Finding the perfect balance — regulating brain activity to improve attention

Researchers from The University of Nottingham have found that balanced activity in the brain’s prefrontal cortex is necessary for attention. 

The research helps to make sense of attention deficits in people suffering from cognitive disorders — like schizophrenia — who often find it hard to sustain their attention. This has a significant effect on many aspects of their lives, including the ability to follow conversations, drive a car and hold down a job.

Activity in a healthy brain is controlled by inhibitory signals between neurons. The research shows that disrupting this healthy inhibition may be just as bad for attention as reducing neuron firing. It is often assumed that increasing brain activity has cognitive benefits, but the findings show that this is not always the case.

The research was carried out by a team in the University’s School of Psychology and involved inhibiting or disinhibiting the prefrontal cortex in rats and monitoring the effect. The researchers found that both of these extremes resulted in attentional deficits and that the ability to pay attention required an appropriate balance where neuron-firing was kept within a certain range.

Schizophrenia and attention deficits 

Studies of the brain in people with schizophrenia suggest aberrant neuron-firing in the prefrontal cortex. There is evidence that neuron firing in this part of the brain is often too high or too low.

Dr Tobias Bast, who led the study together with first author Dr Marie Pezze, said: “The implication of our findings is that the abnormalities we see in the prefrontal cortex of schizophrenia patients, for example, are indeed a plausible cause of the attention deficit these patients have.

“It also means that if we want to treat this pharmacologically, we can’t just boost activity of the prefrontal cortex or inactivate it, because that would actually result in an impairment. What we need to do is look at restoring balance of activity through drugs which keep the activity within a certain range.”

Cognitive deficits associated with schizophrenia

In people with schizophrenia, cognitive deficits — such as problems with attention — are less striking than other issues associated with the disorder, such as hallucinations, but are nevertheless a major problem.

Dr Bast said: “Initially people focused on the so-called ‘psychotic symptoms’, including hallucinations and delusions, so that’s what probably comes to mind when you think of schizophrenia. They have been in the fore because they have been so striking and that’s why referrals are made. But these can be treated, at least in a large proportion of patients, by using anti-psychotic medication, which we have had since the late 1950s.

“The problem is that unfortunately anti-psychotic drugs don’t improve cognitive deficits which are very debilitating, affecting many aspects of the patients’ lives. Cognitive deficits are a big problem and something that is currently not treated so finding something that helps this is really important.”

Researchers use rhythmic brain activity to track memories in progress

University of Oregon researchers have tapped the rhythm of memories as they occur in near real time in the human brain.

Using electroencephalogram (EEG) electrodes attached to the scalps of 25 student subjects, a UO team led by psychology doctoral student David E. Anderson captured synchronized neural activity while they held a held a simple oriented bar located within a circle in short-term memory. The team, by monitoring these alpha rhythms, was able to decode the precise angle of the bar the subjects were locking onto and use that brain activity to predict which individuals could store memories with the highest quality or precision.

The findings are detailed in the May 28 issue of the Journal of Neuroscience. A color image illustrating how the item in memory was tracked by rhythmic brain activity in the alpha frequency band (8 to 12 beats per second) is on the journal’s cover page to showcase the research.

Although past research has decoded thoughts via brain activity, standard approaches are expensive and limited in their ability to track fast-moving mental representations, said Edward Awh, a professor in the UO’s Department of Psychology and Institute of Neuroscience. The new findings show that EEG measures of synchronized neural activity can precisely track the contents of memory at almost the speed of thought, he said.

"These findings provide strong evidence that these electrical oscillations in the alpha frequency band play a key role in a person’s ability to store a limited number of items in working memory," Awh said. “By identifying particular rhythms that are important to memory, we’re getting closer to understanding the low-level building blocks of this really limited cognitive ability. If this rhythm is what allows people to hold things in mind, then understanding how that rhythm is generated — and what restricts the number of things that can be represented — may provide insights into the basic capacity limits of the mind.”

The findings emerged from a basic research project led by Awh and co-author Edward K. Vogel — funded by the National Institutes of Health — that seeks to understand the limits of storing information. “It turns out that it’s quite restricted,” Awh said. “People can only think about a couple of things at a time, and they miss things that would seem to be extremely obvious and memorable if that limited set of resources is diverted elsewhere.”

