Media Briefings

New Research Raises Stimulating Possibilities for the Brain
 
Scientists are making significant progress toward developing computers that are modeled on the human brain.  At the same time, a different line of research is targeting the opposite goal?to make it just as easy to reboot the human brain as it is to turn on a computer.

The brain processes information in the form of electricity.  Dramatic new research, published in several peer-reviewed journals, indicates that stimulating the brain with electricity may provide effective treatments for schizophrenia, Parkinson’s, Alzheimer’s, Tourette syndrome, autism, depression, and other cognitive conditions.  Other studies show that it can boost creativity and memory.
 
Before we explore those studies, you’ll need a very brief overview of the technologies the researchers are using.  According to the website for the Brain Stimulation Program at Johns Hopkins Medicine, the new stimulation therapies “directly regulate brain function without producing the cognitive side-effects associated with ECT.”  ECT (electroconvulsive therapy) is a proven, time-tested method for treating depression that hasn’t responded to medication, and Hopkins uses ECT to treat hundreds of patients every year.

The new treatments are:1

-  Deep brain stimulation (DBS), which involves implanting electrodes in specific parts of the brain that are linked to the disease. The FDA has approved DBS as a treatment for essential tremor, Parkinson’s disease, dystonia, and chronic and severe obsessive-compulsive disorder, while clinical trials are underway on patients with Alzheimer’s and depression.  But according to the journal Cell, the surgery to implant the electrodes exposes the patient to the risks including brain hemorrhage and infection.

-  Transcranial magnetic stimulation (TMS) does not require surgery. Instead of implanting electrodes in the brain, the doctor places an electromagnetic induction coil on the patient’s head.  The coil sends short, painless magnetic pulses, which are exactly like those created by MRI machines, into the part of the brain that is associated with the patient’s disorder.
 
-  Transcranial direct current stimulation (tDCS), like TMS, is a painless non-surgical procedure. The doctor places two electrodes over the patient’s head, and the electrodes transmit direct electrical currents to stimulate specific parts of the brain.  TCDS can be used to either increase or decrease the activity of brain cells, depending on whether those cells could prevent the problem or are the cause of it.
 
Now that we’ve outlined the technologies, let’s look at the latest research, beginning with studies on psychiatric disorders and brain diseases.

According to the American Association of Neurological Surgeons, Laura Salgado Lopez, MD studied seven patients with schizophrenia who were treated with deep brain stimulation.2  In four cases, the electrodes were implanted in the patients’ nucleus accumbens, and in the other three the treatment targeted the subgenual area, in order to test two different theories of which part of the brain would best respond to DBS.

Although the study won’t be completed until later this year, Lopez won an award for her research, which so far has found that all of the patients in both groups improved by reducing their “social isolation type symptoms and auditory hallucinations.”

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Similarly, Krystal Parker of the University of Iowa Neuroscience Institute is studying the cerebellum, the brain region located at the base of the skull just above the spinal column, to determine if stimulation would reduce the symptoms of schizophrenia and other diseases that impair people’s ability to think, concentrate, and plan.

Parker and colleague Nandakumar Narayanan found that stimulating the cerebellum in rats with schizophrenia-like thinking problems normalizes brain activity in the frontal cortex and corrects the rats’ ability to estimate the passage of time, which is a cognitive deficit that is characteristic in people with schizophrenia.

As Parker explained, “Cerebellar interactions with the frontal cortex in cognitive processes has never been shown before in animal models.  In addition to showing that the signal travels from the cerebellum to the frontal cortex, the study also showed that normal timing behavior was rescued when the signal was restored.”

The study, which was published in the journal Molecular Psychiatry, suggests cerebellar stimulation might help improve cognitive problems in patients with schizophrenia.3

The researchers recorded brain activity from the frontal cortex of nine patients with schizophrenia and nine healthy controls while they performed a timing task where they had to estimate the passage of twelve seconds.  The hypothesis is that timing is a window into cognitive function, such as working memory, attention, and planning, which go haywire in patients with schizophrenia.

Compared to healthy individuals, patients with schizophrenia performed poorly on the timing task.  They also lacked a low-frequency burst of brain activity?called the delta brain wave?that occurs right at the start of the trial in healthy subjects.

In schizophrenia, dopamine signaling in the frontal cortex is abnormal.  By blocking dopamine signaling in the frontal cortex of rats, the team was able to reproduce the schizophrenia-like timing problems in the animals.

Next, the researchers stimulated the rats’ cerebellar region at the delta wave frequency of 2 Hz.  This stimulation restored normal delta wave activity in the rats’ frontal cortex and normalized the rats’ performance on the timing test.

The findings explain how cerebellar stimulation might have a therapeutic benefit in schizophrenia.  Parker adds that the research may also inspire new cerebellar-targeted pharmacological treatments for schizophrenia.

