Volume 138, Issue 5, May 2015
Editorial
Seize the moment that is thine: how should we define seizures?
Scientific Commentaries
Cognitive auditory evoked potentials in coma: can you hear me?
This scientific commentary refers to ‘Neural detection of complex sound sequences in the absence of consciousness’, by Tzovara et al. (doi:10.1093/brain/awv041).
REM sleep behaviour disorder: a window on the sleeping brain
This scientific commentary refers to ‘Ictal SPECT in patients with rapid eye movement sleep behaviour disorder’, by Mayer et al. (doi:10.1093/brain/awv042).
Where and what is the PPN and what is its role in locomotion?
This scientific commentary refers to ‘The integrative role of the pedunculopontine nucleus in human gait’, by Lau et al. (doi:10.1093/brain/awv047).
New criteria for Alzheimer’s disease: which, when and why?
This scientific commentary refers to ‘Prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage’ by Vos et al. (doi:10.1093/brain/awv029).
Review Article
Roles of microglia in brain development, tissue maintenance and repair
The number of functions ascribed to microglia has increased greatly in recent years. Michell-Robinson et al. review the roles of microglia in health and disease, in particular their contributions to brain development and tissue maintenance, and discuss the potential of targeting microglia to enhance brain repair.
Report
Neural detection of complex sound sequences in the absence of consciousness
Neural responses to violations of global regularities are thought to require consciousness. However, Tzovara et al. show that some comatose patients can also detect deviations in sequences composed of repeated groups of sounds, suggesting that the unconscious brain has a greater capacity to track sensory inputs than previously believed.
Original Articles
Neuron-specific antioxidant OXR1 extends survival of a mouse model of amyotrophic lateral sclerosis
Oxidative stress is a key factor contributing to motor neuron injury in amyotrophic lateral sclerosis (ALS). Liu et al. show that overexpression of oxidation resistance 1 (Oxr1) in neurons reduces pathology and extends lifespan in an ALS mouse model. Manipulation of OXR1 levels may have therapeutic benefit in neurodegenerative disease.
Structural and functional MRI abnormalities of cerebellar cortex and nuclei in SCA3, SCA6 and Friedreich’s ataxia
Data on the involvement of cerebellar nuclei in common hereditary ataxias are sparse. Stefanescu et al. reveal structural and functional abnormalities of cerebellar cortex and nuclei in spinocerebellar ataxia types 3 and 6, and Friedreich’s ataxia. Structural imaging of cerebellar nuclei should be included in the diagnostic workup of ataxias.
CHD2 variants are a risk factor for photosensitivity in epilepsy
Photosensitivity in epilepsy is common and has high heritability, but its genetic basis remains uncertain. Galizia et al. reveal an overrepresentation of unique variants of CHD2 — which encodes the transcriptional regulator ‘chromodomain helicase DNA-binding protein 2’ — in photosensitive epilepsies, and show that chd2 knockdown in zebrafish causes photosensitivity.
Astrocyte uncoupling as a cause of human temporal lobe epilepsy
Increasing evidence suggests glial cell involvement in CNS disorders. Using techniques including patch clamp recording, EEG/video monitoring and fate mapping in human hippocampal tissue and in a mouse model, Bedner et al. reveal a causal role for astrocyte dysfunction in the aetiology of mesial temporal lobe epilepsy with sclerosis.
Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis
Wang et al. use diffusion basis spectrum imaging (DBSI) to noninvasively differentiate and quantify axon and myelin injury/loss, cellular inflammation and oedema in multiple sclerosis. They validate DBSI-derived metrics by showing close agreement with histological analyses of autopsied multiple sclerosis spinal cord, before applying the method to patients with multiple sclerosis.
Magnetization transfer ratio measures in normal-appearing white matter show periventricular gradient abnormalities in multiple sclerosis
In multiple sclerosis, grey matter pathology occurs mostly next to or near the outer surface of the brain. Using quantitative MRI, Liu et al. reveal that white matter abnormalities are also greatest near the surface of the brain, suggesting common elements in the genesis of grey and white matter pathology.
Post-treatment with an ultra-low dose of NADPH oxidase inhibitor diphenyleneiodonium attenuates disease progression in multiple Parkinson’s disease models
Oxidative stress has been implicated in Parkinson’s disease progression. Wang et al. show that treatment with ultra-low doses of the NADPH oxidase inhibitor diphenyleneiodonium reverses parkinsonian defects and halts progression in three mouse models of the disease, even when treatment is started when over 30% of dopaminergic neurons are lost.
Ictal SPECT in patients with rapid eye movement sleep behaviour disorder
REM sleep behaviour disorder is characterised by dream enactment. Using ‘ictal’ SPECT, Mayer et al. reveal activation in cortical, cerebellar and brainstem regions — but not the basal ganglia — in four patients. The same pathway is activated in individuals with idiopathic disease as in those with comorbid Parkinson’s disease or narcolepsy.
