Fact or Fiction? There ten times more glia than neurons in the brain.

"We only use 10% of our brains" is one of the most commonly held brain myths. But as the Neuroscience for Kids website tells us,

There is no scientific evidence to suggest that we use only 10% of our brains.

Neuroscientists, of course, already know that. But are there other false beliefs about the brain? Brain Mythology is a new column in the journal Brain Structure and Function, edited by Laszlo Zaborszky and Karl Zilles. In the first installment, Hilgetag and Barbas (2009) ask the question, Are there ten times more glia than neurons in the brain?

Neuroscience students take it for granted that there are many more glia than neurons in the brain. Neuroscience textbooks state with confidence: “Although there are many neurons in the human brain…, glia outnumber neurons by tenfold” (Bear et al. 2006) or, not to be outdone, even by “10–50 times”, as claimed in another text (Kandel et al. 2000). This fact is happily invoked by gliologists to promote the status of their field.

Damn those status-conscious gliologists! They've been leading us astray!

Given this well-accepted figure, we were surprised when our cell counts in the prefrontal cortex of the rhesus monkey turned up a glia-to-neuron ratio (GNR) of just about 1 (Dombrowski et al. 2001). There was some regional variation, but no prefrontal area had a GNR larger than 1.2. Maybe the proportion of glia is very different in other cortical regions or other parts of the brain, so that the overall ratio for the whole brain is much larger than 1? Classic studies, however, conducted by O’Kusky and Colonnier (1982) in the opposite pole of the brain, the visual cortex, had reported an even lower GNR of 0.5.

From Fig. 5A (Dombrowski et al., 2001). The ratio of glia/neurons in prefrontal areas or subdivisions of areas.

The origin of the glial dominance myth is not clear at all. Hilgetag and Barbas conclude by mentioning that...

Since the number of synapses increases faster than the number of neurons in larger brains, this affiliation of glia with the multitude of neural connection points may help explain... For example, in large brains such as the human brain... there may be as many as 1.4 astrocytes for each neuron, up from 0.33 in the rodent cortex (Nedergaard et al. 2003). Even that ratio, however, is still a long way from the myth of 10 times more glia than neurons, in any species.

Those species include humans of course, who are like monkeys with a nearly perfect 1:1 neuron:glia ratio [as noted by Jason Snyder].

References

Bear MF, Connors B, Paradiso M (2006). Neuroscience—exploring the brain, 3rd edn. Lippincott Williams & Wilkins, Philadelphia.

Dombrowski S, Hilgetag CC, Barbas H (2001). Quantitative architecture distinguishes prefrontal cortical systems in the rhesus monkey. Cereb Cortex 11:975–988.

Hilgetag, C., & Barbas, H. (2009). Are there ten times more glia than neurons in the brain? Brain Structure and Function, 213 (4-5), 365-366. DOI: 10.1007/s00429-009-0202-z

Kandel ER, Schwartz JH, Jessell TM (eds) (2000). Principles of neural science, nerve cells and behavior, 4th edn. McGraw-Hill, New York, p 22.

Nedergaard M, Ransom B, Goldman SA (2003). New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci 26:523–530

O’Kusky J, Collonnier M (1982). A laminar analysis of the number of neurons, glia, and synapses in the adult cortex (area 17) of adult macaque monkeys. J Comp Neurol 210:278–290.


Image via EduSpaces.

A Highlighted Blog at Nature

The Neurocritic has been mentioned as a highlighted blog at nature.com, along with Good Math, Bad Math. Check out some of the other blogs in the Nature Network and beyond. Of the major non-OA (open access) publishers, NPG has been ahead of the curve in its online presence.

Thanks for the honor!

Neuro Gasm Is Part Of The New Neuro Culture

"Neuro is an innovative beverage company dedicated to developing the highest quality functional beverages available."


One gets PASSION IN EVERY BOTTLE with Neuro Gasm, which

utilizes L-arginine and L-citrulline to improve a healthy blood flow, improve performance and keep you at your best when you need it the most.

Neuro makes a total of 7 different drinks for adults and 7 for kids (junior, however, gets NeuroFun™ instead of Gasm). The company has great product placement, with many celebrity endorsements:


Paris Hilton Drinks Neuro, So Should You



Neuro Gaga

The products are unlikely to help your Neuro Anything, but the shapely packaging has drawn raves from marketers.

Now it's time for some Neuro Sleep...


...ZZzzzZz. If it actually worked.

Tortured Brains Tell Tall Tales

OR: Neuroscience Shows Why Torture Doesn't Work


Former CIA Agent Speaks Out - The controversial interrogation technique known as waterboarding, which the CIA agent says was used on [Abu] Zubaydah [see this Justice Department memo, PDF], occurs when a suspect has water poured over his mouth and nose to stimulate a drowning reflex as demonstrated in the picture [above]. (ABC News)

With the Obama administration's recent release of the voluminous Bush-era memos authorizing torture, much has been written about whether or not "aggressive interrogation of captured terrorists" ¹ works, i.e. produces the desired result of extracting accurate and useful information.

Excerpt of Jay Bybee's memo (see Glen Greenwald's column in salon.com).

In a new Science and Society article in Trends in Cognitive Sciences, ² Shane O'Mara outlines the scientific reasons why a brain subjected to extreme stress will not yield accurate information:

The use of such techniques appears motivated by a folk psychology that is demonstrably incorrect. Solid scientific evidence on how repeated and extreme stress and pain affect memory and executive functions (such as planning or forming intentions) suggests these techniques are unlikely to do anything other than the opposite of that intended by coercive or ‘enhanced’ interrogation.

