Biology subjects

Georgiou-Karistianis, N.

Publications and source records attributed to Georgiou-Karistianis, N..

3 recordsLinked to original sources

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

Longitudinal dentate nuclei iron concentration and atrophy in Friedreich ataxia: IMAGE-FRDA

BackgroundFriedreich ataxia is a recessively inherited, progressive neurological disease characterised by impaired mitochondrial iron metabolism. The dentate nuclei of the cerebellum are characteristic sites of neurodegeneration in the disease, but little is known of the longitudinal progression of pathology in these structures.\n\nMethodsUsing in vivo magnetic resonance imaging, including quantitative susceptibility mapping, we investigated changes in iron concentration and volume in the dentate nuclei in individuals with Friedreich ataxia (n=20) and healthy controls (n=18) over a two-year period.\n\nResultsThe longitudinal rate of iron concentration was significantly elevated bilaterally in participants with Friedreich ataxia relative to healthy controls. Atrophy rates did not differ significantly between groups. Change in iron concentration and atrophy both correlated with baseline disease severity or duration, indicating sensitivity of these measures to disease stage. Moreover, atrophy was maximal in individuals early in the disease course, while the rate of iron concentration increased with disease progression.\n\nConclusionsProgressive dentate nuclei pathology is evident in vivo in Friedreich ataxia, and the rates of change of iron concentration and atrophy in these structures are sensitive to the disease stage. The findings are consistent with an increased rate of iron concentration and atrophy early in the disease, followed by iron accumulation and stable volume in later stages. This pattern suggests that iron dysregulation persists after loss of the vulnerable neurons in the dentate. The significant changes observed over a two-year period highlights the utility of quantitative susceptibility mapping as a longitudinal biomarker and staging tool.

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↗