Brain Network Dysfunction in Poststroke Delirium and Spatial Neglect: An fMRI Study.

BACKGROUND AND PURPOSE: Delirium, an acute reduction in cognitive functioning, hinders stroke recovery and contributes to cognitive decline. Right-hemisphere stroke is linked with higher delirium incidence, likely, due to the prevalence of spatial neglect (SN), a right-brain disorder of spatial processing. This study tested if symptoms of delirium and SN after right-hemisphere stroke are associated with abnormal function of the right-dominant neural networks specialized for maintaining attention, orientation, and arousal. METHODS: Twenty-nine participants with right-hemisphere ischemic stroke undergoing acute rehabilitation completed delirium and SN assessments and functional neuroimaging scans. Whole-brain functional connectivity of 4 right-hemisphere seed regions in the cortical-subcortical arousal and attention networks was assessed for its relationship to validated SN and delirium severity measures. RESULTS: Of 29 patients, 6 (21%) met the diagnostic criteria for delirium and 16 (55%) for SN. Decreased connectivity of the right basal forebrain to brain stem and basal ganglia predicted more severe SN. Increased connectivity of the arousal and attention network regions with the parietal, frontal, and temporal structures in the unaffected hemisphere was also found in more severe delirium and SN. CONCLUSIONS: Delirium and SN are associated with decreased arousal network activity and an imbalance of cortico-subcortical hemispheric connectivity. Better understanding of neural correlates of poststroke delirium and SN will lead to improved neuroscience-based treatment development for these disorders. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03349411.

Impact of Delirium on Outcomes After Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Delirium portends worse outcomes after intracerebral hemorrhage (ICH), but it is unclear if symptom resolution or postacute care intensity may mitigate its impact. We aimed to explore differences in outcome associated with delirium resolution before hospital discharge, as well as the potential mediating role of postacute discharge site. METHODS: We performed a single-center cohort study on consecutive ICH patients over 2 years. Delirium was diagnosed according to DSM-5 criteria and further classified as persistent or resolved based on delirium status at hospital discharge. We determined the impact of delirium on unfavorable 3-month outcome (modified Rankin Scale score, 4-6) using logistic regression models adjusted for established ICH predictors, then used mediation analysis to examine the indirect effect of delirium via postacute discharge site. RESULTS: Of 590 patients (mean age 70.5±15.5 years, 52% male, 83% White), 59% (n=348) developed delirium during hospitalization. Older age and higher ICH severity were delirium risk factors, but only younger age predicted delirium resolution, which occurred in 75% (161/215) of ICH survivors who had delirium. Delirium was strongly associated with unfavorable outcome, but patients with persistent delirium fared worse (adjusted odds ratio [OR], 7.3 [95% CI, 3.3-16.3]) than those whose delirium resolved (adjusted OR, 3.1 [95% CI, 1.8-5.5]). Patients with delirium were less likely to be discharged to inpatient rehabilitation than skilled nursing facilities (adjusted OR, 0.31 [95% CI, 0.17-0.59]), and postacute care site partially mediated the relationship between delirium and functional outcome in ICH survivors, leading to a 25% reduction in the effect of delirium (without mediator: adjusted OR, 3.0 [95% CI, 1.7-5.6]; with mediator: adjusted OR, 2.3 [95% CI, 1.2-4.3]). CONCLUSIONS: Acute delirium resolves in most patients with ICH by hospital discharge, which was associated with better outcomes than in patients with persistent delirium. The impact of delirium on outcomes may be further mitigated by postacute rehabilitation.

Visuomotor misalignment induced through immersive virtual reality to improve spatial neglect: a case-series study.

One evidence-based treatment for spatial neglect is prism adaptation (PA) treatment. PA after-effects, i.e., the implicit shifts in the arm reaching position toward the neglected side of space after prism removal, are considered fundamental to PA treatment effects. In the present study, the arm reaching position was shifted through a visuomotor misalignment procedure using immersive virtual reality (VR). To examine whether this procedure might have a beneficial impact on spatial neglect, we conducted a multi-baseline experiment in three individuals with chronic left-sided neglect post stroke. Improved spatial neglect was observed in all participants immediately after 5 sessions with two rounds in each. Two participants demonstrated lasting or continuous improvement two weeks later. Participants' pattern of brain lesions did not appear to clearly explain performance differences. The findings suggest that VR-induced visuomotor misalignment may improve spatial neglect immediately after a multi-session treatment course. The optimal number of sessions will be determined by future studies with a larger sample size, which may also elucidate the number of sessions sufficient for sustained improvement in most patients. Further investigations will identify the neural mechanisms underlying VR-induced visuomotor misalignment, which may or may not be identical to PA after-effects.

