Volume 138, Issue 3, March 2015

This scientific commentary refers to ‘In vivo detection of nerve injury in familial amyloid polyneuropathy by magnetic resonance neurography’ by Kolmer et al. (10.1093/brain/awu344).

This scientific commentary refers to ‘Differential DNA methylation profiles of coding and non-coding genes define hippocampal sclerosis in human temporal lobe epilepsy’ by Miller-Delaney et al. (10.1093/brain/awu373).

This scientific commentary refers to ‘Imaging acetylcholinesterase density in peripheral organs in Parkinson’s disease with ¹¹C-donepezil PET’ by Gjerløff et al. (10.1093/brain/awu369).

This scientific commentary refers to ‘Independent information from cerebrospinal fluid amyloid-b and florbetapir imaging in Alzheimer's disease’ by Mattsson et al. (10.1093/brain/awu367).

A number of single gene disorders share clinical and MRI characteristics with multiple sclerosis and may be overlooked in the differential diagnosis. Weisfeld-Adams et al. review features that should serve as ‘red flags’, alerting clinicians to the possibility of specific Mendelian or mitochondrial disorders in patients with suspected multiple sclerosis.

Preusser et al. use MRI-based lesion-symptom mapping to confirm the causal role of a ventral pathway in the perception of touch. This pathway originates downstream of the postcentral gyrus in the parietal operculum, passes the insula and the putamen, before terminating in white matter projections extending to inferior lateral prefrontal cortex.

See Morrow and Reilly (doi:10.1093/awu396) for a scientific commentary on this article.

Transthyretin familial amyloid polyneuropathy is a rare, autosomal-dominant multisystem disorder. Kollmer et al. show that high-resolution MR-neurography can quantify and localize lower limb nerve injury in vivo, both in symptomatic patients and in asymptomatic mutation carriers. Lesions appear at thigh-level and are predominantly proximal, although symptoms start and prevail distally.

Santarelli et al. reveal that hearing impairments in patients carrying OPA1 missense mutations are the result of disordered synchrony in auditory nerve fibre activity owing to degeneration of terminal dendrites. Cochlear implantation improves speech perception and synchronous activation of auditory pathways in these patients by bypassing the lesion site.

Understanding the organisation of human spinal locomotor circuitry after severe CNS damage is essential for improving neurorehabilitation strategies. Danner et al. present evidence of flexibly organised burst-generating elements within the functionally isolated human lumbosacral spinal cord that generate rhythmic patterns in response to constant, repetitive epidural stimulation.

Foot drop and toe walking are common in cerebral palsy. Willerslev-Olsen et al. report that four weeks of daily training on a treadmill with an incline boosts corticospinal transmission to ankle dorsiflexors and improves gait in affected children. Improvements are greatest in those aged under 10 years.

Using integrated PET-MRI, Loggia et al. reveal elevated levels of the translocator protein (TSPO) in patients with chronic pain. As TSPO is a glial marker, these results provide the first demonstration of pain-related glial activation in humans. They also lend support to the pain-protective role of TSPO predicted by animal studies.

See Grote et al. (doi:10.1093/awu386) for a scientific commentary on this article.

Miller-Delaney et al. report the first genome-wide analysis of DNA methylation in the hippocampus of patients with temporal lobe epilepsy. They identify altered methylation profiles in protein-coding genes, reveal pathology grade-specific differences and identify methylation-sensitive non-coding RNAs. The findings increase understanding of mechanisms regulating coding/non-coding gene expression in epilepsy.

The presence of antibodies in the CSF is a hallmark of multiple sclerosis, but reasons for patient-to-patient differences in antibody levels remain largely unknown. In a genome-wide association screen of almost 7000 patients from 9 countries, Goris et al. identify six genetic variants that influence antibody levels and disease presentation.

Evidence exists that interferon-beta therapy can modulate inflammasome activity in multiple sclerosis. However, the role of inflammasomes in shaping the interferon-beta response is unclear. Malhotra et al. report that expression of the NLRP3 inflammasome and the related cytokine IL1B in blood cells discriminates between interferon-beta responders and non-responders.

