ELearning/Brain enhancement

A number of techniques have been developed to manipulate the natural patterns of brain activity by modulating neural activity. We look briefly at brain training, external manipulation, neuroprosthetics, and biological and neurological feedback to enhance connectivity between brain components and certain cognitive and emotional processes. This approach to brain functioning deserves monitoring, as we are likely to see advances in current and the invention of new methods.

Brain training

More formally termed cognitive training, brain training is built on the idea that training on one or more cognitive tasks generalizes, or transfers, to performance on other cognitive tasks and to daily life (Simons et al., 2016).

Claims and reality

"Practicing memory games will increase your retention and recall of all memories." This promise is built on the idea that, if cognitive abilities predict real-world performance, then practice in those abilities should improve performance and life in general. Companies such as Luminosity, BrainHQ, and the Scientific Learning Corporation create games and exercises claiming just such results.

Transfer of learning can occur vertically or horizontally. We see vertical transfer when we learn basic skills that can be combined to perform more advanced ones. Learning how to measure and cut wood, sandpaper surfaces, etc. moving toward the ability to create a finished product. Horizontal transfer can be seen when we learn one word processing program and then a different one. Details change but the basic principles still apply. Then there is the degree of transfer, from close to distant. The word processing example is one of close transfer. Far transfer would be seen in learning to translate one language into another and then, using the same approach, translating the second into a third language, which is not very likely because the rules of translation may be completely unrelated to the first instance.

Simons et al. (2016) conducted an exhaustive review of company claims, their research, and academic research of the science of brain training. Their unequivocal findings:

Based on our extensive review of the literature cited by brain-training companies in support of their claims, coupled with our review of related brain-training research, there does not yet appear to be sufficient evidence to justify the claim that brain training is an effective tool for enhancing real-world cognition. We find extensive evidence that brain-training interventions improve performance on the trained tasks, less evidence that such interventions improve performance on closely related tasks, and little evidence that training enhances performance on distantly related tasks or that training improves everyday cognitive performance.

What does work

Given the lack of far transfer of learned skills and the lack of effect on general cognition, training games and exercises may still have their place. Recent research has focused on more limited, and more promising, applications of brain training focused on specific executive functions. Refer to Memory for more on the subject. There are two general conclusions from the research: positive effects are seen for near transfer tasks; those closely related to the trained tasks (Sala & Gobet, 2017; Simons et al., 2016). Second, repeated practice is key (Diamond, 2013). The most demanding tasks and task conditions - pushing individual limits - are the most effective.

Memory training

Research into memory training has thus far concentrated on the elderly in an effort to delay or recover memory loss. We cite them here because of their potential for application to other populations.

N-back training

Blacker et al. (2017) examined two forms of working memory training, double n-back training (DNBT) and complex span training (CST), and found DNBT to be most effective in near-transfer tasks (but not far transfer tasks). Working memory is the ability to maintain and manipulate task-relevant information in the absence of sensory input. In other words, it is the ability to maintain relevant facts, thoughts, ideas, etc. while performing a mental task. While not ideal, in that transfer is rather limited, it demonstrates the value of training for related working memory tasks such as working with mathematical formulas or accounting tasks.

N-back training requires learners to remember a constantly varying sequence of stimuli, such as numbers, letters, math symbols, etc. Stimuli can also be paired, such as viewing a screen photo while hearing a spoken word. Initially, learners are asked to remember if the current stimuli is the same as the previous one (1-back). After a number of successful tries, learners are then asked to remember if the current stimuli matches the one presented two rounds back (2-back or double-back). Difficulty can be increased to 3-back and 4-back, but success rates fall dramatically, discouraging all but the most committed. Therefore, most n-back working memory training has settled on double-back. Training typically calls for daily 5-20 minute practice sessions for about four weeks. Compare this method with CST in which participants listen to a list of numbers, words, formulas, etc., then involved in an unrelated task, and finally asked to recall the original list. CST is more appropriate for testing working memory capacity rather than training to improve working memory.

