Category: Neurology

Scientists Discover the Neurological Basis of Food Cravings in Pregnancy

Photo by Andriyko Podilnyk on Unsplash

By examining mice, which get pregnancy cravings similar to humans, scientists have identified the neurological basis of food craving during pregnancy.

During pregnancy, the mother’s body undergoes a series of physiological and behavioural changes to create an environment facilitating the embryo’s development. Frequent consumption of tasty, high calorie foods driven by the cravings contributes to weight gain and obesity in pregnancy, with possible negative consequences for the baby’s health.

“There are many myths and popular beliefs regarding these cravings, although the neuronal mechanisms that cause them are not widely known,” noted study leader March Claret, at the University of Barcelona and leader of the study published in the journal Nature Metabolism.

The researchers found that the brains of pregnant female mice undergoes changes in the functional connections of the brain reward circuits, as well as the taste and sensorimotor centres. Mice, like pregnant women, are also more sensitive to sweet food, and develop binge-eating behaviours towards high calorie foods. “The alteration of these structures made us explore the mesolimbic pathway, one of the signal transmission pathways of dopaminergic neurons. Dopamine is a key neurotransmitter in motivational behaviours,” notes Claret, member of the Department of Medicine of the UB and the Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM).

The team saw that dopamine levels and dopamine receptor (D2R) activity increased in the nucleus accumbens, a brain region involved in the reward circuit. “This finding suggests that the pregnancy induces a full reorganisation of the mesolimbic neural circuits through the D2R neurons,” noted study leader Roberta Haddad-Tóvolli. “These neuronal cells – and their alteration – would be responsible for the cravings, since food anxiety, typical during pregnancy, disappeared after blocking their activity.”

The team demonstrated that persistent cravings have consequences for the offspring, affecting the metabolism and development of neural circuits that regulate food intake, leading to weight gain, anxiety and eating disorders. “These results are shocking, since many of the studies are focused on the analysis of how the mother’s permanent habits – such as obesity, malnutrition, or chronic stress – affect the health of the baby. However, this study indicates that short but recurrent behaviours, such as cravings, are enough to increase the psychological and metabolic vulnerability of the offspring,” concluded Claret.

The conclusions of the study could contribute to the improvement of nutritional guidelines for pregnant women in order to ensure a proper prenatal nutrition and prevent the development of diseases.

Source: University of Barcelona

Mental Processing of Autistic and Non-autistic People is Similar

Source: Pixabay

Findings published in Journal of Psychopathology and Clinical Science reveal there are fundamental similarities between autistic and non-autistic people in mental processing. The study findings were made available online ahead of ahead of World Autism Day on the 2nd of April.

The brain uses two systems to process information: System 1 for quicker intuitive judgements, and System 2 for slower rational thinking. In autistic people, these systems are thought to work differently ad underlie difficulties they may have in daily life and the workplace.

Yet, this landmark study reports that these fundamental psychological systems are not impaired in autistic people as once thought. The study, involving more than 1000 people, tested the link between autism and ‘quick’ intuitive and ‘slow’ rational thinking.

In three experiments, they analysed the link between autistic personality traits and thinking style. In the fourth, they compared 200 autistic and over 200 non-autistic people. Overall, their results showed that autistic people think as quickly and as rationally as non-autistic people.

Based on these findings, the researchers conclude that certain, fundamental mental processes are more similar between autistic and non-autistic people than prior belief. In light of these findings, they call for a shift in the way that society thinks about autism as a mental processing disorder.

They also recommend that it might be important to redesign educational, clinical, and workplace support for autistic people and their families. Support should be much more targeted, instead of assuming that autistic people all have mental processing difficulties, they say.

The research team argue that the requirement to make ‘reasonable adjustments’ such as allowing extra time in exams and extending deadlines, is not an evidence-based way to support neurodivergent people.

Instead, more fundamental changes could be necessary – for example, changing social and sensory environments, making them more equitable autistic people.

Source: University of Bath

The Claustrum: A Mysterious Brain Region Involved with Pain

Man wearing mask with headache
Source: Usman Yousaf on Unsplash

A new review paper, published in the journal Brain, has shown that a mysterious brain region called the claustrum may play an important role in the experience of pain. This densely interconnected, but difficult to access area of the brain may be the next frontier in improving outcomes for brain damage patients.

The claustrum is a brain region that has been investigated for over 200 years, yet its precise function remains unknown. A 2005 article suggested it to be critically linked to consciousness, which spurred a renewed interest in this region, with recent research revealing its high level of interconnectedness.

