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Background: Stroke is a leading cause of long-term disability. Greater rehabilitation therapy after stroke is known to improve functional outcomes. This study examined therapy doses during the first year of stroke recovery and identified factors that predict rehabilitation therapy dose. Methods: Adults with new radiologically confirmed stroke were enrolled 2 to 10 days after stroke onset at 28 acute care hospitals across the United States. Following an initial assessment during acute hospitalization, the number of physical therapy, occupational therapy, and speech therapy sessions were determined at visits occurring 3, 6, and 12 months following stroke. Negative binomial regression examined whether clinical and demographic factors were associated with therapy counts. False discovery rate was used to correct for multiple comparisons. Results: Of 763 patients enrolled during acute stroke admission, 510 were available for follow-up. Therapy counts were low overall, with most therapy delivered within the first 3 months; 35.0% of patients received no physical therapy; 48.8%, no occupational therapy, and 61.7%, no speech therapy. Discharge destination was significantly related to cumulative therapy; the percentage of patients discharged to an inpatient rehabilitation facility varied across sites, from 0% to 71%. Most demographic factors did not predict therapy dose, although Hispanic patients received a lower cumulative amount of physical therapy and occupational therapy. Acutely, the severity of clinical factors (grip strength and National Institutes of Health Stroke Scale score, as well as National Institutes of Health Stroke Scale subscores for aphasia and neglect) predicted higher subsequent therapy doses. Measures of impairment and function (Fugl-Meyer, modified Rankin Scale, and Stroke Impact Scale Activities of Daily Living) assessed 3 months after stroke also predicted subsequent cumulative therapy doses. Conclusions: Rehabilitative therapy doses during the first year poststroke are low in the United States. This is the first US-wide study to demonstrate that behavioral deficits predict therapy dose, with patients having more severe deficits receiving higher doses. Findings suggest directions for identifying groups at risk of receiving disproportionately low rehabilitation doses.

A 74-year-old man with a past medical history of chronic low back pain presented with two to three weeks of progressive weakness starting in the lower extremities and then spreading to the upper extremities. Distal muscles were more affected than proximal muscles; weakness was accompanied by numbness and paresthesias. There was no preceding acute viral, respiratory, or gastrointestinal illness. Initial workup revealed hepatitis C antibody reactivity, and cerebrospinal fluid (CSF) analysis showed albuminocytologic dissociation. MRI demonstrated multilevel degenerative changes and diffuse enhancement of the cauda equina nerve roots compatible with Guillain-Barré syndrome (GBS). Repeat testing confirmed ongoing hepatitis C infection with increasing quantitative hepatitis C virus (HCV) levels. This case illustrates an interesting presentation of GBS potentially triggered by hepatitis C reactivation. This is the first case, to our knowledge, with serologic evidence demonstrating acute hepatitis C reactivation concurrent with GBS which presented in the absence of immunomodulatory interferon treatment. The patient continues to recover with ongoing rehabilitation at the time of this case report.

Stroke is a leading cause of acquired disability resulting in distal upper extremity functional motor impairment. Stroke mortality rates continue to decline with advances in healthcare and medical technology. This has led to an increased demand for advanced, personalized rehabilitation. Survivors often experience some level of spontaneous recovery shortly after their stroke event, yet reach a functional plateau after which there is exiguous motor recovery. Nevertheless, studies have demonstrated the potential for recovery beyond this plateau. Non-traditional neurorehabilitation techniques, such as those incorporating the brain-computer interface (BCI), are being investigated for rehabilitation. BCIs may offer a gateway to the brain's plasticity and revolutionize how humans interact with the world. Non-invasive BCIs work by closing the proprioceptive feedback loop with real-time, multi-sensory feedback allowing for volitional modulation of brain signals to assist hand function. BCI technology potentially promotes neuroplasticity and Hebbian-based motor recovery by rewarding cortical activity associated with sensory-motor rhythms through use with a variety of self-guided and assistive modalities.

