Spatial neglect treatment: The brain's spatial-motor Aiming systems.

Animal and human literature supports spatial-motor "Aiming" bias, a frontal-subcortical syndrome, as a core deficit in spatial neglect. However, spatial neglect treatment studies rarely assess Aiming errors. Two knowledge gaps result: spatial neglect rehabilitation studies fail to capture the impact on motor-exploratory aspects of functional disability. Also, across spatial neglect treatment studies, discrepant treatment effects may also result from sampling different proportions of patients with Aiming bias. We review behavioural evidence for Aiming spatial neglect, and demonstrate the importance of measuring and targeting Aiming bias for treatment, by reviewing literature on Aiming spatial neglect and prism adaptation treatment, and presenting new preliminary data on bromocriptine treatment. Finally, we review neuroanatomical and network disruption that may give rise to Aiming spatial neglect. Because Aiming spatial neglect predicts prism adaptation treatment response, assessment may broaden the ability of rehabilitation research to capture functionally-relevant disability. Frontal brain lesions predict both the presence of Aiming spatial neglect, and a robust response to some spatial neglect interventions. Research is needed that co-stratifies spatial neglect patients by lesion location and Aiming spatial neglect, to personalize spatial neglect rehabilitation and perhaps even open a path to spatial retraining as a means of promoting better mobility after stroke.

Frontal lesions predict response to prism adaptation treatment in spatial neglect: A randomised controlled study.

Spatial neglect commonly follows right hemisphere stroke. It is defined as impaired contralesional stimulus detection, response, or action, causing functional disability. While prism adaptation treatment is highly promising to promote functional recovery of spatial neglect, not all individuals respond. Consistent with a primary effect of prism adaptation on spatial movements, we previously demonstrated that functional improvement after prism adaptation treatment is linked to frontal lobe lesions. However, that study was a treatment-only study with no randomised control group. The current study randomised individuals with spatial neglect to receive 10 days of prism adaptation treatment or to receive only standard care (control group). Replicating our earlier results, we found that the presence of frontal lesions moderated response to prism adaptation treatment: among prism-treated patients, only those with frontal lesions demonstrated functional improvements in their neglect symptoms. Conversely, among individuals in the standard care control group, the presence of frontal lesions did not modify recovery. These results suggest that further research is needed on how frontal lesions may predict response to prism adaptation treatment. Additionally, the results help elucidate the neural network involved in spatial movement and could be used to aid decisions about treatment.

Prism adaptation and spatial neglect: the need for dose-finding studies.

Spatial neglect is a devastating disorder in 50-70% of right-brain stroke survivors, who have problems attending to, or making movements towards, left-sided stimuli, and experience a high risk of chronic dependence. Prism adaptation is a promising treatment for neglect that involves brief, daily visuo-motor training sessions while wearing optical prisms. Its benefits extend to functional behaviors such as dressing, with effects lasting 6 months or longer. Because one to two sessions of prism adaptation induce adaptive changes in both spatial-motor behavior (Fortis et al., 2011) and brain function (Saj et al., 2013), it is possible stroke patients may benefit from treatment periods shorter than the standard, intensive protocol of ten sessions over two weeks-a protocol that is impractical for either US inpatient or outpatient rehabilitation. Demonstrating the effectiveness of a lower dose will maximize the availability of neglect treatment. We present preliminary data suggesting that four to six sessions of prism treatment may induce a large treatment effect, maintained three to four weeks post-treatment. We call for a systematic, randomized clinical trial to establish the minimal effective dose suitable for stroke intervention.

Kessler Foundation Neglect Assessment Process uniquely measures spatial neglect during activities of daily living.

