A scoping review and critique of the Input-Output subtyping dimension of spatial neglect.

Spatial neglect is a common and debilitating disorder after stroke whereby individuals have difficulty reporting, orienting, and/or responding to the contralesional side of space. Given the heterogeneity of neglect symptom presentation, various neglect subtypes have been proposed to better characterize the disorder. This review focuses on the distinction between Input neglect (i.e., difficulty perceiving and/or attending to contralesional stimuli) and Output neglect (i.e., difficulty planning and/or executing movements toward contralesional stimuli). Conceptualizations of Input and Output neglect have varied considerably. We provide a novel summary of the terminology, measurement approaches, and neural correlates of these subtypes. A protocol detailing our systematic scoping review strategy is registered on the Open Science Framework (https://osf.io/bvtxf/). For feasibility and greater comparability across studies, we limited our inclusion criteria to tasks focused on visual stimuli and upper-limb movements. A total of 110 articles were included in the review. Subtyping tasks were categorized based on whether they mainly manipulated aspects of the input (i.e., congruence of visual input with motor output, presence of visual input) or the output (i.e., modality, goal, or direction of output) to produce an Input-Output subtype dissociation. We used our review results to identify four main critiques of this literature: 1) lack of consistency/clarity in conceptual models; 2) methodological issues of dissociating Input and Output subtypes; 3) a need for updated neural theories; and 4) barriers to clinical application. We discuss the lessons learned from this subtyping dimension that can be applied to future research on neglect subtype assessment and treatment.

Investigating premotor reaching biases after prism adaptation.

Prism adaptation (PA) is both a visuomotor learning task and potential treatment for spatial neglect after stroke. While PA's aftereffects can improve neglect symptoms, therapeutic benefits vary across individuals, possibly due to differences in neglect subtypes. Neglect symptoms can be described along an information processing pathway, yielding perceptual (input) and premotor (output) neglect subtypes. There is some evidence that PA mainly benefits persons with premotor neglect. We investigated whether PA modulates the premotor stage of information processing by examining whether PA could induce a premotor bias in healthy adults. We measured perceptual and premotor biases using a speeded reach task that compares the initiation time of leftward and rightward reaches to lateralized targets from different hand start positions. Using a randomized mixed experimental design, 30 right-handed healthy adults completed this speeded reach task before and after either left-shifting (n = 15) or right-shifting (n = 15) PA. As hypothesized, left-shifting PA speeded initiation time specifically for reaches in the rightward direction, regardless of target location (p = .02, ηp2 = .18), suggesting that PA induced a premotor bias in the direction of the prism aftereffect. These findings have implications for PA's underlying mechanisms, which can inform visuomotor learning theories and PA's use as a treatment for spatial neglect.

Do emotions influence safe browsing? Toward an electroencephalography marker of affective responses to cybersecurity notifications.

Cybersecurity notifications play an important role in encouraging users to use computers safely. Emotional reactions to such notifications are known to positively influence users' adherence to these notifications, though it is challenging for researchers to identify and quantify users' emotional reactions. In this study, we explored electroencephalography (EEG) signals that were elicited by the presentation of various emotionally charged image stimuli provided by the International Affective Picture System (IAPS) and compared signals to those elicited by images of cybersecurity notifications and other computer-related stimuli. Participants provided behavioral assessments of valence and arousal elicited by the images which were used to cross-reference the results. We found that EEG amplitudes corresponding to the late positive potential (LPP) were elevated in reaction to images of cybersecurity notifications as well as IAPS images known to elicit strong positive and negative valence, when compared to neutral valence or other computer-related stimuli. These findings suggest that the LPP may account for emotional deliberation about cybersecurity notifications, which could be a useful measure when conducting future studies into the role such emotional reactions play in encouraging safe computer behavior.

Effect of caffeine on resting-state alpha activity across the human menstrual cycle.