Repetition-lag training

Repetition-lag training appears to assist with the information recall process, and has been quite successful for normal aging adults as well as those with mild cognitive impairment (Bailey, et al., 2011). Originally conceived by Jennings and Jacoby (2003) to improve recall in older adults and subsequently used in various iterations, the procedure appears to bring about robust gains for this population. Here is a summary of the training protocol:

Participants study a list of 30 words, then
Take a recognition memory test containing the studied words as well as new words.
The new words are presented twice during the test phase, with the number of intervening studied words gradually increasing over successive sessions if accuracy criteria are met.
To progress, participants must recollect that either: (1) the repeated item (i.e., new word) was presented in the test list rather than study list and/or they have already responded to that item in the test list, or (2) the item appeared more recently than the study list.
As participants progress, the number of studied words placed between new words increases, thus increasing working memory load.

Cognitive flexibility training

Task switching accuracy can be improved through training, but apparently not response times. Gajewski et al. (2017, 2012) provided a regime of cognitive training targeting attention, working memory, inhibition, and dual-task performance to seniors (age 65 plus, 2012) and adult males (age 45-57, 2017) for three months, and then tested them using a task switching test. In both cases, responding accuracy was significantly increased, but not response times, which remained about the same. Kray and Fehér (2017) found task switching training to significantly improve performance in both young and older adults. Improvements for the young adults faded after six months, but not for the older adults.

Cognitive reasoning training

Chapman et al. (2017) report on a pilot program, involving older adults (ages 56-75), aimed at improving insight and innovative thinking. The authors define innovative thinking as the ability to "synthesize complex information and generate multiple interpretations; the sort of thinking that reinforces and preserves complex decision-making, intellect, and psychological well-being." Training resulted in significantly higher innovations scores (average 27% performance gain) and increased connectivity between components of the central executive network and the default mode network (see Neural networks).

The training regimen, called the Strategic Memory Advanced Reasoning Training (SMART), includes learning cognitive strategies that foster attention, reasoning, and broad based perspective thinking. It involves one hour of training each week, followed by two hours of homework over 12 weeks. The authors conclude that these results add to a growing body of evidence showing that older adults benefit from different forms of cognitive training.

Video gaming and cognitive performance

An impressive body of research supports the positive impact of action video gaming and improvements in a variety of cognitive, visual, and attentional skills. We site some examples. Keep in mind that benefits are evident for near transfer tasks, those similar in nature to the trained tasks. Far transfer has been absent from experimental results.

Probablistic reasoning, used in prediction (weather forecasting, stock picking, determining odds) is stronger for gamers versus nongamers (Schenk et al., 2017), particularly under conditions of high uncertainty. This strong performance is, in part, based on the gamers' better retention and use of related declarative knowledge. In this experiment, higher performance was accompanied by higher neuronal activity in the hippocampus, superior parietal lobe, cingulate cortex, middle temporal lobe, and the occipital lobe.

Working memory. Moisala et al. (2017) found a significant correlation between self-reported daily video gaming activity and performance on a memory task, with increased speed and accuracy. They found heightened activity in the in the dorsolateral PFC and parietal cortex.

Executive control skills. Strobach et al. (2012) saw that gamers performed significantly better than nongamers in dual task (performing two tasks at the same time) and task-switching (sequentially performing tasks) situations. Interestingly, the performance advantage was absent in single-task situations.

Visual-spatial manipulation. Bosch (2012) reported a study in which tenth-grade video gamers and OB/GYN residents performed a simulated video-based surgery. The gamers performed, on average, as well as the medical doctors. The study was not intended to demonstrate surgical abilities in 10th graders, but rather the improved visual-spatial manipulation skills that games provide. The student played an average two hours of video games each day.

