Textbox 5.2: Cognitive-enhancing drugs
The journal Nature published a commentary about ethical issues concerning putative cognitive-enhancing (CE) drugs in 2007 (Sahakian & Morein-Zamir, 2007) and a 2008 commentary (Greely et al., 2008) based on an informal survey of 1,400 scientists from 60 countries about their use of such drugs (Maher, 2008). Ethical questions raised in the 2007 commentary included whether the use of CE drugs in healthy individuals without neurological or psychiatric disorders was cheating or fair, whether CE drugs should be available without medical supervision, and whether someone might feel undue pressure to use CE drugs for themselves or for their children if they knew others were doing so at school or work. The 2008 survey of scientists revealed that 20% already used drugs to improve concentration; 70% would risk mild side effects to boost brainpower; 80% defended their right to take such boosters; and greater than 33% would feel pressure to give their kids brain boosters if other kids used them. The survey report included four specific comments from responders that illustrated basic ethical issues: Safety: “The mild side effects will add up to be profound in due course and may even require stronger therapy to control the addiction,” wrote a young man from Nigeria. Erosion of character: “I wouldn’t use cognitive-enhancing drugs because I think it would be dishonest to myself and all the people who look to me as a role model,” wrote a young person from Guyana. Distributive justice: “Morally puts a disadvantage to people without access,” wrote a middle-aged person from the USA. Peer pressure: “As a professional, it is my duty to use my resources to the greatest benefit of humanity. If using ‘enhancers’ can contribute to this humane service, it is my duty to do so,” wrote a senior citizen from the USA.
The authors of the 2008 Nature commentary argued that, “Society must respond to the growing demand for cognitive enhancement. That response must start by rejecting the idea that ‘enhancement’ is a dirty word.” Since these three articles were published, there have been many new surveys about CE drug use around the world. Different survey methodologies and different samples make it hard to fix rates of regular versus occasional use or the motivations for use. Nonetheless, there is general agreement that CE drug use is increasing, especially for high school and college students in America despite limited evidence of efficacy (Smith & Farah, 2011).
One recent presentation of ethical considerations surrounding pharmacological cognitive enhancement (PCE) formulated six principal issues: “(1) The medical safety profile of PCEs justifies restricting or permitting their elective or required use. (2) The enhanced mind can be an ‘authentic’ mind. (3) Individuals might be coerced into using PCEs. (4) There is a meaningful distinction to be made between the treatment vs. enhancement effect of the same PCE. (5) Unequal access to PCEs would have implications for distributive justice. (6) PCE use constitutes cheating in competitive contexts” (Maslen et al., 2014).
The discussions about enhancement and these issues mostly are limited to cognitive elements of attention, learning, and memory. Specifically enhancing intelligence is not yet a focus of the ethical agenda. If, as I believe, more intelligence is better than less, is there not a moral obligation in favor of enhancement? What do you think about these issues? The 2011 movie “Limitless” may provoke some ideas.
5.5 Magnetic Fields, Electric Shocks, and Cold Lasers Target Brain Processes
This section briefly introduces five odd-sounding technologies that alter brain processes and may have implications for enhancing cognition and intelligence. Most importantly, these techniques allow for the experimental manipulation of cortical activity to study the impact on cognition. This ability provides exciting and important opportunities for determining cause and effect relationships which go beyond studies that report correlations between brain variables and performance on mental tests. They herald the beginning of a new phase of intelligence/brain research.
