Posts tagged brain activity

Physicists and neuroscientists from The University of Nottingham and University of Birmingham have unlocked one of the mysteries of the human brain, thanks to new research using functional Magnetic Resonance Imaging (fMRI) and electroencephalography (EEG).

The work will enable neuroscientists to map a kind of brain function that up to now could not be studied, allowing a more accurate exploration of how both healthy and diseased brains work.

Functional MRI is commonly used to study how the brain works, by providing spatial maps of where in the brain external stimuli, such as pictures and sounds, are processed. The fMRI scan does this by detecting indirect changes in the brain’s blood flow in response to changes in electrical signalling during the stimulus.

Combining techniques

A signal change that happens after the stimulus has stopped is also observed with the fMRI scan. This is called the post-stimulus signal and up until now it has not been used to study how the brain works because its origin was uncertain.

In novel experiments, the research team has now combined fMRI techniques with EEG, which measures electrical activity in the brain, to show that the post-stimulus signal also actually reflects changes in brain signalling.

18 healthy volunteers were monitored by using EEG to measure the electrical activity generated by their brains’ neurons (the signalling cells) while simultaneously recording fMRI measurements. A stimulus of electrical pulses was used to activate the part of the brain that controls movement in the right thumb.

The scientists then compared the EEG and fMRI signals and found that they both vary in the same way after the stimulus stops. This provides compelling evidence that the post-stimulus fMRI signal is a measure of neuronal activity rather than just changes in the brain’s blood flow. Curiously, the team also found the post-stimulus fMRI signal was not consistent, even though the stimulus input to the brain was the same each time. This natural variability in the brain response was also reflected by the EEG activity and the researchers suggest that this signal might help the brain make the transition from processing stimuli back to their internal thoughts in different ways.

New window

Dr Karen Mullinger from The University of Nottingham’s Sir Peter Mansfield Magnetic Resonance Centre said: “This work opens a new window of time in the fMRI signal in which we can look at what the brain is doing. It may also open up new research avenues in exploring the function of the healthy brain and the study of neurological diseases.”

Dr Stephen Mayhew from Birmingham University Imaging Centre said “We do not know what the exact role of the post-stimulus activity is or why this response is not always consistent when the stimulus input to the brain is the same. We have already secured funding through the Birmingham-Nottingham Strategic Collaboration Fund to continue this research into further understanding of human brain function using combinations of neuroimaging methods.”

Director of the Sir Peter Mansfield Magnetic Resonance Centre, Professor Peter Morris, said: “Functional magnetic resonance imaging is the main tool available to cognitive neuroscientists for the investigation of human brain function. The demonstration in this paper, that the secondary fMRI response (the post-stimulus undershoot) is not simply a passive blood flow response, but is directly related to synchronous neural activity, as measured with EEG, heralds an exciting new chapter in our understanding of the workings of the human mind.”

The work has been funded by the Medical Research Council (MRC), Engineering and Physical Science Research Council (EPSRC), The University of Nottingham Anne McLaren Fellowships and University of Birmingham Fellowship and is published in the Proceedings of the National Academy of Sciences (PNAS).

(Source: nottingham.ac.uk)

A boost in the speed of brain scans is unveiling new insights into how brain regions work with each other in cooperative groups called networks.

Scientists at Washington University School of Medicine in St. Louis and the Institute of Technology and Advanced Biomedical Imaging at the University of Chieti, Italy, used the quicker scans to track brain activity in volunteers at rest and while they watched a movie.

“Brain activity occurs in waves that repeat as slowly as once every 10 seconds or as rapidly as once every 50 milliseconds,” said senior researcher Maurizio Corbetta, MD, the Norman J. Stupp Professor of Neurology. “This is our first look at these networks where we could sample activity every 50 milliseconds, as well as track slower activity fluctuations that are more similar to those observed with functional magnetic resonance imaging (fMRI). This analysis performed at rest and while watching a movie provides some interesting and novel insights into how these networks are configured in resting and active brains.”

Understanding how brain networks function is important for better diagnosis and treatment of brain injuries, according to Corbetta.

The study appears online in Neuron.

Researchers know of several resting-state brain networks, which are groups of different brain regions whose activity levels rise and fall in sync when the brain is at rest. Scientists used fMRI to locate and characterize these networks, but the relative slowness of this approach limited their observations to activity that changes every 10 seconds or so. A surprising result from fMRI was that the spatial pattern of activity (or topography) of these brain networks is similar at rest and during tasks.