Deconstructing Poststroke Delirium in a Prospective Cohort of Patients With Intracerebral Hemorrhage.

OBJECTIVES: Poststroke delirium may be underdiagnosed due to the challenges of disentangling delirium symptoms from underlying neurologic deficits. We aimed to determine the prevalence of individual delirium features and the frequency with which they could not be assessed in patients with intracerebral hemorrhage. DESIGN: Prospective observational cohort study. SETTING: Neurocritical Care and Stroke Units at a university hospital. PATIENTS: Consecutive patients with intracerebral hemorrhage from February 2018 to May 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An attending neurointensivist performed 257 total daily assessments for delirium on 60 patients (mean age 68.0 [SD 18.4], 62% male, median intracerebral hemorrhage score 1.5 [interquartile range 1-2], delirium prevalence 57% [n = 34]). Each assessment included the Confusion Assessment Method for the ICU, Intensive Care Delirium Screening Checklist, a focused bedside cognitive examination, chart review, and nurse interview. We characterized individual symptom prevalence and established delirium diagnoses using Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria, then compared performance of the Confusion Assessment Method for the ICU and Intensive Care Delirium Screening Checklist against reference-standard expert diagnosis. Symptom fluctuation (61% of all assessments), psychomotor changes (46%), sleep-wake disturbances (46%), and impaired arousal (37%) had the highest prevalence and were never rated "unable to assess," while inattention (36%), disorientation (27%), and disorganized thinking (18%) were also common but were often rated 'unable to assess' (32%, 43%, and 44% of assessments, respectively), most frequently due to aphasia (32% of patients). Including nonverbal assessments of attention decreased the frequency of 'unable to assess' ratings to 11%. Since the Intensive Care Delirium Screening Checklist may be positive without the presence of symptoms that require verbal assessment, it was more accurate (sensitivity = 77%, specificity = 97%, area under the receiver operating characteristic curve, 0.87) than the Confusion Assessment Method for the ICU (sensitivity = 41%, specificity = 88%, area under the receiver operating characteristic curve, 0.64). CONCLUSIONS: Delirium is common after intracerebral hemorrhage, but severe neurologic deficits may confound its assessment and lead to underdiagnosis. The Intensive Care Delirium Screening Checklist's inclusion of nonverbal features may make it more accurate than the Confusion Assessment Method for the ICU in patients with neurologic deficits, but novel tools designed for such patients may be warranted.

Cerebral perfusion of the left reading network predicts recovery of reading in subacute to chronic stroke.

Better understanding of cerebral blood flow (CBF) perfusion in stroke recovery can help inform decisions about optimal timing and targets of restorative treatments. In this study, we examined the relationship between cerebral perfusion and recovery from stroke-induced reading deficits. Left stroke patients were tested with a noninvasive CBF measure (arterial spin labeling) <5 weeks post-stroke, and a subset had follow up testing >3 months post-stroke. We measured blood flow perfusion within the left and right sides of the brain, in areas surrounding the lesion, and areas belonging to the reading network. Two hypotheses were tested. The first was that recovery of reading function depends on increased perfusion around the stroke lesion. This hypothesis was not supported by our findings. The second hypothesis was that increased perfusion of intact areas within the reading circuit is tightly coupled with recovery. Our findings are consistent with this hypothesis. Specifically, higher perfusion in the left reading network measured during the subacute stroke period predicted better reading ability and phonology competence in the chronic period. In contrast, higher perfusion of the right homologous regions was associated with decreased reading accuracy and phonology competence in the subacute and chronic periods. These findings suggest that recovery of reading and language competence may rely on improved blood flow in the reading network of the language-dominant hemisphere.

Ventral attention and motor network connectivity is relevant to functional impairment in spatial neglect after right brain stroke.