The first technique is transcranial magnetic stimulation (TMS). TMS uses a wand-like device containing a metal coil to produce strong magnetic field pulses when electricity is applied in short bursts. When the coil is placed over a part of the scalp, the magnetic field fluctuations pass through the scalp and skull undistorted into the brain. The fluctuations induce electrical currents that depolarize neurons in the underlying brain cortex. The rate of pulses and their intensity can be varied to increase or decrease cortical excitation. As a research tool, TMS can be used to test whether a particular region of cortex is involved in a cognitive task. For example, inducing cortical deactivation might result in poorer performance and inducing activation might result in better performance, or in the case of efficiency, vice versa. A review of over 60 TMS studies done over the last 15 years (Luber & Lisanby, 2014) concluded that this technique has promise for enhancing a range of cognitive tasks, although intelligence is not specifically discussed and this review is not a quantitative meta-analysis. According to the authors, TMS may affect brain mechanisms to increase task performance in at least two general ways: either by direct impact on neurons that increases the efficiency of task-relevant processing, or by disrupting processing that is task-irrelevant and distracting to performance. Some enhancement effects attributed to the first category are for tasks involving non-verbal working memory, visual analogic reasoning, mental rotation, and spatial working memory, among others (from their table 1). Enhancement effects attributed to the second category include tasks of verbal working memory, spatial attention, and sequential item memory (from their table 2). In addition to laboratory experiments, the authors also discuss some real-world applications for TMS, including cognitive rehabilitation after brain injury. So far the weight of evidence is not clear, but this is an area to watch for additional research and meta-analyses.
The second technique is transcranial direct current stimulation (tDCS). In other words, this delivers electric shocks to the head. The currents are quite mild and the shocks barely noticeable. They are not used as punishment shocks for wrong responses to a cognitive task or like electroconvulsive therapy (ECT), which induces seizures that ameliorate deep clinical depression. tDCS currents are generated by a 9-volt battery and pass between electrodes on the scalp. Depending on the parameters used, this current can increase or decrease neuronal excitability under the electrode locations similar to the effect of TMS. Early tDCS studies were encouraging (Clark et al., 2012; Utz et al., 2010). Writing about enhancement effects for both TMS and tDCS, one research group (McKinley et al., 2012) noted, “These techniques are perhaps best suited for career fields where certain cognitive skills such as vigilance and threat detection are essential to preserving human life. Because such jobs are plentiful in the military, it is no surprise that the US Air Force has recently begun investing in non-invasive brain stimulation for its efficacy in benefiting human cognitive performance.” Another group reviewed tDCS enhancement effects from many studies of attention, learning, and memory in healthy adults (Coffman et al., 2014). This qualitative review concluded that “battery-powered thought” had considerable potential for certain cognitive tasks, although the review did not address intelligence directly. This review included some research on how tDCS might influence brain mechanisms underlying cognitive enhancements. They noted possible roles for aspects of glutamate, GABA, NAA, NMDA, and BDNF regulation and function (see similar findings from molecular genetic studies noted in Chapter 4). Predictably, however, a newer comprehensive quantitative analysis of tDCS and cognition in healthy adults was more discouraging (Horvath et al., 2015b). They found essentially no effects for outcome measures of executive function, language, or memory. They also found no reliable neurophysiological effects (Horvath et al., 2015). Further doubts about any enhancing effects on intelligence were expressed in a study that showed decreased performance on the WAIS-IV intelligence test battery following tDSC stimulation (Sellers et al., 2015). These authors reported two studies (total of 41 adults), both double-blind, between-subjects design (i.e., the same individuals tested before and after tDCS), using a sham stimulation control c
ondition (fake connections to look like the real device but there is no current). tDSC was applied bilaterally to frontal lobe areas in one study and unilaterally in the other study. In both studies, the tDCS condition was compared to the sham condition. In both studies tDCS was associated with degraded performance on certain WAIS subscales. No improved performance was observed. This is the lesson learned for virtually all claims of cognitive enhancement so far: early promising findings must be reliably reproducible by independent investigators and survive comprehensive quantitative analyses.
