Biology subjects

Velakoulis, D.

Publications and source records attributed to Velakoulis, D..

6 recordsLinked to original sources

bioRxiv2023

Plasma neurofilament light protein provides evidence of accelerated brain ageing in treatment-resistant schizophrenia

BackgroundAccelerated brain aging has been observed across multiple psychiatric disorders. Blood markers of neuronal injury such as Neurofilament Light (NfL) protein may therefore represent biomarkers of accelerated brain aging in these disorders. The current study aimed to examine whether relationships between age and plasma NfL were increased in individuals with primary psychiatric disorders compared to healthy individuals. MethodsPlasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), a large reference normative healthy control (HC) group (n= 1,926) and a locally-acquired HC sample (n = 59). A general linear model (GLM) was used to examine diagnosis by age interactions on NfL z-scores using the large normative HC sample as a reference group. Significant results were then validated using the locally-acquired HC sample. Resultsa GLM identified a significant age by diagnosis interaction for TRS vs HCs and BPAD vs HCs. Post hoc analyses revealed a positive correlation between NfL levels and age among individuals with TRS, whereas a negative correlation was found among individuals with BPAD. However, only the TRS findings were replicated using the locally-acquired HC sample. Post hoc analyses revealed that individuals with TRS aged <40 had lower NfL levels compared to same-age HCs, whereas individuals with TRS aged >40 had higher NfL levels compared to same-age HCs. ConclusionsThese findings add to the growing literature supporting the notion of accelerated brain ageing in schizophrenia-spectrum disorders.

neuroscience↗

bioRxiv2020

Perceptual Degradation Affects Stop-Signal Performance in Normal Healthy Adults

During stop-signal task performance, little is known how the quality of visual information of the go stimuli may indirectly affect the interplay between the go and stop processes. In this study, we assessed how perceptual degradation of the visual go stimuli affect response inhibition. Twenty-six healthy individuals (mean age 33.34 {+/-} 9.61) completed a modified 12-minute stop-signal task, where V and Y letters were used as visual go stimuli. The stimuli were subjected to four levels of perceptual degradation using Gaussian smoothing, to parametrically manipulate stop difficulty across low, intermediate-1, intermediate-2 and high difficulty conditions. On 33% of trials, the stop-signal (50ms audio tone) followed a go stimulus after a stop-signal delay, which was individually adjusted for each participant. As predicted, we found that with increased level of stop difficulty (little perceptual degradation), reaction times on go trials and the proportion of successful behavioural inhibitions on stop trials (P(i)) decreased in normal healthy adults. Contrary to our predictions, there was no effect of increased stop difficulty on the number of correct responses on go trials and reaction times on stop trials. Overall, manipulation of the completion time of the go process via perceptual degradation has been partially successful, whereby increased stop difficulty differentially affected P(i) and SSRT. These findings have implications for the relationship between the go and stop processes and the horse-race model, which may be limited in explaining the role of various cortico-basal ganglia loops in modulation of response inhibition. HighlightsO_LIManipulation of the completion time of the go process is partially successful C_LIO_LIPerceptual degradation differentially affects stop-signal performance C_LIO_LIIncreased stop difficulty (easy go) results in lower P(i) C_LIO_LIIncreased stop difficulty (easy go) has no effect on SSRT C_LIO_LIHorse-race model does not fully explain basal ganglia involvement in inhibition C_LI

neuroscience↗

bioRxiv2019

Abbreviated assessment of psychopathology in patients with suspected seizure disorders

PurposePsychopathology is common in patients undergoing investigation for seizure-related disorders. Psychometric examination using self-report instruments, such as the SCL-90-R, can assist diagnosis. The SCL-90-R, however, is a lengthy instrument and might not be tolerated by all patients. We assessed several abbreviated forms of the SCL-90-R in patients undergoing video encephalographic monitoring (VEM).\n\nMethod687 patients completed the SCL-90-R and scores were computed for the full SCL-90-R and five abbreviated forms. Correlations and mean differences were computed between different forms. Classification accuracy was assessed via receiver operating characteristic (ROC) curves, and measurements models were examined using confirmatory factor analysis (CFA).\n\nResultsAll abbreviated forms were strongly correlated with the SCL-90-R for general psychopathology (r = .93 - .99), depression (r = .89 - .95), anxiety (r = .97 - .98), psychosis (r = .95 - .99), and obsessive-compulsive symptoms (r = .97). Classification performance was similar across forms for depression and anxiety, with high negative predictive values (.90 - .94) and lower positive predictive values (.34 - .38). Classification performance for psychotic and obsessive-compulsive disorders was poor. Differences were observed between the full SCL-90-R and its abbreviated forms across most domains (d = 0.00 - 0.65). The published measurement model was most strongly validated for the SCL-27, SCL-14, and the SCL-K-9.\n\nConclusionsThese five SCL-90-R abbreviated forms show high convergent validity with the full version. In patients undergoing investigation for seizure-related disorders, the BSI or BSI-18 are most appropriate where screening for both depression and anxiety is required. The SCL-K-9 is appropriate when only a single measure of global psychological distress is required. None of the instruments were able to detect psychotic or obsessive-compulsive symptoms with great accuracy. Caution should be exercised when making direct comparisons across the different forms.