OBJECTIVES: To explore the factor structure of the Kessler Foundation Neglect Assessment Process (KF-NAP), and evaluate the prevalence and clinical significance of spatial neglect among stroke survivors. DESIGN: Inception cohort. SETTING: Inpatient rehabilitation facility (IRF). PARTICIPANTS: Participants (N=121) with unilateral brain damage from their first stroke were assessed within 72 hours of admission to an IRF, and 108 were assessed again within 72 hours before IRF discharge. INTERVENTIONS: Usual and standard IRF care. MAIN OUTCOME MEASURES: During each assessment session, occupational therapists measured patients' functions with the KF-NAP, FIM, and Barthel Index (BI). RESULTS: The KF-NAP showed excellent internal consistency with a single-factor structure. The exploratory factor analysis revealed the KF-NAP to be unique from both the FIM and BI even though all 3 scales were correlated. Symptoms of spatial neglect (KF-NAP>0) were present in 67.8% of the participants at admission and 47.2% at discharge. Participants showing the disorder at IRF admission were hospitalized longer than those showing no symptoms. Among those presenting with symptoms, the regression analysis showed that the KF-NAP scores at admission negatively predicted FIM scores at discharge, after controlling for age, FIM at admission, and length of stay. CONCLUSIONS: The KF-NAP uniquely quantifies symptoms of spatial neglect by measuring functional difficulties that are not captured by the FIM or BI. Using the KF-NAP to measure spatial neglect, we found the disorder persistent after inpatient rehabilitation, and replicated previous findings showing that spatial neglect adversely affects rehabilitation outcome even after prolonged IRF care.

Ipsilesional neglect: behavioral and anatomical correlates.

UNLABELLED: [Correction Notice: An Erratum for this article was reported in Vol 29(2) of Neuropsychology (see record 2014-42242-001). The funding source information was missing from the author note, and A. M. Barrett's institutional affiliation was incorrect. The funding source information and Barrett's correct institutional affiliation are provided in the erratum.] OBJECTIVE: The sparse existing research on ipsilesional neglect supports an association of this disorder with damage to the right frontal and subcortical brain networks. It is believed that dysfunction in these networks may result in primarily "aiming" motor-intentional spatial errors. The purpose of this study was to confirm whether frontal-subcortical circuits are indeed commonly affected in ipsilesional neglect and to determine the relative presence of "aiming" motor-intentional versus "where" perceptual-attentional spatial errors in these individuals. METHODS: We identified 12 participants with ipsilesional neglect based on a computerized line bisection task and used the line bisection data to quantify participants' perceptual-attentional and motor-intentional errors. We were able to discriminate between these 2 biases using the algebraic solutions for 2 separate equations, one for "aiming" and one for "where" biases. Lesion mapping was conducted for all participants using MRIcron software; lesion checklist and overlap analysis were created from these images. RESULTS: A greater percentage of participants with ipsilesional neglect had frontal/subcortical damage (83%) compared with the expected percentage (27%) observed in published patient samples with contralesional neglect. We observed the greatest area of lesion overlap in frontal lobe white matter pathways. Nevertheless, participants with ipsilesional neglect made primarily "where" rather than "aiming" spatial errors. CONCLUSION: Our data confirm previous research suggesting that ipsilesional neglect may result from lesions to the right frontal-subcortical networks. Furthermore, in our group, ipsilesional neglect was also strongly associated with primarily "where" perceptual-attentional bias, and less so with "aiming" motor-intentional spatial bias.

Differences in the weighting and choice of evidence for plausible versus implausible causes.

Individuals have difficulty changing their causal beliefs in light of contradictory evidence. We hypothesized that this difficulty arises because people facing implausible causes give greater consideration to causal alternatives, which, because of their use of a positive test strategy, leads to differential weighting of contingency evidence. Across 4 experiments, participants learned about plausible or implausible causes of outcomes. Additionally, we assessed the effects of participants' ability to think of alternative causes of the outcomes. Participants either saw complete frequency information (Experiments 1 and 2) or chose what information to see (Experiments 3 and 4). Consistent with the positive test account, participants given implausible causes were more likely to inquire about the occurrence of the outcome in the absence of the cause (Experiments 3 and 4) than those given plausible causes. Furthermore, they gave less weight to Cells A and B in a 2 × 2 contingency table and gave either equal or less weight to Cells C and D (Experiments 1 and 2). These effects were inconsistently modified by participants' ability to consider alternative causes of the outcome. The total of the observed effects are not predicted by either dominant models of normative causal inference or by the particular positive test account proposed here, but they may be commensurate with a more broadly construed positive test account.

Priming interdependence affects processing of context information in causal inference--but not how you might think.