Attention. Boot et al. (2008) found that expert gamers can track moving objects at greater speeds, better detect changes in objects (color, shape, etc.), switch more quickly from one task to another, and mentally rotate objects more efficiently. They also tested nongamers' performance on these tasks before and after extensive (20+ hours) practice, resulting in no improvement on most measures. This result suggests that improvements in executive functions come only after hundreds of hours spent with action video games.

Musical training

Musical ability has long been suspected as a contributor to math abilities. While recent research (Gaab & Zuk, 2017) does not support such a conclusion, the link suggests that both math and music skills depend on highly developed executive functioning. In a two-year longitudinal study, Habibi et al. (2017) found an accelerated rate of cortical thickness maturation (increased thickness) in children ages 6 and 7. Accelerated growth was found in the left superior temporal cortex, and the corpus collosum connecting the dorsal frontal, sensory, and motor cortices of the two hemispheres.

External manipulation

External manipulation of the physical brain takes several forms, including chemicals, hormone and gene manipulation, electricity, magnetism, optics, and, on a more subtle basis, web search bias. Most research has centered on addressing pathologies and the effects of aging, however, there are also important implications for learning and memory in healthy individuals.

Chemical manipulation

The oldest method of brain manipulation, beginning with the depressant alcohol, which slows brain functioning, and hallucinogens like peyote, used in ancient religious ceremonies. Hallucinogenic drugs directly affect the serotonin receptors, resulting in a complex pattern of neuronal activity producing sensory distortions and hallucinations. Caffeine, amphetamines and other stimulants raise levels of dopamine, increasing alertness and focus, elevating mood and increasing motor activity. Caffeine remains a favorite of learners to increase alertness and attention. Amphetamines, at therapeutic doses, increase cognitive control and are used to treat ADHD, among others. Prescribing is highly restrictive due to its high potential for addiction.

Kaplan et al. (2017) report on efforts to find chemical compounds that help spur CREB into action (see Genetics). One compound, called HT-0411, shows promise. HT-0411 doesn't directly activate CREB, but does so indirectly by inhibiting the enzyme monoamine oxidase B, which modulates dopamine and ultimately leads to CREB-mediated gene expression. In memory tests, animals that received the HT-0411 molecule scored much higher than the control group, and they showed no signs of behavioral side effects such as changes in anxiety levels.

Research shows that chemical manipulation of 5-HT neuropeptide formation within hippocampus neurons triggers the formation of new receptors, enhancing memory and learning ability (Gülpınar & Yegen, 2004), acting on the neurotransmitter serotonin. DBI neuropeptides boost the proliferation of neural stem cells and neural progenitor cells (Dumitru et al., 2017), and act on the GABA neurotransmitter. The net result of both processes include increased cognitive performance and memory storage in the hippocampus.

Blundon et al., (2017) found that restricting the production of adenosine helps extend efficient auditory learning in adults. Auditory learning is typically strong during early childhood, a critical factor for language development, but drops off significantly with age. The site of action lies within the thalamus, specifically the auditory thalamus.

Hormone manipulation

Previously unaddressed as a method for cognitive improvement, hormone therapy in the form of klotho injections has been shown to enhance cognitive (spatial and working memory) and motor functions (acceleration and response times), and induce neural resilience independent of age (Leon et al., 2017). Klotho is a protein traveling the blood system with multiple effects, including insulin and fibroblast (fibrous tissue such as muscle) growth factor regulation. Higher concentrations are associated with higher functioning and lower amounts with degeneration. Interestingly, klotho does not cross the blood-brain barrier, thus revealing an alternative path for influencing brain structures and function.

Gene modification

Another avenue of recent research, manipulating genes of DNA is showing promise for improving cognitive functioning. Jenks et al. (2017) have demonstrated that manipulating a single gene, Arc, responsible for the plasticity protein, also referred to as Arc, can rejuvenate the plasticity of the mouse brain, specifically in the visual cortex, increasing its ability to change in response to experience - increased plasticity. Plasticity is essential to learning, memory and adaptation. Normally, Arc is rapidly activated in response to stimuli and is involved in shuttling neurotransmitters out of synapses after transmission has occurred. Normal aging typically reduces plasticity, but Arc manipulation restores "youthful" plasticity.

