Ultra-high-field MRI reveals language centres in the brain in much more detail

In a new investigation by the University Department of Neurology, it has been possible for the first time to demonstrate that the areas of the brain that are important for understanding language can be pinpointed much more accurately using ultra-high-field MRI (7 Tesla) than with conventional clinical MRI scanners. This helps to protect these areas more effectively during brain surgery and avoid accidentally damaging it.

Before brain surgery, it is important to precisely understand the areas of the brain required for language in order to avoid injuring them during the procedure. Their position can shift considerably, especially in patients with tumours or brain injuries. The brain’s flexibility also means that language centres can shift to other regions. If the areas responsible for language control and processing are injured during a brain operation, the patient can be left unable to communicate. In order to create a “map” of the language control centres prior to the operation, functional magnetic resonance imaging (fMRI) is used these days.

A multi-centre study from 2013 demonstrated the advantages of fMRI-assisted localisation of the motor centres in the brain. In a new investigation by the working group led by Roland Beisteiner (University Department of Neurology), it has been possible for the first time to demonstrate that the areas of the brain that are important for understanding language can be pinpointed even more accurately using ultra-high-field MRI (7 Tesla) than with conventional clinical MRI scanners. The focus lies on the two most important language centres in the brain known as Wernicke’s area (which controls the understanding of language) and Broca’s area (which controls the motor functions involved with speech).

The brain is scanned for activity while the patient is carrying out speech exercises. This allows the areas required for speech to be localised much more accurately than previously. “Ultra-high-field MR offers much greater sensitivity than classic MRI scanners”, explains Roland Beisteiner, “allowing even very weak signals to be recorded in areas that would otherwise have been missed.”

(Image caption: Calcium imaging of neurons in a rat hippocampal slice through transparent graphene electrode. Black square at the center is transparent graphene electrode and neurons are shown in green. Yellow traces shows a representative example of electrophysiological recordings with graphene electrode. Credit: Hajime Takano and Duygu Kuzum)

See-Through, One-Atom-Thick, Carbon Electrodes are a Powerful Tool for Studying Epilepsy, Other Brain Disorders

Researchers from the Perelman School of Medicine and School of Engineering at the University of Pennsylvania and The Children’s Hospital of Philadelphia have used graphene — a two-dimensional form of carbon only one atom thick — to fabricate a new type of microelectrode that solves a major problem for investigators looking to understand the intricate circuitry of the brain.

Pinning down the details of how individual neural circuits operate in epilepsy and other neurological disorders requires real-time observation of their locations, firing patterns, and other factors, using high-resolution optical imaging and electrophysiological recording. But traditional metallic microelectrodes are opaque and block the clinician’s view and create shadows that can obscure important details. In the past, researchers could obtain either high-resolution optical images or electrophysiological data, but not both at the same time.

The Center for NeuroEngineering and Therapeutics (CNT), under the leadership of senior author Brian Litt, PhD, has solved this problem with the development of a completely transparent graphene microelectrode that allows for simultaneous optical imaging and electrophysiological recordings of neural circuits. Their work was published this week in Nature Communications.

"There are technologies that can give very high spatial resolution such as calcium imaging; there are technologies that can give high temporal resolution, such as electrophysiology, but there’s no single technology that can provide both," says study co-first-author Duygu Kuzum, PhD. Along with co-author Hajime Takano, PhD, and their colleagues, Kuzum notes that the team developed a neuroelectrode technology based on graphene to achieve high spatial and temporal resolution simultaneously. 

Aside from the obvious benefits of its transparency, graphene offers other advantages: “It can act as an anti-corrosive for metal surfaces to eliminate all corrosive electrochemical reactions in tissues,” Kuzum says. “It’s also inherently a low-noise material, which is important in neural recording because we try to get a high signal-to-noise ratio.”          

While previous efforts have been made to construct transparent electrodes using indium tin oxide, they are expensive and highly brittle, making that substance ill-suited for microelectrode arrays. “Another advantage of graphene is that it’s flexible, so we can make very thin, flexible electrodes that can hug the neural tissue,” Kuzum notes.

