brain to maintain itself at this critical n=1 state (which all natural neural networks do), there has to be active feedback that self-regulates the balance of activating and deactivating pathways.

    Depression is a complex state (as are all brain states). For something “simple” to affect something “complicated”, presumably there is something “complicated” between the “simple” thing and the “complicated” thing it is affecting.

    I very strongly suspect that what ECT is affecting is the regulation of the balance between excitation and inhibition. That is known to be affected and it has to be important to keep the whole brain operating “in sync”.

    How that balance is regulated is extremely important. Following a stroke, there is a generalized loss of neurons in the days and weeks that follow. My understanding of that is that neurons that have lost the upstream inhibitory partners go into states of excitotoxicity and drive themselves to apoptosis. I see this as a “feature”, to ablate neurons that might trigger a seizure at an inopportune time (as when being chased by a bear) which would be certain death. Better to ablate neurons and accept a reduction in cognitive ability for increased stability. That is what all the reserve capacity is there for.

  111. BillyJoe7on 29 Mar 2012 at 11:26 pm

    Sorry to disappoint, but I have given up trying to explain things to you.

  112. cwfongon 30 Mar 2012 at 12:03 am

    If you were talking to me, I second the motion. Not that I won’t explain my positive positions to others, your negative interjections not withstanding..

  113. PhysiPhileon 30 Mar 2012 at 12:31 am

    Daedalus:

    ““We know this is approximately correct because if the average was different than one, the number of cells that were firing would increase exponentially until they all were and there would be a seizure.””

    I do not accept this as a premise. You contradict yourself later because you first say it’s a 1:1 firing ratio then you also realize its a nonlinear system. When dealing with systems in the domains of graph theory or chaos theory you are dealing with very high order nonlinear coupled differential equations and you can’t assume that if you perturb the system (like if you had 1:many firing it will produce X result). You predict f(x)=e^x – some unbounded equation but this is a huge false assumation. You can not predict the a positive or negative value, ergo, you can not say “if it were more than one it would result in continuous positive feedback to seizure”

  114. Dirk Steeleon 30 Mar 2012 at 6:48 am

    @PhysiPhile

    ‘I have issues as far as I don’t think it adds much to the current research but I wouldn’t call it bad science.’

    Really? How about the audacious bias in the first sentence?

    ‘To date, electroconvulsive therapy (ECT) is the most potent treatment in severe depression.’

    Also the use of the Montgomery Asberg Depression Rating Scale? (Cold reading)

    Use a small sample (Why only 9 people? ). No controls. None.

    Show how ECT reduces brain activity and therefore conclude depression is caused by an over active brain?

    I would not call this bad science. I would call it non science. Or to be more accurate. Nonsense.

    Would you submit to a few sessions without reservation?

  115. PhysiPhileon 30 Mar 2012 at 7:29 am

    dirk: You brought up valid points. This study does not help me understand depression and certainly not its neuronal correlate. This study only hurts our collective understanding because even pervy scientist can get suckered in

  116. ccbowerson 30 Mar 2012 at 9:58 am

    “Show how ECT reduces brain activity and therefore conclude depression is caused by an over active brain?”

    I’m not sure where you read this conclusion from… I did not find an assertion that depression is caused by an overactive brain. Reads like a strawman unless I missed this assertion.

    I get your point… a mechanism of a treatment does not necessarily indicate the mechanism of a disease/illness, but who is saying otherwise?

  117. daedalus2uon 30 Mar 2012 at 10:06 am

    I am very aware of how non-linear it is. Natural neural networks self-regulate in the near critical percolation threshold. That is a true critical point, where many properties of the network vary exponentially with connectivity, both positively and negatively.

    My statement about n=1 pertains to the long term average over the whole brain. We know it is correct because the long term average is a steady state. If n was greater or less than one, the long term average would be something different, either saturated-on (a seizure), or saturated-off (zero activity). Neither of those two occur, so the long term average n=1.

    In the short term in a small volume element, n can’t equal one or there would be no differential activity in that volume element. In the long term, the n’s of all the volume elements have to average to one. Because there is communication between volume elements, the n’s of particular elements may be less than or greater than one, but the excess or deficiency of activations has go somewhere else, or be made-up from somewhere else.

    I appreciate that there are mechanisms that limit the degree of activation to be less than a seizure and to be greater than zero activity. One way of expressing that idea is to say that in the long term average n=1.

    If we consider nerve cell firing to be on a cycle, then if the number of nerve cells firing before a cycle is Xi, then after each cycle the number of nerves that are activated is Xj, then n= Xj/Xi. If on average n=1, then the X stays approximately constant. If n=1.1, then after a few hundred cycles, (1.1)^200 = 2×10^8 and X has increased to levels we know do not happen. Therefore the average n is less than 1.1 over those 200 cycles.

