2020-04-06, Sarmukadam, Kimaya, Bitsika, Vicki, Sharpley, Christopher F, McMillan, Mary M E, Agnew, Linda L

Although EEG connectivity data are often used to build models of the association between overt behavioural signs of Autism Spectrum Disorder (ASD) and underlying brain connectivity indices, use of a large number of possible connectivity methods across studies has produced a fairly inconsistent set of results regarding this association. To explore the level of agreement between results from five commonly-used EEG connectivity models (i.e., Coherence, Weighted Phased Lag Index- Debiased, Phase Locking Value, Phase Slope Index, Granger Causality), a sample of 41 young males with ASD provided EEG data under eyes-opened and eyes-closed conditions. There were relatively few statistically significant and/or meaningful correlations between the results obtained from the five connectivity methods, arguing for a re-estimation of the methodology used in such studies so that specific connectivity methods may be matched to particular research questions regarding the links between neural connectivity and overt behaviour within this population.

2021-03, Bitsika, Vicki, Sharpley, Christopher F, Mandy, Will, McMillan, Mary E, Agnew, Linda L

Background: Autistic girls’ change in salivary cortisol concentrations from morning to afternoon were compared with their parents’ own anxiety states as potential correlates of the autistic girls’ self-ratings of their anxiety and those given by their parents about their daughters’ anxiety.

Methods: Thirty-three autistic girls (6 yr to 10 yr, M = 8.21 yr, SD = 1.29 yr) and 19 autistic adolescent females (11 yr to 15 yr, M = 12.74 yr, SD = 1.52 yr) completed anxiety inventories about themselves and provided saliva samples in the morning and afternoon. Their mothers also rated their daughters’ anxiety and their own anxiety.

Results: There were no significant differences between mothers’ and daughters’ ratings of the latter’s GAD. The autistic girls’ self-ratings of their anxiety were more strongly influenced by their mothers’ anxiety in the younger girls, but more responsive to their own chronic stress state (i.e., cortisol) in the adolescent girls.

Conclusions: Mothers’ evaluations of their autistic daughters’ anxiety appear to be strongly influenced by their own anxiety. There was also some indication that autistic girls may disguise their anxiety.

2023-12, Sivarajah, Nivetha, Irranious, Jenevan A, Krishnamoorthy, Sivagini, Kalaineethan, Thayaparan, Kugathasan, Deluxeani, Sivanantham, Uventhikka, McMillan, Mary E, Ketheesan, Natkunam

Travel restrictions, pandemics, economic downturn, and increasing costs in organizing workshops all impact on face-to-face training of undergraduates planning to undertake research. The inability to obtain basic, first-hand information regarding research in practice causes undue stress for students and leads to unrealistic expectations regarding research projects. Here, we describe how a student initiated online workshop, co-designed by a group of undergraduate leaders in conjunction with a panel of international academic researchers, and enabled the delivery of an introductory workshop on research training to meet student needs. Post-workshop, over 80%–95% of the participants rated their understanding of different aspects of research in practice as either being good or excellent. The design of this workshop provides an innovative template, in particular for resource-restricted countries, on how student-initiated workshops with multi-institutional academic collaboration could enhance training in research practice.

2021-01, Sharpley, Christopher F, Bitsika, Vicki, McMillan, Mary E, Jesulola, Emmanuel, Agnew, Linda L

Background: Individual Burden of Illness for Depression (IBI-D) represents a method for assessing the degree to which depressive symptomatology reduces functioning. Although the IBI-D has been shown to provide more information than measures of depressive symptomatology alone, previous studies have relied upon participant self-reports, and have not included an objective measure of physiological functioning. Such an index might add to the validity and informational value of IBI-D data.

Methods: Responses to scales measuring depressive symptoms, functional impairment due to mental and physical health, and saliva samples were collected from 111 community volunteers from rural Australia. Saliva was assayed for cortisol and C-Reactive Protein concentrations, and the ratio of these was used as an indicator of the balance between the Hypothalamic-Pituitary-Adrenal axis and the inflammatory response from the immune system.

Results: Principal Components Analysis (PCA) produced two- and three-factor solutions from the psychological and biological data, and were used to form weighted models of two IBI-D equations. Stepwise regression analysis indicated that the addition of the biological index to the second IBI-D made a significant extra contribution to variance in depression score.

Limitations: No longitudinal data were collected, participants were from a single geo-cultural region, and were self-selecting. Clinician interviews might augment participant self-reports.

Conclusions: Valid assessment of the self-reported symptoms of depression provides one aspect of diagnostic information, but the addition of biological information can further inform clinicians and researchers about the effect that these symptoms have upon individual patient functioning.

