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Is there a way to measure ATP usage in the brain similarly to fMRI?

Is there a way to measure ATP usage in the brain similarly to fMRI?



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Is there a way to measure ATP usage in the brain (or anywhere else) similarly to how fMRI works (measuring changes in iron resonance in oxygenated/deoxygenated blood)? Is there some sort of similar signal that can be used for ATP?


I'm pretty sure this doesn't exist. If it did, that would be awesome.

The following is 100% pure speculation with nothing to back this up at all (as a disclaimer).

Phosphorus-31 (the stable isotope) is NMR active, which means that you could theoretically use an MRI machine to visualize phosphorus. A quick google search shows scientists attempting to use phosphorus MRI for visualizing bone structure.

I don't really know much about MRI, but I do know some about small molecule NMR, which is based on the same principles. This is a pretty cool paper showing phosphorus-31 NMR used to measure ATP synthesis.

Maybe in the distant future it could be possible to use phosphorus-31 MRI to visualize ATP/ADP ratios in various tissues, including the brain. But that would be some amazing sci-fi stuff.


Anatomy and Physiology, Systems

S.B. Eickhoff , V.I. Müller , in Brain Mapping , 2015

Functional Connectivity: Definition and Conceptual Implications

Functional connectivity is defined as the temporal coincidence of spatially distant neurophysiological events ( Friston, 1994 ). That is, two regions are considered to show functional connectivity if there is a statistical relationship between the measures of activity recorded for them. The notion behind this connectivity approach is that areas are presumed to be coupled or are components of the same network if their functional behavior is consistently correlated with each other. In contrast to effective connectivity analyses, which rest on numerous assumptions regarding both the underlying neurobiology and the model chosen to estimate it, functional connectivity represents a much more direct approach to the analysis of functional networks. In particular, it concurs with the intuitive notion that when two things happen together, these two things should be related to each other. By relying very little on a priori assumptions, functional connectivity analysis thus rather reflects a straightforward, observational measure of functional relationships. This definition, however, already clearly reveals two key aspects that need to be considered when dealing with functional connectivity analyses.

The first is the important caveat that functional connectivity per se is purely correlative in nature. As just noted, two regions show functional connectivity, if increased activity in one region is associated above chance with activity in another. As always with correlations, however, this does not imply any causal relationship or even any sort of direct connection between these two regions. Correlated activity in two regions may, for example, be mediated via additional structures relaying information from the first area to the second. Such relay processes could moreover be transmitted through cascades of several intermediates or via cortical–subcortical loops involving, for example, the basal ganglia or the cerebellum. In such cases, activity in one area may represent the ultimate drive of activity in the other even in the absence of a structural connection, that is, fibers running between the two areas. Strong functional connectivity may hence be observed even if structural connections are weak or absent, although in most cases, these two aspects of brain connectivity show at least some level of convergence ( Eickhoff et al., 2010 ). Furthermore, it is also possible that a third area induces correlated activation between regions that actually do not have any form of direct interaction. Therefore, functional connectivity may be driven by an external source inducing concurrent activity in both areas. An example of such situation would be the feedforward of stimulus-driven activity in early sensory areas that is forwarded to parietal sensory areas for perceptual analysis and, in parallel, to premotor cortex for response preparation. Even if both would be implemented in completely segregated streams, this scenario would lead to correlated activity changes in higher sensory areas and motor regions, that is, functional connectivity between them. Thus, functional connectivity may be observed even between regions that are not functionally interacting with each other due to effects of the experimental setup. A similar consideration also holds for structured noise or confounds, such as motion or physiological effects ( Birn, 2012 Duncan & Northoff, 2013 ). If their influence is not removed from the data or accommodated in the analysis, spurious correlations will arise. It follows that while functional connectivity investigations themselves require much less elaborate modeling and a priori assumptions than most approaches to effective connectivity analyses, they at the same time are much more susceptible to biological and technical confounds that may influence the noise spectrum of the data and induce spurious correlations that may be mistaken as functional interactions. Consequently, as will be detailed in the succeeding text, removing or accounting for potential confounds has become a major aspect not only of development but also of conjecture, in particular, with respect to resting-state functional connectivity analyses.

