Transcranial magnetic stimulation follow-up study in early Parkinson's disease: A decline in compensation with disease progression?
Mov Disord. 2015 Mar 5. doi: 10.1002/mds.26167. [Epub ahead of print]
Kojovic M, Kassavetis P, Bologna M, Pareés I, Rubio-Agusti I, Beraredelli A, Edwards MJ, Rothwell JC, Bhatia KP.
Abstract
A number of neurophysiological abnormalities have been described in patients with Parkinson's disease, but very few longitudinal studies of how these change with disease progression have been reported. We describe measures of motor cortex inhibition and plasticity at 6 and 12 mo in 12 patients that we previously reported at initial diagnosis. Given the well-known interindividual variation in these measures, we were particularly concerned with the within-subject changes over time. Patients were assessed clinically, and transcranial magnetic stimulation (TMS) was used to measure motor cortical excitability, inhibition (short interval intracortical inhibition, cortical silent period), and plasticity (response to excitatory paired associative stimulation protocol) in both hemispheres. All measurements were performed 6 mo and 12 mo after the baseline experiments. Asymmetry in clinical motor symptoms was reflected in asymmetry of plasticity and inhibition. In the group as a whole, little change was seen in any of the parameters over 12 mo. However, analysis of within-individual data showed clear correlations between changes in clinical asymmetry and asymmetry of response to paired associative stimulation protocol and cortical silent period. Longitudinal changes in cortical silent period and response to paired associative stimulation protocol in Parkinson's disease reflect dynamic effects on motor cortex that are related to progression of motor signs. They are useful objective markers of early disease progression that could be used to detect effects of disease-modifying therapies. The decline in heightened plasticity that was present at disease onset may reflect failure of compensatory mechanisms that maintained function in the preclinical state.
If you have ever said or done the wrong thing at the wrong time, you should read this. Neuroscientists at The University of Texas Health Science Center at Houston (UTHealth) and the University of California, San Diego, have successfully demonstrated a technique to enhance a form of self-control through a novel form of brain stimulation.
Study participants were asked to perform a simple behavioral task that required the braking/slowing of action – inhibition – in the brain. In each participant, the researchers first identified the specific location for this brake in the prefrontal region of the brain. Next, they increased activity in this brain region using stimulation with brief and imperceptible electrical charges. This led to increased braking – a form of enhanced self-control.
This proof-of-principle study appears in the Dec. 11 issue of The Journal of Neuroscience and its methods may one day be useful for treating attention deficit hyperactivity disorder (ADHD), Tourette's syndrome and other severe disorders of self-control.
"There is a circuit in the brain for inhibiting or braking responses," said Nitin Tandon, M.D., the study's senior author and associate professor in The Vivian L. Smith Department of Neurosurgery at the UTHealth Medical School. "We believe we are the first to show that we can enhance this braking system with brain stimulation."
A computer stimulated the prefrontal cortex exactly when braking was needed. This was done using electrodes implanted directly on the brain surface.
When the test was repeated with stimulation of a brain region outside the prefrontal cortex, there was no effect on behavior, showing the effect to be specific to the prefrontal braking system.
This was a double-blind study, meaning that participants and scientists did not know when or where the charges were being administered.
The method of electrical stimulation was novel in that it apparently enhanced prefrontal function, whereas other human brain stimulation studies mostly disrupt normal brain activity. This is the first published human study to enhance prefrontal lobe function using direct electrical stimulation, the researchers report.
The study involved four volunteers with epilepsy who agreed to participate while being monitored for seizures at the Mischer Neuroscience Institute at Memorial Hermann-Texas Medical Center (TMC). Stimulation enhanced braking in all four participants.
Tandon has been working on self-control research with researchers at the University of California, San Diego, for five years. "Our daily life is full of occasions when one must inhibit responses. For example, one must stop speaking when it's inappropriate to the social context and stop oneself from reaching for extra candy," said Tandon, who is a neurosurgeon with the Mischer Neuroscience Institute at Memorial Hermann-TMC.
The researchers are quick to point out that while their results are promising, they do not yet point to the ability to improve self-control in general. In particular, this study does not show that direct electrical stimulation is a realistic option for treating human self-control disorders such as obsessive-compulsive disorder, Tourette's syndrome and borderline personality disorder. Notably, direct electrical stimulation requires an invasive surgical procedure, which is now used only for the localization and treatment of severe epilepsy.
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The study's co-lead authors are Jan R. Wessel, Ph.D., of the Department of Psychology at the University of California, San Diego; and Christopher R. Conner, student at the UTHealth Medical School. The fourth author is Adam Aron, Ph.D., at the University of California, San Diego.
The study is titled "Chronometric Electrical Stimulation of Right Inferior Frontal Cortex Increases Motor Braking." Authors received support from the National Institutes of Health Center for Clinical and Translational Sciences (KL2RR0224149), the Mischer Neuroscience Institute at Memorial Hermann-TMC and the Keck Center of the Gulf Coast Consortia.