Our increased knowledge of DNA, genes, and genomics has been accompanied by a revolutionary "game changer" technology referred to as CRISPR (short for clustered regularly interspaced short palindrome repeats) and CRISPR-Cas9 (Cas9 is a helper protein). This inexpensive technique, discovered in 2012, allows scientists to locate, cut out, and if necessary, replace pieces of DNA and RNA (nature's method for replicating DNA) to modify or change their function. The method is universal in that it can be used with humans, animals, plants and anything containing DNA (Park, 2016).

Already accomplished with CRISPR:

Removed HIV from human cells (in the laboratory) and from a living organism
Removed a heart disease-causing gene from a human embryo (China)
Reversed Huntington's disease in mouse brain tissue
Modified social behavior in ants
Reprogrammed a yeast strain to convert sugars into biofuels
Corrected genetic defects to treat a form of muscular dystrophy in mice and pigs
Eliminated retinitis pigmentosis, a degenerative eye disease in mice
Created a mushroom that does not brown

Here are a few ideas beginning to bubble up in the literature, foretelling future goals:

Editing out genes known to increase the risk of ovarian and breast cancer
Erasing genetically caused dyslexia and other learning disabilities
Erasing Down's syndrome and autism

A newer and potentially safer approach to gene editing, called CRISPR-Cas13 or REPAIR (RNA Editing for Programmable A to I Replacement), focuses on editing transcription RNA instead of DNA (Cox et al., 2017). Changes to DNA are permanent and passed on through inheritance, whereas RNA is temporary and degrades after accomplishing its purpose: building proteins necessary to cell function. As such, changes can be reversed.

The potential benefits are enormous, but so are the potential risks. Scientists don't know what will happen if these altered organisms are released into the wild or the human gene pool. Unintended consequences are by definition unpredictable. The CIA has declared the technology a threat of mass destruction if let loose by rogue nations or groups. Needless to say, caution and controlled experimentation is called for. However, mass marketed kits are available for as little as $150. There is no putting the cat back in the bag. Learn more.

Direct stimulation

What happens when electric current is imposed on the brain from the outside? Interesting things happen. Implanted electrodes can quiet an overactive brain, silencing nascent seizures. Electroshock therapy can lift the cloud of depression. Through electrical wire implants, the brain can move artificial limbs and communicate directly with computers. Electricity has also been shown to improve learning.

While investigating the use of electric brain stimulation to improve the rate of recovery after strokes, researchers discovered that the same stimulation in healthy adults significantly increases their rate of learning new motor skills, with significant differences in performance after just 10 minutes. Other investigators found the same effect on military volunteers playing a battle simulation, and using arbitrary face-word pairs. The researchers believe the same will be demonstrated for other types of learning as well. In all instances, the electrical current was just a few milliamps and volunteers reported no sensation beyond a slight tingling.

Stimulation methods include deep brain stimulation and transcranial stimulation:

Deep brain stimulation

Deep brain stimulation (DBS) uses insulated electricity-conducting wires, about the width of a human hair, inserted in specific brain structures to stimulate neural activity. Thus far, implants have been used primarily to treat medical conditions such as Parkinson's disease and multiple sclerosis (stimulating portions of the basal nuclei), epilepsy (thalamus, hippocampus, vegas nerve), and mood disorders (Brodmann area 25, vagus nerve). The FDA approved DBS to treat obsessive-compulsive disorder in 2009. Stimulating the hypothalamus has been shown to improve memory recall (Valeo, 2008). More recent studies indicate different responses to intermittent stimulation, which improves working memory, and continuous stimulation, which slows neuron firing, impairing memory and performance (Liu et al., 2017). Intermittent stimulation to the basal forebrain makes more acetylcholine available in the immediate area around the wire implant, and increases blood flow to the area.