2022-04, Sarmukadam, Kimaya, Bitsika, Vicki, Sharpley, Christopher F, McMillan, Mary M E, Agnew, Linda L

Several lines of research suggest that autism is a neurological phenomenon, but the precise associations between neurological activity and the key diagnostic symptoms of autism are yet to be completely clarified. This study examined EEG connectivity and Sensory Features (SF) in a sample of young autistic males by examining bi-directional neural connectivity between separate brain regions as the key potential correlate of SF. Forty male autistic participants aged between 6 and 17 years, with an IQ of at least 70, underwent EEG measurements of their Frontal, Occipital and Temporal region responses to low-, medium-, and high-intensity audiovisual stimulus conditions. EEG connectivity data were analysed via Granger Causality. SF was measured via parent responses about their sons on the Child Sensory Profile (2^nd ed.) (CSP-2). There were significant (p < .05) correlations between right hemisphere Frontal and Temporal connectivity and CSP-2 dominant scores, largely due to lower Temporal-to-Frontal than Frontal-to-Temporal connectivity. There were no significant correlations between general CSP-2 scores and EEG connectivity data collected during audiovisual stimuli. These results confirm and extend previous findings by adding bi-directional connectivity as an index of brain activity to other studies that used only uni-directional connectivity data when measuring SF. Although there may be a discrepancy between the kinds of information collected via instruments such as the CSP-2 and actual brain electrical connectivity across major regions, these results hold implications for the use of brain-training interventions with autistic boys.

2019, Hoang, Phuong, Gray, Peter, Walkden-Brown, Stephen W, McMillan, Mary, Gerber, Priscilla F, Reynolds, Paul

Haemorrhagic enteritis virus (HEV) causes clinical haemorrhagic enteritis in young poults and/or subclinical immunosuppression which is often associated with colibacillosis. This disease is controlled with live vaccines worldwide, however, importation of HEV vaccines or cells that support HEV propagation are not permitted in Australia. A major experiment in isolators was conducted to test the safety and efficacy of a putative HEV vaccine. The study had a factorial design with four factors namely vaccination age (28 and 42 days of age), vaccine dose (0, 10⁵, 10⁶, 10⁷ genomic copies of HEV vaccine), challenge with HEV (yes, no) and vaccination-challenge interval (7, 21 or 42 days). A total of 315 poults were used providing 6-8 birds per treatment combination. Turkey growth rate, mortality, pathological findings, anti-HEV antibodies and viral load were examined. Vaccination lead to significant increases in anti HEV antibody over the following 2-4 weeks. Overall, vaccination with 10⁶ and 10⁷ was protective against increase in relative splenic weight and splenic viral load in challenged birds. Clinical haemorrhagic enteritis was not induced by any treatment but there was an increased incidence of airsacculitis in groups receiving either HEV vaccine or challenge virus compared to the negative control birds (25.8-29.3% vs. 9.4%, P < 0.05). Growth rate, mortality and relative bursal weight were unaffected by vaccination. This laboratory level study indicates that the putative vaccine is safe and likely to be efficacious, but may cause elevated levels of airsacculitis. These findings require confirmation in larger scale field trials.

2019-10-02, Sarmukadam, Kimaya, Sharpley, Christopher, Bitsika, Vicki, Agnew, Linda, McMillan, Mary

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition, characterised by impairments in social communication and the presence of restricted and repetitive behaviours, activities, or interests. ‘Sensory Features’ (SF) are a key symptom of ASD, and affect 90-95% of individuals with ASD, manifesting as atypical behavioural, neurological, and self-regulatory responses to sensory stimuli in the environment. Although the overt behavioural characteristics of SF in people with ASD have been extensively investigated, internal neurophysiological processes of SF in the ASD population have been minimally explored. One method of identifying these internal neurophysiological processes associated with SF is by using electroencephalography (EEG) to measure the brain’s electrical activity, and the ways that regions of the brain communicate or ‘connect’ with each other. There is a paucity of research investigating the direct relationship between SF and brain neural connectivity in children and adolescents with ASD, and this issue was made the focus of this research. Therefore, the current study aimed to investigate the relationship between SF in the ASD population and neural connectivity via (i) analyses of five different types of EEG connectivity measurements based on resting EEG data during eyes-closed and eyes-opened conditions, and (ii) analysis of Granger Causality on naturalistic audiovisual low-, medium-, and high-intensity stimulus conditions. The current study also aimed to investigate whether there was a relationship between age and Granger Causality connectivity indices in the ASD sample.

Forty-one male participants aged between 6 and 17 years, with an IQ of at least 70 and who were diagnosed with ASD took part in the current study. Connectivity analysis (using five methods: Coherence, Weighted Phase Lag Index-Debiased, Phase Locking Value, Granger Causality, and Phase Slope Index) and subsequent statistical analyses (using Pearson product moment and Spearman correlations, MANOVA, and paired samples t-tests) were conducted on EEG data from these participants.

