Elsevier

Cortex

Volume 139, June 2021, Pages 86-98
Cortex

Clinical Neuroanatomy
White matter abnormalities of right hemisphere attention networks contribute to visual hallucinations in dementia with Lewy bodies

https://doi.org/10.1016/j.cortex.2021.03.007Get rights and content

Abstract

Objective

Functional alterations of the visual attention networks in a setting of impaired visual information processing have a role in the genesis of visual hallucinations (VH) in dementia with Lewy bodies (DLB). This multimodal MRI study aims at exploring structural and functional basis of VH.

Methods

23 DLB patients (10 with and 13 without VH) and 13 healthy controls were studied. They underwent MRI with T1-w sequences to measure cortical thickness, DTI for whole-brain and single tract microstructural properties and rs-fMRI of the default mode, dorsal and ventral attention, and visual networks.

Results

In DLB with VH, whole-brain DTI revealed a lower fractional anisotropy and a greater mean diffusivity in the right frontal and temporo-parietal white matter tracts. Tracts dissection showed lower fractional anisotropy in the right inferior and superior (ventral part) longitudinal fasciculi (ILF and SLF) (p < .05, corrected), and greater mean diffusivity (p < .05). The extent of white matter microstructural alterations involving the right ILF and SLF correlated with the severity of VH (r = .55, p < .01; r = .42, p < .05, respectively), and with performance in the visual attention task (r = −.56 and r = −.61; p < .01, respectively). Cortical thickness in the projection areas of the right SLF was significantly reduced (p < .05). Patients with VH also showed an altered functional connectivity in the ventral attention network, connected by the ventral portion of the SLF (p < .05).

Conclusions

Our findings suggest that a combination of microstructural and functional alterations involving the attention networks in the right hemisphere may be important in the genesis of VH.

Introduction

Visual hallucinations (VH) are visual experiences not elicited by external stimuli. They are common in numerous pathological conditions, including: ocular diseases (ffytche & Howard, 1999; ffytche, 2009; Schadlu, et al., 2009); epilepsy (Duarte Mangas, et al., 2017; Panayiotopoulos, 1999; Saha et al., 2016); primary psychiatric disorders with psychosis (Baethge et al., 2005; Bracha et al., 1989; Goodwin et al., 1971); and neurodegenerative diseases (Cagnin et al., 2013; Diederich et al., 2009; Fenelon et al., 2000; Urwyler et al., 2016; Williams et al., 2008).

As reviewed by ffytche (ffytche 2008), the literature on VH originally focused on the abnormal functioning of specific brain regions, such as the occipital lobe, and the role of topological hyperfunction (Holroyd et al., 2000; Panayiotopoulos 1999). There is plenty of evidence of VH being associated with transient increases in activity in localized cortical regions, and the specialization of the regions affected decides the content of the VH. Indirect evidence comes from patients experiencing types of VH that relate to their abilities that are still intact, not to those they have lost (ffytche et al., 2004; Hubl et al., 2007). In many brain diseases, VH are characterized mainly by recurrent complex visions (seeing objects, animals and human beings, for instance), rather than simple VH such as seeing dots, lines, flashes, and amorphous shapes (Collerton et al., 2005). A topology-based approach seems unable to explain the complexity of the symptoms adequately, so a functional model has been proposed that emphasizes the altered integration and segregation of information, and the neural activity involved in promoting efficient information processing (Park & Friston, 2013). This “hodological” view has been applied to neuropsychological theories of VH, according to which they would result from: an abnormal processing of visual information combined with an impaired top-down monitoring of visual attention (Collerton et al., 2005); or from an imbalance between the dorsal and ventral attention networks (Shine et al., 2011; O'Brien et al., 2020). In the last two decades, attention and visual perception networks have been elucidated both anatomically and functionally, and the activity and interaction between networks have been investigated (Corbetta & Shulman, 2011; Thiebaut de Schotten, Dell'Acqua, et al., 2011; Bartolomeo et al., 2012). It has emerged that dorsal and ventral attention networks have different functions, and functional localizations. The dorsal attention network has a bilateral organization, and is involved in representing contralateral spatial information, and in shifting attention and eye movements. The ventral attention network has a right-hemisphere dominance and is involved in vigilance, in re-orienting attention to sensory-driven or behaviorally-relevant stimuli, and in task resetting (Corbetta & Shulman, 2002; He, Snyder, et al., 2007).

