Brain Responses to Virtual Reality-Induced Hallucinations in Schizophrenia

What is it like to experience the frightening auditory and visual hallucinations characteristic of schizophrenia? Yellowlees and Cook (2006) developed a virtual reality program in Second Life based on interviews with schizophrenic patients. The researchers used this as a tool to educate the general public about schizophrenia, in order to increase understanding and reduce stigma. A video sample of the program can be viewed below.



As you can see, these hallucinations are straight out of a horror movie or a terrible nightmare, except they reflect the reality of living with schizophrenia:

• Multiple voices, occasionally overlapping, criticizing the user
  
• A newspaper in which the word “death” would stand out in a headline
• A floor that would fall away, leaving the user walking on stepping stones above a bank of clouds
  
• A television that would play a political speech, but then criticize the user and encourage suicide
  
• A gun that would appear under a cone of light and pulse, with associated voices telling the user to take the gun and commit suicide
  
• A mirror in which a person's reflection would appear to die, becoming gaunt with bleeding eyes

The authors also provide information about accessing the Virtual Hallucination environment directly.

Persons with other psychiatric disorders may be plagued by voices saying they're worthless and directing them to commit suicide, but the voice is a self-deprecating internal monologue and clearly identified as their own (as in nonpsychotic unipolar and bipolar depression). The issue in schizophrenia is one of reality monitoring, so that internal thoughts and impulses are interpreted as external to the self.

The most common type of hallucination is hearing voices. To determine which brain regions are implicated, a number of neuroimaging studies have scanned participants with schizophrenia while they are actively experiencing auditory hallucinations, compared to the non-hallucinating state (Allen et al., 2008; Kompus et al., 2011; Jardri et al., 2011). A common finding is increased activation of auditory cortex in the absence of external stimulation, along with greater activity in Broca's area (speech production) and the medial temporal lobe (memory). One interpretation of this pattern is that memory retrieval triggers aberrant auditory perceptual experiences. Another is that inner speech is attributed to external sources due to defective self-monitoring.

A new study by Kim and colleagues (2012) took a different approach. They constructed a virtual reality environment in the scanner to produce the illusion of burning flames, and compared the neural responses of schizophrenic and control participants. The experimental setup is shown below.


Fig. 1A (adapted from Kim et al., 2012). The virtual flame illusion. A participant could see his/her body through a head-mounted display (HMD) during the “flame off” block and watched a superimposed, animated image of a virtual flame on the right or left index finger during the “flame on” block.


The participants were 16 schizophrenic patients with mild to moderately severe symptoms and 17 controls. They were instructed that the purpose of the experiment was to examine the brain's response to “observing the body.” However, they were not informed about the potentially frightening illusion:

Participants were not told about the virtual flame and were instructed to observe their body without closing their eyes. As shown in Fig. 1, the experiment used a blocked paradigm and consisted of two conditions: 1) a ‘flame off’ block (30 s), during which only a real-time body image was presented, and 2) a ‘flame on’ block (16 s), during which the virtual flame was generated by a computer in real-time and superimposed on the participant's index finger. The blocks were alternatively repeated 8 times, and the presentation of the flame on the left or the right finger was counterbalanced.

Fig. 1B (adapted from Kim et al., 2012). fMRI task sequence. The experiment used a blocked design and alternated between ‘flame off’ blocks (30 s) and ‘flame on’ blocks (16 s).


Lest you think this situation skirts the boundaries of unethical (as I did), the study was approved by the local institutional review board and subjects signed [semi-]informed consent statements.

After the fMRI session was over, the participants filled out a questionnaire which indicated (A) the strength of their reactions from 1 (“not at all”) to 7 (“extremely strong”), and (B) how much their feelings changed when the blocks were repeated, rated from 1 (“severely attenuated”) to 7 (“severely augmented”):

After scanning, most participants reported that they initially felt the ‘flame on their finger,’ but then the feeling disappeared after realizing that the flame was not real. . . . ...both patient and control groups showed similar subjective responses to the task stimuli: moderate strength in feeling the flame (4.6 ± 1.9 and 3.8 ± 1.8, respectively) and slight attenuation in flame strength over time (3.3 ± 1.8 and 2.6 ± 1.3, respectively). [The group differences were not statistically significant.]

The data analysis strategy went beyond the standard boxcar comparison between "flame on" and "flame off." Instead, the authors...

...considered that the process of virtual flame-specific learning (i.e., gaining insight into the reality of a visual image) might be reflected as a linear or quadratic function of fMRI signal changes. A linear function could reflect repetition enhancement, sensitization/repetition attenuation, or habituation to the stimulus. A quadratic function could reflect transitions between repetition enhancement and repetition attenuation.

The brain activation differences between groups were not all that spectacular, once you discard all the p<.001 uncorrected regions that were reported in Table 2. What was left?