Introduction: Many stroke survivors are often left with persistent upper extremity motor impairment that affect their overall quality of life. This study aims to evaluate the efficacy of using non-invasive electroencephalographic (EEG) based brain-computer interface (BCI) therapy to facilitate distal upper extremity motor function. Data was acquired from 18 participants ((mean age = 60 years, F = 9, M = 9, 5 = sub-chronic (over 1 year from stroke onset), 13 = chronic (less than 1 year)). Behavioral outcomes were measured using the Modified Ashworth Scale (MAS), a Motor Activity Log (MAL), and the Stroke Impact Scale (SIS). We investigated whether severely-impaired, chronic stroke survivors could use BCI treatment to recover from stroke at a rate similar to that of severely-impaired, sub-chronic stroke survivors after BCI intervention. Methods: EEG data was acquired using BCI2000 software and 16 channel EEG cap with electrodes positioned according to the standard 10-20 system over the sensorimotor cortex at C3 & C4. Participants were cued to move either their left or right hand to control a cursor towards the right or left side of a monitor. Data acquired at baseline (no more than one week prior to BCI therapy) and post-therapy (no more than one week following BCI therapy) were used in this analyses. Results: No significant decrease in improvement in the chronic group compared to the sub-chronic group (0.95 confidence interval) was observed. The chronic group showed significant improvement in their affected arm in: MAS elbow flexion (p = 0.03746), MAS finger extension (p = 0.01896), MAL arm use (p = 0.02065), MAL how well they could use their arm (p = 0.02065), SIS perceived strength (p = 0.04105), and SIS arm use for daily life tasks (p = 0.01741). Conclusion: For chronic stroke survivors, BCI intervention for restoration of upper extremity motor function may promote recovery at a rate similar to that of sub-chronic survivors.

Background: Brain–computer interface (BCI) devices are being investigated for their application in stroke rehabilitation, but little is known about how structural changes in the motor system relate to behavioral measures with the use of these systems. Objective: This study examined relationships among diffusion tensor imaging (DTI)-derived metrics and with behavioral changes in stroke patients with and without BCI training. Methods: Stroke patients (n = 19) with upper extremity motor impairment were assessed using Stroke Impact Scale (SIS), Action Research Arm Test (ARAT), Nine-Hole Peg Test (9-HPT), and DTI scans. Ten subjects completed four assessments over a control period during which no training was administered. Seventeen subjects, including eight who completed the control period, completed four assessments over an experimental period during which subjects received interventional BCI training. Fractional anisotropy (FA) values were extracted from each corticospinal tract (CST) and transcallosal motor fibers for each scan. Results: No significant group by time interactions were identified at the group level in DTI or behavioral measures. During the control period, increases in contralesional CST FA and in asymmetric FA (aFA) correlated with poorer scores on SIS and 9-HPT. During the experimental period (with BCI training), increases in contralesional CST FA were correlated with improvements in 9-HPT while increases in aFA correlated with improvements in ARAT but with worsening 9-HPT performance; changes in transcallosal motor fibers positively correlated with those in the contralesional CST. All correlations p < 0.05 corrected. Conclusion: These findings suggest that the integrity of the contralesional CST may be used to track individual behavioral changes observed with BCI training after stroke.

Introduction: A better understanding of brain changes underlying functional gains with brain-computer interface (BCI) use in stroke rehabilitation is needed. Hypothesis: BCI therapy will produce observable neuroplastic changes, and behavioral gains will relate to changes in diffusion tensor imaging (DTI) metrics of the corticospinal tracts (CSTs). Methods: We obtained DTI and behavioral data from 16 stroke patients with upper extremity motor impairment before, during, and after BCI therapy. Additional DTI and behavior data were obtained from 9 control subjects at similar time intervals before receiving any BCI therapy. Behavioral measures included Stroke Impact Scale (SIS), Action Research Arm Test (ARAT), 9-Hole Peg Test (9HPT), and grip strength. We performed deterministic tractography of the ipsilesional CST (iCST) and contralesional CST (cCST) and extracted DTI metrics (fractional anisotropy, axial diffusivity, radial diffusivity, trace) from each. DTI and behavioral metrics were analyzed for changes from baseline between therapy and control groups. Individual changes in DTI metrics were analyzed for correlation with behavior changes during the therapy period. Results: Group by time interactions were identified in DTI metrics of the iCST, with multiple metrics increasing with therapy. Changes in individual SIS Activities of Daily Living and 9HPT scores correlated with individual changes in both the iCST and cCST. Similarly, changes in SIS Hand Function correlated with cCST changes, and changes in grip strength correlated with iCST changes. Correlations between changes in ARAT scores and cCST changes trended to significance. Correlations significant at p Conclusions: BCI therapy can induce structural neuroplastic changes during stroke recovery. These changes may be used to track both subjective and objective behavioral gains.