In contrast, a faster technology called magnetoencephalography (MEG) can detect activity at the millisecond level, letting scientists examine waves of activity in frequencies from slow (0.1-4 cycles per second) to fast (greater than 50 cycles per second).

“Interestingly, even when we looked at much higher temporal resolution, brain networks appear to fluctuate on a relatively slow time scale,” said first author Viviana Betti, PhD, a postdoctoral researcher at Chieti. “However, when the subjects went from resting to watching a movie, the networks appeared to shift the frequency channels in which they operate, suggesting that the brain uses different frequencies for rest and task, much like a radio.”

In the study, the scientists asked one group of volunteers to either rest or watch the movie during brain scans. A second group was asked to watch the movie and look for event boundaries, moments when the plot or  characters or other elements of the story changed. They pushed a button when they noticed these changes.

As in previous studies, most subjects recognized similar event boundaries in the movie. The MEG scans showed that the communication between regions in the visual cortex was altered near the movie boundaries, especially in networks in the visual cortex.

“This gives us a hint of how cognitive activity dynamically changes the resting-state networks,” Corbetta said. “Activity locks and unlocks in these networks depending on how the task unfolds. Future studies will need to track resting-state networks in different tasks to see how correlated activity is dynamically coordinated across the brain.”

(Source: news.wustl.edu)

About nine months after suffering a stroke, the patient noticed that words written in a certain shade of blue evoked a strong feeling of disgust. Yellow was only slightly better. Raspberries, which he never used to eat very often, now tasted like blue – and blue tasted like raspberries.

High-pitched brass instruments—specifically the brass theme from James Bond movies—elicited feelings of ecstasy and light blue flashes in his peripheral vision and caused large parts of his brain to light up on an MRI. Music played by a euphonium, a tenor-pitched brass instrument, shut down those sensations.

The patient said he was initially frightened by the mixed messages his brain was sending him and the conflicting senses he was experiencing. He was so worried that something was seriously wrong with him that he raised it with a nurse only as he was leaving an appointment at St. Michael’s Hospital in downtown Toronto.

Physicians and researchers immediately recognized he had synesthesia, a neurological condition in which people experience more than one sense at the same time. They may “see” words or numbers as colours, hear sounds in response to smells or feel something in response to sight.

Most synesthetes are born with the condition, and include some of the world’s most famous authors and artists, including author Vladimir Nabakov, composer Franz Liszt, painter Vasily Kandinsky and singer-songwriter Billy Joel.

The Toronto patient is only the second known person to have acquired synesthesia as a result of a brain injury, in this case a stroke. His case was described in the August issue of the journal Neurology by Dr. Tom Schweizer, a neuroscientist and director of the Neuroscience Research Program at St. Michael’s Li Ka Shing Knowledge Institute.

Dr. Schweizer examined the patient’s brain activity in a functional MRI and compared it to six men of similar age (45) and education (18 years) as each listened to the James Bond Theme and a euphonium solo.

When the James Bond Theme was played, large areas of the patient’s brain lit up including the thalamus (the brain’s information switchboard), the hippocampus (which deals with memory and spatial navigation) and the auditory cortex (which processes sound).

"The areas of the brain that lit up when he heard the James Bond Theme are completely different from the areas we would expect to see light up when people listen to music," Dr. Schweizer said. "Huge areas on both sides of the brain were activated that were not activated when he listened to other music or other auditory stimuli and were not activated in the control group."

The patient and members of the control group also viewed 10-second blocks of words presented in black (which elicits no emotional response in the patient), yellow (mild disgust response) and blue (intense disgust response).

Reading blue letters produced extensive activity in the parts of the patient’s brain responsible for sensory information and processing emotional stimuli and similar but less intense responses for yellow letters. Control groups showed no heightened brain activity in response to the different coloured letters.

Dr. Schweizer said the fact that the patient had very targeted and specific responses to certain stimuli – and that these responses were not experienced by the control group – suggests that his synesthesia was caused as his brain tried to repair itself after his stroke and got cross-wired.

The patient’s stroke occurred in the thalamus, the brain’s central relay station. That’s the same part of the brain affected by the only other reported case of acquired synesthesia.

(Source: eurekalert.org)

Controversy exists over what some mental health experts call “hypersexuality,” or sexual “addiction.” Namely, is it a mental disorder at all, or something else? It failed to make the cut in the recently updated Diagnostic and Statistical Manual of Mental Disorders, or DSM-5, considered the bible for diagnosing mental disorders. Yet sex addiction has been blamed for ruining relationships, lives and careers.