...only five areas including the left anterior prefrontal cortex, left occipito-temporal junction, left occipital gyrus, right amygdala, and left cerebellum were included. As depicted in Fig. 2, the control group demonstrated transitions from repetition enhancement to attenuation in these five brain regions, in contrast to the lack of enhancement and attenuation in the patient group [i.e., a flat response].

Fig. 2 (Kim et al., 2012). Changing patterns of brain activity related to the virtual flame across time in patients with schizophrenia and in healthy controls. The selected regions were significant in the two-sample tests with the quadratic repetition-variant response at p < 0.05, FDR-corrected: the anterior prefrontal cortex (APFC), occipito-temporal junction (OTJ), occipital cortex (OC), amygdala (AMG), and cerebellum (CER). Rt., right; and Lt., left


Have we come away with a better understanding of the neural processes involved in gaining insight into unreality? Becoming aware of the fact that an unexpected and alarming visual illusion isn't real differs from internally generated hallucinations, of course, but the authors suggest that:

Patients with schizophrenia may use a salience-related region¹ instead of reality monitoring-related regions [anterior medial PFC] to react to the unusual stimuli, and this peculiarity of the neural processes may be related to vulnerability to psychosis.

Footnote

¹ The salience-related region (anterior cingulate cortex) did not survive FDR correction for multiple comparisons.


References

Allen P, Larøi F, McGuire PK, Aleman A. (2008). The hallucinating brain: a review of structural and functional neuroimaging studies of hallucinations. Neurosci Biobehav Rev. 32:175-91.

Kim JJ, Ku J, Lee H, Choi SH, & Kim IY (2012). Distinct neural responses used to gain insight into hallucinatory perception in patients with schizophrenia. Journal of psychiatric research PMID: 22770670

Kompus K, Westerhausen R, Hugdahl K. (2011). The "paradoxical" engagement of the primary auditory cortex in patients with auditory verbal hallucinations: a meta-analysis of functional neuroimaging studies. Neuropsychologia 49:3361-9.

Jardri R, Pouchet A, Pins D, Thomas P. (2011). Cortical activations during auditory verbal hallucinations in schizophrenia: a coordinate-based meta-analysis. Am J Psychiatry 168:73-81.

Yellowlees PM, & Cook JN (2006). Education about hallucinations using an internet virtual reality system: a qualitative survey. Academic Psychiatry, 30 (6), 534-9. PMID: 17139026

When we sit at a table there's fire between the guests
When your hands don't touch there's sand in your face
And fire under your nails
Nobody knew so nobody cared
Nobody knew so nobody cared
Nobody knows

Finished
------Throwing Muses

EMPowered to Kill

Mentally ill killer tried vitamin therapy, court told


A man with schizophrenia killed his father and gravely injured his mother at their home in North Vancouver, British Columbia. Jordan Ramsay was off his prescribed antipsychotic medication at the time, instead taking an alternative multivitamin preparation called Truehope EMPowerplus™. He believed his parents were aliens and felt compelled to kill them. Ironically, Wendy and Donald Ramsay were in favor of their son's Truehope treatment. But Jordan Ramsay's paternal aunt and grandmother disagreed strongly with this decision:

Leeann Ramsay, the aunt of the accused, believes the family's attempt to control his illness with an alternative therapy rather than his psychiatrist's prescription had a role in his state of mind at the time of the killing.

. . .

...just two days before the murder, a North Vancouver nurse reported, "His mother stated she wanted him on Empower Plus vitamins, and she believed she had permission to reduce his medication."

Leeann Ramsay told CBC News that Jordan's grandmother had serious concerns about the alternative treatment as well.

"My mom had various conversations with them about Jordan weaning off his anti-psychotics and trying this alternative megavitamin therapy, and my mom was very much against it."

Furthermore, Leeann Ramsay wants to launch an investigation into whether EMPowerplus™ played any role in her brother's death, subverting the antipsychiatry paradigm of blaming psychotropic medications for suicides and homicides.

Truehope EMPowerplus™ is no stranger to controversy. In June 2003 Health Canada advised Canadians not to use Empowerplus, and in July 2003 they executed a search warrant to seize imports from the US. The supplement was being marketed to treat bipolar disorder, anxiety, panic attacks, ADHD, schizophrenia, autism, Tourette’s syndrome, fibromyalgia, and OCD without a doctor's supervision and without an approved Drug Identification Number (DIN).

Our main concern deals with the unproven health claims being made about Empowerplus, and the recommendation that patients decrease the dose of, or eliminate altogether, medications prescribed by their doctors. This can result in serious adverse health consequences.

But no matter. The company continues to make false claims. For starters, the current title of the product webpage is still "Depression symptoms reduced or eleminated [sic] by taking EMPowerplus".