Emerging research suggests spatial neglect after right stroke is linked to dysfunctional attention and motor networks. Advanced functional connectivity analysis clarified brain network recovery, however we need to know how networks participate in adaptive motor performance. We need to verify network changes associated with validated functional measures and spatial-motor performance in spatial neglect, especially in patients with large brain lesions and significant disability. This study tested whether disability-relevant spatial neglect associates with different patterns of resting state functional connectivity between motor, dorsal and ventral attention networks (MN, DAN and VAN). Right stroke patients had spatial neglect (n = 8) or not (n = 10) on the Behavioural Inattention Test-conventional. Spatial neglect patients had weaker intranetwork VAN connectivity, and reduced internetwork connectivity between VAN and left frontal eye field (DAN), and between VAN and the left primary motor area (MN). These network impairments might explain the co-occurrence of attention and motor deficits in spatial neglect, and open a path to assessing functional connectivity in clinical trials of combined spatial retraining and motor rehabilitation after stroke.

Responding to Ten Common Delirium Misconceptions With Best Evidence: An Educational Review for Clinicians.

Delirium (acute confusion) is a serious, common health condition, and it predicts poor outcomes, including greater rates of mortality, institutionalization, prolonged hospitalization, and cognitive impairment. Expedient diagnosis and management are critical to address modifiable delirium causes and improve both quality of care and outcomes. Moreover, more than a third of delirium is preventable. Despite the clear significance of delirium and our increasingly sophisticated understanding of the condition, the gap between evidence and practice persists. The authors provide an educational review of 10 prevalent misconceptions of delirium pertaining to recognition, etiology, natural history, and best management. The authors respond to each with best evidence. Several themes emerge, chief among which is that casual observation is seldom sufficient to detect delirium. Use of open-ended questions, regular neurocognitive testing, and validated delirium screening instruments will aid in accurately identifying cases of delirium. Delirium is typically multifactorial, with several physiological and/or pharmacological contributors. Because of its multidetermined nature and its relationship with cognitive vulnerability, delirium can persist for days to months after acute causes have resolved. Furthermore, patients often have long-term cognitive impairment after delirium rather than returning to their predelirium cognitive baseline. Finally, nonpharmacological management of delirium is first-line, both for prevention and treatment. Psychotropic drugs such as neuroleptics are not recommended for routine use in delirium. They are best reserved for treating dangerous or distressing symptoms, including severe agitation, psychosis, or emotional lability. Challenging these 10 misconceptions stands to improve patient care, quality of life, and clinical outcomes substantially.

Reversing the Standard Neural Signature of the Word-Nonword Distinction.

The distinction between letter strings that form words and those that look and sound plausible but are not meaningful is a basic one. Decades of functional neuroimaging experiments have used this distinction to isolate the neural basis of lexical (word level) semantics, associated with areas such as the middle temporal, angular, and posterior cingulate gyri that overlap the default mode network. In two fMRI experiments, a different set of findings emerged when word stimuli were used that were less familiar (measured by word frequency) than those typically used. Instead of activating default mode network areas often associated with semantic processing, words activated task-positive areas such as the inferior pFC and SMA, along with multifunctional ventral occipitotemporal cortices related to reading, whereas nonwords activated default mode areas previously associated with semantics. Effective connectivity analyses of fMRI data on less familiar words showed activation driven by task-positive and multifunctional reading-related areas, whereas highly familiar words showed bottom-up activation flow from occipitotemporal cortex. These findings suggest that functional neuroimaging correlates of semantic processing are less stable than previously assumed, with factors such as word frequency influencing the balance between task-positive, reading-related, and default mode networks. More generally, this suggests that results of contrasts typically interpreted in terms of semantic content may be more influenced by factors related to task difficulty than is widely appreciated.

Modeling activation and effective connectivity of VWFA in same script bilinguals.

