As usual, our monthly roundup starts with a shout out to a notable researcher whose birthday fell on April: Edvard Moser, a Norwegian neuroscientist and one of 2014’s Nobel Prize in Physiology or Medicine laureates, born 27^th April 1962.

Edvard Moser is the director of the Kavli Institute for Systems Neuroscience and Centre for Neural Computation at the University of Science and Technology (NTNU) in Trondheim, Norway. Moser and his wife, May-Britt Moser, have been doing groundbreaking research on the brain’s mechanisms for special representation, or as they call it, our “inner GPS”. This work has earned them multiple awards, the most outstanding of which being the Nobel Prize that Edvard and May-Britt Moser shared with John O’Keefe in 2014. Happy birthday, Edvard Moser!

Below is the best and worst of the studies I came across in April. These are personal opinions, presented in no particular order and we welcome your comments and suggestions. If you have come across interesting studies, let us know in the comment section.

THE BEST

A possible therapy for cognitive disabilities in Down’s syndrome

Down’s syndrome is the most common form of cognitive disability. The study of brain dysfunction in this disorder has led to some important advances in understanding the pathophysiology of associated cognitive phenotypes. Animal models of the disease have shown that altered GABAergic transmission contributes considerably to learning and memory deficits. A study published in Nature Medicine assessed the efficacy of GABAergic transmission in Down’s syndrome and found that GABA, which is usually inhibitory, is excitatory in the hippocampus of adult Down’s syndrome mice. The study identifies a new therapeutic approach for the potential rescue of cognitive disabilities in individuals with Down’s syndrome.

Repetitive transcranial magnetic stimulation in Parkinson’s disease therapy

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation technique that has been proposed as a possible therapy for Parkinson’s disease. Studies conducted so far on its effectiveness, however, have shown mixed results. A systematic review and meta-analysis published in JAMA Neurology addressed the effects of rTMS on motor dysfunction in patients with Parkinson’s disease and examined potential factors that may modulate those effects. The authors found evidence supporting the efficacy of rTMS in the improvement of motor symptoms in patients with Parkinson’s disease. They also concluded that the site, frequency and number of rTMS pulses are key modulators of its effects.

Inflammatory mechanisms in Alzheimer’s disease

Review articles are a great way to compile and summarize the most recent findings and advances in any given research topic. The Lancet Neurology published an extensive review of the evidences reported in the last 5 years for the existence of neuroinflammatory mechanisms driving the pathogenic process in Alzheimer’s disease. Indeed, increasing evidence has suggested that Alzheimer’s disease is not strictly neuronal, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins can activate microglia and astroglia, and trigger an innate immune response which may contribute to disease progression and severity. These immune mechanisms may become important therapeutic targets in the future.

Are chronic fatigue syndrome and fibromyalgia the same condition? Maybe not.

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) often co-exist, sharing a number of symptoms, including pain, fatigue, sleep problems and cognitive difficulties. This has led to an ongoing discussion on whether or not these are indeed two distinct conditions, with some arguing that they may reflect the same process, somatization. An argument against this view is the data suggesting that FM but not CFS is common in patients with sleep-disordered breathing. Solving this discussion could probably benefit research on both conditions.

Hence, a study published in BMC Neurology addresses this question by exploring the rates of CFS alone, CFS with FM, and FM alone in patients with sleep-disordered breathing compared to those with insomnia. They found that CFS occurred frequently in sleep-disordered breathing and insomnia, but FM occurred frequently only in insomnia. The authors therefore argue that FM and CFS may have different underlying pathophysiological causes.

A new therapeutic approach for Huntington’s disease

Huntington’s disease (HD) is an inherited neurodegenerative disorder with no cure. Palliative treatments are also mostly ineffective. An ideal therapy for Huntington’s should stop disease development at early stages, before neuronal damage occurs. However, the mechanisms of disease progression are poorly understood. Evidence has suggested that hyperfunction of glutamate NMDA receptors, specifically those containing the GluN3A subunit, may play an important part.

JAMA Neurology published a study addressing this hypothesis in animal models of Huntington’s disease. By correcting the NMDAR hyperfunction through inhibition of GluN3A, the authors were able to prevent the full range of Huntington’s signs and symptoms in mouse models. GluN3A-selective antagonists or other therapeutic approaches to block GluN3A may be promising pharmacological targets in Huntington’s disease.

THE WORST

Conversion “therapies” need to end

In April, US President Barack Obama issued a statement calling for an end to the practice of conversion therapies for the LGBTQ+ youth. This statement came as a response to a petition that came about after the suicide, in late December, of Leelah Alcorn, a 17-year-old transgender girl from Ohio, USA, who was subjected to one of these so-called “therapies”. In her suicide note, Leelah said: “My death needs to mean something. My death needs to be counted in the number of transgender people who commit suicide this year. I want someone to look at that number and say “that’s fucked up” and fix it.”

It’s great that President Obama condemned this practice, but it’s absolutely atrocious that such practices and the mindsets they represent exist. As a human being, I feel ashamed for having to write this, I shouldn’t have to. In Leelah Alcorn’s last words: “Fix society. Please.”