Cultural mindset is related to performance on a variety of cognitive tasks. In particular, studies of both chronic and situationally-primed mindsets show that individuals with a relatively interdependent mindset (i.e., an emphasis on relationships and connections among individuals) are more sensitive to background contextual information than individuals with a more independent mindset. Two experiments tested whether priming cultural mindset would affect sensitivity to background causes in a contingency learning and causal inference task. Participants were primed (either independent or interdependent), and then saw complete contingency information on each of 12 trials for two cover stories in Experiment 1 (hiking causing skin rashes, severed brakes causing wrecked cars) and two additional cover stories in Experiment 2 (school deadlines causing stress, fertilizers causing plant growth). We expected that relative to independent-primed participants, those interdependent-primed would give more weight to the explicitly-presented data indicative of hidden alternative background causes, but they did not do so. In Experiment 1, interdependents gave less weight to the data indicative of hidden background causes for the car accident cover story and showed a decreased sensitivity to the contingencies for that story. In Experiment 2, interdependents placed less weight on the observable data for cover stories that supported more extra-experimental causes, while independents' sensitivity did not vary with these extra-experimental causes. Thus, interdependents were more sensitive to background causes not explicitly presented in the experiment, but this sensitivity hurt rather than improved their acquisition of the explicitly-presented contingency information.

Integrity of medial temporal structures may predict better improvement of spatial neglect with prism adaptation treatment.

Prism adaptation treatment (PAT) is a promising rehabilitative method for functional recovery in persons with spatial neglect. Previous research suggests that PAT improves motor-intentional "aiming" deficits that frequently occur with frontal lesions. To test whether presence of frontal lesions predicted better improvement of spatial neglect after PAT, the current study evaluated neglect-specific improvement in functional activities (assessment with the Catherine Bergego Scale) over time in 21 right-brain-damaged stroke survivors with left-sided spatial neglect. The results demonstrated that neglect patients' functional activities improved after two weeks of PAT and continued improving for four weeks. Such functional improvement did not occur equally in all of the participants: Neglect patients with lesions involving the frontal cortex (n = 13) experienced significantly better functional improvement than did those without frontal lesions (n = 8). More importantly, voxel-based lesion-behavior mapping (VLBM) revealed that in comparison to the group of patients without frontal lesions, the frontal-lesioned neglect patients had intact regions in the medial temporal areas, the superior temporal areas, and the inferior longitudinal fasciculus. The medial cortical and subcortical areas in the temporal lobe were especially distinguished in the "frontal lesion" group. The findings suggest that the integrity of medial temporal structures may play an important role in supporting functional improvement after PAT.

Presence of Motor-Intentional Aiming Deficit Predicts Functional Improvement of Spatial Neglect With Prism Adaptation.

UNLABELLED: Background Spatial neglect is a debilitating disorder for which there is no agreed on course of rehabilitation. The lack of consensus on treatment may result from systematic differences in the syndrome's characteristics, with spatial cognitive deficits potentially affecting perceptual-attentional "Where" or motor-intentional "Aiming" spatial processing. Heterogeneity of response to treatment might be explained by different treatment impacts on these dissociated deficits: prism adaptation, for example, might reduce Aiming deficits without affecting Where spatial deficits. OBJECTIVE: Here, we tested the hypothesis that classifying patients by their profile of Where-versus-Aiming spatial deficit would predict response to prism adaptation and specifically that patients with Aiming bias would have better recovery than those with isolated Where bias. Methods We classified the spatial errors of 24 subacute right stroke survivors with left spatial neglect as (1) isolated Where bias, (2) isolated Aiming bias, or (3) both. Participants then completed 2 weeks of prism adaptation treatment. They also completed the Behavioral Inattention Test and Catherine Bergego Scale (CBS) tests of neglect recovery weekly for 6 weeks. Results As hypothesized, participants with only Aiming deficits improved on the CBS, whereas those with only Where deficits did not improve. Participants with both deficits demonstrated intermediate improvement. Conclusion These results support behavioral classification of spatial neglect patients as a potential valuable tool for assigning targeted, effective early rehabilitation.

Advancing the science of spatial neglect rehabilitation: an improved statistical approach with mixed linear modeling.

