August 06

The Appeal of a Limitless Mind

Editor’s Note: With the much-anticipated debut of the Limitless TV show closing in, it’s clear that cameos of Bradley Cooper (and animated sequences of NEURONS FIRING!!!) will be spicing up the Fall TV lineup. From the trailer, it looks like the show will be just as exciting and scientifically questionable as the movie—giving NeuWrite the perfect opportunity to re-post our original musings on Limitless, its science, and the limitless appeal of the brain. 


 

With its slick visuals, wry narration, and unflinching action, the movie Limitless is undeniably fun—just throw in the hunky Bradley Cooper, and you’ve got instant box office gold.  Somehow, the only thing Hollywood forgot to include is more accurate neuroscience…

Act I: The Movie

From artless slob to suave ­­­­­­­sophisticate, the transformation of protagonist Eddie Morra is a classic makeover tale that has you rooting for the underdog-turned-mastermind.  The source of his newfound intelligence?  An underground designer drug by the unprepossessing name of NZT-48.  By boosting his mental abilities, NZT catapults Eddie’s life into the fast-lane.  But before long, his overnight success story starts to crumble; just as NZT’s addictive qualities and unfortunate side effects begin to emerge, so too do mysterious strangers and Russian thugs.

Act II: The Myth

Without divulging the ending, let’s explore a basic premise of Limitless.  Early on, Eddie’s drug-dealing ex-brother-in-law describes how NZT releases the untapped potential of unused brain regions.  He begins with, “You know how they say we can only access 20 percent of our brains?”  And with that, our suspension-of-belief goggles turn on.  While pop culture might persist in this claim, neuroscience certainly doesn’t.  Still, it’s an attractive idea that the key to increased potential lies within one’s (skull?) grasp, which might be why the movie’s plot is so compelling.  But where did this myth come from?

As with most urban legends, origin theories vary, but one of the earliest citations is from the 1936 book, “How to Win Friends and Influence People.”1  The book’s foreword proclaims, “Professor William James of Harvard used to say that the average person develops only 10 percent of his latent mental ability.”2 However, William James, recognized as the “father of American psychology,” never reported such a number.1  Instead, his often referenced line,1,3 “We are making use of only a small part of our possible mental and physical resources,”4 reads more as a philosophical conjecture than a quantifiable biological truth.  In fact, the myth can be easily refuted with neuroimaging methods that measure brain activity.  For example, even during sleep, fMRI scans demonstrate widespread activation across the brain, including in areas responsible for vision, hearing, touch, and language!5

In Hong et al. (2009), fMRI scans indicate widespread activation in the brain during REM sleep.  Left panels indicate areas with statistically significant activity (colored) from sagittal and horizontal sections.  Supplementary right panels provide reference for anatomical regions of interest, e.g. OG=occipital gyrus (for vision); ST=superior temporal gyrus (for hearing, language); GP, Pu, Cd= Globus Pallidus, Putamen, Caudate Nucleus (for voluntary motor control).

In Hong et al. (2009), fMRI scans indicate widespread activation in the brain during REM sleep. Left panels indicate areas with statistically significant activity (colored) from sagittal and horizontal sections. Supplementary right panels provide reference for anatomical regions of interest, e.g. OG=occipital gyrus (for vision); ST=superior temporal gyrus (for hearing, language); GP, Pu, Cd= Globus Pallidus, Putamen, Caudate Nucleus (for voluntary motor control).

Act III: The Drugs

Setting aside the initial neuroscience blunder, Limitless still intrigues with its surprisingly not-so-sci-fi concept.  It’s very human to fantasize about superhuman brainpower, and while the explosive effect of NZT is certainly Hollywood-sized, the hunt for cognitive enhancers is very real.  There’s a pressing need for drugs that address a range of cognitive-related conditions.  From medications that mitigate cognitive decline in Alzheimer’s patients, to pills that promote attentional focus in people with ADHD, cognitive enhancers already exist and have long been in widespread use.

To explain how certain cognitive enhancers work, let’s start with donepezil, a common treatment for Alzheimer’s Disease.  The ‘Cholinergic Hypothesis’ suggests that the cognitive decline seen in Alzheimer’s occurs, in part, from diminished acetylcholine in areas of the brain involved with memory and cognition (i.e. hippocampus, and temporal & parietal neocortices).Donepezil ameliorates this loss of acetylcholine by directly inhibiting acetylcholinesterase (AChE), an enzyme that degrades acetycholine.  Ultimately, by preventing normal breakdown of acetylcholine, donepezil amplifies the level of acetylcholine neurotransmitter in the brain and increases the duration of its signal.  Accordingly, AChE inhibitors, like donepezil, are effective in slowing cognitive decline, and are thus considered the ‘first-choice’ treatment for Alzheimer’s Disease.6