Secondly, it should be remarked that the notion of functional connectivity may pertain to any form of neurophysiological events. That is, any above-chance coincidence of brain activity signals recorded in different parts of the brain may be considered as evidence for coupling between them, which may be direct, indirect, or spurious, and hence functional connectivity. Resting-state analyses, that is, time-series correlations in BOLD fMRI data acquired in a task-free state, may thus be used to assess functional connectivity in the brain. However, it must be remembered that functional connectivity represents a much broader concept that may not be equated with such resting-state analyses. Rather, functional connectivity may, for example, also be realized as correlated spiking patterns or field potentials. This application of functional connectivity analysis is commonly found in electrophysiological experiments in nonhuman species, where direct recordings of individual cells or multiunit activity may be correlated among different recording sites ( Aertsen, Erb, & Palm, 1994 Gerstein & Perkel, 1969 ). In humans, it may also be applied to direct recordings during deep brain stimulation by correlating electrophysiological recordings from the implanted electrodes between different sites or contacts or by correlating them with cortical signals as measured, for example, by magnetoencephalography (MEG) or electroencephalography (EEG) (e.g., Hohlefeld et al., 2013 Lourens et al., 2013 ). Another non-fMRI application of functional connectivity analyses is the delineation of correlations or more precisely coherence between EEG sensors, which due to the high temporal resolution of EEG may be computed as broadband correlations or specific for particular frequency bands. In these instances, functional connectivity analyses indicate coherent oscillations, that is, neuronal mass activity, between different regions of the brain reflecting synchronous activity ( Ruchkin, 2005 ). In terms of fMRI data, functional connectivity may be investigated on measurements that are obtained while the subject is passively lying in the scanner (resting state) or on fMRI data recorded during a particular task (e.g., Ebisch et al., 2013 ). Finally, the analysis of the coactivation patterns across many different task-based fMRI experiments can likewise be used to investigate functional connectivity in the brain ( Eickhoff et al., 2010 ). In such analyses, the individual experiments represent the units of observation, and the analysis aims at identifying the above-chance coincidence of reported activations across different experiments. In summary, functional connectivity may thus be assessed using various data modalities and analysis approaches, rendering it a broad concept rather than a particular method.


The Evil Brain: What Lurks Inside a Killer’s Mind

Homicidal madmen don’t have much of a capacity for gratitude, but if they did, they’d offer a word of thanks to Charles Whitman. Whitman was the 25-year-old engineering student and former Marine who, in 1966, killed 17 people and wounded 32 in a mass shooting at the University of Texas, before being shot and killed himself by police. Earlier that day, he also murdered his wife and mother. Criminal investigators looking for a reason for the rampage got what seemed to be their answer quickly, in the form of a suicide note Whitman left at his home:

I do not really understand myself these days. I am supposed to be an average reasonable and intelligent young man. However, lately (I cannot recall when it started) I have been a victim of many unusual and irrational thoughts … please pay off my debts [and] donate the rest anonymously to a mental-health foundation. Maybe research can prevent further tragedies of this type.

Whitman got his wish — after a fashion. With the approval of his family, an autopsy was conducted and investigators found both a tumor and a vascular malformation pressing against his amygdala, the small and primitive region of the brain that controls emotion. A state commission of inquiry concluded that the tumor might have contributed to the shootings, earning Whitman a tiny measure of posthumous redemption — and providing all killers since at least the fig-leaf defense that something similar might be wrong with them too.

For as long as evil has existed, people have wondered about its source, and you don’t have to be too much of a scientific reductionist to conclude that the first place to look is the brain. There’s not a thing you’ve ever done, thought or felt in your life that isn’t ultimately traceable to a particular webwork of nerve cells firing in a particular way, allowing the machine that is you to function as it does. So if the machine is busted — if the operating system in your head fires in crazy ways — are you fully responsible for the behavior that follows?

That’s a question that has a lot more than just philosophical implications. No sooner were the Tsarnaev brothers identified as the Boston Marathon bombers than speculation arose as to whether the behavior of older-brother Tamerlan might have been influenced by brain damage sustained during his years as a boxer. The answer was almost certainly no: sports-related brain injury usually leads to volatile and impulsive behavior in people his age, and the bombing was coldly and painstakingly planned. (This was made especially clear by the later revelation that the brothers had originally planned their attack for July 4, but by working hard and applying themselves, they completed their bombs earlier than planned — an illustration of perverse diligence if ever there was one.) But the medical histories of uncounted other killers and violent offenders are filled with diagnoses of all manner of brain diseases and traumas, raising both the issue of whether the perps were truly, fully, responsible for their crimes, and the possibility that the acts could have been prevented in the first place if the illnesses had been treated.

“I don’t think there’s any kind of neurological condition that’s 100% predictive,” says neuroscientist Michael Koenigs of the University of Madison-Wisconsin. “But even when psychopaths know that what they’re doing is a crime, that doesn’t mean they’re in control of their behavior when they offend.”

Even before Whitman made it into the medical texts, scientists were already familiar with the case of Phineas Gage, the 25-year-old railroad worker who, in 1848, was helping to blast a path for a new rail line in Vermont when an errant explosion drove an iron rod into the top of his head, through his left frontal lobe and out his cheekbone. Gage, incredibly, didn’t die and nor did he even exhibit much loss of function. But after the bar was removed, there was a sudden change in his personality. Always a peaceable man, he become volatile, combative and, after a lifetime of polite speaking, wildly profane. It was science’s first glimpse at the seemingly direct cause-and-effect connection between trauma to the brain and the very essence of personality. As our ability to image and repair the brain has improved, we’ve been able to detect far less obvious damage than a railroad spike through the skull — damage that nonetheless has every bit as great an effect.

In a celebrated 2003 case published in the Archives of Neurology, for example, a 40-year-old Virginia schoolteacher with no history of pedophilia developed a sudden interest in child pornography and began making sexual overtures to his stepdaughter. His wife reported his behavior, and he was arrested and assigned to a 12-step program for sex offenders. He flunked out of the course — he couldn’t stop propositioning staff members — and was sentenced to prison. Only a day before he was set to surrender, however, he appeared in a local emergency room with an explosive headache and a range of other neurological symptoms. Doctors scanned his brain and found a tumor the size of an egg in the right orbitofrontal cortex, the region that processes decisionmaking and other so-called executive functions. The tumor was removed and the compulsive sexuality vanished along with it. Less than a year later, the tumor returned — and so, almost in lockstep, did his urges.