In the study, Litt, Kuzum, and their colleagues performed calcium imaging of hippocampal slices in a rat model with both confocal and two-photon microscopy, while also conducting electrophysiological recordings. On an individual cell level, they were able to observe temporal details of seizures and seizure-like activity with very high resolution. The team also notes that the single-electrode techniques used in the Nature Communications study could be easily adapted to study other larger areas of the brain with more expansive arrays.

The graphene microelectrodes developed could have wider application. “They can be used in any application that we need to record electrical signals, such as cardiac pacemakers or peripheral nervous system stimulators,” says Kuzum. Because of graphene’s nonmagnetic and anti-corrosive properties, these probes “can also be a very promising technology to increase the longevity of neural implants.” Graphene’s nonmagnetic characteristics also allow for safe, artifact-free MRI reading, unlike metallic implants.

Kuzum emphasizes that the transparent graphene microelectrode technology was achieved through an interdisciplinary effort of CNT and the departments of Neuroscience, Pediatrics, and Materials Science at Penn and the division of Neurology at CHOP.

Ertugrul Cubukcu’s lab at Materials Science and Engineering Department helped with the graphene processing technology used in fabricating flexible transparent neural electrodes, as well as performing optical and materials characterization in collaboration with Euijae Shim and Jason Reed. The simultaneous imaging and recording experiments involving calcium imaging with confocal and two photon microscopy was performed at Douglas Coulter‘s Lab at CHOP with Hajime Takano.  In vivo recording experiments were performed in collaboration with Halvor Juul in Marc Dichter’s Lab. Somatosensory stimulation response experiments were done in collaboration with Timothy Lucas’s Lab, Julius De Vries, and Andrew Richardson.

As the technology is further developed and used, Kuzum and her colleagues expect to gain greater insight into how the physiology of the brain can go awry. “It can provide information on neural circuits, which wasn’t available before, because we didn’t have the technology to probe them,” she says. That information may include the identification of specific marker waveforms of brain electrical activity that can be mapped spatially and temporally to individual neural circuits. “We can also look at other neurological disorders and try to understand the correlation between different neural circuits using this technique,” she says.

Scientists find ‘hidden brain signatures’ of consciousness in vegetative state patients

There has been a great deal of interest recently in how much patients in a vegetative state following severe brain injury are aware of their surroundings. Although unable to move and respond, some of these patients are able to carry out tasks such as imagining playing a game of tennis. Using a functional magnetic resonance imaging (fMRI) scanner, which measures brain activity, researchers have previously been able to record activity in the pre-motor cortex, the part of the brain which deals with movement, in apparently unconscious patients asked to imagine playing tennis.

Now, a team of researchers led by scientists at the University of Cambridge and the MRC Cognition and Brain Sciences Unit, Cambridge, have used high-density electroencephalographs (EEG) and a branch of mathematics known as ‘graph theory’ to study networks of activity in the brains of 32 patients diagnosed as vegetative and minimally conscious and compare them to healthy adults. The findings of the research are published today in the journal PLOS Computational Biology. The study was funded mainly by the Wellcome Trust, the National Institute of Health Research Cambridge Biomedical Research Centre and the Medical Research Council (MRC).

The researchers showed that the rich and diversely connected networks that support awareness in the healthy brain are typically – but importantly, not always – impaired in patients in a vegetative state. Some vegetative patients had well-preserved brain networks that look similar to those of healthy adults – these patients were those who had shown signs of hidden awareness by following commands such as imagining playing tennis.

Dr Srivas Chennu from the Department of Clinical Neurosciences at the University of Cambridge says: “Understanding how consciousness arises from the interactions between networks of brain regions is an elusive but fascinating scientific question. But for patients diagnosed as vegetative and minimally conscious, and their families, this is far more than just an academic question – it takes on a very real significance. Our research could improve clinical assessment and help identify patients who might be covertly aware despite being uncommunicative.”

The findings could help researchers develop a relatively simple way of identifying which patients might be aware whilst in a vegetative state. Unlike the ‘tennis test’, which can be a difficult task for patients and requires expensive and often unavailable fMRI scanners, this new technique uses EEG and could therefore be administered at a patient’s bedside. However, the tennis test is stronger evidence that the patient is indeed conscious, to the extent that they can follow commands using their thoughts. The researchers believe that a combination of such tests could help improve accuracy in the prognosis for a patient.

