Volume 137, Issue 12, December 2014

This scientific commentary refers to ‘Neuroanatomical precursors of dyslexia identified from pre-reading through to age 11’ by Clark et al. (10.1093/brain/awu229).

This scientific commentary refers to ‘The nature of tremor circuits in parkinsonian and essential tremor’ by Cagnan et al. (10.1093/brain/awu250).

This scientific commentary refers to ‘Regional amyloid burden and intrinsic connectivity networks in cognitively normal elderly subjects’ by Lim et al. (doi:10.1093/brain/awu271).

This scientific commentary refers to ‘Unconscious relational encoding depends on hippocampus’ by Duss et al. (doi: 10.1093/brain/awu270).

Mutations in membrane-shaping proteins underlie many axonopathies: neurodegenerative disorders that primarily affect long axons of the CNS or PNS, and which include hereditary spastic paraplegias and sensory neuropathies. Hübner & Kurth review relevant genes and disease mechanisms, and propose that membrane-shaping disorders represent a continuous disease-spectrum of the axon.

Idiopathic REM sleep behaviour disorder is characterized by dream-enactment behaviour and loss of REM atonia, and is considered a prodromal symptom of Parkinson’s disease. Wu et al. identify an abnormal brain metabolic network associated with the disorder, and show that evolution of this network occurs with progression to Parkinson’s disease.

Vo et al. test a rare individual with widespread bilateral damage restricted to the dorsal striatum, and show that he is impaired at tasks that require stimulus-value learning, but can perform those that require action-value learning. The dorsal striatum may be necessary for stimulus-value but not action-value learning in humans.

See Goswami (doi:10.1093/brain/awu296) for a scientific commentary on this article.

Clark et al. present longitudinal MRI data from children at high risk of dyslexia, from before reading instruction began until after dyslexia was diagnosed. Prior to learning to read, children with dyslexia have thinner cortex in visual and auditory processing areas than controls, whereas the “reading network” itself is unaffected.

Recent studies have documented structural changes in the cerebellum in patients with essential tremor. Louis et al. study the structure of Purkinje cells in control brains and in those with essential tremor. They report a consistent pattern of abnormalities including reduced dendritic arborization and loss of dendritic spines.

Lin et al. reveal a reduction in climbing fibre-Purkinje cell synaptic density in postmortem essential tremor brains, and an increased proportion of synapses on Purkinje cell distal spiny branchlets rather than proximal dendrites. The proportion of distal synapses correlates inversely with tremor severity, suggesting preferential pruning of these synapses in severe essential tremor.

Homozygous mutations in BIN1 have been associated with severe autosomal recessive centronuclear myopathies. However, Böhm et al. now report heterozygous BIN1 mutations in patients with mild autosomal dominant centronuclear myopathies. BIN1 mutations act via distinct pathomechanisms to cause either severe recessive or mild dominant forms of disease.

Corrochano Sanchez et al. identify a novel mutation (I588V) in SCN4A, which encodes the Nav1.4 voltage-gated sodium channel, in a patient with myotonia and periodic paralysis. By generating and characterizing a mouse model (‘draggen’) carrying the equivalent point mutation (I582V), they uncover novel pathological and metabolic features of SCN4A channelopathies.

The impact of peripheral entrapment neuropathies on target innervation remains unknown. Using quantitative sensory testing, neurophysiology and skin biopsies, Schmid et al. demonstrate that carpal tunnel syndrome affects large fibres and their nodal complexes, but is also associated with a reduction in the number and functioning of small sensory axons.

Mitochondrial ophthalmoplegia is a genetically heterogeneous disorder. Horga et al. investigate whether peripheral neuropathy can predict the underlying genetic defect in patients with progressive external ophthalmoplegia. Results indicate that neuropathy is highly predictive of a nuclear DNA defect and that it is rarely associated with single mitochondrial DNA deletions.

Berg et al. report that complete remission of paediatric epilepsy occurs in about 60% of patients over the course of 20 years. This outcome can be predicted with fair accuracy based on initial clinical factors, and good accuracy based on early seizure outcomes over the first 2–5 years.

See Arkadir et al. (doi:10.1093/brain/awu285) for a scientific commentary on this article. The mechanisms underlying tremor generation remain unclear. Cagnan et al. use deep brain stimulation of the thalamus or subthalamic nucleus at/near a patient's own tremor frequency to investigate the networks responsible for parkinsonian and essential tremor. The results reveal differences in the circuitry underlying these two tremor types.

Humans heterozygous for a glucocerebrosidase (GBA) mutation show no signs of Gaucher disease, but are at increased risk of Parkinson’s disease. Fishbein et al. reveal that heterozygosity for the L444P Gba mutation disrupts α-synuclein degradation in mice, and exacerbates the phenotype of the A53T α-synuclein mouse model of Parkinson’s disease.

Butler et al. relate behavioural deficits in 31 patients with chronic stroke aphasia to underlying neural structures. Using principal components analysis, they reduce a neuropsychological battery to three independent dimensions: phonological, semantic and executive-cognition. Phonological and semantic processing are linked to dorsal and ventral pathway integrity, respectively

Baldassarre et al. present evidence that spontaneous brain activity provides a neural signature of spatial neglect after focal brain injury. Using resting state fMRI in a large sample of stroke patients, they show that attentional deficits correlate with abnormal interactions among large-scale networks, independently of lesion size.

Visual crowding is a perceptual phenomenon whereby recognition of a stimulus is disrupted by the presence of flanker stimuli. Yong et al. observe excessive crowding in individuals with a neurodegenerative condition (posterior cortical atrophy) and identify associations between prominent crowding and lower grey matter volume in the right collateral sulcus.

The role of autophagy in lipid turnover is largely unknown. Yang et al. reveal macroautophagy to be a route for delivering membrane lipids to lysosomes. They demonstrate defective lysosomal lipid clearance in an Alzheimer’s mouse model leading to lipid accumulation in autolysosomes, which can be prevented by enhancing lysosomal proteolysis.

Accumulation of amyloid-beta leads to loss of functional synapses in Alzheimer’s disease. Dorostkar et al. report that immunotherapy against oligomeric amyloid-beta in the Tg2576 mouse model attenuates synapse loss near plaques, and abolishes it elsewhere. Sequestering oligomeric amyloid-beta may counteract synaptic pathology, even while fibrillar amyloid load remains unchanged.

See Toga and Thompson (doi:10.1093/brain/awu276) for a scientific commentary on this article.

Hyun Kook Lim et al. investigate the relationship between amyloid burden and intrinsic functional connectivity in cognitively normal older adults. Individuals with amyloid deposition show aberrant functional connectivity in the default mode and central executive networks compared to those without detectable amyloid. Changes may reflect early deleterious effects of amyloid deposition.

Sporadic Creutzfeldt-Jakob disease (sCJD) is considered primarily a disease of grey matter. However, Caverzasi et al. now show a global decrease in mean diffusivity in white matter. The changes appear to be associated with reactive astrocytic gliosis and activated microglia, and suggest primary involvement of the white matter in sCJD.

See Mayes (doi:10.1093/brain/awu284) for a scientific commentary on this article.

The hippocampus is thought to support only conscious memory, while neocortex supports both conscious and unconscious memory. Duss et al. show that amnesic patients with damage to the hippocampal–anterior thalamic axis exhibit a diminished form of unconscious encoding and retrieval, suggesting that certain forms of unconscious memory are hippocampus-dependent.