Meanwhile, according to the Journal of Neurosurgery, researchers at NYU Langone Medical Center found that DBS decreases tics, or involuntary movements and vocal outbursts, in young adults with severe Tourette syndrome.4

In many Tourette syndrome patients, the symptoms become so severe that they become socially isolated and unable to work or attend school.  Alon Mogilner, MD, PhD, director of the university’s Center for Neuromodulation, explains, “Our study shows that deep brain stimulation is a safe, effective treatment for young adults with severe Tourette syndrome that cannot be managed with current therapies.  This treatment has the potential to improve the quality of life for patients who are debilitated through their teenage years and young adulthood.”

Mogilner and his colleague, Michael H. Pourfar, MD, insert two electrodes into a region of the brain called the medial thalamus, part of the brain circuit that functions abnormally in Tourette’s.  During a second surgery, a pacemaker-like device called a neurostimulator was connected to the electrodes to emit electrical impulses into the medial thalamus.

The study followed thirteen patients.  The researchers measured the severity of tics before and after surgery using the Yale Global Tic Severity Scale.
They found that the severity of tics decreased on average 37 percent from the time of the operations to the first follow-up visit.  At their latest visit, patients’ tic scores decreased by an average of 50 percent.

More importantly, all patients reported in a survey six months after surgery that their symptoms improved either “much” or “very much,” and all said they would have the surgery again.

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Another study indicates that DBS helps people with Alzheimer’s disease.  A team of researchers led by Dr. Andres Lozano at the Toronto Western Hospital studied forty-two patients who were implanted with DBS electrodes directed at the fornix, a bundle of nerve fibers in the brain that carry signals from the hippocampus.

To better measure the impact of electrical stimulation in the brain, patients were then randomly assigned to either the “on” or “off” stimulation group and monitored for the twelve months following their procedure.  Once the trial follow up was complete, all patients then had their electrodes turned on.
Results from the trial, published in the Journal of Alzheimer’s Disease, showed that DBS stimulation of the fornix continues to be safe and that, although overall there were no differences in cognitive outcomes between the “on” and “off” study participants, those sixty-five years of age and older appeared to experience slower cognitive decline as a result of the treatment.5

Another finding of interest was that the brain’s ability to metabolize glucose increased over the year-long study period in patients receiving electrical stimulation, indicating that the brain networks made dysfunctional by Alzheimer’s improved in some ways.

According to Lozano, “We are encouraged by these findings as they indicate we are headed in the right direction with our research on DBS as a treatment for Alzheimer’s disease.  We now have a better idea of which patients will benefit most from this treatment and how the stimulation might slow the progression of Alzheimer’s.  The next phase of our research will focus on determining what stimulation dosage will have the most impact against this disease.”

Meanwhile, scientists are discovering that stimulating the brains of healthy people can improve creativity.  A team of researchers at Queen Mary University of London and Goldsmiths University of London used transcranial direct current stimulation to temporarily suppress a key part of the frontal brain called the left dorsolateral prefrontal cortex (DLPFC), which is involved in thinking and reasoning.

The results, published in the journal Scientific Reports, show that participants who received the intervention showed an enhanced ability to “think outside the box.”6

According to the study’s first author, Dr. Caroline Di BernardiLuft, “We solve problems by applying rules we learn from experience, and the DLPFC plays a key role in automating this process.  It works fine most of the time, but fails spectacularly when we encounter new problems that require a new style of thinking?our past experience can indeed block our creativity.  To break this mental fixation, we need to loosen up our learned rules.”

The researchers used tDCS to send a weak constant electrical current through electrodes positioned over the scalp to either suppress or activate the DLPFC.

Sixty participants were tested on their creative problem-solving ability before and after receiving one of the following interventions:  DLPFC being suppressed, DLPFC being activated, and DLPFC being unstimulated.

The participants solved “matchstick problems,” some of which are hard, because to solve these problems, participants need to relax the learned rules of arithmetic and algebra.

The participants whose DLPFC was temporarily suppressed by the electrical stimulation were more likely to solve hard problems than other participants whose DLPFC was activated or not stimulated.

This demonstrates that suppressing DLPFC briefly can help breaking mental assumptions learned from experience and thinking outside the box.
In a similar study, a team of researchers led by Georgetown psychology professor Adam Green and Dr. Peter Turkeltaub of Georgetown University Medical Center used tDCS to stimulate the frontopolar cortex, an area of the brain known to be associated with creativity.

The subjects who received the treatment formed more creative analogical connections between sets of words, and generated more creative associations between words.

According to Green, who published the results in the journal Cerebral Cortex, “This work is a departure from traditional research that treats creativity as a static trait.  Instead, we focused on creativity as a dynamic state that can change quickly within an individual when they ‘put their thinking cap on.’“7
The researchers wrote that their study demonstrates that tDCS enhances the “conscious augmentation of creativity elicited by cognitive intervention, and extends the known boundaries of tDCS enhancement to analogical reasoning, a form of creative intelligence that is a powerful engine for innovation.”

Based on this intriguing research, we offer the following forecasts:

First, by 2030, this new technology will become at least as common as heart pacemakers.