Dr Tristan Bekinschtein from the MRC Cognition and Brain Sciences Unit and the Department of Psychology, University of Cambridge, adds: “Although there are limitations to how predictive our test would be used in isolation, combined with other tests it could help in the clinical assessment of patients. If a patient’s ‘awareness’ networks are intact, then we know that they are likely to be aware of what is going on around them. But unfortunately, they also suggest that vegetative patients with severely impaired networks at rest are unlikely to show any signs of consciousness.”

The Neuroscience of Holding It

Wherever you are right now: squeeze your glutes. Feel that? You just also contracted your pelvic floor too, whether you wanted to or not.

Scientists studying the source of chronic abdominal and pelvic floor pain found an unexpected connection in the brain between the pelvic floor – the muscle responsible for, among other things, keeping you from peeing your pants – and various muscles throughout the body. They’ve found some evidence for a link as far away as the toes (try tapping a toe and see if you feel the clench), but the strongest link so far is with the glutes.

“We knew that pelvic floor muscles contract involuntarily in healthy people to make sure they don’t accidently urinate, but we didn’t know what part of the nervous system was doing this,” said Jason Kutch, corresponding author on a study about the research and an assistant professor in the Division of Biokinesiology & Physical Therapy at the USC Ostrow School of Dentistry. “Now we know that there are specific brain regions controlling involuntary pelvic floor contraction.”

Kutch collaborated with colleagues at USC Ostrow, the Keck School of Medicine of USC, and Loma Linda University on the research. Their findings were published on October 8 in the Journal of Neuroscience.

The team used electromyographic recordings – which measure the activation of muscle tissue – to show that pelvic floor activation occurred in conjunction with the activation of certain muscles (like the glutes), but not others (like fingers).

They then used functional magnetic image resonance (fMRI) imaging to show that a specific part of the brain (the medial wall of the precentral gyrus – a part of the primary motor cortex) activates both when the pelvic floor contracts and when the glutes are squeezed – but not when fingers move.

“We hope that this vein of research will help us to find the causes of chronic pelvic floor pain, which disproportionately affect women, and may even yield information that could help people struggling with incontinence,” Kutch said.

Broadly, the finding speaks to the interconnected nature of our bodies and brains, and all of the hard work going on in the pelvic floor muscles – without us even know it.

MRI Technique Detects Evidence of Cognitive Decline Before Symptoms Appear

A magnetic resonance imaging (MRI) technique can detect signs of cognitive decline in the brain even before symptoms appear, according to a new study published online in the journal Radiology. The technique has the potential to serve as a biomarker in very early diagnosis of preclinical dementia.

The World Health Organization estimates that dementia affects more than 35 million people worldwide, a number expected to more than double by 2030. Problems in the brain related to dementia, such as reduced blood flow, might be present for years but are not evident because of cognitive reserve, a phenomenon where other parts of the brain compensate for deficits in one area. Early detection of cognitive decline is critical, because treatments for Alzheimer’s disease, the most common type of dementia, are most effective in this early phase.

Researchers recently studied arterial spin labeling (ASL), a promising MRI technique that doesn’t require injection of a contrast agent. ASL measures brain perfusion, or penetration of blood into the tissue.

"ASL MRI is simple to perform, doesn’t require special equipment and only adds a few minutes to the exam," said study author Sven Haller, M.D., from the University of Geneva in Geneva, Switzerland.

The study group included 148 healthy elderly participants and 65 people with mild cognitive impairment (MCI). The participants underwent brain MRI and a neuropsychological assessment, a common battery of tests used to determine cognitive ability.

Of the 148 healthy individuals, 75 remained stable, while 73 deteriorated cognitively at 18 months clinical follow-up. Those who deteriorated had shown reduced perfusion at their baseline ASL MRI exams, particularly in the posterior cingulate cortex, an area in the middle of the brain that is associated with the default mode network, the neural network that is active when the brain is not concentrating on a specific task. Declines in this network are seen in MCI patients and are more pronounced in those with Alzheimer’s disease.

The pattern of reduced perfusion in the brains of healthy individuals who went on to develop cognitive deficits was similar to that of patients with MCI.