Recent work by Solomon et al. (2017) suggests an avenue for targeting specific brain regions using specific stimulation patterns (theta patterns 3-8 Hz) to improve memory encoding and retrieval. Song et al. (in Hamzelou, 2017) used a memory prosthesis that mimics the brain waves associated with learning and memory, stimulating similar patterns in the hippocampus, with striking results. Twenty patients who were having brain electrodes implanted for the treatment of epilepsy volunteered for the implantation. Their approach is quite novel and further demonstrates the use of brainwave stimulation as a memory enhancing method (see transcranial stimulation below). Briefly, the method involves:

Collecting data on individual patterns of brain activity during a short-term memory test and a working memory test.
Computing the specific patterns of activity associated with each person's best memory performances.
Stimulating the subject's brain according to the computed best performance while they performed additional tests.

Results showed that subjects performed an average 15% better on short-term memory tests and 25% better on working memory tests, compared to periods when they received no stimulation. Song et al. also tried random stimulation, which worsened performance.

Song and his team are working to see if the approach works on other brain functions, such as eye-hand coordination, where skills are localized to particular regions. Cognitive functions such as critical thinking and problem-solving may not be amenable to the method due to the fact that they involve multiple regions working together. They are also investigating the possibility that the method might be used to implant false memories, a chilling prospect.

Transcranial stimulation

2. Transcranial magnetic stimulation (TMS)

Transcranial stimulation transmits targeted signals through the scalp into the uppermost layers of the cortex, and comes in three "flavors": (1) electrical current, (2) magnetic stimulation, and (3) infrared stimulation.

Transcranial alternating current simulation (tACS), which produces a constant electrical current flow back and forth between electrodes.
Transcranial direct current simulation (tDCS), using low-intensity direct current between electrodes.
Transcranial pulsed current stimulation (tPCS) is a non-constant form of stimulation with "on" and "off" periods – or pulsing between the two electrodes.
Transcranial random noise stimulation (tRNS) painless low electrical current applied over the left and right areas on the forehead.
Transcranial magnetic stimulation (TMS), a technique using magnetic pulses (see Figure 2). During a TMS procedure, a magnetic field generator, or "coil", is placed near the head of the person receiving the treatment. TMS can penetrate just a few centimeters into the outer cortex of the brain. Poles are reversed at specific intervals (slow to fast) to produce a steady electromagnetic pulse; the faster the pole reversal, the stronger the pulse.
Transcranial infrared brain stimulation (TIBS) directs infrared lasers at specific brain structures in order to stimulate them.

Researchers are currently investigating the impact of varying methods, intensity levels, and duration on learning.