There are other potentially informative studies at early stages to report in the context of this chapter, albeit with the caution that replication studies remain to be done. Instead of direct stimulation, a variant of this technique uses mild alternating current, called transcranial alternating current stimulation (tACS). This is our third technique. Whereas tDCS produces a general stimulation to the brain, tACS can be targeted to specific areas. Of interest here, two studies have reported tACS-induced enhancement specifically on fluid intelligence tests. In the first study, tACS was used experimentally to alter natural oscillation frequencies that are generated by neuronal activity (Santarnecchi et al., 2013). Oscillation frequencies in the brain are related to mental task performance, but whether they are cause or consequence is an open question. The participants were 20 young adults and the “imperceptible” tACS was applied by scalp electrode over the left middle frontal lobe. Compared to sham stimulation (a control condition), rhythmic stimulation within the gamma band (a particular frequency) induced by tACS resulted in faster solution times for only more difficult items like those on the Raven’s matrices test. This suggested a causal relationship between the oscillations and the influence on the test. Note the enhancement effect was assessed by shorter times to solution, where time is a ratio scale. The authors concluded that their finding “supports a direct involvement of gamma oscillatory activity in the mechanisms underlying higher order human cognition.”
Another study of intelligence in 28 young adults compared tACS in the theta band (a different frequency) applied to either the left frontal lobe or to the left parietal lobe; sham stimulation was also used as a control (Pahor & Jausovec, 2014). tACS was given for 15 minutes prior to completing two tests of fluid intelligence. The tests were a modified version of the RAPM and the paper folding and cutting test (PF&C) of spatial ability from the Stanford–Binet IQ test battery. EEG were also obtained during both tests. The authors concluded that, “Left parietal tACS increased performance on the difficult test items of both tests (RAPM and PF&C) whereas left frontal tACS increased performance only on the easy test items of one test (RAPM). The observed behavioral tACS influences were also accompanied by changes in neuroelectric activity. The behavioral and neuroelectric data tentatively support the P-FIT neurobiological model of intelligence.”
There are some inconsistencies and contradictions in the findings of these two independent tACS studies of fluid intelligence, and in the studies using tDCS, but they may provide hints about the salient brain mechanisms. They further demonstrate the potential of brain stimulation techniques for systematic manipulation of neuron activity in humans to determine effects on cognitive performance. Surely more research will be forthcoming with refined experimental designs that include larger samples, and an emphasis on individual difference variables like age, sex, and pre-existing brain excitability (Krause & Cohen Kadosh, 2014). Brain stimulation with these techniques is experimental, but the mechanics of building tDCS and tACS devices are fairly simple. There are reports of homemade “brain shock” devices used by gamers and others looking for enhanced cognition. Some commercial companies sell such devices for a range of self-uses. Independent replication research supporting their claims, if any, would be important to evaluate. Applying homemade or commercial electrical devices to your brain might have unintended consequences. Please do not compete for a Darwin Award by trying this at home.
Deep brain stimulation (DBS), the fourth technique, is the conceptual equivalent of a heart pacemaker. DBS applies mild electrical stimulation to microelectrodes surgically implanted into specific brain areas by a team of medical specialists. It is a major invasive procedure not easily accomplished at most homes. The stimulation can be constant or applied when needed. DBS has demonstrable clinical applications for alleviating the symptoms of Parkinson’s disease, and clinical depression, and it is under study for other brain disorders. There are also a number of studies of DBS on learning and memory that suggest possible enhancement under some conditions (Suthana & Fried, 2014). There are not yet DBS studies of intelligence. There is an interesting question as to whether brain areas related to cognitive enhancement effects identified with TMS, tDCS or tACS can be more accurately localized with neuroimaging specific to an individual person and then be targeted with precise localization of DBS electrodes. Could constant DBS in multiple areas enhance the g-factor, especially in individuals with low IQ, or could on-demand DBS in a specific area enhance specific mental abilities in any of us? This is a long way from listening to Mozart or n-back training. Do these possibilities sound more enticing than compensatory education? Such rank speculation is offered only in this section to stimulate your imagination about the importance and potential of neuroscience approaches to intelligence research.