Brain–computer interfaces (BCIs) are an emerging novel technology for stroke rehabilitation. Little is known about how dose-response relationships for BCI therapies affect brain and behavior changes. We report preliminary results on stroke patients (n = 16, 11 M) with persistent upper extremity motor impairment who received therapy using a BCI system with functional electrical stimulation of the hand and tongue stimulation. We collected MRI scans and behavioral data using the Action Research Arm Test (ARAT), 9-Hole Peg Test (9-HPT), and Stroke Impact Scale (SIS) before, during, and after the therapy period. Using anatomical and functional MRI, we computed Laterality Index (LI) for brain activity in the motor network during impaired hand finger tapping. Changes from baseline LI and behavioral scores were assessed for relationships with dose, intensity, and frequency of BCI therapy. We found that gains in SIS Strength were directly responsive to BCI therapy: therapy dose and intensity correlated positively with increased SIS Strength (p ≤ 0.05), although no direct relationships were identified with ARAT or 9-HPT scores. We found behavioral measures that were not directly sensitive to differences in BCI therapy administration but were associated with concurrent brain changes correlated with BCI therapy administration parameters: therapy dose and intensity showed significant (p ≤ 0.05) or trending (0.05 < p < 0.1) negative correlations with LI changes, while therapy frequency did not affect LI. Reductions in LI were then correlated (p ≤ 0.05) with increased SIS Activities of Daily Living scores and improved 9-HPT performance. Therefore, some behavioral changes may be reflected by brain changes sensitive to differences in BCI therapy administration, while others such as SIS Strength may be directly responsive to BCI therapy administration. Data preliminarily suggest that when using BCI in stroke rehabilitation, therapy frequency may be less important than dose and intensity.

Introduction: Brain-computer interface (BCI)-EEG is a promising intervention for improving motor function after stroke. However, brain changes following intervention on a BCI-EEG system are not yet fully understood. We examined changes in resting state functional connectivity (RSFC) MRI in the motor network defined by 6 key regions in the left and right primary motor cortex (M1), left and right supplementary motor area (SMA), and left and right premotor cortex (PMC). Additionally, we investigated brain-behavior correlation between rsFC and a battery of outcome measures including the Barthel Index (BI), the Stroke Impact Scale(SIS), and the Action Research Arm Test (ARAT). Methods: Fifteen stroke patients with persistent mild to severe upper extremity impairment following ischemic stroke received intervention using BCI-EEG and were tested before (T1) and at 2-3 weeks (T2) mid intervention. 11 of these patients were also tested a third time at 4-6 weeks at the end of intervention (T3). Eyes closed, 10 minute resting fMRI and anatomical scans were acquired on a GE 3T MRI scanner. Right hemisphere stroke patients’ scans were flipped so that as a group the lesion was in the left (L) hemisphere and the impaired limb right (R). Seed region based connectivity analyses were performed to examine changes in RSFC over time and in inter-hemispheric and intra-hemispheric connectivity, and correlations between brain changes and behavioral changes were investigated. Results: BCI-EEG intervention led to significant increase in intra-hemispheric connectivity (p = .03) from T1 to T3. Inter-hemispheric connectivity increased from T1 to T3, trending towards significance (p = .06). Significant positive correlations were observed between changes in RSFC (L.M1 and L.PMC, L.M1 and R.PMC, L.SMA and R.PMC, and R.PMC and R.SMA) and change in upper extremity BI score (p ranging from .01 to .001); changes in RSFC between L.PMC and R.PMC correlated with hand strength on the SIS (p = .03). A trend was observed between increase in RSFC (L.M1 and R.PMC) and increase in total ARAT score but this was not significant. Conclusions: Results suggest that BCI-EEG intervention facilitate changes in RSFC in the motor network in stroke patients and these changes are associated with improved outcomes.