Past work, mainly using functional magnetic resonance imaging (fMRI), has established that brain activity can track the content of memory. EEG, however, provides a much less expensive approach and can track mental activity with much a higher temporal resolution of about one-tenth of a second compared to about five seconds with fMRI.

"With EEG we get a fine-grained measure of the precise contents of memory, while benefitting from the superior temporal resolution of electrophysiological measures," Awh said. “This EEG approach is a powerful new tool for tracking and decoding mental representations with high temporal resolution. It should provide us with new insights into how rhythmic brain activity supports core memory processes.”

Unlocking the potential of stem cells to repair brain damage

A QUT scientist is hoping to unlock the potential of stem cells as a way of repairing neural damage to the brain.

Rachel Okolicsanyi, from the Genomics Research Centre at QUT’s Institute of Health and Biomedical Innovation, said unlike other cells in the body which were able to divide and replicate, once most types of brain cells died, the damage was deemed irreversible.

Ms Okolicsanyi is manipulating adult stem cells from bone marrow to produce a population of cells that can be used to treat brain damage.

"My research is a step in proving that stem cells taken from the bone marrow can be manipulated into neural cells, or precursor cells that have the potential to replace, repair or treat brain damage," she said.

Ms Okolicsanyi’s research has been published in Developmental Biology journal, and outlines the potential stem cells have for brain damage repair.

"What I am looking at is whether or not stem cells from the bone marrow have the potential to differentiate or mature into neural cells," she said.

"Neural cells are those cells from the brain that make everything from the structure of the brain itself, to all the connections that make movement, voice, hearing and sight possible."

Ms Okolicsanyi’s research is looking at heparin sulfate proteoglycans - a family of proteins found on the surface of all cells.

"What we are hoping is that by manipulating this particular family of proteins we can encourage the stem cells to show a higher percentage of neural markers indicating that they could mature into neural cells rather than what they would normally do, which is form into bone, cartilage and fat," she said.

"We will manipulate these cells by modifying the surrounding environment. For example we will add chemicals such as complex salts and other commonly found biological chemicals to feed these cells and this will either inhibit or encourage cellular processes."

Ms Okolicsanyi said by doing this, it would be possible to see the different reactions stem cells had to particular chemicals and find out whether these chemicals could increase or decrease the neural markers in the cells.

"The proteins that we are interested in are almost like a tree," she said.

"They have a core protein that is attached to the cell surface and they have these heparin sulfate chains that branch off.

"So when the chemicals we add influence the stem cell in different ways, it will help us understand the interactions between proteins and the resulting changes in the cell.

"In the short-term it is proof that simple manipulations can influence the stem cell and in the long-term it is about the possibility of increasing the neural potential of these stem cells."

Ms Okolicsanyi said the big picture plan was to be able to introduce stem cells into the brain that would be able to be manipulated to repair damaged brain cells.

"The idea, for example, is that in stroke patients where the patient loses movement, speech or control of one side of their face because the brain’s electrical current is impaired, that these stem cells will be able to be introduced and help the electrical current reconnect by bypassing the damaged cells."

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How brains remember and correct

Information processing in the brain is complex and involves both the processing of sensory inputs and the conversion of those inputs into behavior. The passing of electrical oscillations between networks of neurons in different parts of the brain is thought to be a critical component of cognition as well as conscious perception and awareness, but so far there has been little direct evidence linking specific neuronal oscillations to discrete thinking and behavior events. 

Jun Yamamoto and colleagues from the RIKEN–MIT Center for Neural Circuit Genetics have now detected a brief burst of nerve activity oscillating in two specific parts of the mouse brain just before a correct choice is made, either when planning an action or when correcting a mistake. 

The researchers searched for evidence of specific neuronal oscillations by studying mice navigating a T-shaped maze with a reward at the end of one arm of the T. Just before trained mice made the correct choice of direction, Yamamoto and his colleagues observed a brief burst of synchronized high-frequency gamma waves oscillating in specific parts of the entorhinal cortex and hippocampus. 