  118. Dirk Steeleon 30 Mar 2012 at 11:10 am

    @ccbowers

    ‘I’m not sure where you read this conclusion from… I did not find an assertion that depression is caused by an overactive brain. Reads like a strawman unless I missed this assertion.’

    I actually read Stevens blog.. the bit were he says.

    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. That hypothesis is supported by a recent study that uses fMRI scanning to look at brain activity’

  119. ccbowerson 30 Mar 2012 at 11:50 am

    “I actually read Stevens blog.. the bit were he says.”

    I see, but you did not read the word “perhaps” and “part of the brain,” I guess. Later, he says that this is “Once (sic) way to interpret this result” and later suggests that TMS studies “would be a good test of the hypothesis, and confirm the above findings if it works.”

    That is how you create a strawman: by changing carefully worded paragraphs with an appropriate amount of uncertainty into him concluding that “depression is caused by an over active brain.”

  120. Dirk Steeleon 30 Mar 2012 at 3:02 pm

    @ccbowers.

    The title of the piece is How Electroconvulsive Therapy Works. No doubt in that phrase. After using the words ‘perhaps’, Steven refers to the study that further supports the hypothesis, thus reducing the uncertainty even more. Straw man? Or splitting hairs?

  121. DarwynJacksonon 30 Mar 2012 at 4:39 pm

    @Dirk:

    “I think it has been proven that the efficacy of ECT is improved when performed on someone you don’t like much.”

    I’m not familiar with any studies proving this statement. If you’re citing a study, please cite. If you’re offering your opinion because you don’t want ECT, that’s fine because no one is forcing it on you. I’m not sure why you’ve formed a hostility toward this treatment, but I don’t think any amount of evidence is going to persuade you to question your preformed opinions. Skepticism is a process of reevaluating our own internalized assumptions just as much as we question the views of others.

    If we’re merely exchanging anecdotes of peoples personal experiences then I’ll say- I’ve performed ECT on several people I like & the results have been fine.

  122. PhysiPhileon 30 Mar 2012 at 6:21 pm

    “My statement about n=1 pertains to the long term average over the whole brain. We know it is correct because the long term average is a steady state. If n was greater or less than one, the long term average would be something different, either saturated-on (a seizure), or saturated-off (zero activity). Neither of those two occur, so the long term average n=1.”

    I can see this being true in a bounded system. But I assume that brain tissue responsible for cognition is not bounded. Let me explain:

    From your method you would first have to say that a specific brain property (eg a face/word, or musical note) is inside a volume where the functions representing the conditions at the surface of the volume are known, then that should set your n=1 because knowing the boundary conditions means that you can account for any energy losses/gains moving through the gaussian surface. It’s a good idea and I think we are heading in the right direction…but here’s my issue

    Unfortunately, I believe there will be less known about the conditions at the surface than inside the volume and so unless we make some big assumptions about the boundary conditions I don’t see how we can say anything about conditions inside the networks (eg it’s steady state).

    Comments?

  123. ccbowerson 30 Mar 2012 at 7:01 pm

    “The title of the piece is How Electroconvulsive Therapy Works. No doubt in that phrase”

    You were the one who said that you read what he wrote, and I assumed beyond the title. Either you have a reading comprehension problem or you are being disingenuous. According to your comments, Steve has concluded that depression is cause by an overactive brain (and he concludes this because ECT reduces brain activity). In my reading of this post he never asserts that as a conclusion, as merely mentions it as a possible mechanism, which requires further testing (and he even had suggestions to test this possibility).

    Its easy to criticize when you misrepresent the argument. If you think this is nitpicking, it is essential to your entire criticism.

  124. Dirk Steeleon 30 Mar 2012 at 7:36 pm

    @ccbowers

    If the correct title “Unsound Scientific Study shows once again that No-one has a Clue what ECT does and how it works or maybe doesn’t…Further tests needed. ‘ had been used, I would not have bothered to read it.

  125. Dirk Steeleon 30 Mar 2012 at 8:33 pm

    @DarwynJacksonon

    Re: “I think it has been proven that the efficacy of ECT is improved when performed on someone you don’t like much.”

    ‘I’m not familiar with any studies proving this statement. If you’re citing a study, please cite.’

    Well… a few days ago I built a little contraption using a couple of wires and the national grid. Let me tell you that I was far more pleased with the results on those I didn’t like very much than those I loved. And I did love my cat quite a bit.