VALID RESEARCH ON NEGLECT REHABILITATION DEMANDS A STATISTICAL APPROACH COMMENSURATE WITH THE CHARACTERISTICS OF NEGLECT REHABILITATION DATA: neglect arises from impairment in distinct brain networks leading to large between-subject variability in baseline symptoms and recovery trajectories. Studies enrolling medically ill, disabled patients, may suffer from missing, unbalanced data, and small sample sizes. Finally, assessment of rehabilitation requires a description of continuous recovery trajectories. Unfortunately, the statistical method currently employed in most studies of neglect treatment [repeated measures analysis of variance (ANOVA), rANOVA] does not well-address these issues. Here we review an alternative, mixed linear modeling (MLM), that is more appropriate for assessing change over time. MLM better accounts for between-subject heterogeneity in baseline neglect severity and in recovery trajectory. MLM does not require complete or balanced data, nor does it make strict assumptions regarding the data structure. Furthermore, because MLM better models between-subject heterogeneity it often results in increased power to observe treatment effects with smaller samples. After reviewing current practices in the field, and the assumptions of rANOVA, we provide an introduction to MLM. We review its assumptions, uses, advantages, and disadvantages. Using real and simulated data, we illustrate how MLM may improve the ability to detect effects of treatment over ANOVA, particularly with the small samples typical of neglect research. Furthermore, our simulation analyses result in recommendations for the design of future rehabilitation studies. Because between-subject heterogeneity is one important reason why studies of neglect treatments often yield conflicting results, employing statistical procedures that model this heterogeneity more accurately will increase the efficiency of our efforts to find treatments to improve the lives of individuals with neglect.

Functional assessment of spatial neglect: a review of the Catherine Bergego scale and an introduction of the Kessler foundation neglect assessment process.

Spatial neglect is a debilitating poststroke neurocognitive disorder associated with prolonged hospitalization and poor rehabilitation outcomes. The literature suggests a high prevalence of this disorder, but clinicians have difficulty reliably identifying affected survivors. This discrepancy may result from suboptimal use of validated neglect assessment procedures. In this article, we suggest use of a validated assessment tool that is sensitive to identification of neglect and its functional consequences - the Catherine Bergego Scale (CBS). We provide detailed item-by-item instructions for observation and scoring - the Kessler Foundation Neglect Assessment Process (KF-NAP). Rehabilitation researchers may be able to use the CBS via the KF-NAP to measure ecological outcomes and specific, separable perceptual-attentional and motor-exploratory spatial behaviors.

Prism adaptation for spatial neglect after stroke: translational practice gaps.

Spatial neglect increases hospital morbidity and costs in around 50% of the 795,000 people per year in the USA who survive stroke, and an urgent need exists to reduce the care burden of this condition. However, effective acute treatment for neglect has been elusive. In this article, we review 48 studies of a treatment of intense neuroscience interest: prism adaptation training. Due to its effects on spatial motor 'aiming', prism adaptation training may act to reduce neglect-related disability. However, research failed, first, to suggest methods to identify the 50-75% of patients who respond to treatment; second, to measure short-term and long-term outcomes in both mechanism-specific and functionally valid ways; third, to confirm treatment utility during the critical first 8 weeks poststroke; and last, to base treatment protocols on systematic dose-response data. Thus, considerable investment in prism adaptation research has not yet touched the fundamentals needed for clinical implementation. We suggest improved standards and better spatial motor models for further research, so as to clarify when, how and for whom prism adaptation should be applied.

Clock drawing in spatial neglect: a comprehensive analysis of clock perimeter, placement, and accuracy.

