Volume 137, Issue 10, October 2014

This scientific commentary refers to ‘Autonomic dysfunction is a major feature of cerebellar ataxia, neuropathy, vestibular areflexia “CANVAS” syndrome’, by Wu et al. (doi: 10.1093/brain/awu196).

This scientific commentary refers to ‘TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment’, by Delplanque et al. (doi: 10.1093/brain/awu202).

This scientific commentary refers to ‘The modern pre-levodopa era of Parkinson's disease: insights into motor complications from sub-Saharan Africa’, by Cilia et al. (doi:10.1093/brain/awu195).

This scientific commentary refers to ‘Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study’, by Nombela et al. (doi: 10.1093/brain/awu201).

Based on the interpretation and reinterpretation of published functional neuroimaging and clinical neuropsychological data, Geranmayeh et al. argue that recovery from aphasic stroke may be due as much to the function of high-order, domain-general networks as to recovery of language-specific networks. This distinction has implications for rehabilitation.

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a recently recognised neurodegenerative ganglionopathy. Wu et al. report a high prevalence of autonomic dysfunction in 26 patients with CANVAS in New Zealand. The combination of ataxia and autonomic dysfunction makes CANVAS an important differential diagnosis for multiple system atrophy.

See La Spada (doi:10.1093/brain/awu217) for a scientific commentary on this article. Spinocerebellar ataxia 21 is an early-onset, slowly progressing ataxia with severe cognitive impairment and mental retardation, previously mapped to chromosome 7p. Using an expanded family pedigree, Delplanque et al. revise the disease locus to chromosome 1p36, and identify causative mutations in the gene encoding the transmembrane protein TMEM240.

Psychotic symptoms may occur along a continuum within the population. Van Lutterveld et al. reveal that individuals with non-clinical auditory verbal hallucinations (AVH) show a similar but less pronounced pattern of cortical thinning to that seen in patients with psychosis and AVH, suggesting a similar but milder underlying pathophysiology.

GNE myopathy is an adult-onset muscle disease caused by genetic defects in sialic acid biosynthesis. In a mouse model of the disorder, Yonekawa et al. reveal that sialic acid supplementation reduces muscle atrophy in aged symptomatic animals. The sialic acid glycoconjugate 6'-sialyllactose has greater therapeutic efficacy than free sialic acid.

Epilepsy is highly heritable, but its genetic architecture is poorly understood. Speed et al. estimate the number of susceptibility loci, show that common variants account for the majority of heritability, and demonstrate that epilepsy consists of genetically distinct subtypes. They conclude that gene-based prediction models may have clinical utility in first-seizure settings.

Ibrahim et al. use functional MRI and MEG to explore the effects of interictal epileptiform discharges on neurocognitive development. Discharges are both preceded and followed by changes in network topology. Children who are more resilient to these changes tend to possess more highly connected networks and to show better neuropsychological outcomes.

Oligoclonal bands in the cerebrospinal fluid are the most important immunological marker of multiple sclerosis. Whereas oligoclonal IgG bands have been intensively studied, little is known about intrathecal IgM antibodies. Using state-of-the-art technologies, including deep sequencing and single-cell PCR, Beltrán et al. identify novel features of the intrathecal IgM repertoire.

Sequence learning and execution are impaired in Parkinson’s disease. Herrojo Ruiz et al. record local field potentials in patients undergoing subthalamic deep brain stimulation while learning sensorimotor sequences. Good performance is associated with suppression of excessive beta-band synchronization prior to sequence boundaries, which may support the encoding of the most salient cues.

Delaying the initiation of levodopa has been proposed to reduce the risk of motor complications in Parkinson’s disease. In a 4-year multicentre study in Ghana, Cilia et al. find that motor fluctuations and dyskinesias are predicted by disease duration and levodopa dose, but not by the duration of levodopa therapy.

See Dujardin (doi:10.1093/brain/awu218) for a scientific commentary on this article. Nombela et al. present data from the ICICLE-PD study of cognition in newly diagnosed Parkinson’s disease. Consistent with the ‘Dual Syndrome’ hypothesis, impairments in executive function reflect a frontal dopaminergic syndrome modulated by COMT genotype, while visuospatial and memory deficits reflect disruption of temporo-parietal systems modulated by MAPT and APOE.

Stimulation of the pedunculopontine nucleus area (PPNa) can improve gait in Parkinson’s disease, but its effects on speech are uncertain. Pinto et al. observe a trend towards speech degradation following PPNa surgery (OFF stimulation). L-DOPA inhibits beneficial effects of subthalamic nucleus stimulation on speech: this interaction is unaffected by PPNa stimulation.

Using direct stimulation in patients undergoing awake mapping of gliomas, Tate et al. report a bilateral probabilistic map of cortical epicentres of brain functions, including sensorimotor and language. The data challenge classical theories, especially of Broca's area as a speech output region, and provide a distributed framework of neural networks.

Josephs et al. use a multi-modal approach to assess neuroanatomical and clinical changes over time in primary progressive apraxia of speech. They demonstrate that progressive atrophy of cortex, basal ganglia and midbrain accompanies the clinical progression, including the emergence of progressive supranuclear palsy five years post-onset in some subjects.

Using voxel-based lesion-symptom mapping in 96 acute left-hemisphere stroke patients, Hoeren et al. determine the lesion locations associated with deficits in the ability to imitate meaningless hand and finger postures, or to pantomime the use of tools. Imitation and pantomime depend on distinct dorsal and ventral processing streams.

Convergent evidence supports a role for anterior prefrontal cortex (PFC) in metacognition—the capacity to evaluate cognitive processes—but whether metacognition relies on global or domain-specific substrates is unknown. Fleming et al. report that patients with anterior PFC lesions show impaired perceptual metacognition despite intact memory metacognition, supporting a domain-specific account.

Barbey et al. investigate the neurobiology of social problem solving and its relation to psychometric intelligence, emotional intelligence, and personality in 144 patients with focal lesions. Results reveal the neural architecture of social problem solving and provide an integrative framework for understanding the social, psychometric, and emotional foundations of human intelligence.

Tau immunotherapy has potential for treating Alzheimer’s disease. Collin et al. show that an anti-Tau/pS422 antibody ameliorates Tau pathology in TauPS2APP transgenic mice. They demonstrate the presence of antibody inside neurons and propose that membrane-associated Tau/pS422 mediates antibody uptake into neurons. This mechanism may contribute to the efficacy of immunotherapy.

The neurobiological basis of fragmented sleep in ageing and Alzheimer’s disease is unknown. In this human clinicopathological study, Lim et al. show that a reduced number of galanin-immunoreactive neurons in the intermediate nucleus of the hypothalamus is accompanied by greater sleep fragmentation in older adults with and without Alzheimer’s disease.