RATIONALE: Caffeine is the most consumed stimulant worldwide, and there is great interest in understanding its neurophysiological effects. Resting-state electroencephalography (EEG) studies suggest that caffeine enhances arousal, which suppresses the spectral power of alpha frequencies associated with reduced alertness. However, it is unclear whether caffeine's neurophysiological effects vary across the human menstrual cycle. OBJECTIVE: The objective of our study was to test whether caffeine's effect on EEG activity differs across the human menstrual cycle. METHODS: Fifty-six female participants were randomly assigned to complete the experiment while in either their menstrual (n = 21), follicular (n = 19), or luteal (n = 16) phase. Each participant completed two study sessions in the same menstrual phase, approximately 1 month apart, during which they were administered either a caffeine pill (200 mg, oral) or a placebo pill in a counterbalanced order using a randomized double-blinded procedure. We measured their eyes-closed resting-state EEG approximately 30 min after pill administration and conducted a spectral power analysis at different frequency bands. RESULTS: Caffeine reduced EEG power in the alpha1 frequency band (8-10 Hz), but only for participants who self-reported higher weekly caffeine consumption. Importantly, caffeine's effects did not differ by menstrual phase. CONCLUSIONS: We conclude that when studying caffeine's effects on resting-state EEG, participants' baseline caffeine consumption is more influential than their menstrual cycle phase. This study has important implications for the inclusion of menstruating individuals in neurophysiological studies of caffeine.

Role of aging and working memory in performance on a naturalistic visual search task.

Studying age-related changes in working memory (WM) and visual search can provide insights into mechanisms of visuospatial attention. In visual search, WM is used to remember previously inspected objects/locations and to maintain a mental representation of the target to guide the search. We sought to extend this work, using aging as a case of reduced WM capacity. The present study tested whether various domains of WM would predict visual search performance in both young (n = 47; aged 18-35 yrs) and older (n = 48; aged 55-78) adults. Participants completed executive and domain-specific WM measures, and a naturalistic visual search task with (single) feature and triple-conjunction (three-feature) search conditions. We also varied the WM load requirements of the search task by manipulating whether a reference picture of the target (i.e., target template) was displayed during the search, or whether participants needed to search from memory. In both age groups, participants with better visuospatial executive WM were faster to locate complex search targets. Working memory storage capacity predicted search performance regardless of target complexity; however, visuospatial storage capacity was more predictive for young adults, whereas verbal storage capacity was more predictive for older adults. Displaying a target template during search diminished the involvement of WM in search performance, but this effect was primarily observed in young adults. Age-specific interactions between WM and visual search abilities are discussed in the context of mechanisms of visuospatial attention and how they may vary across the lifespan.

Visual Feedback Modulates Aftereffects and Electrophysiological Markers of Prism Adaptation.

Prism adaptation (PA) is both a model for visuomotor learning and a promising treatment for visuospatial neglect after stroke. The task involves reaching for targets while prism glasses horizontally displace the visual field. Adaptation is hypothesized to occur through two processes: strategic recalibration, a rapid self-correction of pointing errors; and spatial realignment, a more gradual adjustment of visuomotor reference frames that produce prism aftereffects (i.e., reaching errors upon glasses removal in the direction opposite to the visual shift). While aftereffects can ameliorate neglect, not all patients respond to PA, and the neural mechanisms underlying successful adaptation are unclear. We investigated the feedback-related negativity (FRN) and the P300 event-related potential (ERP) components as candidate markers of strategic recalibration and spatial realignment, respectively. Healthy young adults wore prism glasses and performed memory-guided reaching toward vertical-line targets. ERPs were recorded in response to three different between-subject error feedback conditions at screen-touch: view of hand and target (Experiment 1), view of hand only (Experiment 2), or view of lines to mark target and hand position (view of hand occluded; Experiment 3). Conditions involving a direct view of the hand-produced stronger aftereffects than indirect hand feedback, and also evoked a P300 that decreased in amplitude as adaptation proceeded. Conversely, the FRN was only seen in conditions involving target feedback, even when aftereffects were smaller. Since conditions producing stronger aftereffects were associated with a phase-sensitive P300, this component may index a "context-updating" realignment process critical for strong aftereffects, whereas the FRN may reflect an error monitoring process related to strategic recalibration.

Failure of bumetanide to improve outcome after intracerebral hemorrhage in rat.