But what is EMPowerplus™ exactly? Truehope says it's A Revolutionary Micronutrient Formula...

...proven effective in reducing or eliminating the symptoms of bipolar, anxiety, depression, and ADHD. 16 medical journal publications, plus many individual doctors’ observations, have shown significant reductions in the symptoms of bipolar and other mental disorders.

That's interesting. ONE formulation to treat all of these disorders? Typically, the antidepressants and stimulants used to treat anxiety/depression and ADHD (respectively) are not recommended for bipolar disorder because of the risk of triggering a manic episode. The premise of the Truehope treatment strategy is that a "chemical imbalance" causes all mental illnesses:

The most common explanation for mental disorders is a chemical imbalance in the brain, but how and why these imbalances happen is not yet known. Since a complex web of nutrients, such as zinc, vitamin B6, and vitamin B12, are the building blocks that the brain needs to make the right amounts of important chemicals such as neurotransmitters, it makes sense that a lack of these nutrients could cause the chemical imbalances of mental illnes. [sic]

The thing that I find so fascinating is the simultaneous reliance on a simplistic "chemical imbalance" theory of mental illness and an opposition to traditional pharmaceuticals originally purported to correct those chemical imbalances. This theory has been panned by critics of biological psychiatry and has even fallen out of favor among neuroscientists conducting both basic and clinical research.

However, there is no doubt that vitamin deficiencies can produce neurological and psychiatric disturbances. For instance, a lack of B12 can damage the central nervous system via changes in cytokine and growth factor production (Scalabrino, 2009). Thiamine deficiency is well-known for causing Wernicke's encephalopathy and Korsakoff's syndrome, disorders characterized by severe memory impairments. Previous studies have suggested that vitamins and minerals do have an effect on mood and perhaps even antisocial behavior Kaplan et al., 2007; Bohannon, 2009). The question here is whether broad-spectrum micronutrient treatments (i.e., nutritional supplements) can improve or "cure" bipolar disorder.

Truehope lists 17 published studies on the effectiveness of EMPowerplus™ in treating bipolar, ADHD, autism, and OCD. However, none of these studies is a randomized controlled trial that compares placebo to EMPowerplus™ in a double-blind fashion. Thus, it cannot be established that any improvements are due to the supplement, rather than to expectation or placebo effects.

In one study, Gately and Kaplan (2009) presented results from 358 self-identified bipolar individuals (120 men, 238 women)¹ who purchased EMPowerplus™ from the Truehope website and subsequently filled out a symptom reporting checklist using the company's Self-Monitoring Form.² The diagnosis of bipolar disorder was not confirmed by a mental health professional. We don't know how many have bipolar I vs. bipolar II vs. cyclothymia. Here's a description of how the sample was selected:

There were 682 participants who reported having been diagnosed with bipolar disorder: 378 with no other disorders, 17 with both depression and bipolar disorder,³ and 287 with bipolar disorder as well as additional diagnoses such as ADHD, OCD, anxiety-panic, or schizophrenia. The conservative selection of just the 395 reporting bipolar disorder but no additional disorder except for the 17 also reporting depression was an attempt to reduce the heterogeneity of the sample.

Although physician confirmation of diagnosis was not available, 81% of the sample were taking psychiatric medications at the time they commenced taking the micronutrients, indicating that a physician considered their mood symptoms to be sufficiently severe to warrant medication.

If you're going to ultimately claim that a treatment reduces the symptom severity of an illness, you'd better confirm the clinical diagnosis of that illness (and the presence or absence of any co-morbidities). Of the 358 participants in the primary sample, only 136 were taking a mood stabilizer (e.g., lithium or divalproex sodium), the first-line treatment for bipolar. 145 were taking antidepressants, 75 were on antipsychotics, and 57 on anxiolytics. In addition, reliance on a totally self-selected sample of people who wanted to try an alternative micronutrient treatment is suspect.

Dr. John Grohol made similar points about deficiencies in study design and outcome reporting in a post at PsychCentral:

Some of the published research comes from researchers who have used the company’s own data collection routines through a “Self-Monitoring Form” that’s filled out by customers of the product (a form whose psychometric properties we know nothing of). The majority of customers stop filling out the form after two weeks, however (Rucklidge et al., 2010), suggesting they’ve either stopped using the product or stopped enjoying any positive effects from it.

In the aforementioned study, 120 families (out 709) agreed to monitor symptoms of their children who were taking EMPowerplus over 6 months’ time. Naturally, the researchers found a positive effect for the supplement — a 46% decrease in mean bipolar symptom severity scores at LOCF and a 40% decrease in ADHD symptoms.

But what’s that LOCF thing? Well, it’s a technique called Last Observation Carried Forward that researchers use that carries forward drop-out scores as though they had completed the entire study (in this case, observation of scores over 6 months’ time). In this study, only 49 percent of the participants kept providing the researchers data at 6 months — meaning the majority of them dropped out of the study before the 6 months were up!

