Aims

The aim was to unravel structural/functional MRI connectomic features of motor neuron disease (MND) and behavioral variant of frontotemporal dementia (bvFTD).

Methods

115 MND (including amyotrophic lateral sclerosis [ALS] and primary lateral sclerosis), 35 bvFTD patients and 61 controls underwent clinical/cognitive and MRI evaluations. MND patients were divided in 79 pure-motor (MNDpm), 36 cognitive/behavioral impaired (MNDci/bi). A sub-analysis was performed on ALS patients only (54 ALSpm, 21 ALSci/bi and 8 ALS-FTD). Graph analysis and connectomics assessed structural/functional topological network properties at global, lobar and regional level.

Results

Globally, bvFTD showed altered structural and functional network properties compared to all other groups. Particularly, bvFTD showed altered structural and functional network properties within the frontotemporal and basal ganglia areas relative to all groups. Structural alterations in the parietal lobe discriminated bvFTD from controls and MNDpm only. MND groups showed altered graph metrics within the sensorimotor and basal ganglia areas relative to controls. At regional level, bvFTD showed widespread structural damage and decreased functional connecivity (FC) relative to all groups. MND showed disrupted structural architecture and enhanced FC within sensorimotor, basal ganglia and frontotemporal areas relative to controls. Structural and functional patterns have been replicated in ALS sub-analysis.

Conclusions

The disruption of the structural architecture in MND worsens in relation with cognitive deficits. Functional changes are characterized by enhanced FC in presence of exclusive motor impairment that intensifies with the occurrence of cognitive impairment in MND. The comorbidity of ALS and FTD leads to decreased FC similarly to bvFTD.

Funding:The Italian Ministry of Health(GR-2011-02351217;GR-2013-02357415;RF-2011-02351193) and AriSLA(ConnectALS).

Aims

To investigate the relationship between emotion processing and resting state-functional connectivty (RS-FC) in healthy controls (HC) and in patients with frontotemporal lobar degeneration (FTLD).

Methods

We recruited 80 FTLD (26 bvFTD, 10 PSP, 12 PPA, and 32 ALS) and 65 HC. Participants underwent a RS-functional MRI (RS-fMRI) and the Comprehensive Affect Testing System. In each group, correlation models were performed between each emotion construct and RS-FC changes.

Results

A high performance at the emotion naming was related in HC with decreased RS-FC of the right inferior temporal gyrus within the right frontoparietal-network; and in FTLD patients with increased RS-FC of the frontal regions within salience, frontoparietal and executive-control networks. Furthermore, a high performance at the emotion differentiation was related in HC with decreased RS-FC of the right middle temporal gyrus within the salience-network; and in FTLD patients with increased RS-FC of the left inferior and medial-orbitofrontal gyri, and right thalamus within the subcortical-network. Finally, a high performance at the emotion matching was related in both HC and FTLD groups with increased RS-FC of precuneus and vermis within the visual-network, and with further increased RS-FC of bilateral lingual, middle temporal and calcarine gyri in FTLD group only.

Conclusions

In FTLD compared to HC, RS-FC associated with emotional performances involved a larger number of brain regions which are linked to the disease development and progression. These findings offer new potential markers for detecting functional vulnerability linked to social interactions.

Fundings: Italian Ministry of Health (GR-2013-02357415); European Research Council (StG-2016_714388_NeuroTRACK).

Aims

The aim of this study was to investigate disease propagation in Parkinson’s disease (PD) using stepwise functional connectivity (SFC) analyses.

Methods

146 PD patients performed clinical-cognitive evaluations and resting-state functional MRI (rs-fMRI) at baseline. Cluster analysis using data on demographic information, motor symptoms and signs, cognitive and behavioural testing and non-motor manifestations identified PD subtypes: 86 were classified as “mild” and 60 as “moderate-to-severe”. 60 controls were enrolled. SFC analysis aims to characterize regions that connect to specific seed brain areas (medulla, known to be a pathological epicenter in PD) at different levels of link-step distances. Whole-brain two-sample t-test comparisons between each group were performed.

Results

Starting from medulla, we found direct functional connections to the insular cortex, pericalcarine, lingual and parahippocampal gyri in controls. With subsequent steps, medulla was connected to parietal-occipital-temporal lobes and the isthmus cingulate gyrus. In mild PD patients, we found an involvement of direct and indirect connections from the medulla to the sensorimotor network , cuneus, lateral and medial parietal regions and lateral temporal gyri. At a one-link step distance, moderate-to-severe PD patients showed decreased connectivity in the lateral occipital and inferior parietal gyri, and cuneus. Across 2-4 link-steps, we detected also a reduced functional connectivity within parietal, temporal, frontal and limbic lobes. Interestingly, SFC analysis highlighted a greater extent of damage in moderate-to-severe PD than in mild group.

