Mirror neuron dysfunction in autism spectrum disorders

Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication and obsessive/stereotyped patterns of behaviour. Although there is no reliable neurophysiological marker associated with ASDs, dysfunction of the parieto-frontal mirror neuron system has been suggested as a disturbance linked to the disorder. Mirror neurons (MNs) are visuomotor neurons which discharge both when performing and observing a goal directed action. Research suggests MNs may have a role in imitation, empathy, theory of mind and language. Although the research base is small, evidence from functional MRI, transcranial magnetic stimulation, and an electroencephalographic component called the mu rhythm suggests MNs are dysfunctional in subjects with ASD. These deficits are more pronounced when ASD subjects complete tasks with social relevance, or that are emotional in nature. Promising research has identified that interventions targeting MN related functions such as imitation can improve social functioning in ASDs. Boosting the function of MNs may improve the prognosis of ASDs, and contribute to diagnostic clarity.

Modulation of putative mirror neuron activity by both positively and negatively valenced affective stimuli: a TMS study

Research indicates that mirror neurons are important for social cognition, including emotion processing. Emerging evidence, however, also reveals that emotional stimuli might be capable of modulating human mirror neuron system (MNS) activity.

The current study used transcranial magnetic stimulation (TMS) to assess putative mirror neuron function following emotionally evocative images in twenty healthy adults.

Participants observed videos of either a transitive hand action or a static hand while undergoing TMS of the primary motor cortex. In order to examine the effect of emotion on the MNS, each video was preceded by an image of either a positive, negative or neutral valence.

MNS activity was found to be augmented by both the positive and negative (relative to neutral) stimuli, thus providing empirical support for a bi-directional link between emotion and the MNS, whereby both positively and negatively valenced stimuli are capable of facilitating mirror neuron activity. The potential adaptive significance of this finding is discussed. 

Function and structure of the mirror neuron system in autism

 Utilizing MRI, this thesis identified wide-spread brain abnormalities in autism. White matter deficits were more pronounced in the left hemisphere, attributable to atypical myelination. Regarding the mirror neuron system, functional anomalies were situated in the right, dorsal, premotor cortex which further demonstrated reduced functional connectivity with the inferior parietal lobule.

Exploring associations between gaze patterns and putative human mirror neuron system activity

The human mirror neuron system (MNS) is hypothesized to be crucial to social cognition. Given that key MNS-input regions such as the superior temporal sulcus are involved in biological motion processing, and mirror neuron activity in monkeys has been shown to vary with visual attention, aberrant MNS function may be partly attributable to atypical visual input. To examine the relationship between gaze pattern and interpersonal motor resonance (IMR; an index of putative MNS activity), healthy right-handed participants aged 18-40 (n = 26) viewed videos of transitive grasping actions or static hands, whilst the left primary motor cortex received transcranial magnetic stimulation. Motor-evoked potentials recorded in contralateral hand muscles were used to determine IMR. Participants also underwent eyetracking analysis to assess gaze patterns whilst viewing the same videos. No relationship was observed between predictive gaze and IMR. However, IMR was positively associated with fixation counts in areas of biological motion in the videos, and negatively associated with object areas. These findings are discussed with reference to visual influences on the MNS, and the possibility that MNS atypicalities might be influenced by visual processes such as aberrant gaze pattern.

Emotion processing fails to modulate putative mirror neuron response to trained visuomotor associations

Recent neuroimaging studies have demonstrated that activation of the putative human mirror neuron system (MNS) can be elicited via visuomotor training. This is generally interpreted as supporting an associative learning account of the mirror neuron system (MNS) that argues against the ontogeny of the MNS to be an evolutionary adaptation for social cognition. The current study assessed whether a central component of social cognition, emotion processing, would influence the MNS activity to trained visuomotor associations, which could support a broader role of the MNS in social cognition. Using functional magnetic resonance imaging (fMRI), we assessed repetition suppression to the presentation of stimulus pairs involving a simple hand action and a geometric shape that was either congruent or incongruent with earlier association training. Each pair was preceded by an image of positive, negative, or neutral emotionality. In support of an associative learning account of the MNS, repetition suppression was greater for trained pairs compared with untrained pairs in several regions, primarily supplementary motor area (SMA) and right inferior frontal gyrus (rIFG). This response, however, was not modulated by the valence of the emotional images. These findings argue against a fundamental role of emotion processing in the mirror neuron response, and are inconsistent with theoretical accounts linking mirror neurons to social cognition.

