The thalamus as a putative biomarker in neurodegenerative disorders

Objective: This review provides a brief account of the clinically relevant functional neuroanatomy of the thalamus, before considering the utility of various modalities utilised to image the thalamus and technical challenges therein, and going on to provide an overview of studies utilising structural imaging techniques to map thalamic morphology in the spectrum of neurodegenerative disorders. Methods: A systematic search was conducted for peer-reviewed studies involving structural neuroimaging modalities investigating the morphology (shape and/ or size) of the thalamus in the spectrum of neurodegenerative disorders. Results: Whilst the precise role of the thalamus in the healthy brain remains unclear, there is a large body of knowledge accumulating which defines more precisely its functional connectivity within the connectome, and a burgeoning literature implicating its involvement in neurodegenerative disorders. It is proposed that correlation of clinical features with thalamic morphology (as a component of a quantifiable subcortical connectome) will provide a better understanding of neuropsychiatric dysfunction in various neurodegenerative disorders, potentially yielding clinically useful endophenotypes and disease biomarkers. Conclusions: Thalamic biomarkers in the neurodegenerative disorders have great potential to provide clinically meaningful knowledge regarding not only disease onset and progression, but may yield targets of and perhaps a way of gauging response to future disease-modifying modalities

Cognitive and psychosocial outcomes of mechanically ventilated intensive care patients with and without delirium

Abstract Objective Delirium is common in intensive care patients and is associated with short- and long-term adverse outcomes. We investigated the long-term risk of cognitive impairment and post-traumatic stress disorder (PTSD) in intensive care patients with and without delirium. Methods This is a prospective cohort study in ICUs in two Australian university-affiliated hospitals. Patients were eligible if they were older than 18 years, mechanically ventilated for more than 24 h and did not meet exclusion criteria. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. Variables assessing cognitive function and PTSD symptoms were collected at ICU discharge, after 6 and 12 months: Mini-Mental State Examination, Telephone Interview for Cognitive Status, Impact of Events Scale-Revised and Informant Questionnaire for Cognitive Decline (caregiver). Results 103 participants were included of which 36% developed delirium in ICU. Patients with delirium were sicker and had longer duration of mechanical ventilation and ICU length of stay. After 12 months, 41/60 (68.3%) evaluable patients were cognitively impaired, with 11.6% representing the presence of symptoms consistent with dementia. When evaluated by the patient’s caregiver, the patient’s cognitive function was found to be severely impaired in a larger proportion of patients (14/60, 23.3%). Delirium was associated with worse cognitive function at ICU discharge, but not with long-term cognitive function. IES-R scores, measuring PTSD symptoms, were significantly higher in patients who had delirium compared to patients without delirium. In regression analysis, delirium was independently associated with cognitive function at ICU discharge and PTSD symptoms at 12 months. Conclusions Intensive care survivors have significant rates of long-term cognitive decline and PTSD symptoms. Delirium in ICU was independently associated with short-term but not long-term cognitive function, and with long-term PTSD symptoms. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12616001116415, 15/8/2016 retrospectively registered, https://www.anzctr.org.a

Shape Abnormalities of the Caudate Nucleus Correlate with Poorer Gait and Balance: Results from a Subset of the LADIS Study

Functional deficits seen in several neurodegenerative disorders have been linked with dysfunction in fronto-striatal circuits and with associated shape alterations in striatal structures. The severity of visible white matter changes (WMC) on MRI has been found to correlate with poorer performance on measures of gait and balance. This study aimed to determine whether striatal volume and shape changes were correlated with gait dysfunction

Portents from Orwell’s 1984: Bureaucracies, Ministries of Truth and Plenty – challenges facing the administration of mental healthcare in Australia

We reflect upon the processes of mental health administration in Australia with reference to George Orwell's novel, .Mental healthcare in Australia is distorted by politicisation, spin and a refusal to acknowledge the reality of the current situation. These challenges for mental healthcare demonstrate some similarities with the Ministries of Truth and Plenty, which conversely performed as their opposites in Orwell's novel. Psychiatrists and their professional bodies should play a greater role in advocacy for clinician-led, evidence-based services in partnership with our communities

Midsagittal corpus callosal thickness and cognitive impairment in Parkinson's disease

