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To evaluate the neural correlates of implicit processing of negative emotions in motor conversion disorder (CD) patients. An event related fMRI task was completed by 12 motor CD patients and 14 matched healthy controls using standardised stimuli of faces with fearful and sad emotional expressions in comparison to faces with neutral expressions. Temporal changes in the sensitivity to stimuli were also modelled and tested in the two groups. We found increased amygdala activation to negative emotions in CD compared to healthy controls in region of interest analyses, which persisted over time consistent with previous findings using emotional paradigms. Furthermore during whole brain analyses we found significantly increased activation in CD patients in areas involved in the 'freeze response' to fear (periaqueductal grey matter), and areas involved in self-awareness and motor control (cingulate gyrus and supplementary motor area). In contrast to healthy controls, CD patients exhibited increased response amplitude to fearful stimuli over time, suggesting abnormal emotional regulation (failure of habituation / sensitization). Patients with CD also activated midbrain and frontal structures that could reflect an abnormal behavioral-motor response to negative including threatening stimuli. This suggests a mechanism linking emotions to motor dysfunction in CD.

Individuals born very preterm (before 33 weeks of gestation, VPT) are at risk of damage to developing white matter, which may affect later cognition and behaviour. We used diffusion tensor MRI (DT-MRI) to assess white matter microstructure (fractional anisotropy; FA) in 80 VPT and 41 term-born individuals (mean age 19.1 years, range 17-22, and 18.5 years, range 17-22 years, respectively). VPT individuals were part of a 1982-1984 birth cohort which had been followed up since birth; term individuals were recruited by local press advertisement. General intellectual function, executive function and memory were assessed. The VPT group had reduced FA in four clusters, and increased FA in four clusters relative to the Term group, involving several association tracts of both hemispheres. Clusters of increased FA were associated with more severe neonatal brain injury in the VPT group. Clusters of reduced FA were associated with lower birth weight and perinatal hypoxia, and with reduced adult cognitive performance in the VPT group only. Alterations of white matter microstructure persist into adulthood in VPT individuals and are associated with cognitive function.

BackgroundDebilitating Symptom Complexes Attributed to Ticks (DSCATT) is a new term for an unexplained Australian syndrome—people who suffer from a chronic, multifaceted and debilitating illness, characteristically attributed to tick bites, but in a country without endemic Lyme disease. Despite the profound morbidity of DSCATT, no single causative agent has been identified and there are no recognised treatments for the illness at present. An increasing body of evidence shows psychological therapies such as Acceptance and Commitment Therapy (ACT) can be effective in reducing symptom-related disability and improving quality of life for other unexplained syndromes. Here we present a study protocol to assess the feasibility of an ACT-informed intervention for patients suffering from DSCATT, to be used adjunctively to their pre-existing healthcare. The study aims to assess the acceptability, practicality and demand for the treatment. Additionally, we will examine the effects of therapy on participants’ health and well-being, its safety, potential mediators of response to therapy and its preliminary cost-effectiveness.MethodsWe will assess the feasibility of a 32-week, randomised, waitlist-controlled, parallel convergent mixed-methods pilot trial for DSCATT. Participants will be randomised in a 1:1 ratio to receive either 16 sessions of ACT-informed therapy adjunctive to their pre-existing healthcare, delivered one-to-one with a trial therapist within a 20-week period or be assigned to the waitlist control group where they will continue their treatments as usual. We will collect quantitative and qualitative data to address study aims, with retention rate being the primary feasibility outcome.Ethics and disseminationThe study has ethical approval from Austin Health Human Research Ethics Committee (HREC). The outcomes will be published in peer-reviewed journals. Data from participants who have given extended consent will be available for other HREC-approved studies.Trial registration numberACTRN12623000372684, prospectively registered 13 April 2023, URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385579&isReview=true; the last participant is expected to complete in November 2026.