O'Mara didn't actually study the brains of individuals subjected to torture. Instead, he carefully read the memos and then made inferences from the literature on how memory is affected by physical and psychological stress, sleep deprivation, and anxiety.

Stress causes heightened excitability or arousal in the brain and body, a perception that present or future events will be very unpleasant combined with a lack of controllability over these events. Experiencing stress causes release of stress hormones (cortisol; catecholamines such as noradrenaline). Stress hormones provoke and control the ‘fight or flight’ response (the immediate and rapid preparation by body and brain for action in response to threat) which, if overly-prolonged, may result in compromised cognitive neurobiological function (and even tissue loss) in these brain regions. Both the hippocampus and the prefrontal cortex are particularly rich in receptors activated by stress hormones. Cortisol binds preferentially to glucocorticoid receptors in hippocampus and prefrontal cortex, increasing Ca++ access, and thus neuronal excitability which will compromise normal physiological functioning of neurons if it is sustained.

Importantly, O'Mara then reviews specific evidence that torture is likely to produce the exact opposite of the intended effect: false memories, confabulations, and less accurate information.

Extreme stress studies in Special Operations Soldiers (Morgan et al., 2006) have found impaired visuo-spatial capacity and impaired recall of previously-learned information in stressed soldiers (who undergo stress, including food and sleep deprivation, during training modelled on the experiences of American prisoners-of-war). Brain imaging in persons previously subjected to severe torture suggests that abnormal patterns of activation are present in the frontal and temporal lobes, leading to deficits in verbal memory for the recall of traumatic events (Ray et al., 2006; Catani et al. 2009).

A previous post by The Neurocritic covered The Guantánamo Testimonials Project and The Neurobiology of Psychological Torture. These research projects are being conducted at the Center for the Study of Human Rights in the Americas. CSHRA summarizes their work on The Neurobiology of Psychological Torture as follows:

... Psychological torture (henceforth PT) is a set of practices that are used worldwide to inflict pain or suffering without resorting to direct physical violence. PT includes the use of sleep deprivation, sensory disorientation, forced self-induced pain, solitary confinement, mock execution, severe humiliation, mind-altering drugs and threats of violence—as well as the exploitation of personal or cultural phobias. The psychiatric sequelae of PT are severe. They include delirium, psychosis, regression, self-mutilation, cognitive impairment, and anxiety disorders, including post-traumatic stress disorder. Neuroscience research on these and related mental disorders continues to establish their neurobiological underpinnings, thus challenging the popular view that PT is not physical, not serious, and perhaps not even torture at all.

Rendered brain showing abnormal brain activity in torture victims. This picture (white-gray matter border) shows regions in red with excess slow wave activity which is strongest in the left insula (see Kolassa et al. "Imaging the trauma: altered cortical dynamics after repeated traumatic stress") and the left frontal inferior region (see Ray, Elbert, et al. "Survivors of organized violence often left with traumatic memories." Psychological Science Volume 17, Issue 10, October 2006). Blue indicates less activity than normal. Photo: Courtesy of Dr. Thomas Elbert, Univerity of Konstanz, Germany.

The proceedings from a workshop conducted in 2006 were published as a book, The Trauma of Psychological Torture. Let's see Dick Cheney, John Yoo, Jay Bybee, and their ilk produce any scientific evidence to the contrary.

ADDENDUM: The paper is now available for download from Trends in Cognitive Sciences. DOI: 10.1016/j.tics.2009.09.001 [download PDF]

Footnotes

¹ "The Latest Euphemism From The Torture Party" according to Andrew Sullivan. I also recommend The Gestapo Precedent for "EITs" [Enhanced interrogation techniques]. For more on O'Mara's paper, read The Tortured Brain by Sharon Begley.

² Also covered by ScienceInsider, which made the paper available before it appeared on the TICS website. See Torture Can't Provide Good Information, Argues Neuroscientist (by John Bohannon).

References

Catani C, Adenauer H, Keil J, Aichinger H, Neuner F. (2009). Pattern of cortical activation during processing of aversive stimuli in traumatized survivors of war and torture. Eur Arch Psychiatry Clin Neurosci 259:340-51

Morgan CA 3rd, Doran A, Steffian G, Hazlett G, Southwick SM. (2006). Stress-induced deficits in working memory and visuo-constructive abilities in Special Operations soldiers. Biol Psychiatry 60:722-729.

O'Mara S (2009). Torturing the Brain: On the folk psychology and folk neurobiology motivating ‘enhanced and coercive interrogation techniques’. Trends in Cognitive Sciences. DOI: 10.1016/j.tics.2009.09.001

Ray WJ, Odenwald M, Neuner F, Schauer M, Ruf M, Wienbruch C, Rockstroh B, Elbert T. (2006). Decoupling neural networks from reality: dissociative experiences in torture victims are reflected in abnormal brain waves in left frontal cortex. Psychol Sci. 17:825-829.

Are Antidepressants UNDERprescribed in Primary Care Settings?

