Disrupted thalamocortical connectivity in PSP: A resting-state fMRI, DTI, and VBM study

Abstract

Progressive supranuclear palsy (PSP) is associated with pathological changes along the dentatorubrothalamic tract and in premotor cortex. We aimed to assess whether functional neural connectivity is disrupted along this pathway in PSP, and to determine how functional changes relate to changes in structure and diffusion. Eighteen probable PSP subjects and 18 controls had resting-state (task-free) fMRI, diffusion tensor imaging and structural MRI. Functional connectivity was assessed between thalamus and the rest of the brain, and within the basal ganglia, salience and default mode networks (DMN). Patterns of atrophy were assessed using voxel-based morphometry, and patterns of white matter tract degeneration were assessed using tract-based spatial statistics. Reduced in-phase functional connectivity was observed between the thalamus and premotor cortex including supplemental motor area (SMA), striatum, thalamus and cerebellum in PSP. Reduced connectivity in premotor cortex, striatum and thalamus were observed in the basal ganglia network and DMN, with subcortical salience network reductions. Tract degeneration was observed between cerebellum and thalamus and in superior longitudinal fasciculus, with grey matter loss in frontal lobe, premotor cortex, SMA and caudate. SMA functional connectivity correlated with SMA volume and measures of cognitive and motor dysfunction, while thalamic connectivity correlated with degeneration of superior cerebellar peduncles. PSP is therefore associated with disrupted thalamocortical connectivity that is associated with degeneration of the dentatorubrothalamic tract and the presence of cortical atrophy.

Disrupted Resting-State Functional Connectivity in Progressive Supranuclear Palsy

“…Moreover, in the present study, we did not find any region of enhanced dMT FC, which is in keeping with previous results. 10 With regard to thalamic FC, we confirmed the reduced connectivity in the premotor cortex, SMA, thalamus, basal ganglia, and cerebellum previously described by Whitwell et al 9 in patients with PSP. Unlike us, however, they did not detect decreased FC in the ACC and found increased FC in regions surrounding the perisylvian fissure.…”

“…Unlike us, however, they did not detect decreased FC in the ACC and found increased FC in regions surrounding the perisylvian fissure. 9 These discrepancies between the 2 studies are likely due to differences in the methodology used for the data analysis or in the selection of patients or both.…”

“…41 Regarding the clinical impact of MR imaging structural abnormalities, previous studies that investigated possible relationships between cerebral atrophy measurements and disease severity generally failed to detect a significant correlation. 5,9 There are few reports of correlations between regional measurements of DTI parameters and clinical scores. 42 In the present study, neither regional brain volumes nor mean DTI metrics correlated with the clinical severity of patients with PSP.…”

“…9,10 It is unknown whether FC abnormalities also affect other key subcortical areas in PSP. 3 Owing to the widespread degeneration of subcortical structures in PSP, 3 the FC of the caudate nucleus, putamen, and pallidum may also be affected in this condition.…”

Quantitative electroencephalography as a biomarker for proneness toward developing psychosis

“…This increase in slow rhythmic activity, whilst awake and at rest, leads to disturbances of sensation, cognition and motor performance Llinás et al, 2001;Llinas et al, 1999;Schulman et al, 2011;Schulman et al, 2001;Whitwell et al, 2011). One crucial organising feature of the cortex is its system of inhibitory GABAergic interneurons, which mediate reciprocal cortico-cortical networks (Llinas et al, 2005;Llinas et al, 1999).…”