As concerns structural connectivity, the inferior longitudinal fasciculus (ILF) bi-directionally connects the occipital regions to the medial and lateral anterior temporal lobes. It is involved in processing visual emotion and visual memory information (Latini et al., 2017). The inferior fronto-occipital fasciculus (IFOF) connects regions of the occipital and ventral frontal lobes. Connections between the visual part of the parietal lobe and the frontal cortex are via the superior longitudinal fasciculus (SLF), while those between the occipital and limbic cortex are via the cingulum and the ILF. The SLF and IFOF contain projections of neuronal networks involved in processing visual attention, visual working memory, visual praxis, visuo-vestibular function, and eye movement control (ffytche et al., 2010).

Recurrent complex VH are a core feature pointing to the diagnosis of dementia with Lewy bodies (DLB) (McKeith et al., 2017). They occur in about 60% of suspected cases of DLB (Aarsland et al., 2001), and are considered a strong predictor of this condition (Tiraboschi et al., 2006). Patients with DLB show occipital hypometabolism, one of the neuroimaging hallmarks of the disease, that has revealed no clear relationship with VH (Delli Pizzi et al., 2014; Firbank et al., 2016; Taylor et al., 2012). DLB is consequently an attractive model for investigating the neural mechanisms behind VH.

Some studies have focused on white matter connectivity in subjects with DLB and VH, finding changes in the level of diffusivity in temporo-occipital connections, especially in the right hemisphere (Kantarci et al., 2010; Delli Pizzi, Franciotti, Taylor, Esposito, et al., 2015). Previous association between long white matter tracts and functional brain networks have been reported (Thiebaut de Schotten, Dell'Acqua, et al., 2011; Parlatini et al., 2017), but no multimodal studies to date have assessed the combined interaction of structural and functional changes in cases of DLB-related VH. Here, we use diffusion tensor imaging tractography to examine the involvement of white matter tracts connecting the visual cortex to regions of the attention networks in patients with DLB with and without VH. We also explore: whether changes in the white matter bundles of subjects who experience VH lead to a reduction in cortical thickness; and whether functional changes in the attention and visual networks are detectable on resting-state functional MRI images (rs-fMRI).

Section snippets

Patients

Thirty patients with a diagnosis of probable DLB according to McKeith criteria (McKeith et al., 2017) and 13 age-matched healthy controls were enrolled in the study at the Memory Clinic of the Department of Neurosciences at Padua University (Italy). Among the patients with DLB, 7/30 were not considered in subsequent imaging analyses due to movement artifacts. The final sample thus consisted of: 23 patients with DLB, 10 of whom experienced VH (the VH subgroup), and 13 who never experienced VH

Demographic and clinical features

The sample's demographic and clinical data are summarized in Table 1. The groups of patients with DLB and controls matched for age and education level. The VH subgroup had symptoms of RBD more frequently than the no-VH subgroup. No significant differences emerged for duration of the disease, cognitive fluctuations, severity of parkinsonism, degree of cognitive impairment or burden of behavioral disturbances (excluding the scores obtained from the NPI sub-item of VH burden). Patients in the

Discussion

This multimodal MRI study examined structural and functional connectivity abnormalities in patients with DLB and visual hallucinations (VH). Four findings are worth noting. First, whole-brain tractography analysis showed damage to white matter tracts in patients with VH, especially in the right hemisphere: FA was decreased in the right ILF and SLF3, and MD was increased in the right ILF, SLF3, IFOF, and left UNC. Second, cortical thickness in regions connected through the right SLF3 was reduced

Funding

MTS funding comes from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 81852).

CB received a grant by the Associazione Italiana Ricerca Alzheimer Onlus (AIRAlzh) funded by Consorzio Nazionale delle Cooperative di Consumatori (COOP ITALIA S.C.)

MC funding comes from FLAG-ERA JTC 2017; Dipartimento Eccellenza del MIUR Neuro-DiP; Progetto Strategico UniPD.

No part of the study procedures was pre-registered prior to the

Declaration of competing interest

The authors have no competing interests to disclose.

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