Credit: Oxford University

Oxford University researchers reviewed studies of patients with rare cases of lesions in the claustrum, which show cognitive impairments and seizures. There may be many more cases to be uncovered due to the lack of clinical focus on the claustrum.

They also uncovered an underappreciated link between the claustrum and pain. It is already known that there are links between the claustrum and perception, salience and the sleep-wake cycle, but this is the first time a research team has shown how the claustrum might be more involved in the debilitating experience of pain.

Dr. Adam Packer, the lead author of the study, says that “The problem with understanding how the claustrum works is that it is deep inside the brain, and damage that is specific to it is a very rare occurrence. What makes it more difficult to work out what the claustrum actually does is that these rare occurrences are also linked to such a broad range of symptoms.”

“Clearly, when the claustrum is damaged the effects are severe and better therapies are urgently needed. It is possible that claustrum damage is more common than we currently realise, and it may be a crucial component in many more brain damage cases.”

“This work is important because it gives us some insight into the cognitive and neurological processes in which the claustrum may be involved, and gives us targets to pursue in basic research in the lab.”

The researchers found several recorded instances of either infection, autoimmune, or other process that attacked the claustrum in particular, and by analysing the results of these studies and others the most common symptoms in patients were cognitive impairment and seizures.

Additional research is needed for a better understanding of the claustrum and the impact of damage to the claustrum, which could eventually change clinical guidelines.

Source: University of Oxford

Amygdala Enlargement in Kids with ASD Starts Early

Source: Pixabay

The amygdala, which is enlarged in two-year-old children with autism spectrum disorder (ASD), begins its accelerated growth between 6 and 12 months of age, suggests a study appearing in the American Journal of Psychiatry. The findings indicate that therapies to reduce the symptoms of ASD might have the greatest chance of success if they begin in the first year of life, before the amygdala begins its accelerated growth.

The amygdala, which is involved in processing emotions, such as interpreting facial expression in typically developing children increases substantially in volume from 7.5 to 18.5 years of age. The amygdala in children with autism is initially larger, but does not undergo the age-related increase observed in typically developing children.

The study included 408 infants, 270 of whom with an increased ASD risk from having an older sibling with ASD, 109 typically developing infants, and 29 infants with Fragile X syndrome. The researchers conducted MRI scans of the children at 6, 12 and 24 months of age. They found that the 58 infants who went on to develop ASD had a normal-sized amygdala at 6 months, but an enlarged amygdala at 12 months and 24 months. Moreover, the faster the rate of amygdala overgrowth, the greater the severity of ASD symptoms at 24 months. The infants with Fragile X syndrome had no differences in amygdala growth but enlargement of the caudate, which was linked to increased repetitive behaviours.

The researchers suggested that difficulty in processing sensory information during infancy may stress the amygdala, leading to its overgrowth.

Source: NIH

Experiments to Test Consciousness All Fall Short

Depiction of a human brain
Image by Fakurian Design on Unsplash

A study examining various experiments each designed to prove one of four conflicting theories of consciousness has discovered that they are all flawed: predetermined to prove the theory they are designed to test. The surprising conclusion is that the nature of the experiment largely determines its result.

In neuroscience, there are currently four leading theories trying to explain how the experience of consciousness emerges from neural activity. In this unique study, researchers re-examined hundreds of experiments that support contradictory theories.

The study, published in Nature Human Behaviour, shows that the inconsistencies in the experiments’ findings are mainly due to methodological differences or the methodological choices made by the researchers, predetermines their results.

Employing artificial intelligence, researchers re-examined 412 experiments, and found that scientists’ methodological choices actually determined the result of the experiment – so much so that an algorithm could predict which theory they were designed to support with 80% success.

Professor Liad Mudrik led the study. He explained: “The big question is how consciousness is born out of activity in the brain, or what distinguishes between conscious processing and unconscious processing,” Prof Mudrik explained. “For example, if I see a red rose, my visual system processes the information and reports that there is a red stimulus in front of me. But what allows me – unlike a computer for example – to experience this colour? To know how it feels? In recent years, a number of neuroscientific theories have been proposed to explain how conscious experience arises from neural activity. And although the theories provide utterly different explanations, each of them was able to gather empirical evidence to justify itself, based on multiple experiments that were conducted. We re-examined all these experiments, and showed that the parameters of the experiment actually determine its results. The artificial intelligence we used knew how to predict with an 80% success rate which theory the experiment would support, based solely on the researchers’ methodological choices.”