Despite everything else you've heard and read (and watched on ABC) recently, the answer is yes. Or maybe. At least in Scotland. Antidepressants might be UNDERprescribed by General Practitioners, according to a new study published in the British Journal of General Practice (Cameron et al., 2009). The authors conducted a chart review of 898 adults screened for anxiety and depression in a general practice setting. They concluded:

Rather than prescribing indiscriminately (as has been widely assumed), it is likely that GPs are initiating antidepressant treatment conservatively.

However, another article in the same issue of the journal interviewed 63 GPs to determine their explanations for the dramatically increased rate of prescribing in Scotland (Macdonald et al., 2009). Many thought the present-day level of prescribing was too high and

believed that unhappiness, exacerbated by social deprivation and the breakdown of traditional social structures, was being 'medicalised' inappropriately.

In contrast to Cameron and colleagues, MacDonald et al. concluded that antidepressants are OVERprescribed by GPs in Scotland, and recommended a change in prescribing patterns (as have many others).

So which is it? Who are we to believe? Unfortunately, I don't have access to either paper, so we'll have to make do with the abstracts.

References

Cameron, I., Lawton, K., & Reid, I. (2009). Appropriateness of antidepressant prescribing: an observational study in a Scottish primary-care setting British Journal of General Practice, 59 (566), 644-649 DOI: 10.3399/bjgp09X454061

Background: Since the 1990s, Scottish community-based antidepressant prescribing has increased substantially. Aim: To assess whether GPs prescribe antidepressants appropriately. Design of study: Observational study of adults (aged ≥16 years) screened with the Hospital Anxiety and Depression Scale (HADS) attending a GP. Setting: Four practices in Grampian, Scotland. Method: Patients (n = 898) completed the HADS, and GPs independently estimated depression status. Notes were scrutinised for evidence of antidepressant use, and the appropriateness of prescribing was assessed. Results: A total of 237 (26%) participants had HADS scores indicating 'possible' (15%) or 'probable' (11%) depression. The proportion of participants rated as depressed by their GP differed significantly by HADS depression subscale scores. ... In 101 participants with 'probable' depression, GPs recognised 53 (52%) participants as having a clinically significant depression. Inappropriate initiation of antidepressant treatment occurred very infrequently. Prescribing to participants who were not symptomatic was accounted for by the treatment of pain, anxiety, or relapse prevention, and for ongoing treatment of previously identified depression. Conclusion: There was little evidence of prescribing without relevant indication. Around half of patients with significant symptoms were not identified by their GP as suffering from a depressive disorder: this varied inversely with severity ratings. Rather than prescribing indiscriminately (as has been widely assumed), it is likely that GPs are initiating antidepressant treatment conservatively.

Macdonald, S., Morrison, J., Maxwell, M., Munoz-Arroyo, R., Power, A., Smith, M., Sutton, M., & Wilson, P. (2009). ‘A coal face option’: GPs' perspectives on the rise in antidepressant prescribing British Journal of General Practice, 59 (566), 299-307 DOI: 10.3399/bjgp09X454106

Background: Levels of antidepressant prescribing have dramatically increased in Western countries in the last two decades. Aim: To explore GPs' views about, and explanations for, the increase in antidepressant prescribing in Scotland between 1995 and 2004. Design: Qualitative, interview study. Setting: General practices, Scotland. Participants: GPs in 30 practices (n = 63) purposively selected to reflect a range of practice characteristics and levels of antidepressant prescribing. Method: Interviews with GPs were taped and transcribed. Analysis followed a Framework Approach. Results: GPs offered a range of explanations for the rise in antidepressant prescribing in Scotland. Few doctors thought that the incidence of depression had increased, and many questioned the appropriateness of current levels of prescribing. A number of related factors were considered to have contributed to the increase. These included: the success of campaigns to raise awareness of depression; a willingness among patients to seek help; and the perceived safety of selective serotonin reuptake inhibitors, making it easier for GPs to manage depression in primary care. Many GPs believed that unhappiness, exacerbated by social deprivation and the breakdown of traditional social structures, was being 'medicalised' inappropriately. Conclusion: Most antidepressant prescriptions in Scotland are issued by GPs, and current policy aims to reduce levels of prescribing. To meet this aim, GPs' prescribing behaviour needs to change. ...

Chinese Dissidents Committed to Mental Hospitals

The PBS Newshour reports on political dissidents and petitioners in China who are sentenced to psychiatric hospitals.



Special correspondent Shannon Van Sant reports:

SHANNON VAN SANT: ...I traveled to Wuhan to talk with another Chinese activist, Liu Feiyue, but he was under house arrest. Liu heads an NGO that is currently following 100 cases of wrongful psychiatric detention. Over the last three years, he says he knows of 500 more whistleblowers and protesters who have been detained in mental hospitals.

Robin Munro, who has extensively researched psychiatric detention in China and written two books on the topic, thinks the practice is widespread.

ROBIN MUNRO, human rights activist: China's experience in this area is far more serious and extensive than any other country.

SHANNON VAN SANT: Munro, who is based in Hong Kong, believes that since there are no national mental health laws protecting the rights of people who have been compulsorily hospitalized, but there are rules limiting arbitrary arrest, hospitals are becoming a convenient means of silencing protesters.

ROBIN MUNRO: Once diagnosed in this way, as dangerously mentally ill, citizens have no rights. They have no legal right to see a lawyer; they have no legal right to be brought before a judge so that a judicial determination can be made.

via China Digital Times.