“There’s no one spot in the brain for pedophilia,” says Stephen J. Morse, professor of both law and psychiatry at the University of Pennsylvania. “But damage to the orbitofrontal region is known to be associated with disinhibition. We know that various forms of brain damage can contribute to difficulties in being guided by reason.”

Other, more recent studies are finding roots of criminality in other parts of the brain. As Maia Szalavitz reported in April, a team of researchers led by Kent Kiehl, associate professor of psychology at the University of New Mexico, published a study in the Proceedings of the National Academy of Sciences in which the brains of 96 male felons sentenced to at least a year in jail for crimes including robbery, drug dealing and assault were scanned in a functional magnetic resonance imager (fMRI). While they were in the fMRI, the men performed a task that required them to hit a key on a computer when they saw the letter X on a screen, but refrain when they saw the letter K. Since the X appeared 84% of the time and since the two letters look awfully similar to begin with, it was easy to get into the habit of overclicking. The ability to avoid hitting the key too much calls for a measure of impulse control, a faculty processed in a region of the brain known as the anterior cingulate cortex (ACC). The inmates who did worse on the test turned out to have lower levels of activity in the ACC the ones who performed better had higher levels. Kiehl tracked all of the inmates for four years after their release from prison and found that those with the sleepy ACCs were also more than four times likelier to be rearrested than the others. If you can’t control your impulse to click, the study suggested, you might have equal difficulty controlling the impulse to run afoul of the law.

“There are more papers coming out that show how MRIs predict who reoffends,” said Kiehl in a follow-up e-mail with TIME. “We are examining treatments that increase activity in the anterior cingulate. The goal is to see if we can help identify the best therapies to reduce recidivism.”

Koenigs, who has collaborated with Kiehl, has conducted other work with inmates linking both the amygdala and a region known as the ventromedial prefrontal cortex as possible accomplices in crime. The amygdala is the wild child of that pair, the brain’s seat of fear, suspicion, anger and more. Those are not always bad emotions, provided the ventromedial is able to do one of its assigned jobs, which is to keep the amygdala on a short leash. Working with the Wisconsin Department of Corrections, Koenigs was given access to two groups of volunteer prisoners at a medium-security facility: one diagnosed as psychopathic, one nonpsychopathic.

In the first of two tests, Koenigs scanned the men’s brains with a diffusion tensor imager, a type of MRI that detects how water molecules interact with tissue. In this case, he was trying to determine the soundness of the white matter — the fatty insulation — that protects the neural circuits connecting the ventromedial and the amygdala. In a second test, he used an fMRI to study more directly how clearly the two regions were communicating. In both cases, the brains of the psychopaths were in worse shape than those of the nonpsychopaths, with less robust white-matter insulation and the nerves beneath it doing a poorer job of transmitting signals.

“You can use the findings of this study as a proxy for the connectedness between these two structures,” Koenigs says. “The remorselessness and violence seen in psychopaths may be attributable to the regions not communicating effectively.”

Other studies make a similar case for the mechanistic roots of crime. Enzymes known as monoamine oxidases (MAO) are essential to keeping human behavior in check, breaking down neurotransmitters such as serotonin and dopamine and ensuring that the brain remains in chemical balance. Babies born with a defect in an MAO-related gene — known colloquially as the warrior gene — have been shown to be at nine times higher risk of exhibiting antisocial behavior later in life. Adrian Raine, professor of criminology at the University of Pennsylvania, has found that infants under 6 months old who have a brain structure known as a cavum septum pellucidum — a small gap in a forward region between the left and right hemispheres — are similarly likelier to develop behavioral disorders, and face a higher risk of arrest and conviction as adults as well.

All of this makes the case for a neurological role in many violent crimes hard to deny, but all of it raises a powerful question too: So what? For one thing, brain anomalies are only part of the criminal puzzle. A rotten MAO gene indeed may play a role in later-life criminality, but in most cases it’s only when children have also been exposed to abuse or some other kind of childhood trauma. A child with a stable background and bad genetics may handle his warrior impulses just fine. Koenigs may have found cross-talk problems between the ventromedial and the amygdalae of psychopaths, but he also acknowledges that he didn’t get a look at the men’s brains until they were, on average, 30 years old, and a lot could have gone on in that time. “They’ve had a lifetime of poor socialization, drugs, alcohol, they’ve had their bell rung,” he says. “You don’t know what causes what.”

Even the case of the pedophile schoolteacher, whose pathology switched cleanly off and cleanly on depending on the presence of his tumor, was less clear than it seems. “He touched his stepdaughter only when his wife was not around, and his wife and co-workers had not noticed any problems,” says Morse. “Clearly he had some control or some rational capacity. You can’t say that just because the tumor caused him to have pedophiliac desires, he wasn’t responsible.”