The study of consciousness has four leading theories, with contradicting predictions about the neural underpinnings of conscious experience. The Global Neuronal Workspace Theory maintains that there is a central neural network, and when information enters it, it is being broadcasted throughout the brain, becoming conscious. The Higher Order Thought Theory claims that there is a higher order neural state that ‘points’ at activity in lower-level areas, marking this content as conscious. A third theory, called Recurrent Processing Theory, claims that information that is reprocessed within the sensory areas themselves, in the form of recurrent processing, becomes conscious. And finally, a fourth theory – Integrated Information Theory – defines consciousness as integrated information in the brain, claiming that the posterior regions are the physical substrates of consciousness.

“Each of these theories offers convincing experiments to support them, so the field is polarized, with no agreed-upon neuroscientific account of consciousness,” said Prof Mudrik.

In-depth analysis of all of the 412 experiments designed to test the four leading theories showed that they were constructed differently. For example, some experiments focused on different states of consciousness, such as a coma or a dream, and others studied changes in the content of consciousness of healthy subjects. Some experiments tested connectivity metrics were tested, and others did not. “Researchers make a series of decisions as they build their experiment, and we demonstrated that these decisions alone – without even knowing the results of the experiments – already predict which theory these experiments will support. That is, these theories were tested in different manners, though they try to explain the same phenomenon,” Prof Mudrik said.

“Another one of our findings was that the vast majority of the experiments we analysed supported the theories, rather than challenging them. There appears to be a built-in confirmation bias in our scientific praxis, though the philosopher of science Karl Popper said that science advances by refuting theories, not by confirming them,” added Prof. Mudrik. “Moreover, when you put together all of the findings that were reported in these experiments, it seems like almost the entire brain is involved in creating the conscious experience, which is not consistent with any of the theories. In other words, it would appear that the real picture is larger and more complex than any of the existing theories suggest. It would seem that none of them is consistent with the data, when aggregated across studies, and that the truth lies somewhere in the middle.”

Source: EurekAlert!

Antiepileptics in Comatose Cardiac Arrest Survivors are Ineffective, Study Shows

Image by Falkurian Design on Unsplash

A large scale study of comatose intensive care (ICU) patients admitted after cardiac arrest and resuscitation has shown that antiepileptics to treat epilepsy-like brain activity has no effect, and may even prolong ICU stay.

Following a cardiac arrest and resuscitation, patients may need an ICU stay, and are in a coma. By that stage, the cardiac arrest may have damaged the brain to such an extent that half of the patients will not recover from coma. The other half will also have permanent damage, for example of memory functions. It is extremely difficult to predict if a patient will awaken and what their prognosis is, so clinicians make use of EEG (electroencephalography).

In 10–20% of the patients admitted to the ICU after cardiac arrest and resuscitation, there are signs of brain activity that appear similar to epilepsy: unlike an attack this activity is continuous. For a long time, it was unclear if anti-epileptic medication could help better recovery. As a result, some patients received this medication and some did not.

Now, a large-scale study done between 2014 and 2021 on 172 patients has proven that this medication is ineffective: it does not help recovery, even necessitating a longer ICU stay. The researchers, led by Professor Jeannette Hofmeijer of the University of Twente and Rijnstate Hospital in Arnhem, published their findings in the New England Journal of Medicine.

The conclusion from this study is that anti-epileptic medication does not lead to an improved recovery. The findings show that patients may need to stay longer at the ICU: for the patient an undesired situation, and it puts extra pressure on the health care system. 

Aside from patients who show continuous epileptic signals, a small group of patients show signs of a typical epileptic seizure: a short and heavy attack. In these situations, anti-epileptics could help, but this still needs further research.

“Although the outcome of the trial may be disappointing in terms of chances of recovery, it also takes away uncertainties from the family. The signals point at serious brain damage that would lead to a much longer stay at the ICU,” said Prof Hofmeijer.

Source: University of Twente

Scientists Unravel Neurological Origins of the Placebo Effect

Researchers at Massachusetts General Hospital (MGH) have discovered a network of brain regions activated by the placebo effect overlaps with several regions targeted by brain-stimulation therapy for depression.

The findings of this study, published in Molecular Psychiatry, will help in understanding the neurobiology of placebo effects and could inform how brain stimulation trial results are interpreted. In addition, this could provide insights on how to harness placebo effects for the treatment of a variety of conditions.