Great and Desperate Cures for Addiction

《Chinese Journal of Drug Dependence》1999-04

Does anyone know what aerosol bioelectricity is?? And why it might be used to treat heroin addiction? The entire literature seems to be in Chinese. I came across that particular paper while searching for others, specifically reports on ablative psychosurgery¹ for the treatment of opiate addiction in China (Gao et al., 2003 is the first in English). Hence, the title of the present post is a reference to the book by Elliot Valenstein, Great and Desperate Cures: The Rise and Decline of Psychosurgery and Other Radical Treatments for Mental Illness.

Are there other "unusual" Chinese treatments for addiction, beyond what might be expected (e.g., acupuncture and traditional medicine)? Tetrodotoxin (TTX), a neurotoxin found in puffer fish, is a worthy runner up to aerosol bioelectricity. TTX inhibits action potentials by blocking voltage-dependent sodium channels. It has been tested as a treatment for severe cancer pain, which motivated Shi and colleagues (2009) to compare low dose TTX to placebo in abstinent addicts. After watching a heroin-related video, the group receiving TTX reported lower levels of craving and anxiety, without alterations in heart rate or blood pressure. However, these acute results were from a single session with no long-term follow up.

Although Chinese treatments for internet addiction are getting all the headlines these days, drug addiction is actually a much more serious problem. In their review of the literature, Tang et al. (2006) inform us that:

Historically, China has had extraordinarily high rates of opiate dependence. These rates declined drastically following the 1949 revolution; however, opiate abuse has re-emerged in the late 1980's and has spread quickly since then. ... The number of registered addicts in 2004 was 1.14 million (more than 75% of them heroin addicts), but the actual number is probably far higher. Opiate abuse contributes substantially to the spread of HIV/AIDS in China, with intravenous drug use the most prevalent route of transmission (51.2%). Currently, the main treatments for opiate dependence in China include short-term detoxification with opiate agonists or non-opiate agents, such as clonidine or lofexidine [alpha-2 adrenergic drugs that inhibit norepinephrine release]; Chinese herbal medicine and traditional non-medication treatments are also used. Methadone maintenance treatment (MMT) has not been officially approved by the Chinese government for widespread implementation, but some pilot studies are currently underway.

Which brings us back to neurosurgery. But before discussing the results of Gao et al., a quick review. In the last post, we learned about a new and less desperate cure, the application of Deep Brain Stimulation for Severe Alcoholism. The target region in this small clinical trial (n=3) was the nucleus accumbens (NAcc), which has been called a "pleasure center" and "hedonic hot spot" that responds to food and pharmaceutical and financial and sexual rewards. The idea behind NAcc DBS was to reduce alcohol craving and "incentive sensitization" in severely impaired patients who had failed multiple treatments (Heinze et al., 2009). The researchers drew upon the experimental and theoretical work of Berridge and colleagues (2009) distinguishing between the "wanting" (incentive salience) and "liking" (hedonic impact) aspects of reward:

Usually a brain ‘likes’ the rewards that it ‘wants’. But sometimes it may just ‘want’ them. Research has established that ‘liking’ and ‘wanting’ rewards are dissociable both psychologically and neurobiologically. By ‘wanting’, we mean incentive salience, a type of incentive motivation that promotes approach toward and consumption of rewards, and which has distinct psychological and neurobiological features.

"Liking" has been strongly linked to endogenous opioid systems in the NAcc and ventral pallidum [part of the globus pallidus] as shown below.²


From Fig. 1 (Berridge et al., 2009). Forebrain hedonic hotspots in nucleus accumbens shell and in ventral pallidum where mu opioid agonist microinjections cause amplification of ‘liking’ reactions to sweetness. Red/yellow indicates greatest amplification of ‘liking’ for the sensory pleasure.

In contrast, "wanting" has been most strongly associated with dopamine in the NAcc, but in reality...

...brain substrates for ‘wanting’ are more widely distributed and more easily activated than substrates for ‘liking’. Neurochemical ‘wanting’ mechanisms are more numerous and diverse in both neurochemical and neuroanatomical domains... In addition to opioid systems, dopamine and dopamine interactions with corticolimbic glutamate and other neurochemical systems activate incentive salience ‘wanting’. Pharmacological manipulations of some of those systems can readily alter ‘wanting’ without changing ‘liking’. For example, suppression of endogenous dopamine neurotransmission reduces ‘wanting’ but not ‘liking’.

Addiction is conceived as a process by which drugs of abuse produce neural sensitization and compulsive "wanting" even in the absence of "liking". With this literature in mind, Gao et al. (2003) wished to:

...explore a new way of treating drug addiction by ablating the NAcc... using stereotactic surgery, blocking the mesocorticolimbic dopamine circuit, alleviating craving for drugs and lowering the relapse rate after detoxification. On the basis of animal experiments, stereotactic surgery was performed in 28 patients by making a lesion in the NAcc bilaterally to treat opiate drug dependence.

I'm not so sure the surgeons were able to isolate the "wanting" from the "liking" regions of the NAcc, since they seem to be anatomically adjacent as shown below.

Fig. 2 (Berridge et al., 2009). Expansion of mu opioid hotspot in nucleus accumbens with delineation of ‘liking’ versus ‘wanting’ zones. Green: the entire medial shell mediates opioid-stimulated increases in ‘wanting’ for food reward. Orange-red: circumscribed cubic-millimeter sized hedonic hotspot generates increases in ‘liking’ after the same opioid stimulation. Blue: a small hedonic ‘coldspot’ suppresses ‘liking’ reactions to sucrose, whereas a larger purple zone suppresses ‘disliking’ reactions to quinine.