Method	Location	Findings	Authors
tACS	Dorsolateral prefrontal cortex (PFC) and inferior parietal cortex	Improved working memory performance, especially on the more difficult tasks	Violante et al., 2017
tACS	Bilateral PFC	Improved auditory verbal learning	Hashimoto et al., 2017
tACS	Temporoparietal junction	Improved language learning	Antonenko et al., 2016
tACS	Dorsolateral PFC and primary motor cortex (during sleep spindles only)	Enhanced motor learning memory consolidation, but not declarative learning	Lustenberger et al., 2016
tDCS	Dorsolateral PFC	Improved cognitive control in normal subjects, and potentially applicable to ADHD students.	Gbadeyan et al., 2016; Trumbo et al., 2016
tDCS	Dorsolateral PFC (Nillson: combined with memory training for older adults)	No memory benefit of tDCS (Nillson: beyond benefits of memory training)	Nillson et al., 2017; Wang et al., 2018
tDCS	Dorsolateral PFC	Interference with working memory, disrupting learning	Nikolin et al., 2017
tDCS	Occipitoparietal visual cortex	Increased spatial visual acuity, lasting over an hour	Reinhart et al., 2016
tPCS	Temporal/insular lobe border (middle cerebral artery)	Increased corticospinal excitability (improved motor response); decreased side effects from tDCS.	Jaberzadeh et al., 2015
tRNS	Dorsolateral PFC	Improved mathematical learning for children with learning difficulties.	Looi et al., 2017
tRNS	Frontal cortex or Parietal cortex	Improved declarative memory performance (frontal cortex stimulation only)	Pasqualotto, 2017
tRNS	Bilateral PFC/Posterior parietal cortex (3 days/2 days)	Improved mathematical learning for difficult problems (but not easy to moderate ones) in normal subjects.	Popescu et al., 2016
TMS (high frequency)	Lateral parietal cortex component of the cortical-hippocampal network	Currents served to synchronize various brain regions involved in memory with the hippocampus, increasing connectivity and improving associative (relational/declarative) memory.	Wang et al., 2014
TMS (low frequency)	Hippocampal posterior-medial network	Enhanced retrieval of precise contextual and spatial information (scene of a crime, for example) for 24 hours	Nilakantan et al., 2017
TMS (low frequency)	Dorsal auditory stream (neural pathway connecting the primary visual cortex of the occipital lobe and the parietal lobe)	Improved auditory working memory and processing.	Albuoy et al., 2017
TMS (low frequency)	Primary motor cortex, corticomotor pathway	Improved implicit (unintentional) learning	Hirano et al., 2016
TMS (low frequency)	Superior temporal lobe	Transient inhibition of the gaze behavior (looking into the eyes of the person speaking to you), an important element in social cognition. The goal is to increase gaze behavior in autistic persons, who typically avoid eye contact.	Saitovitch, et al., 2016
TMS	Occipital lobe (visual cortex)	Impaired perceptual learning	Baldassarrea et al., 2016
Inhibitory TMS (low frequency)	Posterior aspect of the medial occipital lobe (primary visual cortex)	Slowed osculation resulting in increased connectivity with the visual association cortex, improving peripheral vision.	Cocchi et al., 2016
TIBS	Prefrontal cortex	Enhance blood flow and efficiency of oxygen usage in the frontal cortex, leading to improvement of memory and cognition.	Liu et al., 2017 (in Agor, 2017)
TIBS	Frontal cortex	Improved attention span, short-term memory, executive function, rule-based learning.	Blanco et al., 2017
TIBS or acute aerobic exercise	Frontal cortex	Similarly effective for cognitive enhancement (sustained attention, working memory tasks), suggesting that they augment prefrontal cognitive functions similarly.	Hwang et al., 2017

While the popular press has touted the benefits of electrical stimulation and "creativity caps" are being sold, scientists warn that it's possible there are detrimental drawbacks and the long-term consequences are unknown (Dubljević et al., 2014). With the advent of electronic devices held to the ear for long periods of time, some worry about detrimental long-term effects while others look forward to a new learning aid.

Optogenetics

3. An imagining of optogenetics (credit: The Cellular Scale)

The combination of genetics and optics to control well-defined events within specific cells of living tissue, most typically neurons. The first step is to insert genes into cells that render them light sensitive. Sensitivity to light then makes it possible to manipulate cell activity by directing light beams to cells at specific times, changing the natural sequence of actions in order to accomplish a purpose (Deisseroth, 2010). Examples include changing neuron firing patterns to reinforce behavior and learning, modifying gene expression to eliminate a physical dysfunction, and to alter behavior (El-Shamayleh et al., 2017). "Imagine if we could use optogenetics or a similar technology to get the input from an artificial sensor into our brain. In principle, we could not only restore function, but we could enhance our current functions" (I-Han Chou, Senior Editor, Nature). The excitement among scientists for optogenetics is the precision it allows: controlling defined events within defined cell types at defined times (Deisseroth, 2010).

