Sebastiano Galantucci

Syntactic processing depends on dorsal language tracts

Frontal and temporal language areas involved in syntactic processing are connected by several dorsal and ventral tracts, but the functional roles of the different tracts are not well understood. To identify which white matter tract(s) are important for syntactic processing, we examined the relationship between white matter damage and syntactic deficits in patients with primary progressive aphasia, using multimodal neuroimaging and neurolinguistic assessment. Diffusion tensor imaging showed that microstructural damage to left hemisphere dorsal tracts--the superior longitudinal fasciculus including its arcuate component--was strongly associated with deficits in comprehension and production of syntax. Damage to these dorsal tracts predicted syntactic deficits after gray matter atrophy was taken into account, and fMRI confirmed that these tracts connect regions modulated by syntactic processing. In contrast, damage to ventral tracts--the extreme capsule fiber system or the uncinate fasciculus--was not associated with syntactic deficits. Our findings show that syntactic processing depends primarily on dorsal language tracts.

Regional patterns of brain tissue loss associated with depression in Parkinson disease

Objective: To investigate, using MRI and voxel-based morphometry (VBM), whether specific patterns of gray matter (GM) and white matter (WM) loss are associated with depression in patients with Parkinson disease (PD). Methods: Forty patients with PD and 26 healthy subjects were studied. Patients were diagnosed with depression using DSM-IV criteria. The Hamilton Depression Rating Scale (HDRS) was administered to patients. The topographic distribution of brain tissue loss in patients with PD and controls was assessed using VBM as implemented in Statistical Parametric Mapping (SPM5). Results: Twenty-four patients with PD were diagnosed as nondepressed (PD-NDep) and 16 as having depression (PD-Dep). Patient groups were similar in terms of clinical findings, except for the HDRS score (p < 0.001). Compared to controls, patients with PD showed common GM loss in the right anterior cingulate (AC) cortex and insula, and in the left middle frontal and angular gyri (p < 0.001). No regions of WM loss common to PD-NDep and PD-Dep patients relative to healthy controls were found. PD-Dep vs PD-NDep patients showed WM loss in the right AC bundle and inferior orbitofrontal (OF) region (p < 0.001). In patients with PD, HDRS score correlated with WM loss in the right inferior OF region (r = −0.51, p < 0.05). Conclusions: Tissue loss in several WM regions within the cortical-limbic network occurs in PD-Dep vs PD-NDep patients. Such pattern of brain atrophy overlaps with key regions involved in major depressive disorders, suggesting an increased vulnerability of this neural circuit in PD. This may partially account for the high prevalence of depression in PD.

The in vivo distribution of brain tissue loss in Richardson’s syndrome and PSP-parkinsonism: a VBM-DARTEL study

In this study, we wished to test, using magnetic resonance imaging and voxel‐based morphometry (VBM), whether specific cortical and subcortical patterns of brain grey (GM) and white matter (WM) tissue loss can be detected in patients with Richardson’s syndrome (PSP‐RS) and progressive supranuclear palsy‐parkinsonism (PSP‐P), and possibly account for their clinical heterogeneity. Twenty patients with PSP, classified as PSP‐RS (10 patients) or PSP‐P (10 patients), and 24 healthy controls were studied. The Statistical Parametric Mapping (SPM5) and the Diffeomorphic Anatomical Registration using Exponentiated Lie algebra method were used to perform a VBM analysis. Compared with controls, both patient groups showed GM loss in the central midbrain, cerebellar lobes, caudate nuclei, frontotemporal cortices and right hippocampus. WM loss was detected in both conditions in the midbrain, left superior cerebellar peduncle, internal capsulae, and left premotor and bilateral prefrontal regions. Compared with PSP‐P, patients with PSP‐RS showed additional regions of GM loss in the midbrain, left cerebellar lobe and dentate nuclei. PSP‐RS was also associated with a more severe WM loss in the midbrain, internal capsulae, and orbitofrontal, prefrontal and precentral/premotor regions, bilaterally. Patients with PSP‐P showed a more pronounced GM loss only in the frontal cortex, bilaterally. This study shows that, albeit the overall pattern of brain atrophy associated with PSP appears remarkably consistent across the spectrum of clinical features recorded in life, major anatomical differences between these two conditions do exist. Such a different topographical distribution of tissue damage may account for the clinical differences between PSP‐RS and PSP‐P.