Now, for the first time, UCLA researchers have measured how the brain behaves in so-called hypersexual people who have problems regulating their viewing of sexual images. The study found that the brain response of these individuals to sexual images was not related in any way to the severity of their hypersexuality but was instead tied only to their level of sexual desire.

In other words, hypersexuality did not appear to explain brain differences in sexual response any more than simply having a high libido, said senior author Nicole Prause, a researcher in the department of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA.

"Potentially, this is an important finding," Prause said. "It is the first time scientists have studied the brain responses specifically of people who identify as having hypersexual problems."

The study appears in the current online edition of the journal Socioaffective Neuroscience and Psychology.

A diagnosis of hypersexuality or sexual addiction is typically associated with people who have sexual urges that feel out of control, who engage frequently in sexual behavior, who have suffered consequences such as divorce or economic ruin as a result of their behaviors, and who have a poor ability to reduce those behaviors.

But, said Prause and her colleagues, such symptoms are not necessarily representative of an addiction — in fact, non-pathological, high sexual desire could also explain this cluster of problems.

One way to tease out the difference is to measure the brain’s response to sexual-image stimuli in individuals who acknowledge having sexual problems. If they indeed suffer from hypersexuality, or sexual addiction, their brain response to visual sexual stimuli could be expected be higher, in much the same way that the brains of cocaine addicts have been shown to react to images of the drug in other studies.

The study involved 52 volunteers: 39 men and 13 women, ranging in age from 18 to 39, who reported having problems controlling their viewing of sexual images. They first filled out four questionnaires covering various topics, including sexual behaviors, sexual desire, sexual compulsions, and the possible negative cognitive and behavioral outcomes of sexual behavior. Participants had scores comparable to individuals seeking help for hypersexual problems.

While viewing the images, the volunteers were monitored using electroencephalography (EEG), a non-invasive technique that measures brain waves, the electrical activity generated by neurons when they communicate with each other. Specifically, the researchers measured event-related potentials, brain responses that are the direct result of a specific cognitive event.

"The volunteers were shown a set of photographs that were carefully chosen to evoke pleasant or unpleasant feelings," Prause said. "The pictures included images of dismembered bodies, people preparing food, people skiing — and, of course, sex. Some of the sexual images were romantic images, while others showed explicit intercourse between one man and one woman."

The researchers were most interested in the response of the brain about 300 milliseconds after each picture appeared, commonly called the “P300” response. This basic measure has been used in hundreds of neuroscience studies internationally, including studies of addiction and impulsivity, Prause said. The P300 response is higher when a person notices something new or especially interesting to them.

The researchers expected that P300 responses to the sexual images would correspond to a person’s sexual desire level, as shown in previous studies. But they further predicted that P300 responses would relate to measures of hypersexuality. That is, in those whose problem regulating their viewing of sexual images could be characterized as an “addiction,” the P300 reaction to sexual images could be expected to spike.

Instead, the researchers found that the P300 response was not related to hypersexual measurements at all; there were no spikes or decreases tied to the severity of participants’ hypersexuality. So while there has been much speculation about the effect of sexual addiction or hypersexuality in the brain, the study provided no evidence to support any difference, Prause said.

"The brain’s response to sexual pictures was not predicted by any of the three questionnaire measures of hypersexuality," she said. "Brain response was only related to the measure of sexual desire. In other words, hypersexuality does not appear to explain brain responses to sexual images any more than just having a high libido."

But debate continues over whether sex addiction is indeed an addiction. A study published in 2012 by Prause’s colleague Rory Reid, a UCLA assistant professor of psychiatry, supported the reliability of the proposed DSM-5 diagnostic criteria for hypersexual disorder. However, Prause notes, that study was not focused on the validity of sex addiction or impulsivity, and did not use any biophysiological data in the analysis.

