This scientific commentary refers to ‘Ictal lack of binding to brain parenchyma suggests integrity of the blood–brain barrier for 11C-dihydroergotamine during glyceryl trinitrate-induced migraine’, by Schankin et al. (doi:10.1093/brain/aww096).
Research into episodic memory loss in Alzheimer’s disease has repeatedly focused on the hippocampus. Aggleton et al. argue that this approach is too narrow, and ignores the early involvement of other brain sites, most notably the anterior thalamic nuclei, which are also vital for episodic memory.
Microvascular complement deposition is a hallmark of dermatomyositis. Through analysis of 50 dermatomyositis and 10 control muscle specimens, Lahoria et al. show that perifascicular atrophy is consistently associated with focal capillary depletion. Assembly of the C5b-9 membrane attack complex is a consequence rather than cause of the microvascular injury.
High-throughput next-generation sequencing can identify disease-causing mutations in extremely heterogeneous disorders. Kara et al. investigate a series of 97 index cases with complex hereditary spastic paraplegia (HSP). They identify SPG11 defects in 30 families, as well as mutations in other HSP genes and genes associated with disorders including Parkinson’s disease.
Hyperphosphorylation of tau may contribute to epileptogenesis. Liu et al. reveal a reduction in the activity of protein phosphatase 2A (PP2A), with concomitant hyperphosphorylation of tau, in animal models of kindling, post-status epilepticus and post-traumatic epilepsy. Sodium selenate, a PP2A activator, prevents epileptogenesis in all three models.
LiorMayo, Andre Pires DaCunha, AsafMadi, VanessaBeynon, ZhipingYang, Jorge I.Alvarez, AlexandrePrat, Raymond A.Sobel, LesterKobzik, HansLassmann, Francisco J.Quintana, Howard L.WeinerBrain(2016)139 (7):
1939-1957DOI: http://dx.doi.org/10.1093/brain/aww113First published online: 31 May 2016 (19 pages)
Current therapies have limited effect on the chronic CNS inflammation observed in progressive multiple sclerosis (MS). Mayo et al. show that CD3-specific antibody ameliorates disease in a mouse model of progressive MS. The effect is dependent on induction of regulatory T-cells, which attenuate astrocyte and microglia activation via secretion of interleukin-10.
EtienneVachon-Presseau, PascalTétreault, BogdanPetre, LejianHuang, Sara E.Berger, SourayaTorbey, Alexis T.Baria, Ali R.Mansour, Javeria A.Hashmi, James W.Griffith, ErikaComasco, Thomas J.Schnitzer, Marwan N.Baliki, A. VaniaApkarianBrain(2016)139 (7):
1958-1970DOI: http://dx.doi.org/10.1093/brain/aww100First published online: 5 May 2016 (13 pages)
Why some individuals progress from acute to chronic pain is unclear. Vachon-Presseau et al. monitor patients with subacute pain for three years, and show that pre-existing structural and functional connectivity within dorsal mPFC-amygdala-accumbens corticolimbic circuitry, as well as amygdala and hippocampal volumes, represent risk factors for transition to chronic pain.
RodrigoNoseda, Carolyn A.Bernstein, Rony-ReuvenNir, Alice J.Lee, Anne B.Fulton, Suzanne M.Bertisch, AlexandraHovaguimian, Dean M.Cestari, RodrigoSaavedra-Walker, DavidBorsook, Bruce L.Doran, CatherineBuettner, RamiBursteinBrain(2016)139 (7):
1971-1986DOI: http://dx.doi.org/10.1093/brain/aww119First published online: 17 May 2016 (16 pages)
Migraine headache is commonly exacerbated by light (photophobia). Noseda, Burstein et al. show that green light alleviates the headache whereas blue, amber and red lights exacerbate it. Using electroretinography and visual evoked potentials in migraineurs and multi-electrode recordings in rats, they provide evidence that this colour-selective photophobia originates in cone-driven retinal pathways.
Migraine is a cyclical disease. Schulte and May describe a migraine patient who underwent functional MRI every day for 30 days, including during three untreated migraine attacks. They find the hypothalamus to be the primary motor of migraine attacks, displaying activation before an attack and exhibiting phase-specific interactions with the brainstem.
See Dreier (doi: 10.1093/aww112) for a scientific commentary on this article.