The neural basis of syntactic deficits in primary progressive aphasia

Patients with primary progressive aphasia (PPA) vary considerably in terms of which brain regions are impacted, as well as in the extent to which syntactic processing is impaired. Here we review the literature on the neural basis of syntactic deficits in PPA. Structural and functional imaging studies have most consistently associated syntactic deficits with damage to left inferior frontal cortex. Posterior perisylvian regions have been implicated in some studies. Damage to the superior longitudinal fasciculus, including its arcuate component, has been linked with syntactic deficits, even after gray matter atrophy is taken into account. These findings suggest that syntactic processing depends on left frontal and posterior perisylvian regions, as well as intact connectivity between them. In contrast, anterior temporal regions, and the ventral tracts that link frontal and temporal language regions, appear to be less important for syntax, since they are damaged in many PPA patients with spared syntactic processing.

Disruption of structural connectivity along the dorsal and ventral language pathways in patients with nonfluent and semantic variant primary progressive aphasia: A DT MRI study and a literature review

Nonfluent (NFV) and semantic (SV) variants of primary progressive aphasia (PPA) are associated with distinct patterns of focal cortical atrophy and underlying pathology. Previous diffusion tensor (DT) MRI studies showed a more ventral white matter (WM) involvement in SV patients and a more widespread frontal involvement in NFV. Aim of this manuscript is twofold. First, we wished to provide a brief state-of-the-art review on WM damage in PPA. Second, we used DT MRI to assess the topography of WM microstructural damage along dorsal and ventral language pathways and corpus callosum in patients with NFV and SV. Our findings show that the two PPA variants share an overlapping pattern of dorsal and ventral pathway abnormalities. In addition to these common abnormalities, variant-specific WM changes were also found, with NFV patients having a more severe damage to the dorsal (fronto-parietal) WM connections within the left superior longitudinal fasciculus/arcuate and SV patients showing a greater left ventral tract involvement (inferior longitudinal and uncinate fasciculi). These findings offer evidence that both dorsal and ventral language networks may contribute to the relatively selective deficits in NFV and SV patients.

Intrahemispheric and interhemispheric structural network abnormalities in PLS and ALS

Using diffusion tensor (DT) magnetic resonance imaging (MRI), damage to brain intrahemispheric and interhemispheric connections was assessed in 26 sporadic primary lateral sclerosis (PLS) patients compared with 28 sporadic amyotrophic lateral sclerosis (ALS) patients with similar disability and 35 healthy controls. DT MRI diagnostic accuracy in distinguishing the two motor neuron disease (MND) variants was tested. PLS and ALS patients showed a distributed pattern of abnormalities of the motor system, including the corticospinal tracts and corpus callosum (CC). PLS versus ALS patients showed a more severe damage to the motor CC fibers and subcortical white matter (WM) underlying the primary motor cortices. Both patient groups showed an extra‐motor damage, which was more severe in PLS. This did not appear to be driven by longer disease duration in PLS. In PLS patients, damage to the CC mid‐body correlated with the severity of upper motor neuron clinical burden. CC fractional anisotropy values had the highest accuracy in distinguishing PLS from controls and ALS. PLS and ALS share an overlapped pattern of WM abnormalities. This underscores that PLS, despite its distinct clinical phenotype and long survival, still lies within the wider MND spectrum. Whether CC diffusivity may be a novel marker to increase confidence in an early diagnostic separation of PLS from ALS still needs to be investigated. Hum Brain Mapp 35:1710–1722, 2014.

Clinical, cognitive, and behavioural correlates of white matter damage in progressive supranuclear palsy

White matter (WM) tract alterations were assessed in patients with progressive supranuclear palsy (PSP) relative to healthy controls and patients with idiopathic Parkinson’s disease (PD) to explore the relationship of WM tract damage with clinical disease severity, performance on cognitive tests, and apathy. 37 PSP patients, 41 PD patients, and 34 healthy controls underwent an MRI scan and clinical testing to evaluate physical disability, cognitive impairment, and apathy. In PSP, the contribution of WM tract damage to global disease severity and cognitive and behavioural disturbances was assessed using Random Forest analysis. Relative to controls, PSP patients showed diffusion tensor (DT) MRI abnormalities of the corpus callosum, superior cerebellar peduncle (SCP), cingulum and uncinate fasciculus bilaterally, and right inferior longitudinal fasciculus. Corpus callosum and SCP DT MRI measures distinguished PSP from PD patients with high accuracy (area under the curve ranging from 0.89 to 0.72). In PSP, DT MRI metrics of the corpus callosum and superior cerebellar peduncles were the best predictors of global disease severity scale scores. DT MRI metrics of the corpus callosum, right superior longitudinal and inferior longitudinal fasciculus, and left uncinate were the best predictors of executive dysfunction. In PSP, apathy severity was related to the damage to the corpus callosum, right superior longitudinal, and uncinate fasciculi. In conclusion, WM tract damage contributes to the motor, cognitive, and behavioural deficits in PSP. DT MRI offers markers for PSP diagnosis, assessment, and monitoring.