That’s the zone in which science and the law always collide — the causation question that can’t simply be brain-scanned or tissue-sampled or longitudinally tested away. People like Morse believe where once we attributed all crime to moral laxity or simple evil, we’ve now overcorrected, too often looking to excuse criminal behavior medically. “I call it the fundamental psycholegal error,” he says. “The belief that if you discover a cause you’ve mitigated or excused responsibility. If you have a bank robber who can show that he commits crimes only when he’s in a hypomanic state, that does not mean he deserves excuse or mitigation.”

Koenigs takes a more forgiving view: “I’ve been part of a Department of Justice project to help inform judges about how to assess culpability,” he says. “The legal system currently goes about it the wrong way, relying on whether criminals know right from wrong. Maybe they do, but the kinds of things that would then give most people pause just don’t register on some of them.”

Where the two camps do agree is on the need to keep society safe from the predations of people whose raging brains — no matter the cause — lead to so much death and suffering. Here legal theory yields a little more easily to hard science. Scanning every inmate’s ACC before making parole decisions will surely raise privacy issues, but if the science can be proven and perfected, isn’t there a strong case for trying it — especially if, as Kiehl suggests, it might lead to therapeutic and rehabilitative strategies? Babies taken from abusive parents might similarly be scanned as part of a routine medical check, just in case a telltale gap in the brain hemispheres could exacerbate the trauma they’ve already endured, making therapeutic intervention all the more important.

Evil is far too complex and far too woven into our natures for us to think that we can always adjudicate it fairly. But the better we can understand the brains that are home to such ugliness, the more effectively we can contain it, control it and punish it. Now and then, with the help of science, we may even be able to snuff it out altogether.


Magnetic Resonance Imaging (MRI)

Magnetic Resonance Imaging (MRI) is a non-invasive imaging technology that produces three dimensional detailed anatomical images. It is often used for disease detection, diagnosis, and treatment monitoring. It is based on sophisticated technology that excites and detects the change in the direction of the rotational axis of protons found in the water that makes up living tissues.

MRIs employ powerful magnets which produce a strong magnetic field that forces protons in the body to align with that field. When a radiofrequency current is then pulsed through the patient, the protons are stimulated, and spin out of equilibrium, straining against the pull of the magnetic field. When the radiofrequency field is turned off, the MRI sensors are able to detect the energy released as the protons realign with the magnetic field. The time it takes for the protons to realign with the magnetic field, as well as the amount of energy released, changes depending on the environment and the chemical nature of the molecules. Physicians are able to tell the difference between various types of tissues based on these magnetic properties.

How Do X-rays Work?

To obtain an MRI image, a patient is placed inside a large magnet and must remain very still during the imaging process in order not to blur the image. Contrast agents (often containing the element Gadolinium) may be given to a patient intravenously before or during the MRI to increase the speed at which protons realign with the magnetic field. The faster the protons realign, the brighter the image.

MRI scanners are particularly well suited to image the non-bony parts or soft tissues of the body. They differ from computed tomography (CT), in that they do not use the damaging ionizing radiation of x-rays. The brain, spinal cord and nerves, as well as muscles, ligaments, and tendons are seen much more clearly with MRI than with regular x-rays and CT for this reason MRI is often used to image knee and shoulder injuries.

In the brain, MRI can differentiate between white matter and grey matter and can also be used to diagnose aneurysms and tumors. Because MRI does not use x-rays or other radiation, it is the imaging modality of choice when frequent imaging is required for diagnosis or therapy, especially in the brain. However, MRI is more expensive than x-ray imaging or CT scanning.

One kind of specialized MRI is functional Magnetic Resonance Imaging (fMRI.) This is used to observe brain structures and determine which areas of the brain “activate” (consume more oxygen) during various cognitive tasks. It is used to advance the understanding of brain organization and offers a potential new standard for assessing neurological status and neurosurgical risk.

Although MRI does not emit the ionizing radiation that is found in x-ray and CT imaging, it does employ a strong magnetic field. The magnetic field extends beyond the machine and exerts very powerful forces on objects of iron, some steels, and other magnetizable objects it is strong enough to fling a wheelchair across the room. Patients should notify their physicians of any form of medical or implant prior to an MR scan.

When having an MRI scan, the following should be taken into consideration:

  • People with implants, particularly those containing iron, — pacemakers, vagus nerve stimulators, implantable cardioverter- defibrillators, loop recorders, insulin pumps, cochlear implants, deep brain stimulators, and capsules from capsule endoscopy should not enter an MRI machine.
  • Noise—loud noise commonly referred to as clicking and beeping, as well as sound intensity up to 120 decibels in certain MR scanners, may require special ear protection.
  • Nerve Stimulation—a twitching sensation sometimes results from the rapidly switched fields in the MRI.
  • Contrast agents—patients with severe renal failure who require dialysis may risk a rare but serious illness called nephrogenic systemic fibrosis that may be linked to the use of certain gadolinium-containing agents, such as gadodiamide and others. Although a causal link has not been established, current guidelines in the United States recommend that dialysis patients should only receive gadolinium agents when essential, and that dialysis should be performed as soon as possible after the scan to remove the agent from the body promptly.
  • Pregnancy—while no effects have been demonstrated on the fetus, it is recommended that MRI scans be avoided as a precaution especially in the first trimester of pregnancy when the fetus’ organs are being formed and contrast agents, if used, could enter the fetal bloodstream.