Sexual dimorphism in human brain structure is well recognised, but little is known about gender differences in white matter microstructure. We used diffusion tensor imaging to explore differences in fractional anisotropy (FA), an index of microstructural integrity. A whole brain analysis of 135 matched subjects (90 men and 45 women) using a 1.5 T scanner. A region of interest (ROI) analysis was used to confirm those results where proximity to CSF raised the possibility of partial-volume artefact. Men had higher fractional anisotropy (FA) in cerebellar white matter and in the left superior longitudinal fasciculus; women had higher FA in the corpus callosum, confirmed by ROI. The size of the differences was substantial--of the same order as that attributed to some pathology--suggesting gender may be a potentially significant confound in unbalanced clinical studies. There are several previous reports of difference in the corpus callosum, though they disagree on the direction of difference; our findings in the cerebellum and the superior longitudinal fasciculus have not previously been noted. The higher FA in women may reflect greater efficiency of a smaller corpus callosum. The relatively increased superior longitudinal fasciculus and cerebellar FA in men may reflect their increased language lateralisation and enhanced motor development, respectively.

Sexual dimorphism in human brain structure is well recognised, but less is known about gender differences in white matter microstructure. We used diffusion tensor imaging to explore gender differences in fractional anisotropy (FA), an index of microstructural integrity. We previously found increased FA in the corpus callosum in women, and increased FA in the cerebellum and left superior longitudinal fasciculus (SLF) in men, using a whole-brain voxel-based analysis. A whole-brain tract-based spatial statistics analysis of 120 matched subjects from the previous analysis, and 134 new subjects (147 men and 107 women in total) using a 1.5T scanner, with division into tract-based regions of interest. Men had higher FA in the superior cerebellar peduncles and women had higher FA in corpus callosum in both the first and second samples. The higher SLF FA in men was not found in either sample. We confirmed our previous, controversial finding of increased FA in the corpus callosum in women, and increased cerebellar FA in men. The corpus callosum FA difference offers some explanation for the otherwise puzzling advantage in inter-callosal transfer time shown in women; the cerebellar FA difference may be associated with the developmental motor advantage shown in men.

Pre-clinical models, postmortem and neuroimaging studies all support a role for muscarinic receptors in the molecular pathology of schizophrenia. From these data it was proposed that activation of the muscarinic M1 and/or M4 receptor would reduce the severity of the symptoms of schizophrenia. This hypothesis is now supported by results from two clinical trials which indicate that activating central muscarinic M1 and M4 receptors can reduce the severity of positive, negative and cognitive symptoms of the disorder. This review will provide an update on a growing body of evidence that argues the muscarinic M1 and M4 receptors have critical roles in CNS functions that are dysregulated by the pathophysiology of schizophrenia. This realization has been made possible, in part, by the growing ability to visualize and quantify muscarinic M1 and M4 receptors in the human CNS using molecular neuroimaging. We will discuss how these advances have provided evidence to support the notion that there is a sub-group of patients within the syndrome of schizophrenia that have a unique molecular pathology driven by a marked loss of muscarinic M1 receptors. This review is timely, as drugs targeting muscarinic receptors approach clinical use for the treatment of schizophrenia and here we outline the background biology that supported development of such drugs to treat the disorder.

Background Functional gait disorder is a common presentation of functional neurological disorder. Altered gait is the defining feature, along with a range of associated motor and nonmotor symptoms. The aim of this study was to explore the prevalence and impact of these symptoms in people with functional gait disorder. Methods A total of 156 people with functional gait disorder completed an online survey that included demographic information, self‐reported symptoms, and standardized questionnaires. Results Weakness (85.9%) and reduced balance (80.1%) were the most prevalent motor symptoms, while fatigue (85.9%), somatosensory (69.9%), and cognitive (69.9%) symptoms were the most prevalent nonmotor symptoms. Logistic regression indicated that dependent ambulation had the greatest association with fear of falling and functional seizures (X2 (11, n = 128) = 40.68, p < 0.001). Stepwise regression indicated that functional seizures, muscle rigidity, depression, fear of falling, pain, and speech symptoms were associated with reduced participation in work and social function (adjusted R2 = 0.39, F (6, 120) = 14.31, p < 0.001). Stepwise regression revealed that lower physical quality of life was associated with pain, bradykinesia, fatigue, and dystonia (adjusted R2 = 0.32, F (4, 122) = 15.92, p < 0.001) while depression, anxiety, and functional seizures were associated with reduced mental quality of life (adjusted R2 = 0.46, F (3, 123) = 36.89, p < 0.001). Conclusions Motor and nonmotor symptoms are highly prevalent in people with functional gait disorder and are associated with high levels of disability, reduced participation in work and social function, and reduced quality of life.

