White matter lesional predictors of chronic visual neglect: a longitudinal study

Abstract

Chronic visual neglect prevents brain-damaged patients from returning to an independent and active life. Detecting predictors of persistent neglect as early as possible after the stroke is therefore crucial to plan the relevant interventions. Neglect signs do not only depend on focal brain lesions, but also on dysfunction of large-scale brain networks connected by white matter bundles. We explored the relationship between markers of axonal degeneration occurring after the stroke and visual neglect chronicity. A group of 45 patients with unilateral strokes in the right hemisphere underwent cognitive testing for neglect twice, first at the subacute phase (<3 months after onset) and then at the chronic phase (>1 year). For each patient, magnetic resonance imaging including diffusion sequences was performed at least 4 months after the stroke. After masking each patient's lesion, we used tract-based spatial statistics to obtain a voxel-wise statistical analysis of the fractional anisotropy data. Twenty-seven patients had signs of visual neglect at initial testing. Only 10 of these patients had recovered from neglect at follow-up. When compared with patients without neglect, the group including all subacute neglect patients had decreased fractional anisotropy in the second (II) and third (III) branches of the right superior longitudinal fasciculus, as well as in the splenium of the corpus callosum. The subgroup of chronic patients showed reduced fractional anisotropy in a portion the splenium, the forceps major, which provides interhemispheric communication between regions of the occipital lobe and of the superior parietal lobules. The severity of neglect correlated with fractional anisotropy values in superior longitudinal fasciculus II/III for subacute patients and in its caudal portion for chronic patients. Our results confirm a key role of fronto-parietal disconnection in the emergence and chronic persistence of neglect, and demonstrate an implication of caudal interhemispheric disconnection in chronic neglect. Splenial disconnection may prevent fronto-parietal networks in the left hemisphere from resolving the activity imbalance with their right hemisphere counterparts, thus leading to persistent neglect.

Synchronization of fronto-parietal beta and theta networks as a signature of visual awareness in neglect

“…These results confirm models according to which disrupted integrity of right-hemisphere frontoparietal networks is a core pathophysiological mechanism in neglect syndrome (Corbetta and Shulman, 2011;Bartolomeo et al, 2012). So far, a disconnection of right fronto-parietal networks in neglect has been demonstrated at the neuroanatomical and neurofunctional level using in-vivo tractography (Thiebaut de Schotten et al, 2005, 2011, lesion mapping (Ptak and Schnider, 2010;Lunven et al, 2015), fMRI (He et al, 2007;Bartolomeo et al, 2012) and resting state networks analysis of MRI and EEG (Baldassarre et al, 2014;Fellrath et al, 2016). However, the role of transient functional synchronization as a network-based mechanism underlying perceptual deficits in neglect has not been identified.…”

“…Thus, consistent with He et al (2007), in acute and subchronic patients studied here, synchronizations of both dorsal and ventral networks were impaired. Critically, as supported by recent neuroanatomical findings (Lunven et al, 2015), the dysfunction of the right dorsal fronto-parietal pair was specific for neglect and predicted independently symptoms of hemi-neglect.…”

“…It has been shown that the functional inhibition of fronto-parietal connections generates an intraoperative neglect-like pattern during a bisection line task in patients undergoing surgery (Thiebaut de Schotten et al, 2005). Using lesion-symptom mapping and fractional anisotropy, specific components of fronto-parietal fibers have been isolated that are responsible for the deficits in modulation of attention by task relevance (Ptak and Schnider, 2010) and for severity of chronic symptoms in neglect (Lunven et al, 2015). By measuring hemodynamic coherent fluctuations in the event-related fMRI signal, He et al (2007) were the first to demonstrate disrupted functional connectivity in fronto-parietal networks in neglect patients, as confirmed recently by analysis of resting state functional connectivity using both MRI (Baldassarre et al, 2014) and highresolution electroencephalographic (EEG) signals (Fellrath et al, 2016).…”

Differential white matter involvement associated with distinct visuospatial deficits after right hemisphere stroke

“…With recent advances in diffusion tensor imaging methods, such as the combination of spherical deconvolution (Dell'Acqua et al, 2007) with adaptive regularization to reject spurious non-physiologic fiber orientations it is possible to tease apart the three components of the SLF (Dell'Acqua & Catani, 2012). It has now been reported that SLF II lateralization is correlated with line bisection bias (Thiebaut de Schotten et al, 2011) and that SLFII damage in particular is associated with spatial neglect (Lunven et al, 2015; Thiebaut de Schotten et al, 2014) refining prior results implicating the SLF (Doricchi & Tomaiuolo, 2003; Leibovitch et al, 1998; Urbanski et al, 2008; Urbanski et al, 2011). …”

“…Other tracts whose damage has been associated with neglect include more ventral pathways that could be considered part of the VAN (Umarova et al, 2010), These include the Inferior Longitudinal Fasciculus (ILF) (Bird et al, 2006) connecting occipital and temporal lobes, and the Inferior Fronto-Occipital Fasciculus (IFOF) (Catani & Thiebaut de Schotten, 2008; Urbanski et al, 2008) which connects the lateral orbitofrontal cortex and marginal gyrus with the inferior middle occipital, ligual and inferior occipital gyri (Forkel et al, 2014; Lawes et al, 2008). More recently, damage to the splenium of the corpus callosum has also been shown to be associated with chronic neglect (Lunven et al, 2015). …”