Sex-related patterns in the electroencephalogram and their relevance in machine learning classifiers.

Deep learning is increasingly being proposed for detecting neurological and psychiatric diseases from electroencephalogram (EEG) data but the method is prone to inadvertently incorporate biases from training data and exploit illegitimate patterns. The recent demonstration that deep learning can detect the sex from EEG implies potential sex-related biases in deep learning-based disease detectors for the many diseases with unequal prevalence between males and females. In this work, we present the male- and female-typical patterns used by a convolutional neural network that detects the sex from clinical EEG (81% accuracy in a separate test set with 142 patients). We considered neural sources, anatomical differences, and non-neural artifacts as sources of differences in the EEG curves. Using EEGs from 1140 patients, we found electrocardiac artifacts to be leaking into the supposedly brain activity-based classifiers. Nevertheless, the sex remained detectable after rejecting heart-related and other artifacts. In the cleaned data, EEG topographies were critical to detect the sex, but waveforms and frequencies were not. None of the traditional frequency bands was particularly important for sex detection. We were able to determine the sex even from EEGs with shuffled time points and therewith completely destroyed waveforms. Researchers should consider neural and non-neural sources as potential origins of sex differences in their data, they should maintain best practices of artifact rejection, even when datasets are large, and they should test their classifiers for sex biases.

Shaping the Sensory-Motor Network by Short-Term Unresolvable Sensory-Motor Mismatch.

Learning from errors as the main mechanism for motor adaptation has two fundamental prerequisites: a mismatch between the intended and performed movement and the ability to adapt motor actions. Many neurological patients are limited in their ability to transfer an altered motor representation into motor action due to a compromised motor pathway. Studies that have investigated the effects of a sustained and unresolvable mismatch over multiple days found changes in brain processing that seem to optimize the potential for motor learning (increased drive for motor adaptation and a weakening of the current implementation of motor programs). However, it remains unclear whether the observed effects can be induced experimentally and more important after shorter periods. Here, we used task-based and resting-state fMRI to investigate whether the known pattern of cortical adaptations due to a sustained mismatch can be induced experimentally by a short (20 min), but unresolvable, sensory-motor mismatch by impaired facial movements in healthy participants by transient facial tapping. Similar to long-term mismatch, we found plastic changes in a network that includes the striatal, cerebellar and somatosensory brain areas. However, in contrast to long-term mismatch, we did not find the involvement of the cerebral motor cortex. The lack of the involvement of the motor cortex can be interpreted both as an effect of time and also as an effect of the lack of a reduction in the motor error. The similar effects of long-term and short-term mismatch on other parts of the sensory-motor network suggest that the brain-state caused by long-term mismatch can be (at least partly) induced by short-term mismatch. Further studies should investigate whether short-term mismatch interventions can be used as therapeutic strategy to induce an altered brain-state that increase the potential for motor learning.

Experiences from treating seven adult 5q spinal muscular atrophy patients with Nusinersen.

BACKGROUND: The antisense oligonucleotide Nusinersen recently became the first approved drug against spinal muscular atrophy (SMA). It was approved for all ages, albeit the clinical trials were conducted exclusively on children. Hence, clinical data on adults being treated with Nusinersen is scarce. In this case series, we report on drug application, organizational demands, and preliminary effects during the first 10 months of treatment with Nusinersen in seven adult patients. METHODS: All patients received intrathecal injections with Nusinersen. In cases with severe spinal deformities, we performed computed tomography (CT)-guided applications. We conducted a total of 40 administrations of Nusinersen. We evaluated the patients with motor, pulmonary, and laboratory assessments, and tracked patient-reported outcome. RESULTS: Intrathecal administration of Nusinersen was successful in most patients, even though access to the lumbar intrathecal space in adults with SMA is often challenging. No severe adverse events occurred. Six of the seven patients reported stabilization of motor function or reduction in symptom severity. The changes in the assessed scores did not reach a significant level within this short time period. CONCLUSIONS: Treating adult SMA patients with Nusinersen is feasible and most patients consider it beneficial. It demands a complex organizational and interdisciplinary effort. Due to the slowly decreasing motor functions in adult SMA patients, long observation phases for this recently approved treatment are needed to allow conclusions about effectiveness of Nusinersen in adults.

Antigen-induced arthritis in rats is associated with increased growth-associated protein 43-positive intraepidermal nerve fibres remote from the joint.

INTRODUCTION: Pain in arthritis may be experienced in regions outside the affected joint, and hyperalgesia may even be widespread. The spread of pain is usually attributed to mechanisms in the central nervous system. We investigated whether rats with antigen-induced arthritis (AIA) exhibit peripheral changes in skin innervation remote from the inflamed joint. METHODS: After immunization, unilateral AIA in the knee joint was induced in rats. Intraepidermal nerve fibre density was determined by immunohistochemical staining for protein gene product 9.5 (PGP 9.5) and for nerve fibres expressing calcitonin gene-related peptide (CGRP), substance P (SP), transient receptor potential vanilloid 1 (TRPV1; the heat and capsaicin receptor), ß-tubulin, and growth-associated protein 43 (GAP-43; a marker of regenerating nerve fibres) in paw pad skin and back skin. Cluster of differentiation 11b (CD11b)-positive macrophages and CD3-positive T cells were quantified in skin, and macrophages were quantified in the lumbar dorsal root ganglia. In addition, pain-related behaviour was assessed. RESULTS: Intraepidermal nerve fibre density (PGP 9.5) and the numbers of fibres expressing CGRP, SP, TRPV1, or ß-tubulin did not show a significant change in the acute (3 days) or chronic phase (21 days) of AIA compared with control rats that were only immunized. However, paw skin and back skin revealed a significantly higher number of nerve fibres expressing GAP-43 at both the acute and chronic stages of AIA. The skin of arthritic rats in these regions did not contain a greater density of CD11b and CD3 immune cells than the skin of control rats. Enhanced expression of GAP-43 in nerve fibres of the skin was not related to hyperalgesia in the joint, but it accompanied persistent secondary cutaneous hyperalgesia in the skin remote from the inflamed joint. CONCLUSIONS: Although the innervation of the skin remote from the joint did not show significant abnormalities of the other nerve fibre markers, the rapid and persistent increase of GAP-43 expression is conspicuous. The data suggest that immune-mediated arthritis is associated with changes in skin innervation remote from the inflamed joint, although the skin is not inflamed, which may contribute to symptoms in nonarticular tissue remote from the affected joint.