neuroscience↗

bioRxiv2018

Compensation Related Utilization of Neural Circuits Hypothesis Model in Response Inhibition in Premanifest Huntington’s Disease

During premanifest stages of Huntingtons disease (pre-HD), individuals typically show increased functional brain activity thought to compensate for widespread brain anomalies. What remains unknown, is to disentangle whether increased functional brain activity reflects compensation or whether it is more of a product of HD-related pathological processes. We used a quantitative model of compensation, known as the CRUNCH (Compensation-Related Utilization of Neural Circuits Hypothesis) to characterise compensatory function in pre-HD using functional magnetic resonance imaging (fMRI). To test CRUNCH predictions, pre-HD individuals (n = 15) and age- and gender-matched controls (n = 15) performed a modified stop-signal task that incremented in four levels of stop difficulty (low, intermediate-1, intermediate-2, and high). Our results did not support the critical assumption of the CRUNCH model - controls did not show increased fMRI activity with increased level of stop difficulty. By contrast, controls showed decreased fMRI activity with increased stop difficulty in right inferior frontal gyrus pars triangularis and right caudate nucleus. Relative to controls, pre-HD individuals showed increased fMRI activity in right inferior frontal gyrus pars triangularis at intermediate-2 and high level of stop difficulty, which is the opposite effect to that predicted by the CRUNCH model. Contrary to the CRUNCH prediction, the pre-HD group showed decreased fMRI activity in right caudate nucleus at low level of stop difficulty, compared with controls. Further to this, fMRI activity patterns in right inferior frontal gyrus pars triangularis and right caudate nucleus were not accompanied by a decline in the number of successful behavioural stops in pre-HD. We therefore suggest that the CRUNCH model does not apply to characterise compensatory processes associated with response inhibition in pre-HD.\n\nHighlightsO_LICRUNCH does not apply to characterise compensation during stop-signal in pre-HD\nC_LIO_LIDeficits in inhibitory control in pre-HD occur 25 years prior to clinical diagnosis\nC_LIO_LICRUNCH may show signs of selective reporting\nC_LI

neuroscience↗

bioRxiv2018

To CRUNCH or not to CRUNCH: Task Difficulty Affects Functional Brain Reorganisation during Visuospatial Working Memory Performance in Premanifest Huntington’s Disease

Presymptomatic Huntingtons disease (pre-HD) individuals tend to increase functional brain activity to compensate for HD-related brain anomalies. We used a quantitative model of compensation, known as the CRUNCH (Compensation-Related Utilization of Neural Circuits Hypothesis) to explicitly characterise compensation in pre-HD. We acquired functionalmagnetic resonance imaging (fMRI) data (n = 15 pre-HD; n = 15 controls) during performance of an 18-minute fMRI visuospatial working memory task with low, intermediate-1, intermediate-2, and high memory loads. Consistent with the CRUNCH prediction, pre-HD individuals showed decreased fMRI activity in left intraparietal sulcus at high memory load, compared to healthy controls who showed increased fMRI activity in left intraparietal sulcus at high memory load. Contrary to the other CRUNCH prediction, the pre-HD group did not show compensatory increase in fMRI activity at lower levels of memory loads in left intraparietal sulcus. Our findings provide partial support for the validity of CRUNCH in pre-HD.\n\nHighlightsO_LIVisuospatial working memory deficits in pre-HD occur 25 years prior to predicted disease onset\nC_LIO_LITask demands differentially affect fMRI activity in left intraparietal sulcus\nC_LIO_LICRUNCH can partially apply in Huntingtons disease\nC_LI

neuroscience↗

bioRxiv2018

CSF biomarkers are differentially related to structural and functional changes in dementia of the Alzheimer’s type

The two cardinal pathologies of Alzheimers disease (AD) develop according to distinct anatomical trajectories. Cerebral tau-related pathology first accumulates in the mesial temporal region, while amyloid-related pathology first appears in neocortex. The eventual distributions of these pathologies reflect their anatomical origins. An implication is that the cardinal pathologies might exert preferential effects on the structurofunctional brain changes observed in AD. We investigated this hypothesis in 39 patients with dementia of the Alzheimers type. Interrelationships were analysed between cerebrospinal fluid (CSF) biomarkers of the cardinal pathologies, volumetric brain changes using magnetic resonance imaging, and brain metabolism using [18F]-FDG-PET. Amyloid-related pathology was preferentially associated with structurofunctional changes in the precuneus and lateral temporal regions. Tau-related pathology was not associated with changes in these regions. These findings support the hypothesis that tau- and amyloid-pathology exert differential effects on structurofunctional changes in the AD brain. These findings have implications for future therapeutic trials and hint at a more complex relationship between the cardinal pathologies and disruption of brain networks.

neuroscience↗