LOCF is generally frowned upon in good research unless there’s a very good rationale for its use. Why? Because research conducted on the effects of LOCF shows that this method gives a biased estimate of the treatment effect while underestimating the variability of the result. In other words, it stacks the deck to demonstrate a treatment’s effectiveness — even when the treatment might not be effective. It’s a research slight of hand.

Retention in the Gately and Kaplan study at the 3 month time point was actually quite high (349 out of 358), but this had dropped to 242 at 6 months. What happened to the other 107 participants? Did they feel worse (i.e., depressed) and decide to stop the supplement, or did they just get tired of filling out the checklist? OR did they get worse in an objective sense (i.e., hypo/manic) and decide they were cured?

One troubling (but not unexpected) aspect of the symptom reporting data is the variability of days that were reported: 15% of the 358 participants reported between 60-90 days of the 180 days, 22% between 91-120 days, 21% between 121-150 days, and 42% reported 150 of the 180 days. A related concern is the failure to include specific symptoms or adverse reactions. The words "hypomanic" and "manic" and "psychotic" do not appear in the text. Furthermore, individuals in those states often lack insight into their mental status and may even feel better than ever (in the case of hypomania).

The table below shows that many participants decreased their dose of psychotropic medication or went off their drugs entirely (just like Jordan Ramsay). In fact, this is generally encouraged by the non-medically trained sales staff, called "Truehope Assistants".

- click on image for a larger view -

Sandra Kiume, blogger at Channel N, made these observations about the dangerous lack of medical monitoring:

When you attempt to purchase the product you are forced to sign a terms of agreement that includes:

“Some of the medications I’m currently taking or have taken (if any) may require that I take extra care when starting the EMPowerplus nutrient program and I agree to follow the guidelines of the program as suggested by my Truehope Assistant.”

A Truehope Assistant is essentially a sales rep for the company. They are not mental health professionals. However, based on your checking a box when you order that states “I am taking or have recently taken medication for sleep or a mood disorder,” they advise you to discontinue taking all psych medications before taking Truehope. Why? If it were really a safe nutritional supplement, there wouldn’t be any interaction, and if it’s not, they don’t say what’s in their proprietary formula so we don’t know what’s in it that might pose a risk. Either way, advising people to discontinue medication – without a professional assessment or medical supervision – is a dangerous ploy. To me, this what’s most disturbing about Truehope, even more than their marketing techniques and lack of rigorous research.

In calls to the Truehope sales team, Dr. Terry Polevoy used scripted scenarios to solicit advice about various ailments. It makes for interesting reading (pdf) and listening (mp3). In one scenario, the caller presents with a recent diagnosis of bipolar disorder, and inquires about the product:

. . .

Caller: and if I start the Empower and I still feel good do I stop my lithium, or…?

Truehope: Ok generally what will happen is that after you start on the Empower it gets into your body and it starts to repair that chemical imbalance a little bit at a time. And each time it repairs a little bit your body’s going to go through an adverse drug reaction and you’re going to need just a little bit less medication. And that will continue happening until you wean off all your medication

Caller: I see so there’s really no risk if I stop taking the lithium.

Truehope: Um, we never recommend that you stop your medication before Empower has a chance to get into your system and before your body’s ready. And we always recommend just very slight gradual reduction over a period of anywhere between a month, two months and some people even longer than that.to come off the medication.

And this is done without medical supervision. Later in the conversation, the Truehope Assistant recommends inositol, which can trigger manic episodes (see Levine et al., 1996) at the suggested dose of 6000 mg/day (Red Bull contains 50 mg, to compare):

Truehope: We also, just for your information, we also carry a product called inositol powder and what that is it’s one specific component of the B complex family and what it does is it gives a gentle calming effect over the body. We found it extremely beneficial in helping with anxiety, irritability, withdrawal from coming off of medication, as well as many people have told me they actually find it a lot of help when they are first starting off on Empower just cause it gives them a little bit of a benefit there when they first start off.

Nonetheless, many satisfied customers have provided testimonials on the supplement's effectiveness and how it has improved their lives. These appear not only on the company's website but on numerous blog posts covering the product. The positive comments even appear on the Gately and Kaplan (2009) paper, which is open access and can be read by all.

But testimonials are not the same as double-blind, placebo controlled studies. EMPowerplus™ believers and skeptics alike might ask if there are any ongoing clinical trials. Well there was one registered in the ClinicalTrials.gov database, but Study NCT00109577 has been terminated.

Footnotes

¹ Already we can see this sample is not representative of the general population with bipolar disorder, because women are overrepresented. Bipolar is equally prevalent in men and women, but in this study women outnumber the men 2:1. Also, these participants had the financial means to purchase their own supply of EMPowerplus™ ($150 for one month). This likely rules out many individuals who are unable to work because of the severity of their illness.