    I am currently (sic) writing up the results of my study which I will be pleased to send to you and Steven.

  126. Dirk Steeleon 31 Mar 2012 at 3:29 am

    @DarwynJackson

    Before you carried out the procedure on those people you liked, I hope you explained the following to them first.

    1. Science has little idea on what ECT does to the brain or how it affects the mind.
    2. The efficacy is at best 50%, in an area where active placebo use can show a 25% improvement, and the relapse rates are also very high.
    3. It is known that memory loss can happen as well as other cognitive defects that may be too subtle to measure effectively.
    4. There are thousands of people who so bitterly regret treatment that they form ‘survivor’ groups and actively campaign against the procedure.
    5. Gave them a copy of “The effectiveness of electroconvulsive therapy: A literature review” by John Read and Richard Bentall to read just for a balance to your optimism.

  127. daedalus2uon 31 Mar 2012 at 10:09 am

    The brain most certainly is bounded by the skull. I am not talking about “energy”, that is supplied by blood-borne substrates. I am talking about activation and propagation of activation from one part of the brain to another (what the paper was trying to measure).

    As I think about it more, I think their data shows the opposite of what they have concluding. Instead of depression being a state of increased neuronal activity that depression is a state of reduced activation.

    Their “measure” of neuronal activation is flawed. They are using fMRI, but that only shows differential blood flow due to relative vasodilation. It only shows deviations from the average blood flow. If there is a change in the average blood flow as a consequence of ECT, this study could not see it.

    It turns out that ECT does change the total blood flow in the brain, it increases it, as does successful antidepressant treatment.

    http://www.ncbi.nlm.nih.gov/pubmed/15163251

    Depression is known to be a state of reduced metabolic activity in the brain. The major metabolic activity is due to nerve being activated. If successful treatment of depression results in increased metabolic activity, it can’t be the case that there is reduced activation.

    I think their result is artifact due to the change in the total brain blood flow and the thresholds set to be “significant” deviations from that total brain blood flow and are also misinterpreted. If the total brain blood flow (which they did not measure) increases, then they will observe decreases in the size of activated regions, even if the degree of “activation” (as measured by actual vasodilation) stays the same.

    They need an independent measure of blood flow if they are going to try and use fMRI to monitor changes in relative blood flow when doing interventions that are known to change the total blood flow.

    To use an analogy, they are imputing connectivity by looking at the contrast between high and low activity levels but they have changed the total activity levels and so are not comparing before activities with after activities. It is like doing visual analysis of the contrast in a picture after you have changed the brightness. If you change the total brightness, you can’t use the same contrast thresholds to compare the contrast between images.

    In summary, this paper does not provide data that supports an over-connectivity idea of depression.

  128. PhysiPhileon 31 Mar 2012 at 3:00 pm

    Daedulus

    “The brain most certainly is bounded by the skull.”

    This is true because of how the brain is defined but, as you probably know, the skull is not going to be to be used as boundary conditions for a network on neurons. I was referring to bounded in the mathematical sense.

    We can both agree that the paper doesn’t add much to our understanding and demonstrates how selection bias is injected into research by how they set their thresholds. But now I am talking about something that I believe many neuroscientists are trying to tackle cognition with a level of analysis that beyond our current experimental methods (eg single/1000 neuron recordings fMRI etc…) AND there are fundamental mathematical flaws with confining any cognitive properties in your model because you can not assume you are looking at a system were n=1.

    “I am not talking about “energy”, that is supplied by blood-borne substrates. I am talking about activation and propagation of activation from one part of the brain to another (what the paper was trying to measure).”

    I am talking about activation/propagation as well. Let me ask some higher level question and then we can zoom in on the details.

    Do you agree or disagree that if a system has more unknowns at boundary then the internal state of the system is undetermined? ie there are many different internal configurations that are valid solutions.

    (I’m heading towards showing you can’t assume steady state).

  129. daedalus2uon 31 Mar 2012 at 9:29 pm

    Since the brain is finite, the brain is most certainly bounded in a mathematical sense.

    I am not sure what you are getting at. Physiology comprises many hundreds of thousands of coupled non-linear interactions per cell. The interactions between cells are non-linear and coupled. There are a couple hundred billion cells and maybe a quadrillion connections, give or take a few hundred trillion.

    How many non-linear and coupled parameters can be dealt with mathematically? We both know that 3 is too many unless there are simplifications. There are no simplifications in the brain that allow it to be analyzed mathematically.

    The point of my n=1 observation is that to keep n=1 as a long term average, there needs to be regulation. There need to be pathways that increase n and there need to be pathways that decrease n. The integration of all of those pathways over time is what causes the long term average of n=1.