Were the surgeries successful? Not so much:

The mean follow-up period was 15 months. Relapse has not occurred in 11 cases up till now. Drug-free time in these patients has been more than half a year in 4 cases (more than a year in 3 cases), and less than half a year in 7 cases. Relapse occurred in 15 cases after surgery. Drug-free time in these patients was more than half a year in 3 cases, between 1 month and half a year in 10 cases and less than 1 month in 2 cases.

Plus there were side effects in some patients: personality changes were seen in 2 and temporary memory loss in 4. Last but not least was the issue of informed consent, which wasn't discussed at all in the paper. Alarmingly, the psychological state of the patients before surgery seems to suggest they lacked capacity to give informed consent:

Analysis of the results showed that the patients’ psychohygienic situation was poor prior to the operation and their personalities were characterized by unstable emotion, being seriously distressed by tonicity and prone to following their own course, running risks and doing everything without considering the consequences, paranoid state, low intelligence level, mental aberration and weak-willedness.

In comparison, the careful screening procedures of Heinze et al. (2009) and the reversible nature of their intervention are vastly superior. Comments on my previous post have ranged from unbridled enthusiasm for DBS ³ (also see Best Before Yesterday) to skepticism ("We still have no idea whether this will this actually work"), with caution and curiosity in between. I suspect the antipsychiatry trolls [the comment is priceless] might come out of the woodwork for this one. In this case, I would agree that criticism is warranted.

Footnotes

¹ Wikipedia warns us that "The medical procedure of psychosurgery should not be confused with psychic surgery — surgery purportedly performed by paranormal means."

² "Liking" has also been associated with endocannabinoid and GABA_A-benzodiazepine systems in the brain.

³ For more information on DBS for intractable depression, see The Neurocritic's archival posts:

The Sad Cingulate

Sad Cingulate on 60 Minutes and in Rats

NAcc Localization for DBS

...and two articles by science writer David Dobbs:

A Wiring Diagram in the Brain for Depression

A Depression Switch?

References

Berridge KC, Robinson TE, Aldridge JW. (2009). Dissecting components of reward: 'liking', 'wanting', and learning. Curr Opin Pharmacol. 9:65-73.



Gao, G., Wang, X., He, S., Li, W., Wang, Q., Liang, Q., Zhao, Y., Hou, F., Chen, L., & Li, A. (2003). Clinical Study for Alleviating Opiate Drug Psychological Dependence by a Method of Ablating the Nucleus accumbens with Stereotactic Surgery. Stereotactic and Functional Neurosurgery, 81 (1-4), 96-104 DOI: 10.1159/000075111

Heinze, H. et al. (2009). Counteracting incentive sensitization in severe alcohol dependence using deep brain stimulation of the nucleus accumbens: clinical and basic science aspects. Frontiers in Human Neuroscience, 3.

Shi J, Liu TT, Wang X, Epstein DH, Zhao LY, Zhang XL, Lu L. (2009). Tetrodotoxin reduces cue-induced drug craving and anxiety in abstinent heroin addicts. Pharmacol Biochem Behav. 92:603-7.

Tang YL, Zhao D, Zhao C, Cubells JF. (2006). Opiate addiction in China: current situation and treatments. Addiction 101:657-65.

Deep Brain Stimulation for Severe Alcoholism

Deep brain stimulation (DBS) for treatment-refractory psychiatric disorders has been gaining in popularity. The procedure involves neurosurgery to implant stimulating electrodes aimed at a target region inside the brain. It works using the same sort of pacemaker-like device used for DBS in Parkinson's disease, which has been remarkably successful at alleviating symptoms. DBS as a treatment for neurological disorders such as Parkinson's, primary generalised dystonia, atypical tremor syndromes, cluster headache, phantom limb pain, and epilepsy has been mostly unobjectionable.

However, the Neurological/Psychiatric Divide makes DBS for mental illnesses such as major depression and obsessive compulsive disorder more ethically problematic. A new paper in the Archives of General Psychiatry (Rabins et al., 2009)¹ summarizes a consensus conference held on this and related issues (such as human subjects protection and the design of clinical trials). A list of 16 guidelines was issued, which included the following:

2. Deep brain stimulation for disorders of MBT [Mood, Behavior, and Thought] is at an early proof-of-principle stage and must be considered investigational. Currently, no single target has been validated or demonstrated to be superior to others in any disorder of MBT. Therefore, it is premature to rule out the study of new implantation sites that have a good scientific rationale...

3. The comparative efficacy and safety of DBS vs other treatments, including ablative surgery, should be studied further. Such studies are ethical and scientifically necessary.

4. Given its history, neurosurgical intervention for disorders of MBT is a socially and culturally sensitive area of research and practice. Therefore, DBS for disorders of MBT should be studied in carefully designed trials and should be performed only at expert centers that are participating in such trials and that adhere to the highest scientific, clinical, and ethical standards.

. . .

12. The consent process should include discussion of what is and is not known about long-term consequences of DBS. Potential adverse outcomes include potentially limiting participation in future research, inability to use certain other treatments, and an inability to undergo certain tests. ... Additionally, the consent process should state explicitly that, even with positive outcomes, DBS for disorders of MBT is unlikely by itself to improve all aspects of the individual's mood, function, and interpersonal relationships: DBS is only one aspect of a comprehensive treatment program.