Breakdown of the blood–brain barrier has long been postulated to occur in migraine. Schankin et al. explore this possibility using PET with [11C]-dihydroergotamine. The radioligand does not bind to the brain parenchyma at rest or during migraine attacks, suggesting that the blood–brain barrier remains intact during attacks.
Anna P.Andreou, Philip R.Holland, SimonAkerman, OliverSumm, JoeFredrick, Peter J.GoadsbyBrain(2016)139 (7):
2002-2014DOI: http://dx.doi.org/10.1093/brain/aww118First published online: 30 May 2016 (13 pages)
Migraine affects 1 billion people worldwide, and is the most common cause of neurological disability. Single pulse transcranial magnetic stimulation (sTMS) has been shown to be effective for the acute treatment of migraine. Using preclinical models, Andreou, Holland et al. explore thalamocortical mechanisms as a basis for this clinical effect.
Migraine with aura is considered a putative risk factor for silent brain infarcts and white matter hyperintensities in women. In an MRI study of Danish female twins aged 30–60 years, Gaist et al. compare 172 affected women with 139 controls, but find no evidence to support the proposed associations.
AntonelloBaldassarre, LennyRamsey, JenniferRengachary, KristiZinn, Joshua S.Siegel, Nicholas V.Metcalf, Michael J.Strube, Abraham Z.Snyder, MaurizioCorbetta, Gordon L.ShulmanBrain(2016)139 (7):
2024-2038DOI: http://dx.doi.org/10.1093/brain/aww107First published online: 25 May 2016 (15 pages)
The behavioural specificity of abnormalities in resting state functional connectivity (rs-FC) after stroke is unclear. Baldassarre et al. provide evidence for a double dissociation: Attentional deficits correlate with disruption of inter-hemispheric FC in the dorsal attention network, whereas motor impairments relate to disruption of inter-hemispheric FC in the motor network.
Allan K.Hansen, KarolineKnudsen, Thea P.Lillethorup, Anne M.Landau, PeterParbo, TatyanaFedorova, HélèneAudrain, DirkBender, KarenØstergaard, David J.Brooks, PerBorghammerBrain(2016)139 (7):
2039-2049DOI: http://dx.doi.org/10.1093/brain/aww098First published online: 5 May 2016 (11 pages)
The progression rate of dopaminergic cell loss in Parkinson’s disease remains uncertain. Using [18F]AV-1451 PET, Hansen et al. demonstrate a decreased midbrain neuromelanin signal in patients in vivo that may reflect the loss of nigral dopamine neurons. [18F]AV-1451 PET could serve as a biomarker in trials of putative neuroprotective agents.
Rasagiline is a monoamine oxidase B inhibitor used to treat Parkinson’s disease, but variability in clinical response has been observed. Using a comprehensive pharmacogenetic approach, Masellis, Collinson et al. identify two genetic variants in the dopamine D2 receptor gene (DRD2) that are associated with a favourable clinical response to rasagiline.
Anti-inflammatory drugs like ibuprofen reduce Alzheimer’s disease risk when taken before cognitive decline begins, but the mechanism behind this protection has remained elusive. Woodling, Colas et al. report that ibuprofen changes neuronal gene expression and prevents memory decline in a mouse model of Alzheimer’s disease, identifying new targets for research.
Claire M.Kaplan, DebjaniSaha, Juan L.Molina, William D.Hockeimer, Elizabeth M.Postell, Jose A.Apud, Daniel R.Weinberger, Hao YangTanBrain(2016)139 (7):
2082-2095DOI: http://dx.doi.org/10.1093/brain/aww095First published online: 23 May 2016 (14 pages)
See Stephan et al. (doi:10.1093/aww120) for a scientific commentary on this work.
The uniquely human anterior prefrontal cortex weighs uncertain contextual beliefs, but its role in delusions is unclear. Kaplan et al. reveal how opposing changes in prefrontal and subcortical function in response to deviations from expectations versus more familiar information patterns may have relevance to delusions and genetic risk for schizophrenia.
One hundred years after the definitive description of Guillain-Barré syndrome, Alastair Compston re-examines two papers from the Brain archive that helped to advance understanding of the disorder. The first, from 1969, reports recurrent episodes separated by (near) complete recovery, while the second, from 1986, describes the axonal variant.