² From the Methods:

...people wanting to take [EMPowerplus™] for amelioration of psychiatric or neurologic symptoms are encouraged to use a checklist to monitor their progress, usually using symptoms specified in the DSM-IV. The Self-Monitoring Form which forms the basis of the current analyses consists of 16 DSM-specified mood symptoms (e.g. loss of interest in hobbies or activities; an excessively high or elated mood). Clients were asked to rate each symptom from 0 (not at all) to 3 (very much), for a maximum score of 48. Use of the Self-Monitoring Form is voluntary, and not all of the company’s clients choose to use it.

³ The diagnosis of bipolar disorder requires both depressive and hypo/manic symptoms, so saying you have both depression and bipolar is redundant.

⁴ aka the Synergy Group of Canada. The founders said, "We have named this work “TRUEHOPE” because we believe true hope can only be found in the healing sustenance God offers. No man, company, or scientist can ever replicate or replace that which our Creator provides."


References

Bohannon J (2009). Psychology. The theory? Diet causes violence. The lab? Prison. Science, 325 (5948), 1614-6. PMID: 19779166

Gately D, Kaplan BJ (2009). Database Analysis of Adults with Bipolar Disorder Consuming a Micronutrient Formula. Clinical Medicine: Psychiatry, 2, 3-16. Link

Kaplan BJ, Crawford SG, Field CJ, & Simpson JS (2007). Vitamins, minerals, and mood. Psychological bulletin, 133 (5), 747-60. PMID: 17723028

Levine J, Witztum E, Greenberg BD, Barak Y. (1996). Inositol-induced mania? Am J Psychiatry 153:839.

Rucklidge JJ, Gately D, Kaplan BJ. (2010). Database analysis of children and adolescents with bipolar disorder consuming a micronutrient formula. BMC Psychiatry 10:74.

Scalabrino G. (2009). The multi-faceted basis of vitamin B12 (cobalamin) neurotrophism in adult central nervous system: Lessons learned from its deficiency. Prog Neurobiol. 88:203-20.


Additional Reading - from CIRCARE (Citizens For Responsible Care and Research Inc.):

EmpowerPlus Research I

EmpowerPlus Research II

EmpowerPlus Research VII


Pig Pills, Inc.

Dr. Terry Polevoy has waged a tireless campaign against Empowerplus. His voluminous research on Truehope Nutritional Support Ltd.⁴ is available at these sites:

Truehope Empowerplus loses lawsuit against Health Canada

Canadian Quackery Watch - Truehope's Empowerplus and other miracles

He also has an ebook: Pig Pills, Inc., The Anatomy of an Academic and Alternative Health Fraud:

It's the unlikely story of a "cure" for psychiatric disorders by "inventors" who were neither doctors nor research scientists. They were, however, seasoned sales people with dubious tragic stories to help them focus their pitch on others in need...

Their pitch was based on the absurd notion that young piglets on their way to becoming ham for your dinner table could be cured of a condition that is know as Ear and Tail Biting Syndrome. They claimed that pigs of course could be healed by just throwing them a haphazard mixture of vitamins, minerals, and herbs - the pig pills. Yes, pig pills! Then in an amazing leap of faith, these two fellows from rural Alberta, Canada, with connections to nutraceutical conglomerates in Utah, came up with the idea that their pig pill formula could help wipe out the scourges of otherwise incurable mental illness in humans.

Appendix

Four Explanatory Models for how vitamins and minerals may influence mood states (Kaplan et al. 2007, in the highly regarded Psychological Bulletin):

1. Unstable Mood May Be the Manifestation of Inborn Errors of Metabolism
2. Unstable Mood May Be the Manifestation of Deficient Methylation Processes
3. Unstable Mood May Be the Result of the Alteration of Gene Expression by Nutrient Deficiency
4. Mood Disorders May Be Long-Latency Deficiency Diseases

"The four models described above are entirely compatible ideas that provide overlapping views of how brain metabolic pathways may become deficient and result in mood symptoms."

Justin Bieber Causes Psychosis, says a leading neuroscientist

Well not really, but it's not too much of a stretch to combine two recent pop neuro threads on the evils of dopamine into one dopameme. In the first, heretofore reputable neuroscientist Dr. Daniel Levitin of McGill University is quoted in the Daily Mail:

'Beliebers' suffer a real fever: How fans of the pop sensation have brains hard wired to be obsessed with him

By Mail On Sunday Reporter
PUBLISHED: 18:29 EST, 30 June 2012 | UPDATED: 07:20 EST, 1 July 2012

Justin Bieber fans can’t help their obsession – it’s hardwired into their brain, says a leading neuroscientist.