The specific indications mentioned by Rabins and his 18 co-authors were major depression, obsessive-compulsive disorder, and Tourette syndrome. Severe alcohol dependence was not included as one of the disorders. DBS for alcoholism sounds rather drastic, doesn't it? Nonetheless, a German research group led by Hans-Jochen Heinze (et al., 2009) was not deterred. They recently reported results from 3 male patients² with severe and refractory alcohol dependence as part of a small clinical trial that will ultimately include 10 patients.

Inclusion criteria are: male gender, age 25–60 years, finished detoxification and subsequent period of abstinence of at least 2 weeks. Moreover, the patients are required to have demonstrated treatment failures of at least two inpatient programs of at least 6 month duration, failure of anti-craving substances (e.g., acamprosate, naltrexone), failure of community and self-help programs. ... Patients are excluded, if they meet any of the following criteria: seizures during the detoxification phase, high score on neuroticism scales, antisocial personality disorder, clinically significant impairments on a neuropsychological test battery Further exclusion criteria were circumscribed brain damage or marked atrophy on MRI, alcohol-related personality change, and use of additional addictive substances.

The target region? The nucleus accumbens (NAcc), the “Universal Addiction Site” -- an oversimplification, they admit, but still, the NAcc is...

...a central place in orchestrating the events related to the “wanting” [Robinson & Berridge, 2008] of alcohol on the one hand and drug-induced neural sensitization on the other hand. Anatomically, the NAcc receives inputs from the prefrontal cortex on the one hand and limbic structures such as the hippocampus and amygdala on the other. This circuitry allows for the integration of contextual information arising from hippocampus and emotional information coming from the amygdala with cognitive information supplied by the PFC in the selection of goal-directed behaviors in general and behaviors related to drug “wanting” in particular, which is why the NAcc has been called a limbic-motor interface.

Since anatomical information was not illustrated in the current paper, a figure from the earlier work of Schlaepfer et al., (2007) is presented below.


The topographical location of the nucleus accumbens in relation to other brain structures on a horizontal plane 3 mm below the AC-PC plane (Schlaepfer et al., 2007).

That protocol was designed to relieve anhedonia (inability to experience pleasure from normally pleasurable life events) in major depression. Why not stimulate the "pleasure center" when you're feeling blue? Extensive research in animals and humans has demonstrated "hedonic hot spots" (Pecina et al., 2006) [or "liking" of pleasant sensory experiences] in the NAcc that respond to food and pharmaceutical and financial and sexual rewards.

But what are the procedures for targeting the same region to reduce reward and pleasure? Well, we don't know from reading Heinze et al. (2009): "Details regarding the stimulation protocols in the different patients can be found elsewhere" [insert citation of an in press paper that is not online yet]. Details on the "clinical aspects" are pretty sparse and the focus is on the "basic science aspects" (electrophysiological recording and cognitive task performance to assess action monitoring and the salience of drug-related cues).

Was the DBS treatment effective? All patients had failed multiple detox treatments, withdrawal therapies, and drug trials (acamprosate). Until the other paper is published, we have only anecdotal reports in the Methods.

Patient HM (age 36) had started to drink alcohol at age 12 and had a family history of alcoholism (father and two uncles). ... The patient was implanted on October 5, 2007 and has been abstinent since then. There were no psychological changes after the operation. The patient reported to have no craving symptoms and that he is thus able to derive pleasure from daily activities of life. He has found a job and has established new social contacts.

Patient GM (age 37) had started to drink alcohol at age 11 and had a positive family history (father, mother, several other relatives). ... Following the operation (January 13, 2008) this patient experienced a period of hypomania which stopped after stimulation parameters were changed. The patient has been abstinent since the operation and reports a complete reduction of his reaction to alcohol-related cues and craving.

Patient TM (age 40) had been alcohol-dependent since age 18 and had a positive family history (father). ... The patient was operated on September 13, 2007 and showed no psychological abnormalities in the postoperative period. He was fully abstinent until September 2008. Subsequently, he has experienced short periods of relapse of 1–2 weeks duration (10 weeks in the past 16 months). The patient remarked that he had never felt as good as currently and reported a considerable reduction in his reaction to alcohol-related cues.

To be continued....

Footnotes

1 Guidelines were also published by the German Deep Brain Stimulation Association (Voges et al., 2009).

² "A fourth had been implanted but electrodes had to be removed because of an infectious complication."

References



Heinze, H. et al. (2009). Counteracting incentive sensitization in severe alcohol dependence using deep brain stimulation of the nucleus accumbens: clinical and basic science aspects Frontiers in Human Neuroscience, 3. DOI: 10.3389/neuro.09.022.2009

Pecina S, Smith KS, Berridge KC. (2006). Hedonic hot spots in the brain. Neuroscientist 12:500-11.

Rabins, P. et al. (2009). Scientific and Ethical Issues Related to Deep Brain Stimulation for Disorders of Mood, Behavior, and Thought. Archives of General Psychiatry, 66 (9), 931-937.

Robinson TE, Berridge KC. (2008). Review. The incentive sensitization theory of addiction: some current issues. Philos Trans R. Soc Lond B Biol Sci. 363:3137-46.