Unless some major side effect emerges, deep brain stimulation is likely to be used in hospitals to treat severe cases of disorders such as schizophrenia and autism, while tDCS is particularly promising for conditions like depression and Alzheimer’s because the technology is portable, with patients able to wear the electrodes in a cap.

Second, transcranial magnetic stimulation could prove to be the weight-loss solution that hundreds of millions of Americans have been seeking. 
According to research findings presented at ENDO 2017, the Endocrine Society’s 99th annual meeting, TMS helps obese people lose weight, partly by changing the composition of their gut microbiota, or their intestinal bacteria.  LivioLuzi, MD, of Italy’s University of Milan and his colleagues studied whether TMS could improve the gut microbiota?the mix of beneficial and harmful microorganisms that inhabit the digestive tract?in people who are obese.8  After five weeks of treatment, subjects receiving TMS lost more than 3 percent of their body weight and more than 4 percent of their fat, significantly more than controls did, and measures of their beneficial bacteria increased to the levels seen in healthy people, while the controls were unchanged.

Third, tDCS will emerge as an extreme approach to enhancing healthy brains.

The mass-market appeal of a technology that can improve creativity is obvious, and some consumer products have already appeared on the market without FDA approval, such as the Foc.us V2 tDCS Device.  While the research studies we’ve considered suggest that brain stimulation does open people’s minds to new ideas, it isn’t just a matter of strapping on electrodes.  According to researcher Roi Cohen Kadosh “tDCS alone is of little use.  The advantage of it is when it is combined with cognitive training, rather than just applied alone to the brain.”  Because study sample sizes have been so small, researchers haven’t been able to determine how individual differences can affect results, and no one has studied the long-term impact of brain stimulation.  Also, according to an article in Wired, “What you do after a brain zapping session can modify or completely nullify any effects of the electricity.9  Walking around or having specific thoughts is all it takes to potentially reverse the effects.  Research on this problem is still in its infancy, so there’s no way you can know how best to behave after a tDCS session to preserve any potential benefits.  If you enhance mental function in one area, it can actually have a negative impact on another aspect of mental function.  Because the neural effects of tDCS can be long-lasting, what might be advantageous in one situation could therefore leave you impaired in a different context later.”  Clearly more research will need to be done?but with each study scientists are gaining more insights into how to use electricity to improve the functioning of the brain.

References
1. To access overviews of the four brain stimulation therapies, visit the John Hopkins Medicine website at:

http://www.hopkinsmedicine.org/psychiatry/specialty_areas/brain_stimulation/index.htm

2. Science Daily, April 25, 2017, “A Pilot Study of Deep Brain Stimulation in Treatment-Resistant Schizophrenia,” by Laura Salgado Lopez, MD ⓒ 2017 American Association of Neurological Surgeons.  All rights reserved.

http://www.sciencedaily.com/releases/2017/04/170425153818.htm

3. Molecular Psychiatry, May 2017, “Delta-Frequency Stimulation of Cerebellar Projections Can Compensate for Schizophrenia-Related Medial Frontal Dysfunction,” by Krystal Parker, Nandakumar Narayanan, et al. ⓒ 2017 MacMillan Publishers Limited, part of Springer Nature.  All rights reserved.

http://www.nature.com/mp/journal/v22/n5/full/mp201750a.html

4. Journal of Neurosurgery, April 7, 2017, “Deep Brain Stimulation for Tourette Syndrome: A Single-Center Series by Richard Dowd, Michael Pourfar, and Alon Y. Mogilner. ⓒ 2017 American Association of Neurological Surgeons.  All rights reserved.

http://thejns.org/doi/full/10.3171/2016.10.JNS161573

5. Journal of Alzheimer’s Disease, 2016, Vol. 54, Iss. 2, “A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer’s Disease,” by Andres Lozano, et al. ⓒ 2016 IOS Press.  All rights reserved.

http://content.iospress.com/articles/journal-of-alzheimers-disease/jad160017

6. Scientific Reports, June 7 2017, “Relaxing Learned Constraints Through Cathodal tDCS on the Left Dorsolateral Prefrontal Cortex,” by Caroline DiBernardiLuft, et al. ⓒ 2017 Macmillan Publishers Limited, part of Springer Nature.  All rights reserved. 

https://www.nature.com/articles/s41598-017-03022-2

7. Cerebral Cortex, April 2017, Vol. 27, Iss. 4, “Thinking Cap Plus Thinking Zap: tDCS of Frontopolar Cortex Improves Creative Analogical Reasoning and Facilitates Conscious Augmentation of State Creativity in Verb Generation,” by Adam Green, Peter Turkeltaub, et al. ⓒ 2017 Oxford University Press.  All rights reserved.

https://academic.oup.com/cercor/article/27/4/2628/3056344/Thinking-Cap-Plus-Thinking-Zap-tDCS-of-Frontopolar

8. Wired, January 2014, “Read this Before Zapping Your Brain,” Christian Jarrett. ⓒ 2014 Conde Nast.  All rights reserved.

https://www.wired.com/2014/01/read-zapping-brain/