According to Professor Daniel Levitin ‘Bieber Fever’ (symptoms include screaming, fainting and constantly tracking the teen idol on Twitter) is a real physical compulsion.

When ‘Beliebers’ – as Bieber’s 44 million fans are known – listen repeatedly to his music, a chemical responsible for feelings of pleasure is released in their brains.

‘It triggers a rush of dopamine, the neurotransmitter stimulated by lots of other pleasurable activities such as orgasms or eating chocolate,’ Professor Levitin said last week.

The neuroscientist, of McGill University, Montreal, added: ‘Dopamine is released at much lower levels by music than, say, the use of drugs and the result usually is an obsession, in which you require more and more Justin Bieber.’

In the second part of our dopameme, a recent post by Dr. Victoria L. Dunckley in Psychology Today explained how computers and video games cause psychosis:

Computer, Video Games & Psychosis: Cause for Concern

. . .

In my practice in the past six months, no less than five youths have reported psychotic symptoms that were attributed to, or exacerbated by, electronic screen devices.

The mechanism for this anecdotal deterioration? Dopamine!

Electronic screens, particularly interactive ones (as opposed to passive ones, like television), increase dopamine in the reward center of the brain. This effect has been demonstrated by brain scan (Koepp, 1998: http://www.nrc-iol.org/cores/mialab/fijc/Files/2002/120402_Koepp_Nature_1998.pdf ) Dopamine is known as the brain's "feel good" chemical, but is also related to stress, addiction, anxiety, mood, and attention. Dopamine in excess can lead to psychotic symptoms--voices, delusions, paranoia, or confusion.

Good god. Dirk Hanson has started a comment thread on this irresponsible claim, Screen Time is Melting Our Children’s Brains—Or Something, at Addiction Inbox. I have a [pending] comment there, along with Neuroskeptic and Professor Keith Laws [edited to add].

Let's Go Back Inside the Brains of Bieber Fans

Did Levitin actually say that Bieber fever is "hardwired"? Probably not. [UPDATE (July 9, 2012) - In a comment, Dr. Levitin has confirmed that he was misquoted by the MAIL. What a surprise!] The Daily Mail might be considered a little less reputable than the Wall Street Journal:

What's Behind Bieber Fever? Neuroscience Offers Explanation; a 'Safe' Infatuation

By MELINDA BECK

. . .

Hearing familiar, favorite music stimulates the release of dopamine, the neurotransmitter involved in pleasure and addiction, providing the same rush as eating chocolate or that winning does for a compulsive gambler, says neuroscientist Daniel Levitin, who was able to observe the process using fMRI scans in his lab at McGill University in Montreal.

Dr. Levitin's research also showed that musical tastes formed in the teen years become part of the brain's internal wiring, as that is the time when some neural pathways are solidifying and others are being pruned away. That's why the music adults tend to be nostalgic for is the music from their teenage years.

But more importantly, I've received an anonymous tip that another leading neuroscientist bears an uncanny resemblance to Justin Bieber.



Disclaimer: Neither Levitin nor Dunckley actually said that Bieber causes psychosis.

Submit #RealWomenInNeuroscience to SfN Video Contest

Submission deadline extended to July 2 at 5 p.m. EST

By now, many of you have seen the European Commission's disastrous "Science: It's a Girl Thing!" video to promote an interest in science among 13-17 year old girls. It features lipstick, makeup, high heels, short skirts, and...



...a gawking male model at a microscope. The 53 second clip drew so many negative comments that the original was taken down (but fortunately a copy was uploaded for all to see).



Reaction across the internet was rather swift. A good place to start is “Science: It’s a Girl Thing”: Lab Barbie, Extra Lipstick by Maryn McKenna. Spoof videos were posted almost immediately, most notably this Unofficial Response. On Twitter, the #sciencegirlthing hashtag was used to mark tweets about the fiasco, and #realwomenofscience started a movement to counter the sexist girlie stereotypes emphasizing the importance of nail polish over scientific knowledge and achievement.




The Society for Neuroscience sponsors an annual video contest to raise public awareness about brain research:

Convey a neuroscience concept on video

The Society for Neuroscience (SfN) challenges you to produce an original video demonstrating a concept about the brain that could be used as a teaching tool or resource. Whether it's an animation, song, or hands-on classroom activity, share the wonders of science through the Brain Awareness Video Contest.

So why not submit a video that incorporates real women in neuroscience? You could win up to $1,000 and a trip to SfN's annual meeting in New Orleans!!

This is my idea of fun Monkeys playing video games

Swinging in the back yard
Pull up in your fast car
Whistling my name

Open up a beer and
Say get over here
And play a video game

Video Games
------Lana Del Rey

from Fig.1, Hosokawa & Watanabe (2012).