  • Claustrophobia—people with even mild claustrophobia may find it difficult to tolerate long scan times inside the machine. Familiarization with the machine and process, as well as visualization techniques, sedation, and anesthesia provide patients with mechanisms to overcome their discomfort. Additional coping mechanisms include listening to music or watching a video or movie, closing or covering the eyes, and holding a panic button. The open MRI is a machine that is open on the sides rather than a tube closed at one end, so it does not fully surround the patient. It was developed to accommodate the needs of patients who are uncomfortable with the narrow tunnel and noises of the traditional MRI and for patients whose size or weight make the traditional MRI impractical. Newer open MRI technology provides high quality images for many but not all types of examinations.

Replacing Biopsies with Sound
Chronic liver disease and cirrhosis affect more than 5.5 million people in the United States. NIBIB-funded researchers have developed a method to turn sound waves into images of the liver, which provides a new non-invasive, pain-free approach to find tumors or tissue damaged by liver disease. The Magnetic Resonance Elastography (MRE) device is placed over the liver of the patient before he enters the MRI machine. It then pulses sound waves through the liver, which the MRI is able to detect and use to determine the density and health of the liver tissue. This technique is safer and more comfortable for the patient as well as being less expensive than a traditional biopsy. Since MRE is able to recognize very slight differences in tissue density, there is the potential that it could also be used to detect cancer.

New MRI just for Kids
MRI is potentially one of the best imaging modalities for children since unlike CT, it does not have any ionizing radiation that could potentially be harmful. However, one of the most difficult challenges that MRI technicians face is obtaining a clear image, especially when the patient is a child or has some kind of ailment that prevents them from staying still for extended periods of time. As a result, many young children require anesthesia, which increases the health risk for the patient. NIBIB is funding research that is attempting to develop a robust pediatric body MRI. By creating a pediatric coil made specifically for smaller bodies, the image can be rendered more clearly and quickly and will demand less MR operator skill. This will make MRIs cheaper, safer, and more available to children. The faster imaging and motion compensation could also potentially benefit adult patients as well.

Another NIBIB-funded researcher is trying to solve this problem from a different angle. He is developing a motion correction system that could greatly improve image quality for MR exams. Researchers are developing an optical tracking system that would be able to match and adapt the MRI pulses to changes in the patient’s pose in real time. This improvement could reduce cost (since less repeat MR exams will have to take place due to poor quality) as well as make MRI a viable option for many patients who are unable to remain still for the exam and reduce the amount of anesthesia used for MR exams.

Determining the aggressiveness of a tumor
Traditional MRI, unlike PET or SPECT, cannot measure metabolic rates. However, researchers funded by NIBIB have discovered a way to inject specialized compounds (hyperpolarized carbon 13) into prostate cancer patients to measure the metabolic rate of a tumor. This information can provide a fast and accurate picture of the tumor’s aggressiveness. Monitoring disease progression can improve risk prediction, which is critical for prostate cancer patients who often adopt a wait and watch approach.


Glucose and the mental performance

Despite this sophisticated regulation, short-term dips in glucose availability do occur in certain brain areas. These may impair various cognitive functions such as attention, memory, and learning. 4

Studies on glucose have demonstrated how administering this sugar can improve cognitive functioning &mdash in particular, short-term memory and attention. 4 Most of these studies give participants a set amount of glucose as a drink. A study by Sünram-Lea and colleagues found that a glucose drink significantly improved long-term verbal memory and long-term spatial memory in young adults. The effect was similar whether the drink was consumed after an overnight fast, a two-hour fast post-breakfast, or a two-hour fast post-lunch. 5 Similarly, Riby and colleagues found glucose enhanced memory. 6

The more demanding mental tasks appear to respond better to glucose than simpler tasks. This may be because the brain&rsquos uptake of glucose increases under conditions of mild stress, which includes challenging mental tasks. 4

Given that the brain is sensitive to short-term drops in blood glucose levels, and appears to respond positively to rises in these levels, it may be beneficial to maintain adequate blood sugar levels in order to maintain cognitive function. 4 Eating regular meals may help to achieve this. In particular, studies in children and adolescents have shown that eating breakfast can help to improve mental performance by boosting ability in memory- and attention-related tasks. 7


Scan a brain, read a mind?

(CNN) -- What we write online may be intercepted, filtered and publicized, but we'd like to think that the thoughts and images in our heads are totally private.

For better or worse, science may change that. Over the last few years, researchers have made significant strides in decoding our thoughts based on brain activity.

How this would work is still at the very early stages of development. But, given what we can already do, it's not a huge leap to imagine that one day we could read the words of people's internal streams of thought, said Jack Gallant, a prominent neuroscientist at the University of California, Berkeley.

"I think decoding the little person in your brain -- we could do that today if we had a good enough method of measuring your brain activity," Gallant said.

Gallant predicts that in 50 years, thought-reading will be commonplace. We'll be wearing "Google Hats," he envisions, that are continuously decoding our thoughts. Such a wonder-cap might transmit and even translate our thoughts into foreign languages.