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University of Washington researchers have performed what they believe is the first noninvasive human-to-human brain interface, with one researcher able to send a brain signal via the Internet to control the hand motions of a fellow researcher.
University of Washington
University of Washington researcher Rajesh Rao, left, plays a computer game with his mind. Across campus, researcher Andrea Stocco, right, wears a magnetic stimulation coil over the left motor cortex region of his brain. Stocco’s right index finger moved involuntarily to hit the “fire” button as part of the first human brain-to-brain interface demonstration.
Using electrical brain recordings and a form of magnetic stimulation, Rajesh Rao sent a brain signal to Andrea Stocco on the other side of the UW campus, causing Stocco’s finger to move on a keyboard.
While researchers at Duke University have demonstrated brain-to-brain communication between two rats, and Harvard researchers have demonstrated it between a human and a rat, Rao and Stocco believe this is the first demonstration of human-to-human brain interfacing.
“The Internet was a way to connect computers, and now it can be a way to connect brains,” Stocco said. “We want to take the knowledge of a brain and transmit it directly from brain to brain.”
The researchers captured the full demonstration on video recorded in both labs. The following version has been edited for length. This video and high-resolution photos also are available on the research website.
Rao, a UW professor of computer science and engineering, has been working on brain-computer interfacing in his lab for more than 10 years and just published a textbook on the subject. In 2011, spurred by the rapid advances in technology, he believed he could demonstrate the concept of human brain-to-brain interfacing. So he partnered with Stocco, a UW research assistant professor in psychology at the UW’s Institute for Learning & Brain Sciences.
On Aug. 12, Rao sat in his lab wearing a cap with electrodes hooked up to anelectroencephalography machine, which reads electrical activity in the brain. Stocco was in his lab across campus wearing a purple swim cap marked with the stimulation site for thetranscranial magnetic stimulation coil that was placed directly over his left motor cortex, which controls hand movement.
The team had a Skype connection set up so the two labs could coordinate, though neither Rao nor Stocco could see the Skype screens.
Rao looked at a computer screen and played a simple video game with his mind. When he was supposed to fire a cannon at a target, he imagined moving his right hand (being careful not to actually move his hand), causing a cursor to hit the “fire” button. Almost instantaneously, Stocco, who wore noise-canceling earbuds and wasn’t looking at a computer screen, involuntarily moved his right index finger to push the space bar on the keyboard in front of him, as if firing the cannon. Stocco compared the feeling of his hand moving involuntarily to that of a nervous tic.
“It was both exciting and eerie to watch an imagined action from my brain get translated into actual action by another brain,” Rao said. “This was basically a one-way flow of information from my brain to his. The next step is having a more equitable two-way conversation directly between the two brains.”
University of Washington
The cycle of the experiment. Brain signals from the “Sender” are recorded. When the computer detects imagined hand movements, a “fire” command is transmitted over the Internet to the TMS machine, which causes an upward movement of the right hand of the “Receiver.” This usually results in the “fire” key being hit.
The technologies used by the researchers for recording and stimulating the brain are both well-known. Electroencephalography, or EEG, is routinely used by clinicians and researchers to record brain activity noninvasively from the scalp. Transcranial magnetic stimulation is a noninvasive way of delivering stimulation to the brain to elicit a response. Its effect depends on where the coil is placed; in this case, it was placed directly over the brain region that controls a person’s right hand. By activating these neurons, the stimulation convinced the brain that it needed to move the right hand.
Computer science and engineering undergraduates Matthew Bryan, Bryan Djunaedi, Joseph Wu and Alex Dadgar, along with bioengineering graduate student Dev Sarma, wrote the computer code for the project, translating Rao’s brain signals into a command for Stocco’s brain.
“Brain-computer interface is something people have been talking about for a long, long time,” said Chantel Prat, assistant professor in psychology at the UW’s Institute for Learning & Brain Sciences, and Stocco’s wife and research partner who helped conduct the experiment. “We plugged a brain into the most complex computer anyone has ever studied, and that is another brain.”
At first blush, this breakthrough brings to mind all kinds of science fiction scenarios. Stocco jokingly referred to it as a “Vulcan mind meld.” But Rao cautioned this technology only reads certain kinds of simple brain signals, not a person’s thoughts. And it doesn’t give anyone the ability to control your actions against your will.
Both researchers were in the lab wearing highly specialized equipment and under ideal conditions. They also had to obtain and follow a stringent set of international human-subject testing rules to conduct the demonstration.
“I think some people will be unnerved by this because they will overestimate the technology,” Prat said. “There’s no possible way the technology that we have could be used on a person unknowingly or without their willing participation.”
Stocco said years from now the technology could be used, for example, by someone on the ground to help a flight attendant or passenger land an airplane if the pilot becomes incapacitated. Or a person with disabilities could communicate his or her wish, say, for food or water. The brain signals from one person to another would work even if they didn’t speak the same language.
Rao and Stocco next plan to conduct an experiment that would transmit more complex information from one brain to the other. If that works, they then will conduct the experiment on a larger pool of subjects.
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