Schlaepfer TE, Cohen MX, Frick C, Kosel M, Brodesser D, Axmacher N, Joe AY, Kreft M, Lenartz D, Sturm V. (2008). Deep Brain Stimulation to Reward Circuitry Alleviates Anhedonia in Refractory Major Depression. Neuropsychopharmacology 33:368–377.

090909090909

In Chinese numerology the number 9 is a homophone of the word for "long-lasting". So today seems like a good day to do something that will last a long time, right? However, from AgarAgar we learn:

Today sounds like a nice date to remember.. 090909.. Lots of ple say it a good date for marriage.. 999 in Chinese means long-lasting. However, as it falls in the lunar 7th mth, aka ghost mth. Therefore no much weddings are held on this date. Maybe some ROMs or non-chinese are having weddings today bah.

In contrast, 080808 was such a lucky number that the Opening Ceremony of the 2008 Olympics in Beijing began at 8:08PM on 08/08/08.

The vagueness of Western Numerology is much like reading your horoscope or going to a fortune teller. Here's some information on the number nine:

In Numerology, the positive characteristics of nine (9) are selflessness, fulfillment, completion, universality, universal understanding, interrelatedness, compassion, idealism tolerance, forgiveness, generosity, benevolence, humanitarianism, emotionalism, and justice. Nine is also associated with accomplished artists and thinkers who are inspired by universal truths. Simultaneously, 9 can represent negative characteristics, from selfishness to extravagance to vulgarity -- essentially the opposites of the positive characteristics.

How very useful and specific!!


From nmnl’s posterous.

RULE 34: WHAT NETPORN TELLS US ABOUT THE BRAIN

That is (or was) the title of a book by Ogi Ogas and Sai Gaddam,¹ to be published by Dutton in 2010. How on earth do I know this? Back in July, The Neurocritic noticed a number of visitors to the post Voodoo Correlations in Social Neuroscience (about the infamous paper by Vul et al.) who came from a link on the LiveJournal of shaggirl. Specifically, the traffic was from her entry A response from our friendly scientists... I took note of it, thought I might write about it but other topics took precedence. But this week, a larger surge of visitors arrived from various LiveJournal sites.² The reason? Let's start at the beginning.



Shaggirl was "contacted by a couple of guys researching and writing about online fanfic."

Hi, Shaggirl:

I'm a cognitive neuroscientist at Boston University writing a book for Dutton (an imprint of Penguin) about how the Internet reveals new insights into some of the oldest circuits in our brain which control romantic attraction and sexual behavior. I was very much hoping you might be willing to chat about Crack Van on LJ.

. . .

For our research, we're quite interested in learning about how people creatively use text and fiction to express and explore sexuality. If you're willing, we'd like to ask questions about Crack Van and about adult fanfic in general. If you'd like, we'd be happy to include a positive mention of you and/or Crack Van in the book (or respect your privacy, if you'd prefer).

If you have any questions about our research or book, please don't hesitate to ask! I look forward to hearing from you! :)

Dr. Ogi Ogas
Department of Cognitive and Neural Systems
Boston University

I do not want to begin a lengthy discourse on fan fiction, other than to quote Wikipedia:

Fan fiction (alternately referred to as fanfiction, fanfic, FF, or fic) is a broadly-defined term for fan labor regarding stories about characters or settings written by fans of the original work, rather than by the original creator. Works of fan fiction are rarely commissioned or authorized by the original work's owner, creator, or publisher; also, they are almost never professionally published. Fan fiction, therefore, is defined by being both related to its subject's canonical fictional universe and simultaneously existing outside the canon of that universe.

So who is Ogi Ogas? While a grad student at Boston University, he entered a well-known game show, won $500,000 and wrote about it in SEED magazine:

Who Wants to Be a Cognitive Neuroscientist Millionaire?

A researcher uses his understanding of the human brain to advance on a popular quiz show.

Even with all 4 choices available, it's obvious the answer is D ("Heroin: the sedative for coughs"). Prescription cough syrup contains codeine, which is a cough suppressant. [However, it is easy to say that when the stakes are nil. ANYWAY.]

In response to some questions about their book project, Gaddam replied:

Before putting any questions, let me give a brief overview of our scientific perspective and how it will inform the book. As cognitive neuroscientists, we are respectful of the fascinating diversity of the neural landscape. And this diversity, we believe, is reflected in the terrain of erotic fantasy.

The internet and e-publishing now allow for a revolutionary and unprecedented disclosure of all our fantasies, not just those decided as marketable and mainstream for print. Digital publishing seems to have lead to an explosion in the array of fantasies we can now experience and learn from; the loop of imagination, desire, and actuality is now tighter. We want to 'neuro-scientifically' explore what this blossoming of fantasy means for us as individuals, and as a society. How does this access to all manner of fantasies imaginable change our brains?

Given this broad overview, we have some specific questions, and more general ones about adult fanfic, that we are hoping you can help us with. I do apologize if some questions seem naive and/or I inadvertently mis-characterize something in my ignorance!

He then goes on to ask a number of questions about adult fanfic. Dana (shaggirl) replied in a lengthy, thoughtful post in which she explains fandom ("composed primarily of well educated women, most of whom self-identify as geeks"), objects to the word "netporn" in their book title, and answers all 7 questions. Then A response from our friendly scientists... where yours truly gets a mention:

. . .