But Dr. Josef Parvizi, a Stanford University neurologist who also studies the relationship between brain and mind, is much more skeptical.

"In order to really read thoughts with methods that are noninvasive, we have a long way to go," he said. "I think it is unwise and simply false to give the general public the impression that we are about to be able to read minds."

What you need to read thoughts

There are several limitations on "mind reading" directly from the brain, Gallant said. You need good mathematical models of brain function and high-speed computing. But the biggest challenge right now is measuring brain activity.

Scientists can measure electrical activity with EEG (electroencephalography) and changes in blood oxygen use with fMRI (functional magnetic resonance imaging). But these are really crude measurements of what's happening inside the brain.

EEG is a two-dimensional, limited signal from the brain. And fMRI is like measuring the total electricity usage in your office at specific times to figure out what's going on at everyone's desk, Gallant said. That wouldn't tell you what any particular person is working on it's just a rough overall description of changes.

"The most optimistic estimates are that you can recover one one-millionth of the information that's available in the brain at any given point in time," Gallant said. "It's probably smaller than that. So, where we are today is just measuring a pale shadow of what you could potentially measure, if you had a better measurement technology."

Meanwhile, Parvizi's lab explores the brain with a completely different technique, making use of electrodes implanted in the brains of patients with severe epilepsy to do direct neural recordings at the brain's surface.

His group wants to know the specific functions of different brain areas so when surgeons cut out parts responsible for seizures, they know what to avoid. This method, however, has so far not extracted the actual content of thoughts and memories, and may not be generalizable to non-epileptic patients.

What we can do now

Despite these limitations of brain activity measurement, scientists have already been able to achieve remarkable results.

For instance, using fMRI scans, scientists can reconstruct a face that a person is viewing, as reported in a March 2014 study in the journal Neuroimage. The study was led by Alan Cowen, then an undergraduate at Yale University, who now studies with Gallant in graduate school.

Researchers analyzed how subjects responded to 300 faces while receiving fMRI scans, creating a statistical "library" of the way the brain reacts to facial images. They then used a computer algorithm to generate a mathematical description of the faces based on brain activity patterns.

Then, researchers scanned the six participants again while they viewed a new set of faces. By comparing the fMRI data from the 300 faces to the new scans, scientists were able to digitally draw the second set of faces that the participants saw based on brain activity.

The computer-reconstructed faces were not exact, but people were able to identify them, and researchers could sufficiently compare the pixel information between the reconstructions and originals by computer, accurately matching them between 60% and 70% of the time.

Marvin Chun, professor of psychology at Yale who co-authored the study, said it could have applications for studying disorders where perception of faces is impaired, such as prosopagnosia‎ and autism.

"We're very excited about it, because any increasing ability to read out activity from the brain and map it onto something useful like faces is going to have very broad usage scientifically," Chun said.

We may soon be able to upload memories Wheelchair driven by thoughts

This research was inspired by studies that Gallant's group had done on determining which photographs people saw based on fMRI scans. Gallant and colleagues have also demonstrated this with videos their 2011 study in Current Biology used fMRI and computational models to reconstruct movie clips that people viewed.

Even dreams may be knowable. Scientists led by Tomoyasu Horikawa at ATR Computational Neuroscience Laboratories, Kyoto, published a report last year in the journal Science suggesting it is possible to decode dreams based on brain activity in slumbering subjects, although this is also early stage research.

Such feats have a certain magical quality. But they still involve large, bulky machinery that can capture only a small slice of our conscious experience.

Scientists are also looking at how two brains can communicate with each other. A group at the University of Washington demonstrated last year that by sending brain signals over the Internet, one scientist could control another scientist's hand motion. But the recipient of the signal was not actively interpreting it true two-way brain communication has been achieved in mice not but yet humans.

Neither Gallant nor Parvizi are primarily interested in decoding thoughts. Their fundamental goals involve understanding how the brain does what it does.

Nonetheless, their research has generated a lot of interest, and also hype about mind reading that is concerning to Parvizi.

"I don't think it serves science well, and I don't think it makes the general public appreciate how difficult it is to really understand the operation of the human brain," Parvizi said.

Beyond the novelty of "thinking" an e-mail, there are other important applications to this line of research. Thought-directed wheelchairs, artificial limbs and other assistance devices would be a huge benefit to people with paralysis and other disabilities. Scientists are making strides in this area in small studies.

Gallant's group is working on modeling how the brain responds to language and represents language in your mind.

Chun is working on studying attention, looking at what happens when people's minds are wandering out of "the zone" of experience.

Then there's the problem of memory, which Parvizi is working on: How your brain retrieves memories from the past.

"We can accurately decode that the patient is retrieving memories but we cannot decipher the memory content," he said.

The issue of mind reading brings up important ethical and public policy questions about privacy. Who can have access to your thoughts, and can you choose to keep certain things to yourself, or will even your strangest dreams be readily accessible? How will we control the use of mind-reading devices?

The actual technology may be far off, but Gallant insisted, "We need to start thinking about this now."