    The mechanism(s) of those n increasing and n decreasing pathway(s) are unknown. We know there must be such pathways. We know they must be important in how the physiology of the brain generates thoughts and thinking.

    ECT changes the regulation of n to make seizures more difficult to trigger. I think trying to understand how ECT changes the regulation of neuronal firing would be a more fruitful research avenue than this fMRI study.

  130. Dirk Steeleon 31 Mar 2012 at 10:39 pm

    Humbug! Depression is just the new drapetomania. The real question is why do we want to cure it?

  131. DarwynJacksonon 01 Apr 2012 at 1:03 am

    @Dirk:

    “Before you carried out the procedure on those people you liked, I hope you explained the following to them first.”

    It should be noted that medical ethics dictates that all benefits/risks of any treatment be explained to a patient in full, regardless of our personal feelings towards them. Risks that are valid as well as the actual estimates of efficacy are explained to each person.

    Seeing as how you’ve openly expressed a total disinterest in the established scientific literature, it’s surprising that you would even visit a blog about scientific skepticism. If you are only looking to attack others for endorsing standard medical practices, I would rather you not address your posts to me.

  132. DarwynJacksonon 01 Apr 2012 at 1:44 am

    @Daedalus2u:

    Please correct me if I’m mistaken, but I was under the impression that current research had shown MDD to be correlated with reduced activity in the anterior cingulate gyrus (BA25). TMS usually targets this region with magnetic pulses at frequencies which increase neuronal activity.

  133. daedalus2uon 01 Apr 2012 at 9:03 am

    @DarwynJackson, I am not up on the details of where relative activity in the brain occurs during different conditions. My perspective is to look at the brain as a whole, and try to facilitate its normal functioning, and lately from the perspective of control theory.

    The brain is the most complex assembly of matter that humans have ever encountered. It must also have the most complicated control system that humans have ever encountered, which control system regulates that most complex assembly of matter to do the most complex things that humans have ever encountered, instantiate human behaviors.

    Whacking that very complex system with something is unlikely to directly improve its function. That whacking the brain with ECT, TMS, drugs, or other simple and crude interventions does something, indicates to me that the whacking isn’t correcting something that is wrong, but rather that the whacking triggers compensatory pathways and those compensatory pathways fix what ever was wrong.

  134. Dirk Steeleon 01 Apr 2012 at 10:06 am

    @daedalus2u

    ‘whacking triggers compensatory pathways and those compensatory pathways fix what ever was wrong.’

    Similar to Max Fink’s contention that ‘there is a relation between clinical improvement and the production of brain damage’.

    I think use of the word fix is currently a moot point.

  135. daedalus2uon 01 Apr 2012 at 9:01 pm

    Damage is not necessary to trigger compensatory pathways. Not eating causes compensatory hunger, holding your breath causes compensatory hyperventilation, not drinking causes compensatory thirst. Taking opiates causes compensatory changes in receptor expression. Normally compensatory pathways can be triggered without damage.

  136. Dirk Steeleon 02 Apr 2012 at 6:09 am

    ‘Seeing as how you’ve openly expressed a total disinterest in the established scientific literature’

    I have read the papers quoted above in depth. For every paper you can cite me regarding ECT, I can show one that demonstrates different results.

    ECT, TMS, DBS. It is just big boys playing with the latest new fangled techie toys, pretending to be doctors whilst stuffing research grants into their back pocket. With the ghost of Walter Freeman looking down with approval. What next? Leucotomy for ADHD anyone? It is all woo. At least homeopathy is relatively harmless.

  137. Dirk Steeleon 04 Apr 2012 at 8:26 pm

    @DarwynJackson

    ‘Please correct me if I’m mistaken, but I was under the impression that current research had shown MDD to be correlated with reduced activity in the anterior cingulate gyrus (BA25). TMS usually targets this region with magnetic pulses at frequencies which increase neuronal activity.’

    I think science has shown that environmental influence can alter the structure of the brain. Science has also demonstrated that, via a measurable and objective test, neurological damage can result in ‘mental’ disorders. But your view that all depression must be caused by the latter is an ideological view and is not scientific. Correlation is not causality.

    Therefore your recommended treatment of ECT is also an ideological idea, unless backed up by neurological objective science. Can you explain the theoretical scientific understanding that underpins your treatment? Are you denying the environmental cause of MDD? Is it possible that your ECT treatment results in ‘acceptance’ of conflicting situations that may cause depression through neurological damage?

  138. Dirk Steeleon 04 Apr 2012 at 8:30 pm

    @daedalus2u

    ‘Damage is not necessary to trigger compensatory pathways.’

