Volume 138, Issue 2, February 2015

This scientific commentary refers to ‘Physical activity and risk of Parkinson's disease in the Swedish National March Cohort’ by Yang et al. (doi:10.1093/brain/awu323).

This scientific commentary refers to ‘Targeting pharmacoresistant epilepsy and epileptogenesis with a dual-purpose antiepileptic drug’ by Doeser et al. (doi: 10.1093/brain/awu339).

This scientific commentary refers to ‘A network centred on the inferior frontal cortex is critically involved in levodopa-induced dyskinesias’ by Cerasa et al. (doi: 10.1093/brain/awu329).

This scientific commentary refers to ‘Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome’ by Worbe et al. (doi:10.1093/brain/awu311).

Congenital myopathies are traditionally defined by the underlying gene mutation and by characteristic histological features in the muscle biopsy. Ravenscroft et al. propose that it may be more informative to study these myopathies on the basis of their underlying pathophysiological mechanisms to establish commonalities across traditional histological and genetic boundaries.

Physical exercise has been suggested to be neuroprotective in the nigrostriatal system. Yang et al. prospectively investigate the association between physical activity and Parkinson’s disease risk in 43 368 Swedish subjects. They show that increased levels of physical activity are associated with a lower risk of Parkinson’s disease.

See Tanner and Comella (doi:10.1093/brain/awu351) for a scientific commentary on this article.

Inherited ataxias are difficult to diagnose genetically. Pyle et al. use whole-exome sequencing to provide a likely molecular diagnosis in 14 of 22 families with ataxia. The approach reveals de novo mutations, broadens the phenotype of other disease genes, and is equally effective in young and older-onset patients.

Adult-onset genetic leukoencephalopathies are rare and heterogeneous disorders. Ayrignac et al. identify 154 patients using an MRI pattern-based algorithm that focuses on the presence of vascular or cavitary lesions. They are able to verify the diagnosis genetically in 64% of cases, confirming the value of the MRI classification system.

Rossor et al. report the clinical characteristics of the largest cohort to date of individuals with spinal muscular atrophy caused by mutations in the gene encoding the dynein adaptor protein BICD2. Individuals develop characteristic early-onset lower limb wasting that allows for targeted genetic testing and interpretation of next-generation sequencing data.

Maarbjerg et al. perform the first blinded 3.0 Tesla MRI study of a large cohort of classical trigeminal neuralgia patients with unilateral symptoms. Neurovascular contact is prevalent on both symptomatic and asymptomatic sides, but contact causing displacement or atrophy of the trigeminal nerve is significantly more common on the symptomatic side.

Machado-Joseph disease is a neurodegenerative disorder associated with mutant ataxin-3 inclusions and atrophy of the cerebellum. Mendonça et al. reveal that transplantation of cerebellar neural stem cells into the cerebellum of adult Machado-Joseph disease transgenic mice alleviates the disease phenotype, and exerts neuroprotective effects.

Why seizures arise from normal-appearing human cortex is unclear. Using a pairwise transcriptional method to compare high and low-spiking tissues from patients with epilepsy, Dachet et al. generate a ‘cellular interactome’ that reveals millimetre-sized ‘microlesions’ in deeper cortical layers of high-spiking regions. These layer-specific abnormalities may underlie many ‘non-lesional’ forms of epilepsy.

Pharmacoresistance is common in epilepsy. Doeser et al. reveal that the active metabolite of eslicarbazepine acetate can overcome a common pharmacoresistance mechanism to show sustained efficacy in chronic human and experimental epilepsy in vitro. Eslicarbazepine acetate also inhibits progression of experimental epilepsy in vivo, implying both anticonvulsant and antiepileptogenic effects.

See Lerche (doi:10.1093/brain/awu357) for a scientific commentary on this article.

In a randomized double-blind placebo-controlled trial, O’Gorman et al. show that administration of erythropoietin within the first 42 hours after preterm birth improves white matter development in preterm infants. Improvements are seen in the corpus callosum, the anterior and posterior limbs of the internal capsule, and the corticospinal tract bilaterally.

Skripuletz et al. show that exogenous CDP-choline enhances CNS remyelination in two different mouse models of multiple sclerosis. The substance acts via the choline metabolic pathway and has the potential to enter clinical trials in the near future, having already shown a robust safety profile in more than 11 000 individuals.

The pathophysiological mechanisms of levodopa-induced dyskinesias (LIDs) in Parkinson’s disease are a matter of debate. Combining functional neuroimaging and repetitive TMS, Cerasa et al. provide evidence that LIDs result from reduced inhibitory control mediated by inferior frontal cortex. The findings open up new possibilities for the development of therapeutic tools.

See Rothwell and Obeso (doi:10.1093/brain/awu365) for a scientific commentary on this article.

Bolognini et al. report that transcranial electrical stimulation of the left posterior parietal lobe improves left-hand ideomotor apraxia in patients with left-hemisphere damage. The time required for the planning, but not execution, of gesture imitation is reduced both in patients and in controls, with implications for the rehabilitation of apraxia.

Richetin et al. demonstrate that retroviral expression of the transcription factor NeuroD1 in neural progenitor cells of the adult mouse hippocampus promotes differentiation, maturation and synaptic integration of newborn granule cells in vivo. When applied to a mouse model of Alzheimer’s disease, the gene-targeting strategy abolishes hippocampus-dependent memory deficits.

Lagarde et al. reveal impairments in verbal concept formation in patients with frontal lobe dysfunction, emphasizing the need for integrity of the prefrontal–basal ganglia functional network. They further show that concept formation can be divided into two separate cognitive processes (“abstraction” and “linking”), supported by partially distinct neural networks.

See Jackson (doi:10.1093/brain/awu338) for a scientific commentary on this article.

The neural substrate of Gilles de la Tourette syndrome is unknown. Worbe et al. use probabilistic tractography to demonstrate widespread structural abnormalities in cortico-striato-pallido-thalamic white matter pathways—likely arising from abnormal brain development—in patients with this syndrome.

Using TMS and EEG, Radhu et al. reveal reductions in long-interval cortical inhibition specific to the dorsolateral prefrontal cortex in patients with schizophrenia compared to healthy subjects and individuals with obsessive-compulsive disorder (OCD). The absence of such changes in OCD confirms that reductions in inhibition are not a generalized deficit associated with severe psychopathology.