Poststroke suicide

Stroke survivors commonly face complications over time, one of them being an increased risk of attempted or completed suicide. A group from Lund University in Sweden performed a nationwide cohort study that included stroke patients from 2001 to 2012 to examine attempted and completed suicides after stroke. They also studied whether they were associated with socioeconomic status, other patient characteristics, or time after stroke. They observed 220,336 stroke patients; during follow-up, there were 1,217 suicide attempts, of which 260 were fatal. They found that patients with lower education or income and patients living alone had an increased risk of attempted suicide. Male sex, young age, severe stroke, and poststroke depression were factors associated with an increased risk of attempted suicide after stroke, with the risk being highest during the first two years after stroke.

Traumatic brain injury increases the risk of Parkinson’s disease

Traumatic brain injury has been considered a risk factor for Parkinson’s disease, although results are conflicting. A new study published in the Annals of Neurology has established a causal association between traumatic brain injury and Parkinson’s disease. The study shows that in patients aged over 55 years, traumatic brain injury is associated with a 44% increased risk of developing Parkinson’s disease over 5 to 7 years. In addition, the risk of developing Parkinson’s disease doubles after more severe or more frequent traumatic brain injury, compared with mild or single cases.

Neonatal Vitamin A supplementation does not decrease mortality

Vitamin A supplementation in children aged 6 months to 5 years has been shown to reduce mortality, but neonatal supplementation, before 6 months of age, has shown inconsistent results. The Lancet published a double-blind, placebo-controlled trial of infants born in Tanzania on the efficacy of oral supplementation with vitamin A. Supplementation was given to infants in the first 3 days of life to reduce mortality before 6 months of age. Unfortunately, the authors found that neonatal vitamin A supplementation had no beneficial effect on survival. A parallel study with children in Ghana reached the same conclusion.

Internet gaming disorder and the adolescent brain

Internet gaming disorder is one of the main behavior disorders among adolescents. Frontiers in Behavioral Neuroscience published a study evaluating the relationship between alteration of gray matter volume and cognitive control in adolescents with internet gaming disorder. The authors observed a reduction in the gray matter volume of multiple brain regions in participants with internet gaming disorder, particularly in the anterior cingulate cortex, which participates in cognitive control, such as inhibitory control, error monitoring, and decision making. These gray matter changes seemingly compromised both behavioral activity and neural structure, suggesting they may be associated with changes in cognitive control in adolescents with internet gaming disorder.

References

Chou YH, Hickey PT, Sundman M, Song AW, & Chen NK (2015). Effects of Repetitive Transcranial Magnetic Stimulation on Motor Symptoms in Parkinson Disease: A Systematic Review and Meta-analysis. JAMA neurology, 72 (4), 432-40 PMID: 25686212

Deidda G, Parrini M, Naskar S, Bozarth IF, Contestabile A, & Cancedda L (2015). Reversing excitatory GABAAR signaling restores synaptic plasticity and memory in a mouse model of Down syndrome. Nature medicine, 21 (4), 318-26 PMID: 25774849

Eriksson M, Glader EL, Norrving B, & Asplund K (2015). Poststroke suicide attempts and completed suicides: A socioeconomic and nationwide perspective. Neurology, 84 (17), 1732-8 PMID: 25832661

Gardner RC, Burke JF, Nettiksimmons J, Goldman S, Tanner CM, & Yaffe K (2015). Traumatic brain injury in later life increases risk for Parkinson disease. Annals of neurology PMID: 25726936

Heneka MT, Carson MJ, Khoury JE, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K, Frautschy SA, Finsen B, Brown GC, Verkhratsky A, Yamanaka K, Koistinaho J, Latz E, Halle A, Petzold GC, Town T, Morgan D, Shinohara ML, Perry VH, Holmes C, Bazan NG, Brooks DJ, Hunot S, Joseph B, Deigendesch N, Garaschuk O, Boddeke E, Dinarello CA, Breitner JC, Cole GM, Golenbock DT, & Kummer MP (2015). Neuroinflammation in Alzheimer’s disease. The Lancet. Neurology, 14 (4), 388-405 PMID: 25792098

Masanja H, Smith ER, Muhihi A, Briegleb C, Mshamu S, Ruben J, Noor RA, Khudyakov P, Yoshida S, Martines J, Bahl R, Fawzi WW, & Neovita Tanzania Study Group (2015). Effect of neonatal vitamin A supplementation on mortality in infants in Tanzania (Neovita): a randomised, double-blind, placebo-controlled trial. Lancet, 385 (9975), 1324-32 PMID: 25499543

Pejovic S, Natelson BH, Basta M, Fernandez-Mendoza J, Mahr F, & Vgontzas AN (2015). Chronic fatigue syndrome and fibromyalgia in diagnosed sleep disorders: a further test of the ‘unitary’ hypothesis. BMC neurology, 15 PMID: 25884538

Wang H, Jin C, Yuan K, Shakir TM, Mao C, Niu X, Niu C, Guo L, & Zhang M (2015). The alteration of gray matter volume and cognitive control in adolescents with internet gaming disorder. Frontiers in behavioral neuroscience, 9 PMID: 25852507

Wesseling JF, & Pérez-Otaño I (2015). Modulation of GluN3A Expression in Huntington Disease: A New N-Methyl-d-Aspartate Receptor-Based Therapeutic Approach? JAMA neurology, 72 (4), 468-73 PMID: 25686081

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