Clock drawings produced by right-brain-damaged (RBD) individuals with spatial neglect often contain an abundance of empty space on the left while numbers and hands are placed on the right. However, the clock perimeter is rarely compromised in neglect patients' drawings. By analysing clock drawings produced by 71 RBD and 40 healthy adults, this study investigated whether the geometric characteristics of the clock perimeter reveal novel insights to understanding spatial neglect. Neglect participants drew smaller clocks than either healthy or non-neglect RBD participants. While healthy participants' clock perimeter was close to circular, RBD participants drew radially extended ellipses. The mechanisms for these phenomena were investigated by examining the relation between clock-drawing characteristics and performance on six subtests of the Behavioral Inattention Test (BIT). The findings indicated that the clock shape was independent of any BIT subtest or the drawing placement on the test sheet and that the clock size was significantly predicted by one BIT subtest: the poorer the figure and shape copying, the smaller the clock perimeter. Further analyses revealed that in all participants, clocks decreased in size as they were placed farther from the centre of the paper. However, even when neglect participants placed their clocks towards the centre of the page, they were smaller than those produced by healthy or non-neglect RBD participants. These results suggest a neglect-specific reduction in the subjectively available workspace for graphic production from memory, consistent with the hypothesis that neglect patients are impaired in the ability to enlarge the attentional aperture.

Psychometric evaluation of neglect assessment reveals motor-exploratory predictor of functional disability in acute-stage spatial neglect.

OBJECTIVE: To determine the psychometric properties of 2 neglect measures, the Behavioral Inattention Test (BIT)-conventional and the Catherine Bergego Scale (CBS), in acute spatial neglect. Spatial neglect is a failure or slowness to respond, orient, or initiate action toward contralesional stimuli, associated with functional disability that impedes stroke recovery. Early identification of specific neglect deficits may identify patients likely to experience chronic disability. However, psychometric evaluation of assessments has focused on subacute/chronic populations. DESIGN: Correlational/psychometric study. SETTING: Inpatient rehabilitation hospital. PARTICIPANTS: Screening identified 51 consecutive patients with a right-hemisphere stroke with left neglect (BIT score <129 or CBS score >11) tested an average of 22.3 days poststroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We obtained BIT, CBS, and Barthel Index assessments for each participant and clinical and laboratory measures of perceptual-attentional and motor-intentional deficits. RESULTS: The BIT showed good reliability and loaded onto a single factor. Consistent with our theoretical prediction, principal components analysis of the CBS identified 2 underlying factors: Where perceptual-attentional items (CBS-PA) and embodied, motor-exploratory items (CBS-ME). The CBS-ME uniquely predicted deficits in activities of daily living (ADLs) assessed by using the Barthel Index, but did not predict clinical and laboratory assessments of motor-intentional bias. More severe neglect on the CBS-PA correlated with greater Where perceptual-attentional bias on clinical and laboratory tests, but did not uniquely predict deficits in ADLs. CONCLUSIONS: Our results indicate that assessments of spatial neglect may be used to detect specific motor-exploratory deficits in spatial neglect. Obtaining CBS-ME scores routinely might improve the detection of acute-stage patients with spatial action deficits requiring increased assistance that may persist to the chronic stage.

Effects of prism adaptation on motor-intentional spatial bias in neglect.

Prism adaptation may alleviate some symptoms of spatial neglect. However, the mechanism through which this technique works is still unclear. This study investigated whether prism adaptation differentially affects dysfunction in perceptual-attentional 'where' bias versus motor-intentional 'aiming' bias. Five neglect patients performed a line bisection task in which lines were viewed under both normal and right-left reversed viewing conditions, allowing for the fractionation of 'where' and 'aiming' spatial bias components. After two consecutive days of prism adaptation, participants demonstrated a significant improvement in 'aiming' spatial bias, with no effect on 'where' spatial bias. These findings suggest that prism adaptation may primarily affect motor-intentional 'aiming' bias in poststroke spatial neglect patients.

Prism adaptation differently affects motor-intentional and perceptual-attentional biases in healthy individuals.

Prism adaptation (PA) has been shown to affect performance on a variety of spatial tasks in healthy individuals and neglect patients. However, little is still known about the mechanisms through which PA affects spatial cognition. In the present study we tested the effect of PA on the perceptual-attentional "where" and motor-intentional "aiming" spatial systems in healthy individuals. Eighty-four participants performed a line bisection task presented on a computer screen under normal or right-left reversed viewing conditions, which allows for the fractionation of "where" and "aiming" bias components (Schwartz et al., 1997). The task was performed before and after a short period of visuomotor adaptation either to left- or right-shifting prisms, or control goggles fitted with plain glass lenses. Participants demonstrated initial leftward "where" and "aiming" biases, consistent with previous research. Adaptation to left-shifting prisms reduced the leftward motor-intentional "aiming" bias. By contrast, the "aiming" bias was unaffected by adaptation to the right-shifting prisms or control goggles. The leftward "where" bias was also reduced, but this reduction was independent of the direction of the prismatic shift. These results mirror recent findings in neglect patients, who showed a selective amelioration of right motor-intentional "aiming" bias after right prism exposure (Fortis et al., 2009; C.L. Striemer & J. Danckert, 2010). Thus, these findings indicate that prism adaptation primarily affects the motor-intentional "aiming" system in both healthy individuals and neglect patients, and further suggest that improvement in neglect patients after PA may be related to changes in the aiming spatial system.