People diagnosed with Parkinson's disease (PD) can experience significant neuropsychiatric symptoms, including cognitive impairment and dementia, the neuroanatomical substrates of which are not fully characterised. Symptoms associated with cognitive impairment and dementia in PD may relate to direct structural changes to the corpus callosum via primary white matter pathology or as a secondary outcome due to the degeneration of cortical regions. Using magnetic resonance imaging, the corpus callosum can be investigated at the midsagittal plane, where it converges to a contiguous mass and is not intertwined with other tracts. The objective of this project was thus twofold: First, we investigated possible changes in the thickness of the midsagittal callosum and cortex in patients with PD with varying levels of cognitive impairment; and secondly, we investigated the relationship between the thickness of the midsagittal corpus callosum and the thickness of the cortex. Study participants included cognitively unimpaired PD participants (n = 35), PD participants with mild cognitive impairment (n = 22), PD participants with dementia (n = 17) and healthy controls (n = 27). We found thinning of the callosum in PD-related dementia compared with PD-related mild cognitive impairment and cognitively unimpaired PD participants. Regression analyses found thickness of the left medial orbitofrontal cortex to be positively correlated with thickness of the anterior callosum in PD-related mild cognitive impairment. This study suggests that a midsagittal thickness model can uncover changes to the corpus callosum in PD-related dementia, which occur in line with changes to the cortex in this advanced disease stage

Increased functional connectivity of thalamic subdivisions in patients with Parkinson\u27s disease

Parkinson’s disease (PD) affects 2–3% of the population over the age of 65 with loss of dopaminergic neurons in the substantia nigra impacting the functioning of basal ganglia-thalamocortical circuits. The precise role played by the thalamus is unknown, despite its critical role in the functioning of the cerebral cortex, and the abnormal neuronal activity of the structure in PD. Our objective was to more clearly elucidate how functional connectivity and morphology of the thalamus are impacted in PD (n = 32) compared to Controls (n = 20). To investigate functional connectivity of the thalamus we subdivided the structure into two important regions-of-interest, the first with putative connections to the motor cortices and the second with putative connections to prefrontal cortices. We then investigated potential differences in the size and shape of the thalamus in PD, and how morphology and functional connectivity relate to clinical variables. Our data demonstrate that PD is associated with increases in functional connectivity between motor subdivisions of the thalamus and the supplementary motor area, and between prefrontal thalamic subdivisions and nuclei of the basal ganglia, anterior and dorsolateral prefrontal cortices, as well as the anterior and paracingulate gyri. These results suggest that PD is associated with increased functional connectivity of subdivisions of the thalamus which may be indicative alterations to basal ganglia-thalamocortical circuitry

Increased functional connectivity of thalamic subdivisions in patients with Parkinson’s disease

Parkinson’s disease (PD) affects 2–3% of the population over the age of 65 with loss of dopaminergic neurons in the substantia nigra impacting the functioning of basal ganglia-thalamocortical circuits. The precise role played by the thalamus is unknown, despite its critical role in the functioning of the cerebral cortex, and the abnormal neuronal activity of the structure in PD. Our objective was to more clearly elucidate how functional connectivity and morphology of the thalamus are impacted in PD (n = 32) compared to Controls (n = 20). To investigate functional connectivity of the thalamus we subdivided the structure into two important regions-of-interest, the first with putative connections to the motor cortices and the second with putative connections to prefrontal cortices. We then investigated potential differences in the size and shape of the thalamus in PD, and how morphology and functional connectivity relate to clinical variables. Our data demonstrate that PD is associated with increases in functional connectivity between motor subdivisions of the thalamus and the supplementary motor area, and between prefrontal thalamic subdivisions and nuclei of the basal ganglia, anterior and dorsolateral prefrontal cortices, as well as the anterior and paracingulate gyri. These results suggest that PD is associated with increased functional connectivity of subdivisions of the thalamus which may be indicative alterations to basal ganglia-thalamocortical circuitry

Striatal changes in Parkinson disease : An investigation of morphology, functional connectivity and their relationship to clinical symptoms

We sought to investigate morphological and resting state functional connectivity changes to the striatal nuclei in Parkinson disease (PD) and examine whether changes were associated with measures of clinical function. Striatal nuclei were manually segmented on 3T-T1 weighted MRI scans of 74 PD participants and 27 control subjects, quantitatively analysed for volume, shape and also functional connectivity using functional MRI data. Bilateral caudate nuclei and putamen volumes were significantly reduced in the PD cohort compared to controls. When looking at left and right hemispheres, the PD cohort had significantly smaller left caudate nucleus and right putamen volumes compared to controls. A significant correlation was found between greater atrophy of the caudate nucleus and poorer cognitive function, and between greater atrophy of the putamen and more severe motor symptoms. Resting-state functional MRI analysis revealed altered functional connectivity of the striatal structures in the PD group. This research demonstrates that PD involves atrophic changes to the caudate nucleus and putamen that are linked to clinical dysfunction. Our work reveals important information about a key structure-function relationship in the brain and provides support for caudate nucleus and putamen atrophy as neuroimaging biomeasures in PD