See Stoessl (doi: 10:1093/awu392) for a scientific commentary on this article.

Parkinson's disease is associated with early parasympathetic dysfunction. Using 5-[¹¹C]-methoxy-donepezil PET, Gjerløff et al. demonstrate reduced acetylcholinesterase binding in the small intestine and pancreas of 12 patients with Parkinson's disease compared to matched controls. [¹¹C]donepezil PET could thus have validity for in vivo imaging of systemic parasympathetic function.

Using connectivity analyses based on functional MRI, Michely et al. investigate dopaminergic modulation of neural network dynamics involved in motor control in Parkinson’s disease. The findings provide insights into the pathophysiology underlying bradykinesia and deficits in executive function, and help to explain why dopaminergic treatments have a greater effect on the former.

Weiss et al. demonstrate maladaptive cortical activity and large-scale cortico-cortical synchronization in Parkinson’s disease, and its modulation by subthalamic stimulation. Stimulation facilitates cortical movement-related processing, and decouples motor-inhibitory cortical oscillators from the processing stream. Both sets of changes to network function predict clinical improvements in response to subthalamic stimulation.

Using DTI, Chang et al. reveal reduced white matter connectivity among major speech-language regions in young children who stutter compared to age-matched peers. Greater stuttering severity is associated with greater reduction in connectivity. These findings provide the first glimpses into the neuroanatomical deficits that may underlie early childhood stuttering.

Speech production is a remarkable motor feat, but how the brain orchestrates articulators to produce fluent, well-intonated speech is unclear. Neef et al. verify the proposed uncoupling of motor output cells from motor plan cells in left primary motor cortex in fluent speech, and reveal its disruption in stuttering.

In a controlled, prospective, electrophysiological study, Imbach et al. demonstrate increased sleep need and excessive daytime sleepiness 6 months after traumatic brain injury. Sleep is more consolidated after brain trauma, and an increase in sleep need is associated with intracranial haemorrhage. Trauma patients underestimate their increased sleep need and sleepiness.

Microvascular ischaemic disease increases the risk of clinical stroke and results in subclinical damage to white matter. Using post-mortem tissue, Hinman et al. reveal increased nodal and paranodal length in axons adjacent to lacunar infarcts and microinfarcts, indicating altered distribution of molecules required for saltatory conduction and axon–oligodendrocyte signalling.

Visual neglect can persist for extended periods after stroke. In a longitudinal MRI/DTI study of patients with unilateral right-hemisphere stroke, Lunven et al. confirm the role of fronto-parietal disconnection in the emergence and persistence of neglect, and suggest that caudal interhemispheric disconnection can contribute to neglect chronicity.

Vemuri et al. show that amyloid and vascular pathologies are independent processes, and that both are major drivers of cognitive decline in the elderly. Cognitive reserve as measured by educational/occupational level and mid/late-life cognitive activity seems to offset the deleterious effects of both pathologies on cognitive trajectories.

See Fagan (doi:10.1093/awu387) for a scientific commentary on this article.

CSF and PET biomarkers of β-amyloid are not always fully congruent. Mattsson et al. reveal that the markers provide partly independent information in Alzheimer's disease. CSF biomarkers may be more sensitive to early stages of disease pathogenesis, while PET imaging may reflect downstream pathology.

Marko et al. show that during motor learning, children with autism are more sensitive to proprioceptive error and less sensitive to visual error than controls. These altered patterns of error sensitivity predict the volume of the anterior cerebellum—which supports this learning—and may affect the development of motor control.

Banca et al. investigate the neural correlates of symptom generation and mechanisms leading to compulsive avoidance behaviours in OCD. Using brain imaging, they detect a dual dissociation between cortical and striatal activity during symptom provocation, suggesting an imbalance in circuitry underlying habitual and goal-directed action control that may contribute to compulsivity.

Schott examines the ability of pictures to evoke empathy, and the controversy over whether mirror neurons are implicated in this process. Focusing on pictures of pain, he argues that both mirror neuron and other networks can be engaged, and that pictures can be valuable tools in the study of pain.