Functional neurological disorder (FND) is a common and disabling disorder that is often considered difficult to treat, particularly in adults. Psychological therapies are often recommended for FND. Outcome research on psychological therapies for FND has grown in recent years but has not been systematically evaluated since 2005. This study aims to build on that by systematically reviewing the evidence-base for individual outpatient cognitive behavioural and psychodynamic psychotherapies for FND. Medical databases were systematically searched for prospective studies of individual outpatient psychotherapy for FND with at least five adult participants. Studies were assessed for methodological quality using a standardised assessment tool. Results were synthesised, and effect sizes calculated for illustrative purposes. The search strategy identified 131 relevant studies, of which 19 were eligible for inclusion: 12 examining cognitive behavioural therapy (CBT) and 7 investigating psychodynamic therapy (PDT). Eleven were pre–post studies and eight were randomised controlled trials. Most studies recruited a single symptom-based subtype rather than all presentations of FND. Effect sizes, where calculable, showed generally medium-sized benefits for physical symptoms, mental health, well-being, function and resource use for both CBT and PDT. Outcomes were broadly comparable across the two therapy types, although a lack of high-quality controlled trials of PDT is a significant limitation, as is the lack of long-term follow-up data in the majority of identified CBT trials. In conclusion, both CBT and PDT appear to potentially offer some benefit for FND, although better quality studies are needed.

Background Debilitating Symptom Complexes Attributed to Ticks (DSCATT) is a chronic, debilitating illness associated with tick bites in Australia. DSCATT is of unknown aetiology, can impact emotional well‐being and has no recognised treatments. Objective The development and piloting of a novel psychotherapeutic adjunctive intervention for DSCATT that aimed to increase daily functioning, improve quality of life and reduce the impact of symptoms in people with DSCATT. Methods This is a single‐site, intervention development and acceptability study. The intervention was developed iteratively according to a Human‐Centred Design (HCD) approach and manualised across four phases, with input from end users at each phase: qualitative interviews, development of the intervention, piloting, and revising and refining the intervention. Acceptability of the prototype intervention was evaluated through thematic template analysis of exit interviews. Self‐report measures were completed before and after intervention delivery. Results Following qualitative interviews with 13 participants (11 females and 2 males; aged 35–70 years), the intervention was informed by an Acceptance and Commitment Therapy (ACT) model interwoven with cognitive and behavioural strategies that targeted DSCATT‐specific difficulties. The manualised intervention consisted of 12 1‐h weekly individual sessions, delivered by psychologists via Telehealth (video call or telephone). Modules addressed the six core psychological processes of ACT, alongside DSCATT‐specific modules addressing cognitive function, sleep and social relationships. Pilot testing and follow‐up interviews were conducted in a separate sample of six individuals with DSCATT (all females; aged 46–71 years). All participants reported that the approach benefited their emotional well‐being and overall health and would recommend it to others with DSCATT. Conclusions This is a novel and theoretically driven psychotherapeutic intervention for DSCATT, co‐produced with patient involvement across four phases. Pilot testing suggested the manualised intervention was feasible and acceptable, supporting future evaluation of feasibility and treatment outcomes with randomised controlled trials. Patient or Public Contribution This study involved the engagement and participation of individuals with DSCATT across four stages of the project, according to an HCD approach—the choice of the intervention; the development of the intervention; the piloting of the intervention, and the assessment of the intervention. Trial Registration The pilot study component of this project was prospectively registered on the Australian and New Zealand Clinical Trial Registry (ANZCTR); trial ID: ACTRN12621001032842.