Correction to: Automatic identification of atypical clinical fMRI results.

The above article was published online with an incorrect affiliation.

Automatic identification of atypical clinical fMRI results.

PURPOSE: Functional MRI is not routinely used for neurosurgical planning despite potential important advantages, due to difficulty of determining quality. We introduce a novel method for objective evaluation of fMRI scan quality, based on activation maps. A template matching analysis (TMA) is presented and tested on data from two clinical fMRI protocols, performed by healthy controls in seven clinical centers. Preliminary clinical utility is tested with data from low-grade glioma patients. METHODS: Data were collected from 42 healthy subjects from seven centers, with standardized finger tapping (FT) and verb generation (VG) tasks. Copies of these "typical" data were deliberately analyzed incorrectly to assess feasibility of identifying them as "atypical." Analyses of the VG task administered to 32 tumor patients assessed sensitivity of the TMA method to anatomical abnormalities. RESULTS: TMA identified all atypical activity maps for both tasks, at the cost of incorrectly classifying 3.6 (VG)-6.5% (FT) of typical maps as atypical. For patients, the average TMA was significantly higher than atypical healthy scans, despite localized anatomical abnormalities caused by a tumor. CONCLUSION: This study supports feasibility of TMA for objective identification of atypical activation patterns for motor and verb generation fMRI protocols. TMA can facilitate the use and evaluation of clinical fMRI in hospital settings that have limited access to fMRI experts. In a clinical setting, this method could be applied to automatically flag fMRI scans showing atypical activation patterns for further investigation to determine whether atypicality is caused by poor scan data quality or abnormal functional topography.

Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke.

Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients, and used machine-learning models to predict neurological impairment in individual subjects. We found that visual memory and verbal memory were better predicted by FC, whereas visual and motor impairments were better predicted by lesion topography. Attention and language deficits were well predicted by both. Next, we identified a general pattern of physiological network dysfunction consisting of decrease of interhemispheric integration and intrahemispheric segregation, which strongly related to behavioral impairment in multiple domains. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains. These results link key organizational features of brain networks to brain-behavior relationships in stroke.

Normalization of network connectivity in hemispatial neglect recovery.

OBJECTIVE: We recently reported that spatial and nonspatial attention deficits in stroke patients with hemispatial neglect are correlated at 2 weeks postonset with widespread alterations of interhemispheric and intrahemispheric functional connectivity (FC) measured with resting-state functional magnetic resonance imaging across multiple brain networks. The mechanisms underlying neglect recovery are largely unknown. In this study, we test the hypothesis that recovery of hemispatial neglect correlates with a return of network connectivity toward a normal pattern, herein defined as "network normalization." METHODS: We measured attention deficits with a neuropsychological battery and FC in a large cohort of stroke patients at, on average, 2 weeks (n = 99), 3 months (n = 77), and 12 months (n = 64) postonset. The relationship between behavioral improvement and changes in FC was analyzed both in terms of a priori regions and networks known to be abnormal subacutely and in a data-driven manner. RESULTS: Attention deficit recovery was mostly complete by 3 months and was significantly correlated with a normalization of abnormal FC across many networks. Improvement of attention deficits, independent of initial severity, was correlated with improvements of previously depressed interhemispheric FC across attention, sensory, and motor networks, and a restoration of the normal anticorrelation between dorsal attention/motor regions and default-mode/frontoparietal regions, particularly in the damaged hemisphere. INTERPRETATION: These results demonstrate that abnormal network connectivity in hemispatial neglect is behaviorally relevant. A return toward normal network interactions, and presumably optimal information processing, is therefore a systems-level mechanism that is associated with improvements of attention over time after focal injury. Ann Neurol 2016;80:127-141.

Brain connectivity and neurological disorders after stroke.

PURPOSE OF REVIEW: An important challenge in neurology is identifying the neural mechanisms underlying behavioral deficits after brain injury. Here, we review recent advances in understanding the effects of focal brain lesions on brain networks and behavior. RECENT FINDINGS: Neuroimaging studies indicate that the human brain is organized in large-scale resting state networks (RSNs) defined via functional connectivity, that is the temporal correlation of spontaneous activity between different areas. Prior studies showed that focal brain lesion induced behaviorally relevant changes of functional connectivity beyond the site of damage. Recent work indicates that across domains, functional connectivity changes largely conform to two patterns: a reduction in interhemispheric functional connectivity and an increase in intrahemispheric functional connectivity between networks that are normally anticorrelated, for example dorsal attention and default networks. Abnormal functional connectivity can exhibit a high degree of behavioral specificity such that deficits in a given behavioral domain are selectively related to functional connectivity of the corresponding RSN, but some functional connectivity changes allow prediction across domains. Finally, as behavioral recovery proceeds, the prestroke pattern of functional connectivity is restored. SUMMARY: Investigating changes in RSNs may shed light on the neural mechanisms underlying brain dysfunction after stroke. Therefore, resting state functional connectivity may represent an important tool for clinical diagnosis, tracking recovery and rehabilitation.

Re-emergence of modular brain networks in stroke recovery.

Studies of stroke have identified local reorganization in perilesional tissue. However, because the brain is highly networked, strokes also broadly alter the brain's global network organization. Here, we assess brain network structure longitudinally in adult stroke patients using resting state fMRI. The topology and boundaries of cortical regions remain grossly unchanged across recovery. In contrast, the modularity of brain systems i.e. the degree of integration within and segregation between networks, was significantly reduced sub-acutely (n = 107), but partially recovered by 3 months (n = 85), and 1 year (n = 67). Importantly, network recovery correlated with recovery from language, spatial memory, and attention deficits, but not motor or visual deficits. Finally, in-depth single subject analyses were conducted using tools for visualization of changes in brain networks over time. This exploration indicated that changes in modularity during successful recovery reflect specific alterations in the relationships between different networks. For example, in a patient with left temporo-parietal stroke and severe aphasia, sub-acute loss of modularity reflected loss of association between frontal and temporo-parietal regions bi-hemispherically across multiple modules. These long-distance connections then returned over time, paralleling aphasia recovery. This work establishes the potential importance of normalization of large-scale modular brain systems in stroke recovery.

Early diffusion evidence of retrograde transsynaptic degeneration in the human visual system.

OBJECTIVE: We investigated whether diffusion tensor imaging (DTI) indices of white matter integrity would offer early markers of retrograde transsynaptic degeneration (RTD) in the visual system after stroke. METHODS: We performed a prospective longitudinal analysis of the sensitivity of DTI markers of optic tract health in 12 patients with postsynaptic visual pathway stroke, 12 stroke controls, and 28 healthy controls. We examined group differences in (1) optic tract fractional anisotropy (FA-asymmetry), (2) perimetric measures of visual impairment, and (3) the relationship between FA-asymmetry and perimetric assessment. RESULTS: FA-asymmetry was higher in patients with visual pathway lesions than in control groups. These differences were evident 3 months from the time of injury and did not change significantly at 12 months. Perimetric measures showed evidence of impairment in participants with visual pathway stroke but not in control groups. A significant association was observed between FA-asymmetry and perimetric measures at 3 months, which persisted at 12 months. CONCLUSIONS: DTI markers of RTD are apparent 3 months from the time of injury. This represents the earliest noninvasive evidence of RTD in any species. Furthermore, these measures associate with measures of visual impairment. DTI measures offer a reproducible, noninvasive, and sensitive method of investigating RTD and its role in visual impairment.