Regional structural hypo- and hyperconnectivity of frontal-striatal and frontal-thalamic pathways in behavioral variant frontotemporal dementia

Behavioral variant frontotemporal dementia (bvFTD) has been predominantly considered as a frontotemporal cortical disease, with limited direct investigation of frontal–subcortical connections. We aim to characterize the grey and white matter components of frontal–thalamic and frontal–striatal circuits in bvFTD. Twenty‐four patients with bvFTD and 24 healthy controls underwent morphological and diffusion imaging. Subcortical structures were manually segmented according to published protocols. Probabilistic pathways were reconstructed separately from the dorsolateral, orbitofrontal and medial prefrontal cortex to the striatum and thalamus. Patients with bvFTD had smaller cortical and subcortical volumes, lower fractional anisotropy, and higher mean diffusivity metrics, which is consistent with disruptions in frontal–striatal–thalamic pathways. Unexpectedly, regional volumes of the striatum and thalamus connected to the medial prefrontal cortex were significantly larger in bvFTD (by 135% in the striatum, p = .032, and 217% in the thalamus, p = .004), despite smaller dorsolateral prefrontal cortex connected regional volumes (by 67% in the striatum, p = .002, and 65% in the thalamus, p = .020), and inconsistent changes in orbitofrontal cortex connected regions. These unanticipated findings may represent compensatory or maladaptive remodeling in bvFTD networks. Comparisons are made to other neuropsychiatric disorders suggesting a common mechanism of changes in frontal–subcortical networks; however, longitudinal studies are necessary to test this hypothesis.Miller Family Bridgewater Illawarra Health and Medical Research Initiative Summer Scholarship; The Swedish Alzheimer foundation; Thureus foundation; The Swedish Society for Medical Research; The Bente Rexed Gersteds Foundation for Brain Researc

An MRI study of white matter tract integrity in regular cannabis users: effects of cannabis use and age

Rationale Conflicting evidence exists on the effects of cannabis use on brain white matter integrity. The extant literature has exclusively focused on younger cannabis users, with no studies sampling older cannabis users. Objectives We recruited a sample with a broad age range to examine the integrity of major white matter tracts in association with cannabis use parameters and neurodevelopmental stage. Methods Regular cannabis users (n = 56) and non-users (n = 20) with a mean age of 32 (range 18-55 years) underwent structural and diffusion MRI scans. White matter was examined using voxel-based statistics and via probabilistic tract reconstruction. The integrity of tracts was assessed using average fractional anisotropy, axial diffusivity and radial diffusivity. Diffusion measures were compared between users and non-users and as group-by-age interactions. Correlations between diffusion measures and age of onset, duration, frequency and dose of current cannabis use were examined. Results Cannabis users overall had lower fractional anisotropy than healthy non-users in the forceps minor tract only (p = .015, partial eta = 0.07), with no voxel-wise differences observed. Younger users showed predominantly reduced axial diffusivity, whereas older users had higher radial diffusivity in widespread tracts. Higher axial diffusivity was associated with duration of cannabis use in the cingulum angular bundle (beta = 5.00 x 10−5, p = .003). Isolated higher AD in older cannabis users was also observed. Conclusions The findings suggest that exogenous cannabinoids alter normal brain maturation, with differing effects at various neurodevelopmental stages of life. These age-related differences are posited to account for the disparate results described in the literature

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 morphology correlates with frontostriatal electrophysiological motor processing in Huntington\u27s disease: an IMAGE-HD study

Background: Huntington\u27s disease (HD) causes progressive atrophy to the striatum, a critical node in frontostriatal circuitry. Maintenance of motor function is dependent on functional connectivity of these premotor, motor, and dorsolateral frontostriatal circuits, and structural integrity of the striatum itself. We aimed to investigate whether size and shape of the striatum as a measure of frontostriatal circuit structural integrity was correlated with functional frontostriatal electrophysiological neural premotor processing (contingent negative variation, CNV), to better understand motoric structure-function relationships in early HD. Methods: Magnetic resonance imaging (MRI) scans and electrophysiological (EEG) measures of premotor processing were obtained from a combined HD group (12 presymptomatic, 7 symptomatic). Manual segmentation of caudate and putamen was conducted with subsequent shape analysis. Separate correlational analyses (volume and shape) included covariates of age, gender, intracranial volume, and time between EEG and MRI. Results: Right caudate volume correlated with early CNV latency over frontocentral regions and late CNV frontally, whereas right caudate shape correlated with early CNV latency centrally. Left caudate volume correlated with early CNV latency over centroparietal regions and late CNV frontally. Right and left putamen volumes correlated with early CNV latency frontally, and right and left putamen shape/volume correlated with parietal CNV slope. Conclusions: Timing (latency) and pattern (slope) of frontostriatal circuit-mediated premotor functional activation across scalp regions were correlated with abnormalities in structural integrity of the key frontostriatal circuit component, the striatum (size and shape). This was accompanied by normal reaction times, suggesting it may be undetected in regular tasks due to preserved motor performance. Such differences in functional activation may reflect atrophy-based frontostriatal circuitry despecialization and/or compensatory recruitment of additional brain regions

Post-traumatic amnesia

Of patients hospitalised for traumatic brain injury (TBI), most pass through a state of altered consciousness known as "post-traumatic amnesia" (PTA). Despite the lack of a consistent definition, PTA is widely used as a construct in neurosurgical practice to guide decision-making and prognosis. Accurate PTA assessment is important, because over-evaluation leads to excess social, financial and opportunity costs, whilst under-evaluation risks patient welfare. Whilst anterograde memory is certainly disrupted in PTA, PTA in fact involves a far more extensive memory disturbance. More instructively, the complete "post-TBI syndrome" also comprises an extensive cognitive deficit which includes a confusional state, as well as a behavioural disturbance characterised by acute agitation. Recently, impairments in attention and executive functioning have also been emphasised; indeed, some consider these the primary disturbance with PTA. Although all of these features were fully described (or implied) by the earliest pioneers, most current PTA scores do not assess the complete "post-TBI syndrome". Currently, the Westmead PTA scale (WPTAS) directs most in-hospital TBI management throughout Australasia: however, in addition to general defects, specific limitations have been identified in the levels of evidence for WPTAS validity. We review the literature regarding PTA and, in particular, the continued role of the WPTAS in directing neurosurgical practice. © 2013 Elsevier Ltd. All rights reserved

Hippocampal morphology in Huntington's disease, implications for plasticity and pathogenesis: The IMAGE-HD study.

While striatal changes in Huntington's Disease (HD) are well established, few studies have investigated changes in the hippocampus, a key neuronal hub. Using MRI scans obtained from the IMAGE-HD study, hippocampi were manually traced and then analysed with the Spherical Harmonic Point Distribution Method (SPHARM-PDM) in 36 individuals with presymptomatic-HD, 37 with early symptomatic-HD, and 36 healthy matched controls. There were no significant differences in overall hippocampal volume between groups. Interestingly we found decreased bilateral hippocampal volume in people with symptomatic-HD who took selective serotonin reuptake inhibitors compared to those who did not, despite no significant differences in anxiety, depressive symptoms, or motor incapacity between the two groups. In symptomatic-HD, there was also significant shape deflation in the right hippocampal head, showing the utility of using manual tracing and SPHARM-PDM to characterise subtle shape changes which may be missed by other methods. This study confirms previous findings of the lack of hippocampal volumetric differentiation in presymptomatic-HD and symptomatic-HD compared to controls. We also find novel shape and volume findings in those with symptomatic-HD, especially in relation to decreased hippocampal volume in those treated with SSRIs

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