    So what are your views on ECT? That it causes no damage? What does it do to reduce depression? I am interested in your opinions.

  139. daedalus2uon 08 Apr 2012 at 12:58 pm

    I don’t consider myself to be an expert on ECT. Whether a particular ECT treatment causes “damage” or not, and what “damage” means in the context of treatments such as ECT is not clear.

    Following a stroke, most of the “damage” occurs long after the stroke and there is persistent ongoing “damage” for weeks. This “damage” is the natural pruning of neurons that occurs when they have lost contact with the upstream neurons which have been killed during the stroke.

    Brains lose cells all the time. Is that normal loss of brain cells to be considered “damage”? There is a great deal of redundancy in the brain, and it can be difficult to notice when there is loss of brain cells because function is preserved pretty well even with substantial losses.

    In the case of neuron die-off following stroke, my understanding of it is that it occurs via apoptosis and is an evolved “feature” to preserve functionality of the brain. The brain is active tissue and can support non-functional uncontrolled activation as in a seizure. If you have a seizure when you are running from a bear, the bear is going to catch you and you are going to die. Ablating neurons to minimize the chances of having a seizure would be a good feature to have that might save your life. If you are a cave man and are apt to die before age 40 from being caught by a predator, preserving brain stability is likely more important that preserving neurons that will stave off dementia when you are 70, 30 years past when you are likely to be dead from other causes.

    Does ECT cause “damage”? Does untreated depression cause damage? Uncontrolled MDD probably does cause brain damage and increased loss of nerve cells. People with MDD do experience brain shrinkage, reduced blood flow in the brain, reduced metabolic activity in the brain. What triggers brain cells to go into apoptosis is (usually), excitotoxicity. In excitotoxicity, cells are driven into a very high metabolic state which they cannot sustain, which depletes ATP levels, which triggers apoptosis. In this way the cells that are the “weakest link” are ablated, the cells least able to sustain their metabolic activity.

    When people experience repeated seizures, there is progressive nerve cell loss. My understanding of that is that the brain is ablating excess neurons to lower the metabolic demand to something that can be sustained. Some of that happens following a stroke, where cells are ablated to reduce local metabolic demand. Does that happen following ECT? I don’t know. There is increased blood flow and increased metabolic activity following successful treatment of MDD by any method.

    If there is increased metabolic activity, there is increased neuronal activity. There could be both increased activity and loss of neurons. Neurons are thought to mostly not be replaced, so any loss might be permanent, but there are some indications that there is neurogenesis even in adult brains. There are some indications that SSRIs do increase neurogenesis, and that some of the antidepressant effect of some SSRIs is due to their stimulation of neurogenesis.

    If ECT does cause some increased loss of neurons in the short term (weeks), but restores a more normal level of neurogenesis such that there are more neurons present years after treatment than would be present without treatment, I don’t think it is fair to call that “brain damage”. MDD is extremely debilitating. Patients with MDD have an extremely low quality of life, perhaps the lowest quality of life that it is possible to experience. If you have never experienced MDD, it is difficult to appreciate just how low that quality of life is.

  140. Dirk Steeleon 14 Apr 2012 at 5:51 pm

    @daedalus2u

    Thanks for taking the time to respond in such detail. There is much there which I must mull over.

    ‘Patients with MDD have an extremely low quality of life, perhaps the lowest quality of life that it is possible to experience.’

    I agree. I have a difficulty in deciding whether it is environment, or life’s experiences, that cause the neuron malfunctions (Szasz’s position) or if depression is the result of a brain disorder, aside from strokes and alzheimers. I think that depression, like physical pain, persists because of an evolutionary benefit to the individual. So the fact that the DSM5 will be removing the bereavement clause from the diagnosis of MDD is a bit depressing. So if ECT can cause an increase in neurons which will benefit us all eventually why not give it to everyone? I myself, am worried about exactly which neurons I will lose. My father, who had a course of ECT for a milder depression, came back in a state of confusion, cognitive impairments, loss of memory and therefore of the self, and a personality change from which he never recovered. Although I know this is only anecdotal experience, I do remain skeptical of the claims.

  141. Dirk Steeleon 17 Apr 2012 at 9:36 pm

    @daedalus2u

    So do you think that suffering is a disease?

  142. Dirk Steeleon 17 Apr 2012 at 9:37 pm

    This is an interesting (altho non scientific) concept.

  143. Dirk Steeleon 05 May 2012 at 7:29 am

    http://www.youtube.com/watch?v=nH2F30jSO3E&feature=relmfu

  144. Philip Hickeyon 21 Nov 2013 at 3:43 pm

    I have written a critique of this post here.

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