Blue light therapy

Light therapy has been used for a number of years to treat seasonal affective disorder (SAD) using bright lights that mimic natural outdoor light. Blue light (high energy visible wavelength, just below ultraviolet) is also used to treat skin damage. Now there is clinical evidence that as little as one-half hour exposure to blue light enhances cognitive functioning (Alkozei et al., 2016). Specifically, blue light exposure increases activity in the dorsolateral and ventrolateral prefrontal cortices, leading to quicker reaction times and increased cognitive capacity (successful performance under increased cognitive load) in working memory. The effect is short-term, lasting for up to 40 minutes after exposure has ceased.

Externally applied electrical and magnetic stimulation, chemical manipulation, and optical stimulation have proven to artificially improve brain functioning. What are the implications of this development for learning?

Indirect influence

Nootropics

An emerging, largely unproven, class of drugs designed to enhance cognitive function (e.g., Modafinil, Piracetam, Spermidine). The concept is to target some metabolic or nutritional aspect of brain function, especially a function involved with memory or attention, and then to provide a nutritional precursor to that metabolic pathway, or a drug that enhances the activity of a neurotransmitter, enzyme, or other metabolic factor (Novella, 2015). Scientists generally believe that this approach is promising, but no drug created thus far has proven more effective than placebos. Spermidine has shown promise for treatment of age-induced memory impairment in seniors (Gupta et al., 2016). Nootropic enthusiasts promote the practice of stacking, combining two or more individual ingredients (e.g., Piracetam, Oxiracetam and Aniracetam).

Google effect

A discussion of external manipulation would not be complete without citing the so-called google effect or, as a topic of research, the search engine manipulation effect (Epstein, 2016). In a series of research projects, Epstein and colleagues used artificial search engine results that favored different candidates in Australian and Indian elections. Results showed a consistent 37% to 80% shift in user preferences for the favored candidate. In all instances, users were completely unaware of the manipulation. Test subjects were American, so no election was impacted. In another experiment, biased search results shifted subjects' opinions about the value of fracking by 34%. This phenomena has clear implications for anyone seeking to educate themselves about virtually any topic based on search results. According to the European Union, Google search has persistently favored, in their search results, companies in which the company has interests. While research has focused on search engines, sites like Facebook have the same potential for abuse.

Neuroprosthetics

In its simplest form, a neuroprosthetic is a device that replaces or supplements the input and/or output of the nervous system (Leuthardt et al., 2014). Devices can be targeted at bypassing neural deficits or augmenting existing function for enhanced performance. Perhaps the most exciting development in this new field is an exoskeleton controlled by the brain of a spinal cord–injured patient. A typical approach uses a setup that records brain signals from the user, computationally analyzes those signals to infer the user’s intentions (look right), and then relays the information to an external effector (machine rotates the head to the right) that acts on those intentions. Some systems are able to convert environmental stimuli into perceptions by capturing an external input and translating it into an appropriate stimulus delivered directly to the nervous system.

Researchers are exploring applications in motor, sensory, visual, auditory, and speech areas. The most obvious use in learning is for persons with physical and neurological limitations. There is also the possibility of a neurologically-based brain-computer interface to enhance cognitive abilities. The science is very complicated, and results thus far are best described as limited.

Bio- and Neurofeedback

Biofeedback

Biofeedback refers to monitoring and feedback mechanisms (e.g., electromyography [EMG] to monitor the electrical activity that causes muscle contraction) that users employ to lower heart rate, raise temperature in their extremities, and generally reduce tension. Practiced properly, it can reduce chronic headaches, lower blood pressure, improve digestion, and more. Most scientists believe that relaxation is a key component in biofeedback treatment of many disorders, particularly those brought on or made worse by stress.