Polymorphism of the dopamine transporter type 1 gene modifies the treatment response in Parkinson’s disease
Responses to L-dopa vary within and between individuals. Moreau et al. reveal that polymorphisms in the dopamine transporter gene (SLC6A3) influence the response to L-dopa and to the dopamine transporter inhibitor methylphenidate. This may help physicians to optimise L-dopa dose and to assess the risk/benefit balance for treatment with methylphenidate.
The integrative role of the pedunculopontine nucleus in human gait
Gait disorders are untreatable in the elderly because the physiology of gait control is poorly understood. Lau et al. present electrophysiological evidence that the brainstem pedunculopontine nucleus is modulated by visual stimulation, voluntary movement and imaginary gait, suggesting that the brainstem controls gait in manners extending beyond driving pattern generation.
Sodium selenate reduces hyperphosphorylated tau and improves outcomes after traumatic brain injury
Hyperphosphorylation of tau is implicated in traumatic brain injury (TBI) pathology. Shultz et al. show that TBI reduces protein phosphatase 2A (PP2A) activity and increases tau phosphorylation in rats, with similar findings in human post-mortem tissue. Sodium selenate, a PP2A activator, prevents TBI-induced abnormalities in rats and improves behavioural outcomes.
Acute post-traumatic stress symptoms and age predict outcome in military blast concussion
In the first such study to be conducted, Mac Donald et al. assess US military personnel 0–7 days after blast-related concussion in Afghanistan and 6–12 months later in the United States. Military personnel who remain on duty after concussion frequently show poor outcomes, driven largely by impaired mental health.
Prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage
Vos et al. compare the prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage based on the IWG-1, IWG-2 and NIA-AA criteria. All three aid identification of early Alzheimer’s disease, but combining amyloid and neuronal injury markers according to the NIA-AA criteria offers the most accurate prognosis.
HS3ST2 expression is critical for the abnormal phosphorylation of tau in Alzheimer’s disease-related tau pathology
Heparan sulfate 3-O-sulfotransferase-2 (3OST2) is a heparan sulfate modifying enzyme predominantly expressed in brain. Sepulveda-Diaz, Alavi Naini, Huynh et al. show in vitro and in a zebrafish model of tauopathy that inhibiting 3ost2 expression, or preventing tau interaction with 3-O-sulfated heparan sulfates, blocks abnormal tau phosphorylation of the type seen in Alzheimer’s disease.
Memory binding and white matter integrity in familial Alzheimer’s disease
Individuals with familial Alzheimer’s disease (E280A-PSEN1) are impaired in both short- and long-term memory binding, whereas preclinical mutation carriers are impaired only in the former. By combining diffusion tensor MRI with cognitive testing, Parra et al. identify regional cerebral differences in white matter integrity that could account for this dissociation.
Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer’s disease spectrum
Murray et al. examine the correspondence between Thal amyloid phase, tau pathology and clinical characteristics in a large Alzheimer’s disease autopsy series. They extrapolate their findings to an autopsy cohort for which Pittsburgh compound-B imaging data are available, and evaluate the neuropathological significance of a quantitative amyloid-β imaging cut-off point.
Autism: reduced connectivity between cortical areas involved in face expression, theory of mind, and the sense of self
Cheng, Rolls et al. examine whole-brain voxel-based resting-state functional connectivity in 418 people with autism. They reveal reduced connectivity between regions involved in facial expression processing and theory of mind (middle temporal gyrus), emotion processing (ventromedial prefrontal cortex), and the representation of self (precuneus and related posterior cingulate areas).
Somatosensory cortex functional connectivity abnormalities in autism show opposite trends, depending on direction and spatial scale
Studies of functional connectivity in autism have yielded mixed results. Khan et al. use MEG to compare directional long-range and local functional connectivity in somatosensory cortex of individuals with autism and healthy controls. Based on their data, they propose a unifying framework for functional connectivity abnormalities in autism.
Auditory mismatch impairments are characterized by core neural dysfunctions in schizophrenia
Reduced mismatch negativity is a well-established phenomenon in schizophrenia, but its underlying mechanisms are unclear. Using fMRI, Gaebler et al. reveal that auditory mismatch stimuli trigger multiple neural dysfunctions associated with schizophrenia. The fMRI response enables diagnostic separation of patients and controls with high accuracy, suggesting biomarker potential.
Shared dimensions of performance and activation dysfunction in cognitive control in females with mood disorders
Deficits in cognitive control may represent an endophenotype for mood disorders. Ryan et al. demonstrate impaired ‘Go/No Go’ task performance in women with major depressive disorder or bipolar disorder compared to controls. However, distinct disease and performance-related activation patterns are seen with functional MRI, suggesting that the impairments are not uniform.
Dorsal Column
Grey Matter
Hughlings Jackson on joking
Hughlings Jackson devoted his 1887 presidential address to the Medical Society of London to the psychology of joking. Based on an analysis of that lecture, York offers insights into Hughlings Jackson’s personality and ideas about neurophysiology, and comments on the continuing utility of Hughlings Jackson’s views on humour for physicians and patients.