Previous neuroimaging research revealed a small area in the inferior occipito-temporal cortex (VWFA), which seems to be involved in recognition of written words. The specialized response of the VWFA to words could result from repeated exposure to print in the course of functional fine-tuning of the brain. Research with bilingual speakers holds promise in helping to reveal response properties of the VWFA by assessing its sensitivity to language proficiency, word-form similarity, and meaning overlap across two languages. Using fMRI, we compared VWFA activity for cognate and homograph prime-target pairs in a group of fluent Spanish-English speakers. Cognates share form and meaning in two languages, while homographs only share form. Relative to baseline, the VWFA showed repetition suppression to pairs of homographs, but not to pairs of cognates, suggesting that this area is sensitive to word meaning. The different response to cognates and homographs was only observed when English was the prime language and Spanish was the target language. To help explain this result we compared patterns of effective connectivity between the VWFA and other parts of the reading network implicated in semantic and phonological processing. Our neural models showed that English targets engaged a direct ventral route from the VWFA to the frontal lobe and Spanish targets engaged an indirect dorsal route. Considering that frontal cortex has been implicated in semantic processing, a direct connection to this area could signal a fast and automatic access to meaning and would facilitate early semantic influences in visual word recognition.

Identifying Spatial Neglect in Chronic Right Hemisphere Stroke Survivors Using the RHDBank Outcomes.

PURPOSE: The chronicity of spatial neglect (SN) and the utility of existing diagnostic measures used by speech-language pathologists remain poorly understood. In this retrospective study, we examined how the RHDBank test battery informs the identification of SN after right hemisphere brain damage (RHD) during the chronic phase of recovery. METHOD: Data from 29 right hemisphere stroke survivors were extracted from the RHDBank, including SN tests, for which we performed laterality index scoring: a 51-item demographic survey, the Apples Test, the Indented Paragraph Test, and the clock drawing task from the Cognitive Linguistic Quick Test (CLQT). Two groups (SN+ and SN-) were identified using the Apples Test. A hierarchical cluster analysis explored CLQT performance clusters in association with SN, and group comparisons of demographic variables and test scores were conducted. RESULTS: Ten patients were identified as having SN+ (34%) using the Apples Test. The Indented Paragraph Test and the CLQT's clock drawing test identified only two of the 20 stroke survivors with SN+. Cluster analyses showed that domain and task scores on the CLQT carried information to classify participants into SN+ and SN- in concordance with performance on the Apples Test. Participants in the SN+ cluster had moderately impaired attention and executive function skills and mildly impaired visuospatial skills. CONCLUSIONS: The Apples Test differentiated SN in a group of chronic right hemisphere stroke survivors. Using multiple measures from the CLQT seemed to capture a greater range of problems than clock drawing and paragraph reading tests alone. Therefore, the RHDBank test battery as a whole-and in part the CLQT, Apples Test, and Indented Paragraph Test-can detect certain subtypes of SN in the chronic deficit profile after RHD and is a starting point for diagnostic integration by speech-language pathologists.

An inclusive multivariate approach to neural localization of language components.

To determine how language is implemented in the brain, it is important to know which brain areas are primarily engaged in language processing and which are not. Existing protocols for localizing language are typically univariate, treating each small unit of brain volume as independent. One prominent example that focuses on the overall language network in functional magnetic resonance imaging (fMRI) uses a contrast between neural responses to sentences and sets of pseudowords (pronounceable nonwords). This contrast reliably activates peri-sylvian language areas but is less sensitive to extra-sylvian areas that are also known to support aspects of language such as word meanings (semantics). In this study, we assess areas where a multivariate, pattern-based approach shows high reproducibility across multiple measurements and participants, identifying these areas as multivariate regions of interest (mROI). We then perform a representational similarity analysis (RSA) of an fMRI dataset where participants made familiarity judgments on written words. We also compare those results to univariate regions of interest (uROI) taken from previous sentences > pseudowords contrasts. RSA with word stimuli defined in terms of their semantic distance showed greater correspondence with neural patterns in mROI than uROI. This was confirmed in two independent datasets, one involving single-word recognition, and the other focused on the meaning of noun-noun phrases by contrasting meaningful phrases > pseudowords. In all cases, areas of spatial overlap between mROI and uROI showed the greatest neural association. This suggests that ROIs defined in terms of multivariate reproducibility can help localize components of language such as semantics. The multivariate approach can also be extended to focus on other aspects of language such as phonology, and can be used along with the univariate approach for inclusively mapping language cortex.

Association of delirium and spatial neglect in patients with right-hemisphere stroke.