After intracerebral hemorrhage (ICH), brain edema commonly occurs and can cause death. Along with edema, there are significant alterations in the concentrations of key ions such as sodium, potassium, and chloride, which are essential to brain function. NKCC1, a cation-chloride cotransporter, is upregulated after brain damage, such as traumatic injury and ischemic stroke. NKCC1 brings sodium and chloride into the cell, possibly worsening ion dyshomeostasis. Bumetanide, a specific NKCC1 antagonist, blocks the transport of chloride into cells, and thus should attenuate the increases in chloride, which should lessen brain edema and improve neuronal functioning post-ICH, as with other injuries. We used the collagenase model of ICH to test whether bumetanide treatment for three days (vs. vehicle) would improve outcome. We gave bumetanide beginning at two hours or seven days post-ICH and measured behavioural outcome, edema, and brain ion content after treatment. There was some evidence for a minor reduction in edema after early dosing, but this did not improve behaviour or lessen injury. Contrary to our hypothesis, bumetanide did not normalize ion concentrations after late dosing. Bumetanide did not improve behavioural outcome or affect lesion volume. After ICH, bumetanide is safe to use in rats but does not improve functional outcome in the majority of animals.

Mild Contralesional Hypothermia Reduces Use of the Unimpaired Forelimb in a Skilled Reaching Task After Motor Cortex Injury in Rats.

Therapeutic hypothermia (TH) mitigates neuronal injury in models of ischemic stroke. Although this therapy is meant for injured tissue, most protocols cool the whole body, including the contralesional hemisphere. Neuroplasticity responses within this hemisphere can affect functional outcome. Thus, cooling the contralesional hemisphere serves no clear neuroprotective function and may instead be detrimental. In this study, we cooled the contralesional hemisphere to determine whether this harms behavioral recovery after cortical injury in rats. All rats were trained on skilled reaching and walking tasks. Rats then received a motor cortex insult contralateral to their dominant paw after which they were randomly assigned to focal contralesional TH (∼33°C) for 1-48, 1-97, or 48-96 hours postinjury, or to a normothermic control group. Contralesional cooling did not impact lesion volume (p = 0.371) and had minimal impact on neurological outcome of the impaired limb. However, rats cooled early were significantly less likely to shift paw preference to the unimpaired paw (p ≤ 0.043), suggesting that cooling reduced learned nonuse. In a second experiment, we tested whether cooling impaired learning of the skilled reaching task in naive rats. Localized TH applied to the hemisphere contralateral or ipsilateral to the preferred paw did not impair learning (p ≥ 0.677) or dendritic branching/length in the motor cortex (p ≥ 0.105). In conclusion, localized TH did not impair learning or plasticity in the absence of neural injury, but contralesional TH may reduce unwanted shifts in limb preference after stroke.

Rehabilitation Augments Hematoma Clearance and Attenuates Oxidative Injury and Ion Dyshomeostasis After Brain Hemorrhage.

BACKGROUND AND PURPOSE: We assessed the elemental and biochemical effects of rehabilitation after intracerebral hemorrhage, with emphasis on iron-mediated oxidative stress, using a novel multimodal biospectroscopic imaging approach. METHODS: Collagenase-induced striatal hemorrhage was produced in rats that were randomized to enriched rehabilitation or control intervention starting on day 7. Animals were euthanized on day 14 or 21, a period of ongoing cell death. We used biospectroscopic imaging techniques to precisely determine elemental and molecular changes on day 14. Hemoglobin content was assessed with resonance Raman spectroscopy. X-ray fluorescence imaging mapped iron, chlorine, potassium, calcium, and zinc. Protein aggregation, a marker of oxidative stress, and the distribution of other macromolecules were assessed with Fourier transform infrared imaging. A second study estimated hematoma volume with a spectrophotometric assay at 21 days. RESULTS: In the first experiment, rehabilitation reduced hematoma hemoglobin content (P=0.004) and the amount of peri-hematoma iron (P<0.001). Oxidative damage was highly localized at the hematoma/peri-hematoma border and was decreased by rehabilitation (P=0.004). Lipid content in the peri-hematoma zone was increased by rehabilitation (P=0.016). Rehabilitation reduced the size of calcium deposits (P=0.040) and attenuated persistent dyshomeostasis of Cl- (P<0.001) but not K+ (P=0.060). The second study confirmed that rehabilitation decreased hematoma volume (P=0.024). CONCLUSIONS: Rehabilitation accelerated clearance of toxic blood components and decreased chronic oxidative stress. As well, rehabilitation attenuated persistent ion dyshomeostasis. These novel effects may underlie rehabilitation-induced neuroprotection and improved recovery of function. Pharmacotherapies targeting these mechanisms may further improve outcome.