Results indicated (i) minimal agreement between functional and effective connectivity for eyes-closed and eyes-opened conditions, (ii) significant (p < .05) deficits in connectivity between right hemisphere frontal and temporal brain regions, and a lack of significant correlations between this connectivity and Sensory Quadrant data collected on the Child Sensory Profile ( 2^nded.) for audiovisual stimuli, (iii) no significant differences in connectivity between frontal and occipital regions for all resting and stimulus conditions, and (iv) no significant correlations between age and neural connectivity in frontal, temporal, and occipital regions in response to audiovisual stimuli.

The results from this research add to the current literature and provide more evidence of atypical neuronal communication, especially between frontal and temporal regions, in regards to SF in male children and adolescents with ASD. Further research using a consistent connectivity method to analyse the associations between EEG connectivity and naturalistic experimental stimuli may provide more meaningful insights and suggestions for neurophysiological interventions to reduce the adverse effects of SF in individuals with ASD.

2014, McMillan, Mary, Pereg, Lily

'Azospirillum brasilense' is a nitrogen fixing bacterium that has been shown to have various beneficial effects on plant growth and yield. Under normal conditions 'A. brasilense' exists in a motile flagellated form, which, under starvation or stress conditions, can undergo differentiation into an encapsulated, cyst-like form. Quantitative RT-PCR can be used to analyse changes in gene expression during this differentiation process. The accuracy of quantification of mRNA levels by qRT-PCR relies on the normalisation of data against stably expressed reference genes. No suitable set of reference genes has yet been described for A. brasilense. Here we evaluated the expression of ten candidate reference genes ('16S' 'rRNA', 'gapB', 'glyA', 'gyrA', 'proC', 'pykA', 'recA', 'recF', 'rpoD', and 'tpiA') in wild-type and mutant 'A. brasilense' strains under different culture conditions, including conditions that induce differentiation. Analysis with the software programs BestKeeper, NormFinder and GeNorm indicated that 'gyrA', 'glyA' and 'recA' are the most stably expressed reference genes in 'A. brasilense'. The results also suggested that the use of two reference genes ('gyrA and glyA') is sufficient for effective normalisation of qRT-PCR data.

2017, Sharpley, Christopher, Christie, David R H, Bitsika, Vicki, Agnew, Linda, Andronicos, Nicholas, McMillan, Mary, Richards, Timothy M

Cortisol is a neurohormone released after a cascade response to stressors that begins in the hypothalamus, moves to the pituitary gland, and then to the adrenals, which secrete cortisol into the bloodstream as the final stage in this cascade. Cortisol affects many physiological functions, including vital anti‐inflammatory and immunosuppressive actions, as well as metabolism and homeostasis. Consequently, a basal concentration of cortisol is required at all times but may become immediately elevated in response to physical or mental stressors, usually returning to basal levels later. Underneath this immediate response to stressors, cortisol displays a diurnal variation so that concentrations are at their apex about 45 min after waking in the morning and decrease to their nadir in the early evening, a process referred to as the diurnal fluctuation in cortisol. However, this variation may become dysregulated by chronic stress and instead become consistently elevated, resulting in hypercortisolemia, which is characterized by an ongoing elevated concentration of cortisol in the bloodstream that is associated with pain, fatigue, increased risk of heart disease, and the symptoms of anxiety, muscle wastage, and hyperglycemia.

2018-09, Sharpley, Christopher F, Christie, David R H, Bitsika, Vicki, Andronicos, Nicholas M, Agnew, Linda L, Richards, Timothy M, McMillan, Mary E

Purpose: Some prostate cancer (PCa) patients become clinically anxious or depressed after diagnosis and treatment. Some also show the physiological signs of chronic stress. However, there are currently no data describing how these particular patients might be identified at intake. This study tested the individual and combined predictive power of a psychological factor and a genetic factor as potential predictors of anxiety, depression, and chronic stress in a sample of PCa patients. Methods: Ninety-five PCa patients completed psychological inventories for anxiety, depression, and psychological resilience (PR) and also gave a saliva sample for cortisol and a mouthwash sample for genetic testing for the presence of the BDNF Val66Met polymorphism. Results: High PR patients had significantly lower anxiety and depression than low PR patients, but showed no significant differences in their salivary cortisol. Carriers of the Met allele of the BDNF Val66Met polymorphism had significantly higher salivary cortisol concentrations than patients who did not carry this allele. Conclusions: Each of these two factors may provide valuable information regarding the vulnerability of PCa patients to anxiety, depression, or chronic stress. Suggestions are made for their inclusion in clinical settings.