| Higher Cortical Functions  

Persisting spatial neglect correlates with transneuronal damage to the attention network in the contralesional hemisphere

This important study is the first to present neuroanatomical evidence for transneuronal damage to functional homologues of the attention  network in the contralesional hemisphere being critical for impaired recovery of stroke-induced hemispatial neglect.

by Wolfgang Heide

This important study is the first to present neuroanatomical evidence for transneuronal damage to functional homologues of the attention  network in the contralesional hemisphere being critical for impaired recovery of stroke-induced hemispatial neglect. It thus supports the compensational role of the contralesional hemisphere in residual performance, for which they had presented evidence in a previous study investigating the functional connectivity within this network using task-related f-MRI1. Another study published 1 month ago has presented analogous findings for damage to fiber tracts in the ipsilesional hemisphere2.

Here, the authors uncovered structural signatures for remote dysfunction within the spatial attention network, corroborating the interdependence of functional and structural networks in the human brain. The findings are in line with data discussing neglect as an imbalance of distributed brain networks3 and disruption syndrome. The findings should be confirmed for left hemisphere syndromes. A limitation of the study is that it did not assess separately the nonlateralized attentional deficit. Neglect is a multicomponent syndrome, and future studies are required to further investigate the longitudinal stroke-induced brain dynamics.

Patients with visuospatial attention deficit exhibit remote white matter remodeling with distinct signatures: (1) axonal degeneration in the ipsilesional hemisphere, including areas remote from the lesion; and (2) transneuronal alterations to the contralesional frontoparietal and bilateral occipital connections, suggestive of primary periaxonal involvement. Whereas the extent of both types of white matter remodeling is predicted by lesion size, initial NIHSS, and initial neglect severity, only the transneuronal changes are network-specific by correlating with persisting deficit.

The authors performed diffusion tensor imaging and global fiber tracking in 41 patients with right hemispheric stroke with (n=24) or without (n=17) visual neglect in the acute (6-7 days post stroke) or chronic stage (4-5 months post stroke).

Compared to stroke controls, patients with spatial neglect/extinction displayed longitudinal white matter alterations with 2 defining signatures:

(1) perilesional degenerative changes characterized by congruently reduced fractional anisotropy, suggestive of direct axonal damage by lesion and therefore nonspecific for impaired attention network and

(2) transneuronal changes characterized by an increased radial diffusivity in contralesional fronto-parietal and bilateral occipital connections, suggestive of primary periaxonal involvement; these changes were distinctly related to the degree of unrecovered neglect symptoms in chronic stroke, hence emerging as network-specific alterations.

In conclusion, sufficiently large lesions of widely interconnected association cortex induce distinct, large-scale structural reorganization in domain-specific network connections. Besides their relevance to unrecovered domain-specific symptoms, these effects might also explain mechanisms of domain-general deficits in stroke patients,

1Umarova RM, Nitschke K, Kaller CP, Klöppel S, Beume L, Mader I, Martin M, Hennig J, Weiller C. Predictors and signatures of recovery from neglect in acute stroke. Ann Neurol. 2016 Apr;79(4):673-86. doi: 10.1002/ana.24614. Epub 2016 Mar 15.

2Hattori T, Ito K, Nakazawa C, Numasawa Y, Watanabe M, Aoki S, Mizusawa H, Ishiai S, Yokota T. Structural connectivity in spatial attention network: reconstruction from left hemispatial neglect. Brain Imaging Behav. 2017 Mar 13. doi: 10.1007/s11682-017-9698-7. [Epub ahead of print]

3Baldassarre A, Ramsey L, Hacker CL, et al. Large-scale changes in network interactions as a physiological signature of spatial neglect. Brain 137: 3267-3283. Epub 2014 Oct 31.