It's you, it's you, it's all for you

Two Japanese researchers (Hosokawa & Watanabe, 2012) have trained three Japanese macaques to play competitive and noncompetitive video shooting games by manipulating a joystick to shoot bullets at a target. While the monkeys were playing video games, the researchers recorded the activity of neurons in the lateral prefrontal cortex:

We examined whether neurons in the lateral prefrontal cortex (LPFC) showed response sensitivity related to a competitive game. In this study, monkeys played a video shooting game, either competing with another monkey or the computer, or playing alone without a rival. Monkeys performed more quickly and more accurately in the competitive than in the noncompetitive games, indicating that they were more motivated in the competitive than in the noncompetitive games. LPFC neurons showed differential activity between the competitive and noncompetitive games showing winning- and losing-related activity. Furthermore, activities of prefrontal neurons differed depending on whether the competition was between monkeys or between the monkey and the computer. These results indicate that LPFC neurons may play an important role in monitoring the outcome of competition and enabling animals to adapt their behavior to increase their chances of obtaining a reward in a socially interactive environment.

Everything I do
I tell you all the time
Heaven is a place on earth with you
Tell me all the things you want to do

Video Games
------Lana Del Rey

Reference

Hosokawa T, Watanabe M. (2012). Prefrontal Neurons Represent Winning and Losing during Competitive Video Shooting Games between Monkeys. J Neurosci. 32:7662-71.

I say you the bestest
Lean in for a big kiss
Put his favorite perfume on
Go play a video game

Video Games
------Lana Del Rey

Textmania: a Modern Manifestation of Manic Hypergraphia?

Continuing with the theme of reading and writing, a new study reports on the case of a 23 yr old woman with bipolar I disorder whose output of text messages was "1333.33% more" during a manic episode (Emeagwali et al., 2012):

The patient reported a dramatic increase in the quantity of both texting and sex-texting (or sexting) in addition to a decrease in quality of the message content. In addition, there was a substantial increase in the number of people with whom the patient engaged in simultaneous texting conversations. This case provides evidence for the need to consider non-traditional forms of communication when evaluating a patient’s communication pattern during mania.

How many texts per day are we talking about? At least 200, up from her usual 15-20 texts/day.¹ In the grand scheme of things, 200 is not all that unusual, because the mean number of text messages sent by young adults in the 18-24 age group is 109.5, according to a Pew Internet Survey.² The change in the patient's behavior is the critical factor here.

Hypergraphia (an overpowering urge to write) is probably seen more frequently in mania than in temporal lobe epilepsy, but the latter gets more attention in the medical literature due to the sometimes spectacular nature of the output (e.g., the novels of Dostoevsky, a 17 million word diary, and a copious collection of rhyming poetry). The neurological case studies are often illustrated with EEG traces showing abnormal spiking activity, along with examples of the person's handwriting (Kalamangalam, 2009):

The patient was observed to write for much of her waking hours. The document, a letter to her husband, numbered 29 pages by the time of her discharge from hospital and remained unfinished. The writing was cramped, dense, and used all the available space on both sides of the sheet, including the margins. The contents of the letter were rambling, though with specific details. She wrote about her hospital stay, often mentioning exact times, her intake of medications, and minor details of conversations with staff.

-- click on image for a larger view --

Fig 1 (left). Sleep EEG, bipolar longitudinal montage: a single spike maximum over the right anterior temporal region (arrow). Fig. 3 (right). Close up of page 16. The patient writes about her medication dosing, including minor details. (modified from Kalamangalam, 2009).


You don't see such reports in the psychiatric literature.³ There are no obvious manifestations of a manic episode on EEG or PET scans where you can say, in an individual person, "oh yes, this reduced gamma coherence and inhibition of theta activity in the lateral inferior prefrontal cortex, coupled with increased dopaminergic transmission in the midbrain, are clear indicators of mania." A PubMed search for mania OR manic AND hypergraphia returns one result, while a search for temporal lobe epilepsy and hypergraphia yields 22 hits.

There have of course been books on bipolar disorder and creativity, such as Touched With Fire: Manic-Depressive Illness and the Artistic Temperament by Dr. Kay Redfield Jamison. More specifically, Dr. Alice W. Flaherty covered the phenomenology and neurobiology of hypergraphia. In The Midnight Disease: The Drive to Write, Writer's Block, and the Creative Brain:

Flaherty writes compellingly of her bout with manic hypergraphia, when "the sight of a computer keyboard or a blank page gave me the same rush that drug addicts get from seeing their freebasing paraphernalia." Dissecting the role of emotion in writing and the ways in which brain-body and mood disorders can lead to prodigious — or meager — creative output, Flaherty uses examples from her own life and the lives of writers from Kafka to Anne Lamott, from Sylvia Plath to Stephen King [and Fyodor Dostoevsky].

