Volume 141, Issue 11, November 2018

This scientific commentary refers to ‘De novo PHACTR1 mutations in West syndrome and their pathophysiological effects’, by Hamada et al. (doi:10.1093/brain/awy246).

This scientific commentary refers to ‘Brain and retinal atrophy in African-Americans versus Caucasian-Americans with multiple sclerosis: a longitudinal study’, by Gonzalez Caldito et al. (doi:10.1093/brain/awy245).

This scientific commentary refers to ‘LGI1 antibodies alter K_v1.1 and AMPA receptors changing synaptic excitability, plasticity and memory’, by Petit-Pedrol et al. (doi:10.1093/brain/awy253).

This scientific commentary refers to ‘Robust EEG-based cross-site and cross-protocol classification of states of consciousness’, by Engemann et al. (doi:10.1093/brain/awy251).

See Eid et al. (doi:10.1093/brain/awy272) for a scientific commentary on this article.

West syndrome is characterized by infantile spasms with intellectual disability. Hamada et al. identify two de novo heterozygous missense mutations in PHACTR1 in affected individuals. In vivo and in vitro analyses suggest that PHACTR1 mutations cause morphological and functional defects in cortical neurons during brain development.

See Aly and Korn (doi:10.1093/brain/awy269) for a scientific commentary on this article.

African Americans with multiple sclerosis demonstrate higher inflammatory disease activity and poorer prognosis than Caucasian Americans. Gonzalez Caldito et al. report that African Americans patients exhibit faster rates of brain and retinal tissue loss, emphasizing the need for future studies involving this group to identify individual differences in treatment responses.

Frigerio et al. report that pro-resolving mechanisms of neuroinflammation are dysregulated during epileptogenesis, thereby promoting a persistent neuroinflammatory response that contributes to seizure generation and cognitive deficits. Boosting endogenous resolution responses by administering a specific lipid mediator improves disease outcomes in a murine epilepsy model, suggesting a novel treatment avenue.

See Debanne and El Far (doi:10.1093/brain/awy271) for a scientific commentary on this article.

Anti-LGI1 encephalitis is the most frequent cause of autoimmune limbic encephalitis, but the antibody-related mechanisms are unclear. Petit-Pedrol et al. demonstrate in a mouse model of cerebroventricular antibody transfer that anti-LGI1 antibodies cause impairment of memory and plasticity, neuronal hyperexcitability, and decreased levels of Kv1.1 potassium channels and AMPA receptors.

HCN channels are activated by hyperpolarization, and help to control neuronal excitability. Marini et al. describe how de novo or inherited missense variants leading to loss- or gain-of-function of HCN1 are associated with a wide range of seizure disorders ranging from lethal neonatal epilepsy to benign generalized epilepsy.

See Sokoliuk and Cruse (doi:10.1093/brain/awy267) for a scientific commentary on this article.

Detecting awareness in patients who recover from coma but remain behaviourally unresponsive is a major challenge. Engemann, Raimondo et al. demonstrate that machine learning on EEG signals enables robust classification of state-of-consciousness in data from brain-injured patients in multiple hospitals.

Le Heron et al. demonstrate, using behavioural, physiological and imaging techniques, converging evidence that reduced reward sensitivity underlies apathy in patients with a monogenic form of cerebral small vessel disease. This specific change in effort-based decision making points to potential treatment avenues for apathy.

The pathological brain is characterized by distributed structural alterations in grey matter, which tend to follow identifiable network-like patterns. Cauda et al. investigate how different types of brain connectivity – functional, anatomical, genetic – guide the spread of structural alterations, and show that co-alterations are distributed according to brain connectivity constraints.

Roe et al. examine the time-course of biomarker changes during conversion to Clinical Dementia Rating >0. The rate of change of cognitive and structural, but not molecular, biomarkers is greater in those who progress versus do not progress. Molecular biomarkers may become abnormal earlier, consistent with theoretical models.

Avolitional tics in Tourette syndrome may be worsened by stress and triggered by social cues such as the facial expressions of others. Rae et al. show that during viewing of emotional faces, the insula is hyperactive in Tourette syndrome and displays increased functional connectivity with cortical and subcortical motor regions.

On the 150^th anniversary of Korbinian Brodmann’s birth, and the 100^th anniversary of his death, Zilles celebrates his pioneering role in brain mapping. With the aid of hitherto unpublished documents and figures, he explains the concepts behind Brodmann’s cytoarchitectonic maps and considers their impact on current neuroimaging approaches.