While you are thinking about this, here is one more non-invasive brain stimulation technique that invites speculation. Our fifth technique is based on lasers. Light from low-power “cold” lasers in the near-infrared range penetrates the scalp and skull and can affect brain function. One group of researchers reported preliminary evidence that this technique can enhance some kinds of cognition when aimed at different brain areas (Gonzalez-Lima & Barrett, 2014). They describe how laser light affects the brain this way: “Photoneuromodulation involves the absorption of photons by specific molecules in neurons that activate bioenergetic signaling pathways after exposure to red-to-near-infrared light.” Imagine this special laser light aimed from a distance at an unsuspecting person’s brain to either enhance or disrupt cognition. Sounds like a screenplay idea. Enough speculation. The data are preliminary and lasers can be quite dangerous. Do not try this at home either.
5.6 The Missing Weight of Evidence for Enhancement
In Chapters 1, 2, 3 and 4, the weight of empirical evidence supported, respectively: the g-factor concept; an important role for genetics in explaining individual differences in intelligence; intelligence-related networks distributed throughout the brain; and to a lesser extent, the idea that efficient information flow around the brain was related to intelligence. In this chapter, despite many provocative claims and intriguing findings, no weight of evidence yet supports any means or methods for enhancing intelligence.
From time to time I am asked by magazine health writers to offer tips on increasing IQ. My answer is always the same and usually induces a long silence from the writer. There are no such tips – not even one that is supported by the weight of evidence. Eat better? Exercise? Engage in mentally challenging activity? All are good suggestions for general health and well-being, but no specific effects for boosting intelligence can be substantiated. Not surprisingly, these writers never quote me, although science writers sometimes do in more substantial articles. I am happy to be the voice of reasonable skepticism to help stop the spread of bad information. One online magazine listed 10 tips for boosting IQ, including listening to classical music, memory training, playing computer games, and learning a new language. For each tip, they listed the putative IQ point increase claimed by someone, and then they added up all the points to support the nonsensical headline promising ways of boosting your IQ by 17–40 points. Really.
Although enhancement of intelligence is an important goal for neuroscience research, the weight of evidence to date indicates there is a long and winding road ahead for meeting this goal with drugs, genetics, electric or magnetic stimulation, or lasers. The road appears no shorter for education and cognitive training approaches. These roads hav
e no posted speed limits or guardrails so crashes are inevitable. Moreover, my assertion that enhancement is an important goal is not universally recognized. If it were, considerably more federal and foundation funding would be directed toward achieving it and not just for disadvantaged children. After all, many national challenges, from technological and economic innovation to cyber crime and cyber warfare, pit the smartest against the smartest. This is serious business. Silly magazine tips are not helpful.
If I had to bet, the most likely path toward enhancing intelligence would be a genetic one. In Chapter 2 we discussed Doogie mice, a strain bred to learn maze problem-solving faster than other mice. In Chapter 4 we enumerated a few specific genes that might qualify as relevant for intelligence and we reviewed some possible ways those genes might influence the brain. Even if hundreds of intelligence-relevant genes are discovered, each with a small influence, the best case for enhancement would be if many of the genes worked on the same neurobiological system. In other words, many genes may exert their influence through a final common neurobiological pathway. That pathway would be the target for enhancement efforts (see, for example, the Zhao et al. paper summarized in Section 2.6). Similar approaches are taken in genetic research on disorders like autism and schizophrenia and many other complex behavioral traits that are polygenetic. Finding specific genes, as difficult as it is, is only a first step. Learning how those genes function in complex neurobiological systems is even more challenging. But once there is some understanding at the functional system level, then ways to intervene can be tested. This is the step where epigenetic influences can best be explicated. If you think the hunt for intelligence genes is slow and complex, the hunt for the functional expression of those genes is a nightmare. Nonetheless, we are getting better at investigations at the molecular functional level and I am optimistic that, sooner or later, this kind of research applied to intelligence will pay off with actionable enhancement possibilities. The nightmares of neuroscientists are the driving forces of progress.
The Neuroscience of Intelligence Page 22