"If our study can be replicated," she said, "these findings would represent a major challenge to existing theories of a sex ‘addiction.’ "

(Source: newsroom.ucla.edu)

Pioneering experiments back in 1982 by Tasaki and Iwasa at the NIH revealed that action potentials in neurons are more than just the electrical blips that physiologists readily amplify and record. These so-called “spikes” are in fact multi-modal signalling packages that include mechanical and thermal disturbances propagating down the axon at their own rates. Nobel Laureate Francis Crick published a paper that same year, in which he postulated potential mechanisms that would explain twitching in dendritic spines, adding to an emerging picture of a brain more vibrant and motile than had been previously imagined. More recently, researchers have developed diffusion-based MRI methods, like diffusion tensor imaging (DTI), to trace the trajectories of axons, and perhaps more intriguingly, determine their directional polarity. Working at the EPFL in Switzerland, Denis Le Bihan and his co-workers have been using diffusional MRI in slightly different way. They now appear to be able to directly measure neuronal activity from the subtle movements of membranes, the water within them, and in the extracellular space around them. Their work, just published in PNAS, provides a much needed conceptual shift away from currently established, but typically nebulous, ideas regarding neurovascular coupling of brain activity to blood flow.

Present-day imaging methods, like blood oxygen level-dependent (BOLD) MRI, are only indirectly and remotely related to the cortical activity they often claim to measure. In 2006, Le Bihan reported a water “phase transition” response that preceded the neurovascular response normally detected by functional MRI. He attributed the changes in water diffusion to previously established effects involving membrane expansion and cell swelling secondary to activity. At the biophysical level, interpreting action potentials as phase transitions is a little off the beaten path from traditional neurobiology, but it can be an informative approach when to trying to understand what might be going on when cells fire.

As biophysicist Gerald Pollack has previously pointed out, spikes may involve the propagation of the line of transition of water from the ordered phase, (as patterned by hydrophic interactions nucleated at the surfaces of membranes and proteins) to a disordered phase.
Traditionally, the so-called bound surface water only extends out a only a couple of molecules from the surface of nondiffusable features. That idea may need to be revisited in light of more recent understanding when attempting to account for the diffusion of water in axons. A decrease in water diffusion as measured by MRI may be in part explained by a decrease in extracellular space, and that has been suggested from experiments measuring intrinsic optical effects. The larger picture of water diffusion, however, is likely a bit more complicated than this.

In his new study, Le Bihan stimulated the forepaw of a rat and looked at responses in the somatosensory cortex. The key experiment was to infuse nitroprusside in attempt to inhibit neurovascular coupling. It is a tricky alteration because nitroprusside apparently has many diffuse effects. It can induce potent vasodilation, particularly on the vascular end (mainly the smaller venules), after it breaks down to produce nitric oxide. It is also a diamagnetic molecule, and each molecule releases five cyanide ions, which are presumably detoxified by the mitochondrial enzyme rhodanese. The experiments were done under isoflurane anesthesia, which also introduces a few uncertainties, particularly with regard to responses to different frequencies of forepaw stimulation.

If nitroprusside is indeed a realistic experimental proxy for neurovascular uncoupling, then the results of Le Bihan appear to show that the diffusion response is not of vascular origin, and that it is closely linked to neural activation. He found that the standard BOLD MRI responses were completely quenched under nitroprusside, whereas the diffusion MRI responses were only slightly suppressed. Local field potentials were also simultaneously measured and suggested at least, that the neuronal responses were also intact.

The work of Le Bihan indicates that diffusion-based MRI can be used to infer neural activity directly from the structural changes that affect the molecular displacements of water. The ability to use shape changes in neurons, astrocytes, or even spines, raises the question of whether these kinds of techniques might eventually be of use in creating larger scale, and more detailed, Brain Activity Maps (BAMs). I asked Konrad Kording, author on the recent theoretical paper which discussed the theoretical limits to MRI and other activity recording methods, whether methods that probe water movements might be applied to this end.

Kording observed that the spatial resolution of standard MRI is ultimately limited by the diffusion of water, but more importantly perhaps, the temporal resolution of all known MRI methods is nowhere near that required to create spike maps. None-the-less, detecting mechanical responses in the brain could provide many unique insights into function. For example, experiments using agents that dissolve the extracellular matrix, like the clot-busting drug TPA, result in more twitching, or vibration if you will, in dendritic spines. Other studies have shown that the greater the electrical drive on a spine, the less it tends to twitch or change size, particularly during periods of rapid development.

Similarly, sensory deprivations appear to increase these kinds of movements as neurons grow and reorganize connections. While these effects are far below that which could be detected by any large external method of MRI, new tools may permit us to access these newly-revealed activities. Diffusional MRI in particular, can be done with a little modification of the standard MRI procedure. For example, to determine directional diffusion parameters, or diffusion tensors, typically six gradients are used to measure three directional vectors. As these capabilities become more common, hopefully the results of Le Bihan can be further explored and verified.