Optimal feature subset selection for neuron spike sorting using the genetic algorithm

It is crucial for a neuron spike sorting algorithm to cluster data from different neurons efficiently. In this study, the search capability of the Genetic Algorithm (GA) is exploited for identifying the optimal feature subset for neuron spike sorting with a clustering algorithm. Two important objectives of the optimization process are considered: to reduce the number of features and increase the clustering performance. Specifically, we employ a binary GA with the silhouette evaluation criterion as the fitness function for neuron spike sorting using the Super-Paramagnetic Clustering (SPC) algorithm. The clustering results of SPC with and without the GA-based feature selector are evaluated using benchmark synthetic neuron spike data sets. The outcome indicates the usefulness of the GA in identifying a smaller feature set with improved clustering performance.

A monster that lives in our lives: experiences of caregivers of people with motor neuron disease and identifying avenues for support

BACKGROUND: A developing body of evidence has provided valuable insight into the experiences of caregivers of people with motor neuron disease; however, understandings of how best to support caregivers remain limited. AIM: This study sought to understand concepts related to the motor neuron disease caregiver experience which could inform the development of supportive interventions.

DESIGN: A qualitative thematic analysis of a one-off semistructured interview with caregivers was undertaken.

SETTING/PARTICIPANTS: Caregivers of people with motor neuron disease were recruited from a progressive neurological diseases clinic in Melbourne, Australia.

RESULTS: 15 caregivers participated. Three key themes were identified: (1) The Thief: the experience of loss and grief across varied facets of life; (2) The Labyrinth: finding ways to address ever changing challenges as the disease progressed; (3) Defying fate: being resilient and hopeful as caregivers tried to make the most of the time remaining.

CONCLUSIONS: Caregivers are in need of more guidance and support to cope with experiences of loss and to adapt to changeable care giving duties associated with disease progression. Therapeutic interventions which target these experiences of loss and change are worth investigation.

Identification and outcomes of clinical phenotypes in amyotrophic lateral sclerosis/motor neuron disease: Australian National Motor Neuron Disease observational cohort

OBJECTIVE: To capture the clinical patterns, timing of key milestones and survival of patients presenting with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) within Australia.

METHODS: Data were prospectively collected and were timed to normal clinical assessments. An initial registration clinical report form (CRF) and subsequent ongoing assessment CRFs were submitted with a completion CRF at the time of death.

DESIGN: Prospective observational cohort study.

PARTICIPANTS: 1834 patients with a diagnosis of ALS/MND were registered and followed in ALS/MND clinics between 2005 and 2015.

RESULTS: 5 major clinical phenotypes were determined and included ALS bulbar onset, ALS cervical onset and ALS lumbar onset, flail arm and leg and primary lateral sclerosis (PLS). Of the 1834 registered patients, 1677 (90%) could be allocated a clinical phenotype. ALS bulbar onset had a significantly lower length of survival when compared with all other clinical phenotypes (p<0.004). There were delays in the median time to diagnosis of up to 12 months for the ALS phenotypes, 18 months for the flail limb phenotypes and 19 months for PLS. Riluzole treatment was started in 78-85% of cases. The median delays in initiating riluzole therapy, from symptom onset, varied from 10 to 12 months in the ALS phenotypes and 15-18 months in the flail limb phenotypes. Percutaneous endoscopic gastrostomy was implemented in 8-36% of ALS phenotypes and 2-9% of the flail phenotypes. Non-invasive ventilation was started in 16-22% of ALS phenotypes and 21-29% of flail phenotypes.

CONCLUSIONS: The establishment of a cohort registry for ALS/MND is able to determine clinical phenotypes, survival and monitor time to key milestones in disease progression. It is intended to expand the cohort to a more population-based registry using opt-out methodology and facilitate data linkage to other national registries.