BACKGROUND: Delirium, an acute and fluctuating decline in cognitive functioning, increases mortality and length of hospital stays (LOS) and adversely affects functional outcomes. Previous studies suggested that the incidence of delirium may be increased in right-hemisphere strokes. Similarly, spatial neglect, a disabling deficit in unilateral spatial processing, is more common and more severe following a right-sided stroke. Spatial neglect has been established as a risk factor for delirium. OBJECTIVE: It was hypothesized that functionally relevant spatial neglect and delirium are associated in patients with right-hemisphere stroke during acute inpatient rehabilitation. Data were examined from consecutive unilateral stroke patients evaluated with the 3-minute diagnostic interview for confusion assessment method (3D-CAM) and the Catherine Bergego Scale (CBS) via the Kessler Foundation Neglect Assessment Process (KF-NAP). DESIGN: A retrospective, cohort study. SETTING: Data collected in an acute inpatient rehabilitation facility. PARTICIPANTS: Six hundred twenty six patients with stroke were included. MAIN OUTCOME MEASURES: The measures were the relative risk of patients with right-hemisphere stroke having delirium when also positive for spatial neglect compared to patients with right-hemisphere stroke without spatial neglect, the incidence of 3D-CAM positive results by stroke hemisphere, and the effect of spatial neglect and delirium on functional outcomes for patients with right-brain stroke patients. RESULTS: There was a significantly higher risk of delirium in patients with right-hemisphere stroke with spatial neglect compared to patients with right-hemisphere stroke without spatial neglect. The rates of 3D-CAM positive results were not statistically different for left- compared to right-hemisphere strokes. Both delirium and spatial neglect had significant adverse effects on right-hemisphere stroke patients' functional independence. CONCLUSIONS: The results demonstrate an association between spatial neglect and delirium in patients with right hemisphere stroke in the acute inpatient rehabilitation setting. Because of the negative effect of these impairments on functional outcomes after stroke, prevention, early detection, and targeted treatments should be prioritized for these patients.

Targeted neurorehabilitation strategies in post-stroke aphasia.

BACKGROUND: Aphasia is a debilitating language impairment, affecting millions of people worldwide. About 40% of stroke survivors develop chronic aphasia, resulting in life-long disability. OBJECTIVE: This review examines extrinsic and intrinsic neuromodulation techniques, aimed at enhancing the effects of speech and language therapies in stroke survivors with aphasia. METHODS: We discuss the available evidence supporting the use of transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation, and functional MRI (fMRI) real-time neurofeedback in aphasia rehabilitation. RESULTS: This review systematically evaluates studies focusing on efficacy and implementation of specialized methods for post-treatment outcome optimization and transfer to functional skills. It considers stimulation target determination and various targeting approaches. The translation of neuromodulation interventions to clinical practice is explored, emphasizing generalization and functional communication. The review also covers real-time fMRI neurofeedback, discussing current evidence for efficacy and essential implementation parameters. Finally, we address future directions for neuromodulation research in aphasia. CONCLUSIONS: This comprehensive review aims to serve as a resource for a broad audience of researchers and clinicians interested in incorporating neuromodulation for advancing aphasia care.

Neural Mechanisms of Prism Adaptation in Healthy Adults and Individuals with Spatial Neglect after Unilateral Stroke: A Review of fMRI Studies.

Functional disability due to spatial neglect hinders recovery in up to 30% of stroke survivors. Prism adaptation treatment (PAT) may alleviate the disabling consequences of spatial neglect, but we do not yet know why some individuals show much better outcomes following PAT than others. The goal of this scoping review and meta-analysis was to investigate the neural mechanisms underlying prism adaptation (PA). We conducted both quantitative and qualitative analyses across fMRI studies investigating brain activity before, during, and after PA, in healthy individuals and patients with right or left brain damage (RBD or LBD) due to stroke. In healthy adults, PA was linked with activity in posterior parietal and cerebellar clusters, reduced bilateral parieto-frontal connectivity, and increased fronto-limbic and sensorimotor network connectivity. In contrast, RBD individuals with spatial neglect relied on different circuits, including an activity cluster in the intact left occipital cortex. This finding is consistent with a shift in hemispheric dominance in spatial processing to the left hemisphere. However, more studies are needed to clarify the contribution of lesion location and load on the circuits involved in PA after unilateral brain damage. Future studies are also needed to clarify the relationship of decreasing resting state functional connectivity (rsFC) to visuomotor function.