Discussion and Conclusions

While a number of ATP imaging technologies are available, there are still gaps in our ability to fully probe ATP metabolism and signaling. Quantitative imaging could be improved by engineering sensors with 1) a variety of ATP affinity ranges, 2) faster ATP binding and response kinetics, 3) higher brightness and contrast ratios, 4) selectivity for ATP hydrolysis products, and 5) spectral color variation. The engineering of sensors with different affinity ranges is important because ATP concentrations vary widely: from nanomolar extracellular levels in some tissues, to millimolar concentrations in cytosolic pools. Likewise, developing sensors that have faster kinetics will be helpful for capturing ATP concentration changes that possibly occur on the millisecond timescale, such as during the initial phases of vesicular ATP release. Improving the brightness of fluorescent sensors and the contrast ratio between unbound and ATP-bound states will improve signal-to-noise ratios and quantitation, and even spatial and temporal resolution in practice. Engineering sensors with selectivity for ATP hydrolysis products will expand the toolbox to include ADP, AMP, and adenosine as measurable analytes. Similarly, those sensors that offer spectral color variation will enable simultaneous imaging of multiple sensors, providing a means to directly correlate ATP with, for example, Ca 2+ signaling and kinase activities. Finally, engineering spectral variants with luminescence and fluorescence in the far-red and infrared spectral ranges will ultimately enable, in live animals, ATP imaging with specificity and subcellular resolution in timescales from subseconds to lifetime.

With current technologies and these future improvements, there is great potential to study ATP with a systems biology perspective of energy metabolism and purinergic signaling. Continued use of these methods to image activity-dependent bioenergetics will improve our understanding of the mechanisms of neurotransmission (Tantama et al., 2013 Rangaraju et al., 2014). Bioenergetic deficits have been linked to a number of aging-related neurodegenerative diseases such as Huntington’s and Parkinson’s diseases, and imaging approaches will aid the study of neurodegenerative mechanisms (Surmeier et al., 2012 Zala et al., 2013 Rangaraju et al., 2014). Across cell types, these technologies can probe metabolic and mitochondrial function at the single-cell level. This is becoming important for understanding diseases such as cancer, in which links to metabolism are increasingly being found (Mayers and Vander Heiden, 2015). In both healthy and disease-state biology, live-cell imaging is becoming an integral approach, and our growing ability to quantitatively visualize ATP dynamics will allow us to link phenomenology and mechanism.

MT acknowledges support from the Showalter Foundation, the Purdue Research Foundation, and National Institutes of Health grants no. NS092010 and no. EY026425.


What is the Glasgow Coma Scale?

Most medical staff know what the Glasgow Coma Scale is and have been specifically trained to use it. Even though non-medical staff might find this scale helpful on the scene of an accident, it is much more important that they work according to the ABC of emergency care – Airway, Breathing, and Circulation.

Named after the university in which it was developed by neurosurgeons Graham Teasdale and Bryan Jennett, the Glasgow Coma Scale (GCS) was first published in The Lancet in 1974. Only in the 1980s, when recommended in the first edition of Advanced Trauma and Life Support, did its use become common.

The scale is still used today even though there are various modern Glasgow Coma Scale alternatives, the GCS is one of the quickest methods of determining brain function.

The initial version scored on fourteen different points this was later increased to fifteen with the separation of extension and flexion within motor (movement) responses. In modern emergency, intensive care, and surgical settings the GCS is usually part of a wider group of scales such as the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the Revised Trauma Score, the Trauma and Injury Severity Score (TRISS), and the Circulation, Respiration, Abdomen, Motor, Speech (CRAMS) scale.

The Glasgow Coma Scale score indicates levels of arousal and awareness one does not naturally mean that the other is present.

Eye movement is an indication of arousal – by speaking to an individual who has their eyes closed, the eyes will usually open. Even so, a brain vegetative state does not mean that someone always has their eyes closed. People in a coma state can open their eyes to auditory stimuli.

Awareness is the ability of a person to interact with their environment and with themselves. Lower verbal forms such as moaning can be made when in a vegetative state.

A Glasgow Coma Scale of 8 or less indicates a severe injury that has dramatically affected the person’s state of consciousness. Scores between 9 and 12 indicate a moderate injury but are also normal scores in a recovery ward. Minor injuries rarely score less than 13 on a Glasgow Coma Scale assessment.

Three assessments are made, and it is important to note that the best responses should be measured, not the worst. If, for example, a motor vehicle crash victim switches rapidly between incomprehensible and confused speech, scores should be given for confused speech.

Eye Opening Response

As already mentioned, coma patients can open their eyes this can affect the eye-opening response score given by the Glasgow Coma Scale. One study also reports that coma patients may close their eyes in response to pain rather than open them. However, as the GCS is now integrated into larger neurological function scores like APACHE II, its value as a medical scoring system is not affected.

Eye-opening responses score from a maximum of four to a minimum of one and are:

  1. Eyes open spontaneously
  2. Eyes open to verbal stimuli
  3. Eye open to pain
  4. No response

Verbal Response

Verbal responses may be the result of existing problems such as speech impediments, dementia, or an unrecognized foreign language GCS results can change dramatically as a caregiver learns more about the patient.