"There is a known close link between neural activity and brain perfusion in the posterior cingulate cortex," Dr. Haller said. "Less perfusion indicates decreased neural activity."

The results suggest that individuals with decreased perfusion detected with ASL MRI may temporarily maintain their cognitive status through the mobilization of their cognitive reserve, but will eventually develop subtle cognitive deficits.

Previous research done with positron emission tomography (PET), the current gold standard for brain metabolism imaging, found that patients with Alzheimer’s disease had reduced metabolism in the same area of the brain where the perfusion abnormalities were found using ASL MRI. This points to a close link between brain metabolism and perfusion, according to Dr. Haller.

ASL MRI has potential as a standalone test or as an adjunct to PET for dementia screening, Dr. Haller said. While PET can identify markers of Alzheimer’s disease in the brain and cerebrospinal fluid, it exposes the patient to radiation. ASL does not expose the patient to radiation and is easy to perform in routine clinical settings.

"ASL might replace the classic yet unspecific fluordesoxyglucose PET that measures brain metabolism. Instead, PET could be done with the new and specific amyloid PET tracers," Dr. Haller said.

The results also support a role for ASL MRI as an alternative to neuropsychological testing.

The researchers plan to perform follow-up studies on the patient group to learn more about ASL and long-term cognitive changes.

Neuroimaging could be the key to a better society

Neuroimaging techniques are a strongly emerging technology and could bring about a revolution in various areas of society, as long as we choose the direction we want to steer these developments in on time. This is one of the conclusions from a series of dialogues between neuroscientists and future users, organised for the research project Towards an appropriate societal embedding of neuroimaging. The project is part of the NWO research programme Responsible Innovation.

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Study suggests neurobiological basis of human-pet relationship

It has become common for people who have pets to refer to themselves as  “pet parents,” but how closely does the relationship between people and their non-human companions mirror the parent-child relationship? A small study from a group of Massachusetts General Hospital (MGH) researchers makes a contribution to answering this complex question by investigating differences in how important brain structures are activated when women view images of their children and of their own dogs. Their report is being published in the open-access journal PLOS ONE.

“Pets hold a special place in many people’s hearts and lives, and there is compelling evidence from clinical and laboratory studies that interacting with pets can be beneficial to the physical, social and emotional wellbeing of humans,” says Lori Palley, DVM, of the MGH Center for Comparative Medicine, co-lead author of the report.  “Several previous studies have found that levels of neurohormones like oxytocin – which is involved in pair-bonding and maternal attachment – rise after interaction with pets, and new brain imaging technologies are helping us begin to understand the neurobiological basis of the relationship, which is exciting.”

In order to compare patterns of brain activation involved with the human-pet bond with those elicited by the maternal-child bond, the study enrolled a group of women with at least one child aged 2 to 10 years old and one pet dog that had been in the household for two years or longer. Participation consisted of two sessions, the first being a home visit during which participants completed several questionnaires, including ones regarding their relationships with both their child and pet dog. The participants’ dog and child were also photographed in each participants’ home.

The second session took place at the Athinoula A. Martinos Center for Biomedical Imaging at MGH, where functional magnetic resonance imaging (fMRI) – which indicates levels of activation in specific brain structures by detecting changes in blood flow and oxygen levels – was performed as participants lay in a scanner and viewed a series of photographs. The photos included images of each participant’s own child and own dog alternating with those of an unfamiliar child and dog belonging to another study participant. After the scanning session, each participant completed additional assessments, including an image recognition test to confirm she had paid close attention to photos presented during scanning, and rated several images from each category shown during the session on factors relating to pleasantness and excitement.

Of 16 women originally enrolled, complete information and MR data was available for 14 participants. The imaging studies revealed both similarities and differences in the way important brain regions reacted to images of a woman’s own child and own dog. Areas previously reported as important for functions such as emotion, reward, affiliation, visual processing and social interaction all showed increased activity when participants viewed either their own child or their own dog. A region known to be important to bond formation – the substantia nigra/ventral tegmental area (SNi/VTA) – was activated only in response to images of a participant’s own child. The fusiform gyrus, which is involved in facial recognition and other visual processing functions, actually showed greater response to own-dog images than own-child images.