The placebo effect occurs when a patient’s symptoms improve because they expect a therapy to help (due to a variety of factors), but not from the specific effects of the treatment itself. Recent research indicates that there is a neurological basis for the placebo effect, with imaging studies identifying a pattern of changes that happen in certain brain regions when a person experiences this phenomenon.

The use of brain-stimulation techniques for patients with depression that doesn’t respond adequately to medication or psychotherapy has gained wider use in recent years. Transcranial magnetic stimulation (TMS) delivers electromagnetic pulses to the brain, and its effect on brain activity has been established over the last three decades in animal and human research studies, with several TMS devices approved by the Food and Drug Administration for treating depression. In addition, for treatment depression, deep brain stimulation (DBS, which requires an implanted device) has shown some promise.

Senior author Emiliano Santarnecchi, PhD, saw studies of brain stimulation as a unique opportunity to learn more about the neurobiology of the placebo effect. Santarnecchi and his co-investigators conducted a meta-analysis and review of neuroimaging studies involving healthy subjects and patients to create a “map” of brain regions activated by the placebo effect. They also analysed studies of people treated with TMS and DBS for depression to identify brain regions targeted by the therapies. The team found that several sites in the brain that are activated by the placebo effect overlap with brain regions targeted by TMS and DBS.

Dr Santarnecchi and his colleagues believe that this overlap has critical importance in interpreting the results of research on brain stimulation for conditions such as depression. In clinical trials, a significant portion of depression patients receiving brain stimulation improve — but so do many patients receiving placebo (sham) treatment, in which no stimulation is administered, which has led to confusion over the therapy’s benefits.

A possible explanation is “that there is a significant placebo effect when you do any form of brain stimulation intervention,” said Dr Santarnecchi. TMS involves a clinical setting, with loud clicks as the pulse is delivered. “So the patient thinks, ‘Wow, they are really activating my brain’, so you get a lot of expectation,” said Dr Santarnecchi.

Elevated placebo effects associated with brain stimulation may create problems when studying the intervention, said first author Matthew Burke, MD, a cognitive neurologist. If brain stimulation and the placebo effect overlap in activating the same brain regions, then those circuits could be maximally activated by placebo effects, which could make it difficult to show any additional benefit from TMS or DBS, said Dr Burke. If so, this could explain the disparity of results in neurostimulation treatment of depression. Screening out placebo from brain stimulation’s direct impact on brain activity will help in designing studies where the real potential of techniques such as TMS will be more easily quantified, thus improving the effect of treatment protocols.

The findings from this study also suggest broad applications for the placebo effect, said Dr Santarnecchi. “We think this is an important starting point for understanding the placebo effect in general, and learning how to modulate and harness it, including using it as a potential therapeutic tool by intentionally activating brain regions of the placebo network to elicit positive effects on symptoms,” he said.

Dr Santarnecchi and his colleagues are currently designing trials that they hope will “disentangle” the effects of brain stimulation from placebo effects and offer insights about how they can be leveraged in clinical settings.

Source: Massachusetts General Hospital

Reduced Antiepileptic Drug Effectiveness in Pregnancy Uncovered

Photo by Shvets Productions on Pexels

Blood levels of many commonly used antiepileptic drugs drop dramatically with the onset of pregnancy, which can result in ‘breakthrough seizures’ according to a study published in JAMA Neurology.

The findings, collected as part of the multicentre study Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), explain why many people with epilepsy start experiencing breakthrough seizures after conception, underscoring the need to increase antiseizure medication doses and closely monitor blood levels over the course of pregnancy.

A fine-tuned medication regime is critical in epilepsy. “Some people mistakenly believe that changes in the drugs’ blood concentration won’t occur until after 20 weeks of pregnancy, but our study shows how important it is to start monitoring and adjusting patients’ medication dosages early on,” said lead author Dr Page Pennelll. “Nearly half of all pregnancies in the United States are unplanned, so it is important to ensure that doctors have a clear picture of each patient’s baseline drug level even if they are not trying to conceive.”

A life-altering neurological condition, two-thirds of epilepsy cases do not have a known cause. In people with epilepsy, nerve cells in the brain are hyper-reactive, causing them to change the pattern of their electrical activity and become spontaneously active. That synchronous activation is manifested in seizures.

Epilepsy has a fraught history of diagnosis and management; people with epilepsy go undiagnosed or under-treated. First-generation drugs to control it had many dangerous side effects and were contraindicated for people who are trying to conceive.