And certainly the evidence for manic/hypomanic hypergraphia has been plainly obvious for as long as the internet has existed. There are thousands of bipolar bloggers and Tweeters and Facebook users and online journalers before that. Unlike PubMed, Google Blog Search returns 3,670 hits for bipolar hypergraphia and 4,230 hits for manic hypergraphia. And those are just the posts that use the term hypergraphia.⁴ One could envision a study on quantitative changes⁵ in written output on Twitter or blogs as a possible sign of bipolar cycling.

So it seems that contemporary psychiatrists are not all that interested in publishing case studies about their frantically writing patients, unlike the neurologists. Perhaps it's so commonplace that they just don't see the point?


Footnotes

¹ As you can see, the mathematical calculation quoted in the first sentence is rather imprecise.

² The median, which is less sensitive to the effects of gabby outliers, is 50 texts per day.

³ This raises the issue of Neurology vs Psychiatry and the Neurological/Psychiatric Divide.

⁴ For another interesting personal perspective see Bipolar 101 on HYPERGRAPHIA - the compulsion to write in bipolar disorder.

⁵ And of course qualitative changes in content and themes, when such writing hasn't been purged or accounts deleted at a later point in time...


References

Emeagwali, N., Bailey, R., & Azim, F. (2012). Textmania: Text Messaging During the Manic Phase of Bipolar I Disorder. Journal of Health Care for the Poor and Underserved, 23 (2), 519-522. DOI: 10.1353/hpu.2012.0062

Kalamangalam, G. (2009). Hypergraphia in temporal lobe epilepsy. Annals of Indian Academy of Neurology, 12 (3): 193–194. DOI: 10.4103/0972-2327.56323

G r e a t e r / l e t t e r / s p a c i n g / helps reading in dyslexia

Simply increasing the spacing between letters improves the reading ability of children with developmental dyslexia, according to a group of Italian and French researchers (Zorzi et al., 2012). Dyslexic children were 20% faster and twice as accurate when reading the altered text. This impressive result was obtained without any prior training whatsoever.

The study was based on the phenomenon of crowding, where the recognition of individual letters is impaired by the close proximity of surrounding letters. Children with dyslexia are disproportionately affected by crowding, compared to normally developing children (Martelli et al., 2009). Other aspects of the printed word are known to affect reading ability, but surprisingly little is known about letter spacing. The recommendations of the British Dyslexia Association include optimizing the size and type of font, page layout, headings, type of paper, and line spacing but not letter spacing.¹

The collaborative effort was a deliberate attempt to compare two languages that have different types of spelling-to-sound translation. Italian has completely regular spelling rules (a transparent orthography), meaning there are no exception words. Each combination of printed letters is always pronounced in a consistent way. By contrast, written French is orthographically opaque, meaning that pesky irregular spellings can trip you up. This is true in English as well: compare the pronunciation of the word "pint" to "hint", "mint", and "lint". The /i/ sound wins out over the /ī/ sound, in terms of regularity.

In the study, 34 Italian and 40 French children with dyslexia were tested on two separate occasions at least two weeks apart. They read 24 short sentences, which were written in standard text in one session and highly spaced text in the other. The order of sessions was counterbalanced to control for practice effects,² with half assigned to read the spaced text at T1 and the other half at T2. Reading accuracy (number of errors) and reading speed (number of syllables per second) both interacted with test session (p<.0001), indicating a drastic improvement with the highly spaced text. This was true for both the Italian and the French children with dyslexia.


Fig. 2 (Zorzi et al., 2012). (C) Reading accuracy (number of errors) in the normal and spaced text conditions for Italian dyslexics, French dyslexics, and a younger group of Italian control children matched for reading level (RL) to the Italian dyslexic sample.


It came as quite a surprise to me that no one had demonstrated this letter spacing effect before. But then again, I'm not familiar with the literature on developmental reading disorders, so perhaps Professor Dorothy Bishop or Livia Blackburne can provide a more critical take on an [apparently] amazing finding.

Finally, the authors have developed DYS, a free iPhone/iPad application. You can test out the spacing effect for yourself and submit your results anonymously, in the name of science!

For more information, see the WSJ Health Blog.


Footnotes

¹ Also note that bold is preferable to italic, as the latter induces crowding.

² A control experiment in a different group of children presented the normal and spaced text within a single session, again in counterbalanced order. The critical difference here was that different sentences were used in each condition, so practice effects wouldn't be an issue.


References

Martelli M, Di Filippo G, Spinelli D, Zoccolotti P (2009). Crowding, reading, and developmental dyslexia. J Vis 9: 14, 1–18.

Marco Zorzi, Chiara Barbiero, Andrea Facoetti, Isabella Lonciari, Marco Carrozzi, Marcella Montico, Laura Bravar, Florence George, Catherine Pech-Georgel, and Johannes C. Ziegler (2012). Extra-large letter spacing improves reading in dyslexia. PNAS. doi:10.1073/pnas.1205566109.