“Although this is a small study that may not apply to other individuals, the results suggest there is a common brain network important for pair-bond formation and maintenance that is activated when mothers viewed images of either their child or their dog,” says Luke Stoeckel, PhD, MGH Department of Psychiatry, co-lead author of the PLOS One report. “We also observed differences in activation of some regions that may reflect variance in the evolutionary course and function of these relationships. For example, like the SNi/VTA, the nucleus accumbens has been reported to have an important role in pair-bonding in both human and animal studies. But that region showed greater deactivation when mothers viewed their own-dog images instead of greater activation in response to own-child images, as one might expect. We think the greater response of the fusiform gyrus to images of participants’ dogs may reflect the increased reliance on visual than verbal cues in human-animal communications.”

Co-author Randy Gollub, MD, PhD, of MGH Psychiatry adds, “Since fMRI is an indirect measure of neural activity and can only correlate brain activity with an individual’s experience, it will be interesting to see if future studies can directly test whether these patterns of brain activity are explained by the specific cognitive and emotional functions involved in human-animal relationships. Further, the similarities and differences in brain activity revealed by functional neuroimaging may help to generate hypotheses that eventually provide an explanation for the complexities underlying human-animal relationships.”

The investigators note that further research is needed to replicate these findings in a larger sample and to see if they are seen in other populations – such as women without children, fathers and parents of adopted children – and in relationships with other animal species. Combining fMRI studies with additional behavioral and physiological measures could obtain evidence to support a direct relationship between the observed brain activity and the purported functions.

(Image: Fotolia)

What happens in our brain when we unlock a door?

People who are unable to button up their jacket or who find it difficult to insert a key in lock suffer from a condition known as apraxia. This means that their motor skills have been impaired – as a result of a stroke, for instance. Scientists in Munich have now examined the parts of the brain that are responsible for planning and executing complex actions. They discovered that there is a specific network in the brain for using tools. Their findings have been published in the Journal of Neuroscience.

Researchers from Technische Universität München (TUM) and the Klinikum rechts der Isar hospital have analyzed the brain networks that control the use of tools or other utensils. Their chosen method of functional magnetic resonance imaging (fMRI) shows the areas of the brain that are activated when a person thinks, moves and performs actions.

The use of tools is an essential human skill. “Numerous studies are investigating the neural processes at play when we pick up a tool,” says Prof. Joachim Hermsdörfer from TUM’s Chair of Human Movement Science. “But many of these studies are restricted to test subjects observing an action, miming it, or simply visualizing it.” The aim of this latest study was to analyze the basic neural principles of tool use under the most realistic conditions possible.

In the MRI study, the subjects received ten everyday objects, including a hammer, a bottle-opener, a key, a lighter and a scissors as well as some unfamiliar objects. Their task was to either use the objects or simply lift them up and place them down again, first with the left and then with the right hand. When they analyzed the data, the scientists looked at the planning phase and the actual execution phase separately. In this way, they were able to identify the brain networks that were activated while the subjects planned and used a tool and those that controlled execution.

Tool-specific network in the brain

One important finding was that the left hemisphere was activated when the subjects planned to use a tool – regardless of the hand they held it in. In addition, the researchers recognized a distributed network responsible for both planning and execution. When working with unfamiliar objects, these regions of the brain were less activated. 

The “tool network” consists of brain regions of the parietal and frontal lobes as well as regions in the posterior temporal lobe and another area in the lateral occipital lobe. What the researchers found, therefore, was a neural activation pattern that covered all elements of a complex action. This includes recognizing the objects as tools, understanding how they are used, and the motor action to actually use the tool. 

“The study also allowed us to confirm that there are different streams of perception in the brain for different tasks,” explains Hermsdörfer. The dorsal stream of perception conducts signals to the posterior parietal lobe and is generally responsible for controlling actions. “It can be divided into two function-specific processing pathways. The dorso-dorsal stream controls basic gripping and movement processes, regardless of whether the person is familiar with the object or not. A second ventro-dorsal stream becomes active when we use tools that are familiar to us.

Armed with knowledge about the localization of these “action modules”, doctors could in future provide a more differentiated diagnosis of apraxia and develop improved therapeutic approaches.