The next logical progression would be to wonder if drugs like donepezil work on healthy people too.  That is, do cognitive enhancers just alleviate deficiencies in disease states, or can they also heighten normal levels of cognition?  Indeed, many studies show that these cognitive enhancers also improve healthy individuals’ performances on learning and memory tasks.7-11  Use of these drugs to augment normal cognition is especially prevalent in the military.  In the case of pilots with long flight missions, drug treatment enhances cognition even over 40 hours of sustained wakefulness.11  Somewhat controversially, for decades, the U.S. military’s psychostimulant drug-of-choice was… you guessed it—amphetamine.12  Though it acts on a variety of neurotransmitter systems, amphetamine also, like donepezil, enhances acetylcholine release in the hippocampus, a brain region for memory.13  Perhaps unsurprisingly, given the dangers of repeated use (stimulant psychosis, eek!), it’s low doses of amphetamine that enhance cognitive performance; high doses (like the amount taken by addicts) actually impair cognition, in addition to other symptoms.9

Ritalin, pictured above, is another ADHD  medication with pyschostimulant properties.

Ritalin, another ADHD medication with pyschostimulant properties.

Today, amphetamine is commonly distributed as Adderall, an ADHD medication.  Illicit use of prescription stimulants is becoming increasingly popular in healthy students seeking study aids.  A 2012 study of nearly 1300 college students shows that over four years, 31% admitted to non-medical use of prescription stimulants;14 another study, surveying only fraternity members, reported prescription stimulant use as high as 55%.15  In the majority of cases, academic motives are the predominant reason for stimulant use,14,15 with Twitter content showing a marked increase in “Adderall-”containing tweets during typical university final exam periods!16  Still, the prevalence, as well as the apparent socially normative use,16 of prescription stimulants highlights the very real and present demand for a real-life NZT.

Final Remarks

Taken together, this all points to the very human desire for more—the hope that there’s still hidden potential yet to unlock in our minds. But already, the brain is arguably the most sophisticated, baffling computing device in existence.  That unassuming glob of gelatinous stuff in our heads, made from tens of billions of neurons and containing more synapses17 than there are stars in our galaxy, is easily the most complex machine in the observable universe.  In the years to come, pop culture may still insist that we only use a fraction of our brains, but really it’s that we only understand a fraction of our brains.  In actuality, it’s the amount we can learn from the brain that’s truly limitless.


 

REFERENCES

1. Aamodt, Sandra & Wang, Sam. Welcome to Your Brain: Why You Lose Car Keys but Never Forget How to Drive and Other Puzzles of Everyday Life. New York, NY: Bloomsbury USA, 2008.

2. Carnegie, Dale. How to Win Friends and Influence People. New York, NY: Simon and Schuster, 1936.

3. Boyd, Robynne. Do People Only Use 10 Percent of Their Brains?  Scientific American. (7 Feb 2008)  

4. James, Williams. (1907) The energies of men.

5. Hong, Charles C. et al. (2009) fMRI Evidence for Multisensory Recruitment Associated With Rapid Eye Movements During Sleep.  Human Brain Mapping 30:1705-1722.

6. Tsuno, Norifumi. (2009) Donepezil in the treatment of patients with Alzheimer’s disease. Expert Rev. Neurother. 9(5): 591-598.

7. Rokem, A et al. (2013) The benefits of cholinergic enhancement during perceptual learning are long-lasting. Front Comput Neurosci 7:66.

8. Zeeuws, I et al. (2010) Effect of an acute d-amphetamine administration on context information memory in healthy volunteers: evidence from a source memory task. Hum Psychopharmacol: 25(4):326-34.

9.  Wood, SC et al. (2009) Memory and psychostimulants: modulation of Pavlovian fear conditioning by amphetamine in C57BL/6 mice. Psychopharmacology (Berl). 202(1-3):197-206.

10. Yesavage, JA et al. (2002) Donepezil and flight simulator performance: effects on retention of complex skills. Neurology 59(1):123-5.

11. Estrada, A et al. (2012) Modafinil as a replacement for dextroamphetamine for sustaining alertness in military helicopter pilots. Aviat Space Environ Med. 83(6):556-64.

12. Borin, Elliot. The U.S. Military Needs Its Speed. Wired (10 Feb 2003).

13. Imperato, A et al. (1993) Effects of cocaine and amphetamine on acetylcholine release in the hippocampus and caudate nucleus. Eur J Pharmacol 238(2-3):377-81.

14. Garnier-Dykstra, LM et al. (2012) Nonmedical use of prescription stimulants during college: four-year trends in exposure opportunit, use, motives, and sources. J Am Coll Health. 60(3):226-34.

15.  Desantis, A et al. (2009) Nonmedical ADHD stimulant use in fraternities. J Stud Alcohol Drugs 70(6):952-4.

16. Hanson, CL et al. (2013) Tweaking and tweeting: exploring Twitter for nonmedical use of a psychostimulant drug (Adderall) among college students. J Med Internet Res. 15(4):e62.

17. Tang, Y et al. (2001) Total regional and global number of synapses in the human brain neocortex. Synapse 41(3):258-73.

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