One quick note about the subtitle of the book: the current title is largely driven by the pre-publication marketing needs of the publication industry, and was determined by our editor. The eventual subtitle will likely change; it may still contain the term netporn, though this is increasingly unlikely [NOTE: Unlike the screenshot above, the current book project list from Gail Ross shows the NETPORN subtitle has indeed been removed]. ...

In terms of turning this into hard science, our primary goal is to make a strong case for the study of fantasy as being accessible in this era of copious datastreams from humans. To give you one example of the kind of current study in neurosexual behavior that we feel is quite limited, there was an article in the Time magazine (http://www.time.com/time/health/article/0,8599,1911103,00.html) on how girls focus more on best friends while boys are more interested in group dynamics and 'packs'. The authors of the study tied this observation to the differential activation patterns in the brain based on how the subject group of boys and girls rated pictures of strangers. The article state that the "nucleus accumbens (which is associated with reward and motivation), hypothalamus (associated with hormone secretion), hippocampus (associated with social learning) and insula (associated with subjective feelings) all become more active."

The suspect and cavalier methodology of this study evoke some of the general problems that plague brain imaging experiments that purportedly examine social behavior [1]. We hope to make the case that such methodological contortions are not required when a vast pool of people provide behavioral data on the internet through quantifiable activity.

Polling feedback from groups would be immensely useful. We would definitely love your help in reaching other fans...

[1] Here's a paper criticizing such casual treatment of the brain-behavior linkage, which has received a lot of attention in the neuroscience community (http://cns.bu.edu/~gsc/Articles/Vul_09_Voodoo.pdf). The content requires an understanding of imaging methodology, but the abstract is definitely accessible. Here's a posting from a popular neuroscience blog describing the article (http://neurocritic.blogspot.com/2009/01/voodoo-correlations-in-social.html)

Two things:

(1) They said the content of their book will be "Using new digital sources of data to illuminate brain regions and neural pathways involved in romantic and sexual behavior." However, they did not actually propose to measure brain function at all. They might be skeptical of fMRI, but it's a lot better than no real neural data at all.

(2) A poll. That generated an enormous amount of controversy in the fanfic community. [They're a very prolific bunch.] Hundreds of posts. Thousands of comments.

SurveyFail - an entire wiki devoted to the controversy.


For Science!

The poll was taken down (although you can view the questions elsewhere: part 1, part 2) and the ogi_ogas LiveJournal deleted (but here's a remnant):

So what kind of scientists are you anyway?

We're brain modelers. We're aligned with the relatively new field of cognitive neuroscience...

. . .

Our current research project will result in a model that makes novel behavioral and physiological predictions.

From a poorly written survey? And just when you think their project is a wee bit grandiose, the pomposity reaches stunning proportions:

The greater one's mathematical ability, the greater the opportunity for designing a powerful and sophisticated model. Superior models, such as those of Stephen Grossberg and Gail Carpenter, may include unsolvable systems of differential equations. Still, useful and productive models can be constructed using relatively straightforward mathematics.

Oh, and here's a ridiculous question:

How is straight female interest in slash fiction like straight male interest in "shemale"* models? And why in the world does this matter?

* ...We are aware that the term "shemale" may be used as a pejorative, but we are here referring to the narrowly defined term used in the adult industry for certain models.

One does not need to be an expert in any of these fields to see the problems inherent in the Ogas and Gaddam approach of inferring brain function from data on netporn usage (broadly construed) and unscientific polls. But it gets worse...

The structure and activity of our subcortical circuits are shaped by neurohormones such as testosterone, estrogen, oxytocin, progesterone, and vasopressin; these circuits function differently in men and women. As cognitive neuroscientists, we draw upon a wide variety of empirical data sources to model these circuits, including brain imaging studies, primate research, cognitive science experiments, machine learning algorithms--and behavioral data. The Internet offers large, unprecedented sources of data on human activity: one of these data sets is fan fiction.

We're deeply interested in broad-based behavioral data that involves romantic or erotic cognition and evinces a clear distinction between men and women. Fan fiction matches this criteria perfectly. Let us make clear, however: fan fiction is not the subject of our research. Our subject is the human brain. For us, fan fiction is a wonderfully rich source of data--like single-neuron recordings in rhesus monkeys--albeit a unique and invaluable one.

...because fan fiction is just as precise as single-unit recording at revealing putative sex differences in subcortical circuits. In spite of a wink and a nod to "erotic cognition" Ogas & Gaddam reveal elsewhere in their manifesto that they're not at all interested in cortical function.

Furthermore, were the ethics of conducting research on human subjects taken into consideration? Did the pair have proper approval from Boston University's Institutional Review Board? Here's deadlychameleon's investigation:

I called the Boston University IRB office. The direct approach works.

They've gotten a lot of emails regarding Dr. Ogas. He is no longer in any way affiliated with Boston University, except as a recent graduate. They have asked him to stop using his official Boston University email address in connection with this project, or his website. He is officially on his own, and this project is NOT IRB APPROVED.

That is the official status as stated by the Boston University IRB office.

And in the end, from a neuroscientific viewpoint, the premise of their work was fatally flawed. Dutton, are you listening?

Footnotes

¹ You'll notice these links are from the Google cache, because they took down their websites after the resulting furor. Both are recent graduates from the Department of Cognitive and Neural Systems at Boston University. Gaddam had not yet updated his resume to reflect this.

² Other visitors were from dreamwidth.org, a LiveJournal knockoff that had escaped my awareness until now.