Since then, safer medications have entered the U.S. market and become widely available, but clinicians started noticing a new problem – patients whose epilepsy was successfully managed with medications started having seizures soon after becoming pregnant.

“Identifying which antiseizure medications may have changes in concentrations and at what point in pregnancy those changes occur is important for determining which patients may need to be monitored more closely during pregnancy and after delivery,” said senior author Professor Angela Birnbaum at the University of Minnesota.

To solve the mystery, the researchers embarked on a study to analyse blood concentrations of 10 commonly used antiseizure drugs and compare them across different stages of pregnancy and after childbirth.

The study found that blood levels of seven out of 10 of the medications they examined dropped dramatically — from 29.7% for lacosamide, a commonly prescribed anticonvulsant, and up to 56.4% for lamotrigine.

In addition, the researchers noted that the drop in drug levels occurred mere days after conception.

Source: University of Pittsburgh

Body Fat Linked to Risk of Reduced Cognitive Function

Photo by Andres Ayrton from Pexels

A new study published in JAMA Network Open has found that greater body fat is a risk factor for reduced cognitive function, such as processing speed, in adults.

Even when accounting for cardiovascular risk factors or vascular brain injury, the association between body fat and lower cognitive scores persisted. This suggests other, currently unknown, mechanisms linking excess body fat to reduced cognitive function.

For the study, 9166 participants were measured by bioelectrical impedance analysis to assess their total body fat. In addition, 6733 underwent magnetic resonance imaging (MRI) to measure abdominal fat packed around the organs known as visceral fat, and the MRI measured vascular brain injury, including silent brain infarctions and high white matter hyperintensities. Cardiovascular risk factors were measured using health and lifestyle questions and physical measures, and cognitive assessment was measured by the Digital Symbol Substitution Test and the Montreal Cognitive Assessment.

Lead author Sonia Anand, lead author, professor of medicine of McMaster University said: “Our results suggest that strategies to prevent or reduce having too much body fat may preserve cognitive function.”

She added that “the effect of increased body fat persisted even after adjusting for its effect on increasing cardiovascular risk factors like diabetes and high blood pressure, as well as vascular brain injury, which should prompt researchers to investigate which other pathways may link excess fat to reduced cognitive function.”

Co-author Eric Smith, associate professor of clinical neurosciences at the University of Calgary, said that “preserving cognitive function is one of the best ways to prevent dementia in old age. This study suggests that one of the ways that good nutrition and physical activity prevent dementia may be by maintaining a healthy weight and body fat percentage.”

Participants had no existing cardiovascular diseases, and ranged in age from 30 to 75, with an average age of about 58 and 56% were women. Most were White European origin, with about 16% other ethnic backgrounds. 

Source: McMaster University

An Updated Look at the Link Between Alcohol and Epilepsy

Photo by Pavel Danilyuk on Pexels

A new meta-analysis has established an association between alcohol and epilepsy, in contrast to previous studies which reported conflicting results on the relationship.

Epilepsy is one of the most common neurological conditions, with an annual incidence of 40–70 per 100 000 people in industrialised countries. It is also a  disease that is highly stigmatised.

A number of studies have focused on how alcohol consumption leads to provoked seizures, commonly resulting from alcohol withdrawal, or heavy intoxication. Very few of these however focused on the link between alcohol consumption and unprovoked seizures. A 2010 meta-analysis found that alcohol users were more prone to developing unprovoked seizures – but data from recent cohort studies contradict these findings. A 2018 meta-analysis suggested that the relationship may only hold true for heavy drinkers.

Now, using more accurate diagnostic methods and recent data, a team of scientists from Pusan National University, South Korea, conducted an updated meta-analysis to conclusively clarify the relationship between alcohol consumption and unprovoked seizures and epilepsy.

For this meta-analysis, appearing in Drug and Alcohol Dependence, the researchers included a total of eight studies, of which five were case-control studies and three were cohort studies. They analysed the data to assess the dose-response relationship between alcohol intake and epilepsy. The results suggested that overall, compared to non-drinkers, alcohol drinkers were at a significantly higher risk of developing epilepsy, which increased with alcohol intake. These findings are consistent with previous meta-analyses.

An important finding was that cohort studies did not show a positive association between alcohol intake and epilepsy. In fact, 2 out of 3 cohort studies suggested that alcohol intake reduces the risk of epilepsy.

More large cohort studies are needed to prove a causal relationship between alcohol drinking and epilepsy, as well as a threshold of onset, said second author Professor Yun Hak Kim.

Source: EurekAlert!