Yamamoto was fascinated to notice that the burst of gamma waves also occurred just before mice that had originally turned in the wrong direction realized their mistake and turned round. He called this the “oops” moment, and the results indicate that similar neuronal activity occurs when making a correct choice either immediately or on realization of an error. No such gamma-wave activity was detected when mice made the wrong choice without correcting it.

To further test the link between the gamma synchrony and the memory recall process, the researchers genetically engineered mice with light-activated ion channels that could block the gamma waves. When these channels were activated, the gamma waves ceased and the mice could no longer accurately choose the right direction or correct their wrong choices.

“Our work is telling us about how the brain recalls remembered information at critical moments,” says Yamamoto. “It suggests that synchronized gamma oscillations actually contribute to the animal’s correct choice rather than being a consequence of their choice.” The finding sheds light on the fundamental mechanism underlying the successful retrieval of working memory. Yamamoto now intends to see if these initial findings apply to other brain regions. 

The results also provide new insight into the phenomenon of animal consciousness. “Our findings provide evidence that animals employ a behavior monitoring process called metacognition that typically requires conscious awareness,” says Yamamoto.

Losing the left side of the world: Rightward shift in human spatial attention with sleep onset

Unilateral brain damage can lead to a striking deficit in awareness of stimuli on one side of space called Spatial Neglect. Patient studies show that neglect of the left is markedly more persistent than of the right and that its severity increases under states of low alertness. There have been suggestions that this alertness-spatial awareness link may be detectable in the general population. Here, healthy human volunteers performed an auditory spatial localisation task whilst transitioning in and out of sleep. We show, using independent electroencephalographic measures, that normal drowsiness is linked with a remarkable unidirectional tendency to mislocate left-sided stimuli to the right. The effect may form a useful healthy model of neglect and help in understanding why leftward inattention is disproportionately persistent after brain injury. The results also cast light on marked changes in conscious experience before full sleep onset.

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(Image: ALAMY)

Brain signals link physical fitness to better language skills in children

Children who are physically fit have faster and more robust neuro-electrical brain responses during reading than their less-fit peers, researchers report.

These differences correspond with better language skills in the children who are more fit, and occur whether they’re reading straightforward sentences or sentences that contain errors of grammar or syntax.

The new findings, reported in the journal Brain and Cognition, do not prove that higher fitness directly influences the changes seen in the electrical activity of the brain, the researchers say, but offer a potential mechanism to explain why fitness correlates so closely with better cognitive performance on a variety of tasks.

“All we know is there is something different about higher and lower fit kids,” said University of Illinois kinesiology and community health professor Charles Hillman who led the research with graduate student Mark Scudder and psychology professor Kara Federmeier. “Now whether that difference is caused by fitness or maybe some third variable that (affects) both fitness and language processing, we don’t know yet.”

The researchers used electroencephalography (EEG), placing an electrode cap on the scalp to capture some of the electrical impulses associated with brain activity. The squiggly readouts from the electrodes look like seismic readings captured during an earthquake, and characteristic wave patterns are associated with different tasks.

These patterns are called “event-related potentials” (ERPs), and vary according to the person being evaluated and the nature of the stimulus, Scudder said.

For example, if you hear or read a word in a sentence that makes sense (“You wear shoes on your feet”), the component of the brain waveform known as the N400 is less pronounced than if you read a sentence in which the word no longer makes sense (“At school we sing shoes and dance,” for example), Scudder said.

“We focused on the N400 because it is associated with the processing of the meaning of a word,” he said. “And then we also looked at another ERP, the P600, which is associated with the grammatical rules of a sentence.” Federmeier, a study co-author, is an expert in the neurobiological basis of language. Her work inspired the new analysis.

The researchers found that children who were more fit (as measured by oxygen uptake during exercise) had higher amplitude N400 and P600 waves than their less-fit peers when reading normal or nonsensical sentences. The N400 also had shorter latency in children who were more fit, suggesting that they processed the same information more quickly than their peers.

Most importantly, the researchers said, these differences in brain activity corresponded to better reading performance and language comprehension in the children who were more fit.

“Previous reports have shown that greater N400 amplitude is seen in higher-ability readers,” Scudder said.