Neurofeedback

Neurofeedback focuses on providing audio and/or visual feedback of neuronal firing within the brain, and includes EEG (electroencephalogram) and real-time fMRI (functional magnetic resonance imaging). Keynan et al. (2016) demonstrated the use of EEG to modulate the firing of the amygdala to control their emotional responses to external stimuli. Using a nanowire to reach the deeply embedded amygdala, Keynan had healthy subjects listen to an auditory signal reflecting amygdala activity and to use any method they chose (e.g., meditation, slow breathing) to slow the signal and thus amygdala firing. fMRI imaging confirmed the lowered activity. Ossadtchi et al. (2017) demonstrated that individuals can be trained to enter an alpha state (where alpha waves predominate), associated with relaxation and reduced stress, using ten two-minute sessions over two days. Feedback came in the form of a screen that changed colors as alpha waves increased.

Other scientists have demonstrated how to manipulate specific neural circuits using thoughts, imagery, and fMRI neurofeedback. (MacInnes, et al. (2016) demonstrated a technique that moves beyond using EEG, which produces only a rough picture of brain activity, to fMRI allowing for more precise localized measurements. In their experiment, researchers provided real-time fMRI imaging of an area of the midbrain called the ventral tegmentum, a dopamine producing area of the midbrain projecting into the neocortex and limbic system, and known to activate in the presence of rewards, thus playing an important role in motivation. Participants trained using the fMRI imaging until they were able to increase and decrease the activity of the ventral tegmentum at will. Once practiced, they were able to continue this voluntary manipulation without the visual feedback.

4. Neurofeedback training for ADHD

Treating attention deficit hyperactivity disorder (ADHD) with various neurofeedback protocols has been an active area of research. As recently as 2014, the National Institutes of Health proclaimed that it is no better than chance. This has not slowed additional research. For example, Mohagheghi et al. (2017) found two protocols to significantly (p<0.001) alleviate the symptoms of ADHD (hyperactivity, inattention, commission errors - turning attention to nontargeted stimuli, and omission errors - failing to attend to targeted stimuli) for up to eight weeks following training, with one difference. One protocol trained subjects to suppress theta wave activity and enhance beta activity (theta/beta), while the other focused on theta suppression and and alpha enhancement (theta/alpha). The theta/alpha protocol was more effective at decreasing omission errors.

Cohen et al. (2017) used real-time fMRI feedback to train for attentiveness in normal subjects, using a computer screen that faded as attention waned and brightened as attention recovered. They are also experimenting with the method to help patients train their brains to weaken intrusive memories.

Yamashita et al. (2017) used neurofeedback to increase and decrease connectivity (synchronicity of brainwave activity) between brain areas. "We selected the connectivity between the left primary motor cortex and the left lateral parietal cortex as the target. Subjects were divided into 2 groups, in which only the direction of change (an increase or a decrease in correlation) in the experimentally manipulated connectivity differed between the groups. As a result, subjects successfully induced the expected connectivity changes in either of the 2 directions. Furthermore, cognitive performance significantly and differentially changed from preneurofeedback to postneurofeedback training between the 2 groups. These findings indicate that connectivity neurofeedback can induce the aimed direction of change in connectivity and also a differential change in cognitive performance." In this study, cognitive performance was measured with three tests: reaction time, response suppression, and overcoming interference.

A call for an ethical framework

The quick advances being made in brain manipulation has begun to concern many scientists. Medaglia et al. (2017) have published a proposed framework for clinical practitioners, using neuroanatomy, cognition, and control engineering principles. "New brain-focused therapies are becoming more specific, targeted, and effective at manipulating individuals' mental states. As these techniques and technologies mature, we need systems in place to make sure they are applied ... to maximize beneficial effects and minimize unwanted side effects."

Tidbits

Therapeutic games for dyslexic children or head-trauma patients are planned that monitor the subject's brainwaves to adjust level of play automatically (Bavelier & Green, 2016).
Cognitive behavioral therapy has been shown to increase the strength of neural connections between brain regions in people with psychosis, increasing their ability to process social interactions and aiding recovery (Mason et al., 2017).

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