Spatial bias and right hemisphere function: sex-specific changes with aging.

Patterns of cerebral asymmetry related to visuospatial functions may change with age. The typical leftward bias on a line bisection task may reflect cerebral asymmetry. With age, such leftward bias decreases. This study demonstrated that the age-related decrease of leftward bias may actually be sex-specific. In addition, previous research suggests that young adults' deviation in line bisection may reflect asymmetric hemispheric activation of perceptual-attentional "where" spatial systems, rather than motor-intentional "aiming" spatial systems; thus, we specifically fractionated "where" and "aiming" bias of men and women ranging in age from 22 to 93 years old. We observed that older men produced greater rightward line bisection errors, of primarily "where" spatial character. However, women's errors remained leftward biased, and did not significantly change with age. "Where" spatial systems may be linked to cortico-cortical processing networks involving the posterior part of the dorsal visuospatial processing stream. Thus, the current results are consistent with the conclusion that reduced right dorsal spatial activity in aging may occur in the male, but not female, adult spatial system development.

Asymmetrical effects of adaptation to left- and right-shifting prisms depends on pre-existing attentional biases.

Proposals that adaptation with left-shifting prisms induces neglect-like symptoms in normal individuals rely on a dissociation between the postadaptation performance of individuals trained with left- versus right-shifting prisms (e.g., Colent, Pisella, & Rossetti, 2000). A potential problem with this evidence is that normal young adults have an a priori leftward bias (e.g., Jewell & McCourt, 2000). In Experiment 1, we compared the line bisection performance of young adults to that of aged adults, who as a group may lack a leftward bias in line bisection. Participants trained with both left- and right-shifting prisms. Consistent with our hypothesis, while young adults demonstrated aftereffects for left, but not right prisms, aged adults demonstrated reliable aftereffects for both prisms. In Experiment 2, we recruited a larger sample of young adults, some of whom were right-biased at baseline. We observed an interaction between baseline bias and prism-shift, consistent with the results of Experiment 1: Left-biased individuals showed a reduced aftereffect when training with right-shifting prisms and right-biased individuals showed a reduced aftereffect when training with left-shifting prisms. These results suggest that previous failures to find generalizable aftereffects with right-shifting prisms may be driven by participants' baseline biases rather than specific effects of the prism itself.

Causal discounting in the presence of a stronger cue is due to bias.

People use information about the covariation between a putative cause and an outcome to determine whether a causal relationship obtains. When there are two candidate causes and one is more strongly related to the effect than is the other, the influence of the second is underestimated. This phenomenon is called causal discounting. In two experiments, we adapted paradigms for studying causal learning in order to apply signal detection analysis to this phenomenon. We investigated whether the presence of a stronger alternative makes the task more difficult (indexed by differences in d') or whether people change the standard by which they assess causality (measured by beta). Our results indicate that the effect is due to bias.

Spacing practice sessions across days earlier rather than later in training improves performance of a visuomotor skill.

Our goal was to determine whether the extent of off-line performance improvements on a visuomotor task depends on the amount of practice individuals experience prior to a 24-h between-session break. Subjects completed ten trials of a mirror-tracing task over two days. On Day 1, subjects experienced either one, three or seven trials. Twenty-four hours later subjects completed the remainder of the ten trials. Despite experiencing an equivalent number of total training trials, subjects experiencing the 24-h delay after one or three trials demonstrated off-line performance improvements, but those experiencing the delay after seven trials did not. Furthermore, the one- and three-trial groups reached a superior level of performance by the end of training relative to the seven-trial group.