“Our study shows that the brain function of higher fit kids is different, in the sense that they appear to be able to better allocate resources in the brain towards aspects of cognition that support reading comprehension,” Hillman said.

More work must be done to tease out the causes of improved cognition in kids who are more fit, Hillman said, but the new findings add to a growing body of research that finds strong links between fitness and healthy brain function.

Many studies conducted in the last decade, on children and older adults, ”have repeatedly demonstrated an effect of increases in either physical activity in one’s lifestyle or improvements in aerobic fitness, and the implications of those health behaviors for brain structure, brain function and cognitive performance,” Hillman said.

Children with autism have elevated levels of steroid hormones in the womb

Children who later develop autism are exposed to elevated levels of steroid hormones (for example testosterone, progesterone and cortisol) in the womb, according to scientists from the University of Cambridge and the Statens Serum Institute in Copenhagen, Denmark. The finding may help explain why autism is more common in males than females. However, the researchers caution it should not be used to screen for the condition.

The team of researchers, led by Professor Simon Baron-Cohen and Dr Michael Lombardo in Cambridge and Professor Bent Nørgaard-Pedersen in Denmark, utilized approximately 19,500 amniotic fluid samples stored in a Danish biobank from individuals born between 1993-1999. Amniotic fluid surrounds the baby in the womb during pregnancy and is collected when some women choose to have an amniocentesis around 15-16 weeks of pregnancy. This coincides with a critical period for early brain development and sexual differentiation, and thus allows scientists access into this important window in fetal development. The researchers identified amniotic fluid samples from 128 males later diagnosed with an autism spectrum condition and matched these up with information from a central register of all psychiatric diagnoses in Denmark.

Within the amniotic fluid the researchers looked at four key ‘sex steroid’ hormones that are each synthesized, step-by-step from the preceding one*. They also tested the steroid hormone cortisol that lies outside this pathway. The researchers found that levels of all steroid hormones were highly associated with each other and most importantly, that the autism group on average had higher levels of all steroid hormones, compared to a typically developing male comparison group. The results of the study, which was funded by the Medical Research Council, are published today in the journal Molecular Psychiatry.

Professor Baron-Cohen said: “This is one of the earliest non-genetic biomarkers that has been identified in children who go on to develop autism. We previously knew that elevated prenatal testosterone is associated with slower social and language development, better attention to detail, and more autistic traits. Now, for the first time, we have also shown that these steroid hormones are elevated in children clinically diagnosed with autism. Because some of these hormones are produced in much higher quantities in males than in females, this may help us explain why autism is more common in males.”

He added: “These new results are particularly striking because they are found across all the subgroups on the autism spectrum, for the first time uniting those with Asperger Syndrome, classic autism, or Pervasive Developmental Disorder Not-Otherwise-Specified. We now want to test if the same finding is found in females with autism.”

Dr Michael Lombardo said: “This result potentially has very important implications about the early biological mechanisms that alter brain development in autism and also pinpoints an important window in fetal development when such mechanisms exert their effects.”

Steroid hormones are particularly important because they exert influence on the process of how instructions in the genetic code are translated into building proteins. The researchers believe that altering this process during periods when the building blocks for the brain are being laid down may be particularly important in explaining how genetic risk factors for autism get expressed.

Dr Lombardo adds: “Our discovery here meshes nicely with other recent findings that highlight the prenatal period around 15 weeks gestation as a key period when important genetic risk mechanisms for autism are working together to be expressed in the developing brain.”

Professor Baron-Cohen said: “These results should not be taken as a reason to jump to steroid hormone blockers as a treatment as this could have unwanted side effects and may have little to no effect in changing the potentially permanent effects that fetal steroid hormones exert during the early foundational stages of brain development.”

He cautioned further: “Nor should these results be taken as a promising prenatal screening test. There is considerable overlap between the groups and our findings showed differences found at an average group level, rather than at the level of accurately predicting diagnosis for individuals. The value of the new results lies in identifying key biological mechanisms during fetal development that could play important roles in atypical brain development in autism.”

*Within the amniotic fluid the researchers looked at 4 key ‘sex steroid’ hormones that are each synthesized, step-by-step from the preceding one, in the ‘Δ4 sex steroid’ pathway: progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone.