Disruptions of the Human Connectome Associated With Hemispatial Neglect

Background and ObjectivesHemispatial neglect is a heterogeneous and complex disorder that can be classified by frame of reference for “left” vs “right,” including viewer-centered neglect (VCN, affecting the contralesional side of the view), stimulus-centered neglect (SCN, affecting the contralesional side of the stimulus, irrespective of its location with respect to the viewer), or both. We investigated the effect of acute stroke lesions on the connectivity of neural networks that underlie VCN or SCN.MethodsA total of 174 patients within 48 hours of acute right hemispheric infarct underwent a detailed hemispatial neglect assessment that included oral reading, scene copy, line cancellation, gap detection, horizontal line bisection tests, and MRI. Each patient's connectivity map was generated. We performed a linear association analysis between network connectivity strength and continuous measures of neglect to identify lesion-induced disconnections associated with the presence or severity of VCN and SCN. Results were corrected for multiple comparisons.ResultsAbout 42% of the participants with right hemisphere stroke had at least one type of neglect. The presence of any type of neglect was associated with lesions to tracts connecting the right inferior parietal cortex, orbitofrontal cortex, and right thalamus to other right-hemispheric structures. VCN only was strongly associated with tracts connecting the right putamen to other brain regions and tracts connecting right frontal regions with other brain regions. The presence of both types of neglect was most strongly associated with tracts connecting the right inferior and superior parietal cortex to other brain regions and those connecting left or right mesial temporal cortex to other brain regions.DiscussionOur study provides new evidence for the specific white matter tracts where disruption can cause hemispatial neglect in a relatively large number of participants and homogeneous time after onset. We obtained MRI and behavioral testing acutely, before the opportunity for rehabilitation or substantial recovery.Classification of EvidenceThis study provides Class II evidence that damage to specific white matter tracts identified on MRI are associated with the presence of neglect following right hemispheric stroke.

Engagement of the contralateral limb can enhance the facilitation of motor output by loud acoustic stimuli

When intense sound is presented during light muscle contraction, inhibition of the corticospinal tract is observed. During action preparation, this effect is reversed, with sound resulting in excitation of the corticospinal tract. We investigated how the combined maintenance of a muscle contraction during preparation for a ballistic action impacts the magnitude of the facilitation of motor output by a loud acoustic stimulus (LAS) – a phenomenon known as the StartReact effect. Participants executed ballistic wrist flexion movements and a LAS was presented simultaneously with the imperative signal in a subset of trials. We examined whether the force level or muscle used to maintain a contraction during preparation for the ballistic response impacted reaction time and/or the force of movements triggered by the LAS. These contractions were sustained either ipsilaterally or contralaterally to the ballistic response. The magnitude of facilitation by the LAS was greatest when low force flexion contractions were maintained in the limb contralateral to the ballistic response during preparation. There was little change in facilitation when contractions recruited the contralateral extensor muscle, or when they were sustained in the same limb that executed the ballistic response. We conclude that a larger network of neurons which may be engaged by a contralateral sustained contraction prior to initiation may be recruited by the LAS, further contributing to the motor output of the response. These findings may be particularly applicable in stroke rehabilitation where engagement of the contralesional side may increase the benefits of a LAS to the functional recovery of movement.

Working Memory in Unilateral Spatial Neglect: Evidence for Impaired Binding of Object Identity and Object Location

Working memory (WM) is known to be impaired in patients with stroke experiencing unilateral spatial neglect (USN). Here, we examined in a systematic manner three WM components: memory of object identity, memory of object location, and binding between object identity and location. Moreover, we used two different retention intervals to isolate maintenance from other mnemonic and perceptual processes. Fourteen USN first-event stroke patients with right-hemisphere damage were tested in two different WM experiments using long and short retention intervals and an analog response scale. Patients exhibited more identification errors for items displayed on the contralesional side. Localization errors were also more prominent in the contralesional side, especially after a long retention interval. These localization errors were often a result of swap errors, that is, erroneous localizations of correctly identified contralesional objects in correctly memorized locations of ipsilesional objects. We conclude that a key WM deficit in USN is a lateralized impairment in binding between the identity of an object and its spatial tag.

The clinical course of vestibular neuritis from the point of view of the video Head Impulse Test

Vestibular neuritis (VN) is one of the most common causes of acute vestibular syndrome (AVS). Quantifying the vestibulo-ocular reflex (VOR) gain by the video Head Impulse Test (vHIT) could provide useful information to diagnose VN. This retrospective study is aimed to investigate the clinical course of VN evaluating the horizontal VOR gain (hVOR) values in acute and subacute stages and to correlate these values with the patients’ quality of life. Medical record of 28 patients with VN were reviewed. Patients were assigned to two groups according to the time since the acute vestibular syndrome (AVS). One group with patients assessed within seventy-two hours since the AVS (AVSg) and one group with patients evaluated from four days to six weeks since the AVS (PAVSg). hVOR gain was evaluated in all selected patients and correlated to Dizziness Handicap Inventory (DHI). Significant differences were found in the between-subjects analysis in DHI score (p=0.000) and in the ipsilesional hVOR gain values (p=0.001). The correlation analysis showed significant results (p=0.017) between DHI score ( 40±16.08) and ipsilesional VOR gain (0.65±0.22) in the PAVSg. Patients evaluated within 72 hours since the AVS showed anticompensatory saccades (AcS) turning the head toward the contralesional side. Patients with VN could have dissimilar hVOR gain values and DHI score according to the damage of the VIII pair of cranial nerves. AcS in the contralesional side is a sign of acute phase in patients with VN.

Abstract WP199: Change of Corticospinal Tract Integrity and 6-month Motor Outcome After Stroke: DTI Study

Objective: Corticospinal tract (CST) changes with time after stroke. However, few studies have investigated longitudinal change of CST and its relationship with motor outcomes. Primary goal of this study is to investigate the changes of CST after stroke using diffusion tensor image (DTI) and the relationship between CST changes and functional motor outcome in upper and lower extremities at 6 months after onset of stroke. Methods: We collected data from STroke Outcome Prediction (STOP) database that is prospective data collecting system for functional recovery prediction after stroke based on neuroimaging study. Fifty-five patients with first-ever stroke who performed functional assessment and underwent DTI at 30 days and 6 months poststroke were included. Clinical evaluation included Fugl-Meyer Assessment (FMA), Manual Function Test (MFT), Berg Balance Scale (BBS), and Functional Ambulation Category (FAC). DTI parameters were fiber number (FN), average fiber length (AL), fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), radial diffusivity (RD), laterality index (LI) and delta (Δ) changes of these values. Also type of CST by diffusion tensor tractography was included for analysis. Results: FA decreased and diffusivity indices (AD, MD, RD) increased in ipsilesional hemisphere; Decrease of FA and increase of RD were also noted in contralesional side. Type of CST were changed in 19 patients (34.6%). Spearman correlation analysis showed strong correlations between DTI values (FN, AL, FA, RD) and motor outcomes (FMA, MFT, BBS, FAC) at 30 days and 6 months. However, ΔFA or ΔRD did not show significant correlation with Δ changes of motor outcomes. In the CART analysis, overall prediction accuracy of DTI parameters for 6-month motor outcome ranged from 81.8 to 90.9 %. Conclusion: The integrity of CST changed not only on the lesion side but also on contralesional side. Integrity of CST using DTI at early phase of rehabilitation is useful to predict 6-month motor outcome after stroke. Acknowledgement: No potential conflict of interests relevant to this article were reported. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1A2C2003020).

The caudal fastigial nucleus and the steering of saccades toward a moving visual target

The caudal fastigial nuclei (cFN) are the output nuclei by which the medio-posterior cerebellum influences the production of visual saccades. We investigated in two head-restrained monkeys their contribution to the generation of interceptive saccades toward a target moving centrifugally by analyzing the consequences of a unilateral inactivation (10 injection sessions). We describe here the effects on saccades made toward a centrifugal target that moved along the horizontal meridian with a constant (10, 20, or 40°/s), increasing (from 0 to 40°/s over 600 ms), or decreasing (from 40 to 0°/s over 600 ms) speed. After muscimol injection, the monkeys were unable to foveate the current location of the moving target. The horizontal amplitude of interceptive saccades was reduced during contralesional target motions and hypermetric during ipsilesional ones. For both contralesional and ipsilesional saccades, the magnitude of dysmetria increased with target speed. However, the use of accelerating and decelerating targets revealed that the dependence of dysmetria upon target velocity was not due to the current velocity but to the required amplitude of saccade. We discuss these results in the framework of two hypotheses, the so-called “dual drive” and “bilateral” hypotheses. NEW & NOTEWORTHY Unilateral inactivation of the caudal fastigial nucleus impairs the accuracy of saccades toward a moving target. Like saccades toward a static target, interceptive saccades are hypometric when directed toward the contralesional side and hypermetric when they are ipsilesional. The dysmetria depends on target velocity, but the use of accelerating or decelerating targets reveals that velocity is not the crucial parameter. We extend the bilateral fastigial control of saccades and fixation to the production of interceptive saccades.

Dissociating ego- and allocentric neglect after stroke: prevalence, laterality and outcome predictors

Visuospatial neglect is a neuropsychological condition commonly experienced after stroke, whereby a patient is unable to attend to stimuli on their contralesional side. We aimed to investigate whether egocentric and allocentric neglect are functionally dissociable and differ in prevalence, laterality and outcome predictors. A consecutive sample of 366 acute stroke patients completed the Broken Hearts test from the Oxford Cognitive Screen. A subsample of 160 patients was followed up 6 months later. We evaluated the association between egocentric and allocentric neglect, contrasted the prevalence and severity of left-sided versus right-sided neglect, and determined the predictors of persistence versus recovery at follow up. Clinically, we found a double dissociation between ego- and allocentric neglect, with 50% of the neglect patients showing ‘only’ egocentric neglect and 25% ‘only’ allocentric neglect. Importantly, patients with only allocentric neglect did not demonstrate any egocentric spatial bias in the locations of the allocentric errors. Left-sided egocentric neglect was more prevalent and more severe than right-sided egocentric neglect, though right-sided neglect was still highly prevalent in the acute stroke sample (35%). Leftsided allocentric neglect was more severe but not more prevalent than right-sided allocentric neglect. Overall recovery of neglect was high: 81% of egocentric and 75% of allocentric neglect patients recovered. Severity of neglect was the only significant behavioural measure for predicting recovery at 6 months.

“Nonspatial” Attentional Deficits Interact with Spatial Position in Neglect

A widely debated question concerns whether or not spatial and nonspatial components of visual attention interact in attentional performance. Spatial neglect is a common consequence of brain injury where individuals fail to respond to stimuli presented on their contralesional side. It has been argued that, beyond the spatial bias, these individuals also tend to exhibit nonspatial perceptual deficits. Here we demonstrate that the “nonspatial” deficits affecting the temporal dynamics of attentional deployment are in fact modulated by spatial position. Specifically, we observed that the pathological attentional blink of chronic neglect is enhanced when stimuli are presented on the contralesional side of the trunk while keeping retinal and head-centered coordinates constant. We did not find this pattern in right brain-damaged patients without neglect or in patients who had recovered from neglect. Our work suggests that the nonspatial attentional deficits observed in neglect are heavily modulated by egocentric spatial position. This provides strong evidence against models that suggest independent modules for spatial and nonspatial attentional functions while also providing strong evidence that trunk position plays an important role in neglect.

Abstract WP263: Feasibility and Utility Of EEG for Estimating Infarct Volume During ER Assessment of Suspected Acute Stroke--A Pilot Study

Introduction: Endovascular therapy (EVT) improves outcomes in the setting of acute ischemic stroke (AIS) in a time-dependent manner, highlighting the need for improved methods to rapidly identify eligible patients, particularly in the pre-hospital setting. Current pre-hospital assessments are imprecise for this goal. Pre-hospital measurement of brain injury via EEG might provide additional useful diagnostic information regarding EVT eligibility. As a first step, the current study examined (1) feasibility of obtaining EEG early during ER assessment of patients with suspected AIS, and (2) EEG metrics predicting infarct volume. Methods: In subjects transported to the UC Irvine Medical Center for suspected AIS, a 3 min dense-array resting EEG was obtained during ED assessment. Results: EEG was acquired in 25 subjects (mean age 65 yr), 12 of whom were discharged with a diagnosis of radiologically confirmed AIS and 13 of whom were discharged with a non-stroke diagnosis. Median time from ED arrival to EEG = 114 min (and as early as 32 min after arrival), and time from last known well to EEG = 333 min. EEG was acquired in 24 subjects, with data lost due to human error in 1 subject. Among patients with AIS, median NIHSS score = 4 (range 0-19) and median infarct volume = 12 cc (range 0.3- 83). Infarct volume was found to correlate inversely with power in the low beta (13-19Hz) frequency range, bilaterally: larger infarcts were associated with reduced beta power in the leads over motor cortex (C3, C4) on the ipsilesional side (rho = -0.57, p=0.03) and on the contralesional side (rho = -0.60, p=0.02). Conclusions: The current findings support the potential of rapid EEG methods to identify patients with large infarcts who may be ideal candidates for EVT. Future studies will examine how well current findings extend to the pre-hospital setting, and how specific these EEG findings are for patients eligible for EVT.