Progressive modulation of resting-state brain activity during neurofeedback of positive-social emotion regulation networks.

Neurofeedback allows for the self-regulation of brain circuits implicated in specific maladaptive behaviors, leading to persistent changes in brain activity and connectivity. Positive-social emotion regulation neurofeedback enhances emotion regulation capabilities, which is critical for reducing the severity of various psychiatric disorders. Training dorsomedial prefrontal cortex (dmPFC) to exert a top-down influence on bilateral amygdala during positive-social emotion regulation progressively (linearly) modulates connectivity within the trained network and induces positive mood. However, the processes during rest that interleave the neurofeedback training remain poorly understood. We hypothesized that short resting periods at the end of training sessions of positive-social emotion regulation neurofeedback would show alterations within emotion regulation and neurofeedback learning networks. We used complementary model-based and data-driven approaches to assess how resting-state connectivity relates to neurofeedback changes at the end of training sessions. In the experimental group, we found lower progressive dmPFC self-inhibition and an increase of connectivity in networks engaged in emotion regulation, neurofeedback learning, visuospatial processing, and memory. Our findings highlight a large-scale synergy between neurofeedback and resting-state brain activity and connectivity changes within the target network and beyond. This work contributes to our understanding of concomitant learning mechanisms post training and facilitates development of efficient neurofeedback training.

Considerations of power and sample size in rehabilitation research.

With the current emphasis on power and reproducibility, pressures are rising to increase sample sizes in rehabilitation research in order to reflect more accurate effect estimation and generalizable results. The conventional way of increasing power by enrolling more participants is less feasible in some fields of research. In particular, rehabilitation research faces considerable challenges in achieving this goal. We describe the specific challenges to increasing power by recruiting large sample sizes and obtaining large effects in rehabilitation research. Specifically, we discuss how variability within clinical populations, lack of common standards for selecting appropriate control groups; potentially reduced reliability of measurements of brain function in individuals recovering from a brain injury; biases involved in a priori effect size estimation, and higher budgetary and staffing requirements can influence considerations of sample and effect size in rehabilitation. We also describe solutions to these challenges, such as increased sampling per participant, improving experimental control, appropriate analyses, transparent result reporting and using innovative ways of harnessing the inherent variability of clinical populations. These solutions can improve statistical power and produce reliable and valid results even in the face of limited availability of large samples.

Exploratory examination of lexical and neuroanatomic correlates of neglect dyslexia.

OBJECTIVE: This study examined lexical and neuroanatomic correlates of reading errors in individuals with spatial neglect, defined as a failure to respond to stimuli in the side of space opposite a brain lesion, causing functional disability. METHOD: One-hundred and ten participants with left spatial neglect after right-hemisphere stroke read aloud a list of 36 words. Reading errors were scored as "contralesional" (error in the left half of the word) or as "other." The influence of lexical processing on neglect dyslexia was studied with a stepwise regression using word frequency, orthographic neighborhood (number of same length neighbors that differ by 1 letter), bigram and trigram counts (number of words with the same 2- and 3-letter combinations), length, concreteness, and imageability as predictors. MRI/CT images of 92 patients were studied in a voxelwise lesion-symptom analysis (VLSM). RESULTS: Longer length and more trigram neighbors increased, while higher concreteness reduced, the rate of contralesional errors. VLSM revealed lesions in the inferior temporal sulcus, middle temporal and angular gyri, precuneus, temporal pole, and temporo-parietal white matter associated with the rate of contralesional errors. CONCLUSIONS: Orthographic competitors may decrease word salience, while semantic concreteness may help constrain the selection of available word options when it is based on degraded information from the left side of the word. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Brain activation patterns associated with paragraph learning in persons with multiple sclerosis: The MEMREHAB trial.