Diffusion tensor magnetic resonance imaging tractography in progressive supranuclear palsy.

Diffusion tensor magnetic resonance imaging tractography allows quantification of in vivo white matter tract damage.

Extramotor damage is associated with cognition in primary lateral sclerosis patients.

Objectives This is a cross-sectional study aimed at investigating cognitive performances in patients with primary lateral sclerosis (PLS) and using diffusion tensor (DT) magnetic resonance imaging (MRI) to determine the topographical distribution of microstructural white matter (WM) damage in patients with or without cognitive deficits. Methods DT MRI scans were obtained from 21 PLS patients and 35 age- and sex-matched healthy controls. All PLS patients underwent a comprehensive neuropsychological battery. Tract-based-spatial-statistics (TBSS) was used to perform a whole-brain voxel-wise analysis of fractional anisotropy (FA), axial, radial (radD) and mean diffusivity (MD). Results Ten PLS patients had abnormal scores in at least one neuropsychological test (PLS with cognitive deficits, PLS-cd). Compared with healthy controls and cognitively unimpaired PLS patients (PLS-cu), PLS-cd cases showed decreased FA and increased MD and radD in the corticospinal tract (CST), corpus callosum, brainstem, anterior limb of internal capsule, superior and inferior longitudinal fasciculi, fornix, thalamic radiations, and parietal lobes, bilaterally. Compared with healthy controls, PLS-cd patients showed further decreased FA and increased radD in the cerebellar WM, bilaterally. Compared with controls, PLS-cu patients showed decreased FA in the mid-body of corpus callosum. In PLS, executive and language test scores correlated with WM damage. Conclusions This is the first study evaluating the relationship between cognitive performance and WM tract damage in PLS patients. PLS can be associated with a multi-domain cognitive impairment. WM damage to interhemispheric, limbic and major associative WM tracts seem to be the structural correlate of cognitive abnormalities in these patients.

Structural Brain Connectome and Cognitive Impairment in Parkinson Disease

Purpose To investigate the structural brain connectome in patients with Parkinson disease (PD) and mild cognitive impairment (MCI) and in patients with PD without MCI. Materials and Methods This prospective study was approved by the local ethics committees, and written informed consent was obtained from all subjects prior to enrollment. The individual structural brain connectome of 170 patients with PD (54 with MCI, 116 without MCI) and 41 healthy control subjects was obtained by using deterministic diffusion-tensor tractography. A network-based statistic was used to assess structural connectivity differences among groups. Results Patients with PD and MCI had global network alterations when compared with both control subjects and patients with PD without MCI (range, P = .004 to P = .048). Relative to control subjects, patients with PD and MCI had a large basal ganglia and frontoparietal network with decreased fractional anisotropy (FA) in the right hemisphere and a subnetwork with increased mean diffusivity (MD) involving similar regions bilaterally (P < .01). When compared with patients with PD without MCI, those with PD and MCI had a network with decreased FA, including basal ganglia and frontotemporoparietal regions bilaterally (P < .05). Similar findings were obtained by adjusting for motor disability (P < .05, permutation-corrected P = .06). At P < .01, patients with PD and MCI did not show network alterations relative to patients with PD without MCI. Network FA and MD values were used to differentiate patients with PD and MCI from healthy control subjects and patients with PD without MCI with fair to good accuracy (cross-validated area under the receiver operating characteristic curve [principal + secondary connected components] range, 0.75-0.85). Conclusion A disruption of structural connections between brain areas forming a network contributes to determine an altered information integration and organization and thus cognitive deficits in patients with PD. These results provide novel information concerning the structural substrates of MCI in patients with PD and may offer markers that can be used to differentiate between patients with PD and MCI and patients with PD without MCI.