A verbal response usually requires a conversation. This is why you will hear paramedics on TV shows asking a patient if they know what day it is or what their name is. Scores of 5 and 4 mean that a form of conversation between two people is occurring. Inappropriate words and incomprehensible speech do not allow for proper conversation.

  1. Oriented speech
  2. Confused conversation
  3. Inappropriate words
  4. Incomprehensible speech
  5. No response

Motor Response

Getting the top score of motor response may be affected by something as simple as a language barrier – a common problem for medical staff at international airports and tourist attractions. Asking someone who does not understand English to “stick out your tongue” will rarely get the required response.

To determine flexor or extensor posturing, medical staff usually use pressure on the nail bed as a pain stimulus.

  1. Obeys commands for movement
  2. Purposely moves in response to a painful stimulus
  3. Withdraws to pain
  4. Decorticate posturing (flexion) in response to pain
  5. Decerebrate posturing (extension) in response to pain
  6. No response

Decorticate posturing (above) relates to a stiff posture with bent arms, clenched fists, and straight legs. The arms are bent towards the body.

Decerebrate posturing (below) relates to a similarly stiff posture but with both arms and legs stretched, pointed (down) toes, and arched head and neck.


Beyond the PFC

The PFC is not, however, the only area where damage may increase propensity toward behaviours deemed criminal or anti-social. It has long been known that ablation of the monkey temporal lobe, including the amygdala, results in blunted emotional responses [13] (Figure 1C). In humans, brain-imaging and lesion studies have suggested a role of the amygdala in theory of mind, aggression [14], and the ability to register fear and sadness in faces [15]. According to the violence inhibition model, both sad and fearful facial cues act as important inhibitors if we are violent towards others. In support of this model, recent investigations have shown that individuals with a history of aggressive behaviour have poorer recognition of facial expressions [16], which might be due to amygdala dysfunction [17]. Others have recently demonstrated how the low expression of X-linked monoamine oxidase A (MAOA)—which is an important enzyme in the catabolism of monoamines, most notably serotonin (5-HT), and has been associated with an increased propensity towards reactive violence in abused children [18]—is associated with volume changes and hyperactivity in the amygdala [19].

(A) Medial and lateral view of the PFC.

(B) View of the ventral surface of the PFC and temporal poles.

(C) Coronal slice illustrating the amygdalar and insular cortex.

ACC, anterior cingulate cortex dlPFC, dorsolateral PFC MFd, medial PFC oMFC, orbitomedial PFC TP, temporal pole vlPFC, ventrolateral PFC vmPFC, ventromedial PFC.

The amygdala has been a major focus of attempts to understand the poor empathy and fear responses observed in psychopathic criminals. Using functional magnetic resonance imaging (fMRI), Birbaumer and coworkers [20] presented individuals with a paradigm in which the appearance of a face on a screen was followed by a painful shock in one condition but not in a second condition. Analysis showed normal volunteers to have increased activity in the amygdala (see Figure 1) in response to faces associated with shock, whereas psychopathic individuals showed no significant change in activity in this region. In addition, psychopaths also failed to show normal increases in skin conductance responses. Importantly, Birbaumer et al.'s findings are supported by studies showing that the limbic structures (i.e., amygdala and hippocampus) are functionally abnormal in psychopathic criminals during emotional memory [21] and by studies showing how activity in the amygdala decreases with increased scores on the Psychopathy Personality Inventory [12,22]. A prevailing hypothesis is that in psychopathic criminals the prefrontal–amygdala connections are disrupted, leading to deficits in contextual fear conditioning [23], regret [24], guilt [25], and affect regulation [26].


How is Adenosine Triphosphate Used?

As the energetic currency of living organisms, ATP is used in many different ways, and for thousands of different purposes. Once an ATP molecule is created via ATP synthase, it will be moved to where it is needed through diffusion from an area of high concentration to low concentration. When adenosine triphosphate reaches the area where it is needed, energy can be released by breaking the bond between the second and third phosphate groups. When that final phosphate group is transferred to another molecule, often through a process called hydrolysis, the energy of that bond is released and can be used to power other essential processes in the cell. This leaves behind a adenosine diphosphate molecule, which can then move back towards an ATP synthase complex and start the process all over again.

As mentioned earlier, there are many different functions of ATP, because there are many different processes and pathways that demand energy in order for work to be performed. The three main types of work that involve ATP are chemical, mechanical and transport.

A common form of chemical work performed by ATP is the synthesis of macromolecules. Imagine that there is a substrate and an enzyme the enzymatic reaction may only be catalyzed through an influx of energy, which can be acquired when an ATP molecule is converted into an ADP molecule. The reaction occurs, resulting in a product from the substrate, in addition to the ADP molecule.

In terms of transport work, ATP is heavily relied on to help materials move through cellular membranes. For example, ATP is needed to power the proton pumps that push hydrogen molecules across the plasma membrane.

(Photo Credit: Mariana Ruiz/Wikimedia Commons)

Finally, when it comes to mechanical work, things like muscle contraction and the movement of key proteins along a cytoskeleton are only possible in the presence of ATP, which can be broken down to release energy, leaving ADP and an inorganic phosphate molecule behind.