The modified Story Memory Technique (mSMT) is a memory rehabilitation program that combines training in visualization and context formation to improve learning and memory. Previous studies have shown improvement in learning and memory in individuals with multiple sclerosis (MS) after undergoing the mSMT, including changes in brain activity related to working memory and word encoding. The current study examined changes in brain activity in 16 individuals diagnosed with MS (n treatment = 6; n placebo control = 10) when they were presented with to-be-remembered information within a meaningful context (i.e. a paragraph) from before to after mSMT treatment. We expected treatment-related changes in brain activation in the language network (LAN), default mode network (DMN), and executive control network (ECN). Consistent with this prediction, fMRI results revealed reduced brain activation in the LAN, DMN and ECN after completing the mSMT treatment in the context of paragraph learning. While no significant behavioral changes were observed, a marginally significant improvement with a large effect size was noted between baseline and follow-up performance on the Rivermead Behavioral Memory Test in persons who completed treatment. Results are discussed in terms of the impact of imagery training on patterns of cerebral activation when learning words presented within a context.

A multi-path 2.5 dimensional convolutional neural network system for segmenting stroke lesions in brain MRI images.

Automatic identification of brain lesions from magnetic resonance imaging (MRI) scans of stroke survivors would be a useful aid in patient diagnosis and treatment planning. It would also greatly facilitate the study of brain-behavior relationships by eliminating the laborious step of having a human expert manually segment the lesion on each brain scan. We propose a multi-modal multi-path convolutional neural network system for automating stroke lesion segmentation. Our system has nine end-to-end UNets that take as input 2-dimensional (2D) slices and examines all three planes with three different normalizations. Outputs from these nine total paths are concatenated into a 3D volume that is then passed to a 3D convolutional neural network to output a final lesion mask. We trained and tested our method on datasets from three sources: Medical College of Wisconsin (MCW), Kessler Foundation (KF), and the publicly available Anatomical Tracings of Lesions After Stroke (ATLAS) dataset. To promote wide applicability, lesions were included from both subacute (1 to 5 weeks) and chronic ( >  3 months) phases post stroke, and were of both hemorrhagic and ischemic etiology. Cross-study validation results (with independent training and validation datasets) were obtained to compare with previous methods based on naive Bayes, random forests, and three recently published convolutional neural networks. Model performance was quantified in terms of the Dice coefficient, a measure of spatial overlap between the model-identified lesion and the human expert-identified lesion, where 0 is no overlap and 1 is complete overlap. Training on the KF and MCW images and testing on the ATLAS images yielded a mean Dice coefficient of 0.54. This was reliably better than the next best previous model, UNet, at 0.47. Reversing the train and test datasets yields a mean Dice of 0.47 on KF and MCW images, whereas the next best UNet reaches 0.45. With all three datasets combined, the current system compared to previous methods also attained a reliably higher cross-validation accuracy. It also achieved high Dice values for many smaller lesions that existing methods have difficulty identifying. Overall, our system is a clear improvement over previous methods for automating stroke lesion segmentation, bringing us an important step closer to the inter-rater accuracy level of human experts.

Neural Effects of Gender and Age Interact in Reading.

There has been an enduring fascination with the possibility of gender differences in the brain basis of language, yet the evidence has been largely equivocal. Evidence does exist, however, for women being at greater risk than men for developing psychomotor slowing and even Alzheimer disease with advancing age, although this may in part at least be due to women living longer. We examined whether gender, age, or their interaction influenced language-related or more general processes in reading. Reading consists of elements related to language, such as the processing of word sound patterns (phonology) and meanings (semantics), along with the lead-in processes of visual perception and orthographic (visual word form) processing that are specific to reading. To test for any influence of gender and age on either semantic processing or orthography-phonology mapping, we tested for an interaction of these factors on differences between meaningful words and meaningless but pronounceable non-words. We also tested for effects of gender and age on how the number of letters in a word modulates neural activity for reading. This lead-in process presumably relates most to orthography. Behaviorally, reading accuracy declined with age for both men and women, but the decline was steeper for men. Neurally, interactions between gender and age were found exclusively in medial orbitofrontal cortex (mOFC). These factors influenced the word-non-word contrast, but not the parametric effect of number of letters. Men showed increasing activation with age for non-words compared to words. Women showed only slightly decreasing activation with age for novel letter strings. Overall, we found interactive effects of gender and age in the mOFC on the left primarily for novel letter strings, but no such interaction for a contrast that emphasized visual form processing. Thus the interaction of gender with age in the mOFC may relate most to orthography-phonology conversion for unfamiliar letter strings. More generally, this suggests that efforts to investigate effects of gender on language-related tasks may benefit from taking into account age and the type of cognitive process being highlighted.