Conclusions

SFC approach might help to predict a network-spread model of Parkinson-related pathology from 'a priori’ epicenter regions in PD. Funding:Ministry of Education and Science Republic of Serbia (Grant#175090).

Aims

The aim of this study was to identify early neuroimaging biomarkers of the need for deep brain stimulation (DBS) use in patients with Parkinson’s Disease (PD).

Methods

PD patients performed clinical-cognitive evaluations and resting-state functional MRI (RS-fMRI) at baseline and every year for 4 years. Patients were divided into two groups: 19 patients eligible for DBS (PD-DBS) over 48 months and 41 patients who did not meet the criteria to undergo DBS surgery (PD-noDBS). 60 age- and sex-matched controls performed baseline assessments. Graph analysis/connectomics assessed global and local topological network properties and regional functional connectivity (FC) at baseline and changes over-time.

Results

Lobar network analysis showed a significant higher mean nodal strength, local efficiency and clustering coefficient of the occipital areas in PD-DBS relative to both controls and PD-noDBS at baseline. These results were then confirmed by regional analysis. A significant increased FC between frontal and basal ganglia networks was found in PD-noDBS compared to both controls and PD-DBS patient at baseline. Referring to longitudinal analysis, PD-DBS patients showed a progressive decreased FC within occipital and between occipital and parietal networks compared to PD-noDBS (stable over time). Progressive decreased FC between frontal and basal ganglia networks occurred in PD-noDBS relative to PD-DBS (stable over time). Functional alterations within occipital network were positively related to tremor only in PD-DBS at baseline and over time.

Conclusions

RS-fMRI analysis might represent an early biomarker that helps clinicians to establish the correct indication for DBS in PD patients. Funding:Ministry of Education and Science Republic of Serbia (Grant#175090).

Aims

To assess longitudinal patterns of atrophy shown by magnetic resonance imaging (MRI) in the cortical and subcortical GM of patients affected by different clinical variants of the FTLD spectrum.

Methods

Fifty-nine patients, including 26 with behavioral variant of frontotemporal dementia (bvFTD), 10 non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA), 12 semantic variant of PPA (svPPA), and 11 MND, in the absence of known pathogenic mutations, underwent MRI on a 3T scanner at 6-month intervals for one year. Thirty-three healthy controls underwent the same protocol. 3D T1-weighted MRI sequences were analyzed using voxel-based morphometry to assess the longitudinal evolution of GM atrophy in patients, compared with HC.

Results

At baseline, severe diffuse atrophy of frontotemporal cortical regions and basal ganglia was found in bvFTD, nfvPPA and svPPA groups, whereas MND did not show significant GM atrophy. At 6-month follow-up, bvFTD and PPA showed progression of atrophy in the insular (bvFTD, nfvPPA and svPPA) and anterior cingulate cortices (bvFTD and nfvPPA), bilaterally, as well as in the left caudate nucleus and middle temporal cortex (svPPA). At 12-month follow-up, similar patterns of atrophy progression were found, with the additional involvement of the superior frontal cortical gyri in nfvPPA, and right hippocampus in svPPA. No significant progression of atrophy was found in MND.

Conclusions

Atrophy of insular and anterior cingulate cortical regions closely reflects the progression of neurodegeneration across the behavioral and linguistic presentations of FTD, in contrast with a substantial sparing of GM in MND.

Supported by: European Research Council (StG-2016_714388_NeuroTRACK).

Aims

Glucocerebrosidase gene (GBA) mutations are the greatest genetic cause of Parkinson’s disease (PD). We studied the longitudinal disease course of GBA-positive compared to GBA-negative patients along a 5-year follow-up, evaluating changes in cortical thickness and clinical outcomes.

Methods

10 GBA-positive PD and 20 GBA-negative PD matched for age, sex, disease duration and severity underwent clinical, neuropsychological and MRI assessments at study entry and once a year for 5 years. At baseline and at the last visit, each group of patients was compared in terms of cortical thinning to a group of 22 age-matched healthy controls (HC), who underwent one MRI at the study entry. Clinical, cognitive and cortical features were compared between patient groups at baseline and over time.

Results

At baseline, GBA-positive and GBA-negative patients had similar clinical and cognitive profiles. Compared to GBA-negative and HC, GBA-positive patients showed cortical thinning of the left temporal, parietal and occipital gyri. Over time, compared to GBA-negative PD, GBA-positive worsened significantly in motor symptoms and showed a greater pattern of bilateral cortical thinning involving also frontal cortices. After 60 months, compared to HC, GBA-negative PD showed a pattern of cortical thinning similar to that showed by GBA-positive at baseline.

Conclusions

Compared to GBA-negative, GBA-positive PD patients showed a greater and earlier cortical thinning which worsened over time. GBA-negative PD patients reached the pattern of cortical thinning of GBA-positive at the baseline only after 5 years, reflecting a slower disease progression.

Supported by: Ministry of Education and Science Republic of Serbia (Grant #175090).