Introduction: Brain-computer interface (BCI) is an emerging technology for stroke rehabilitation, but little is known about how the administration of these therapies affects brain and behavior. We examine relationships between BCI therapy dose, intensity, and frequency with changes in laterality index (LI), Action Research Arm Test (ARAT), and Stroke Impact Scale (SIS). Methods: We collected ARAT and SIS scores as well as anatomical and functional MRI of 16 stroke patients with upper extremity motor impairment before, during, and after therapy using a BCI system with tongue and functional electrical stimulation. We acquired fMRI during finger tapping of each hand and computed LI with 3 mask sets at 2 thresholds. Changes from baseline LI and behavioral scores were assessed for correlation with cumulative therapy sessions, cumulative BCI runs, and overall runs/session using Spearman analysis and generalized estimating equations (GEE). Changes from baseline were also compared between subjects with different therapy frequencies. Results: Increased sessions correlated with changes in impaired finger tapping LI in 2 of 6 mask-threshold combinations (p Conclusions: Patterns of brain activation shift toward contralesional hemisphere with additional therapy sessions and additional BCI runs. Increased BCI therapy intensity also correlates with increased self-reported strength. When using BCI in stroke rehabilitation, therapy frequency may be less important than dose and intensity, and neuroimaging and self-report measures may be more sensitive to differences in therapy administration.

Date Presented 3/31/2017 A study was conducted to evaluate the efficacy of a 6-wk brain–computer interface with functional electrical stimulation (BCI–FES) therapy in improving upper-extremity (UE) motor function in adults poststroke. Data suggest BCI–FES therapy is promising for UE rehabilitation poststroke. Primary Author and Speaker: Samantha Evander Elmore Additional Authors and Speakers: Laura Kiekhoefer, Jessica Abrams, Rebecca Vermilyea Contributing Authors: Dorothy Farrar-Edwards, Muhammad Al-Heizan, Brittany Young, Alexander Remsik

Background and purpose Functional magnetic resonance imaging (fMRI) is a non-invasive pre-surgical tool used to assess localization and lateralization of language function in brain tumor and vascular lesion patients in order to guide neurosurgeons as they devise a surgical approach to treat these lesions. We investigated the effect of varying the statistical thresholds as well as the type of language tasks on functional activation patterns and language lateralization. We hypothesized that language lateralization indices (LIs) would be threshold- and task-dependent. Materials and methods Imaging data were collected from brain tumor patients (n = 67, average age 48 years) and vascular lesion patients (n = 25, average age 43 years) who received pre-operative fMRI scanning. Both patient groups performed expressive (antonym and/or letter-word generation) and receptive (tumor patients performed text-reading; vascular lesion patients performed text-listening) language tasks. A control group (n = 25, average age 45 years) performed the letter-word generation task. Results Brain tumor patients showed left-lateralization during the antonym-word generation and text-reading tasks at high threshold values and bilateral activation during the letter-word generation task, irrespective of the threshold values. Vascular lesion patients showed left-lateralization during the antonym and letter-word generation, and text-listening tasks at high threshold values. Conclusion Our results suggest that the type of task and the applied statistical threshold influence LI and that the threshold effects on LI may be task-specific. Thus identifying critical functional regions and computing LIs should be conducted on an individual subject basis, using a continuum of threshold values with different tasks to provide the most accurate information for surgical planning to minimize post-operative language deficits., Highlights • FMRI calculation of language lateralization is valuable for pre-surgical planning. • Both applied statistical thresholds and task specificity affect lateralization index. • A continuum of threshold values provides a dynamic range for presurgical planning. • Reorganization of language function is dependent on brain pathology. • Identification of critical language areas will optimize lesion resection (e.g. tumor).

The relationship of the structural integrity of white matter tracts and cortical activity to motor functional outcomes in stroke patients is of particular interest in understanding mechanisms of brain structural and functional changes while recovering from stroke. This study aims to probe these underlying mechanisms using diffusion tensor imaging (DTI) and fMRI measures. We examined the structural integrity of the posterior limb of the internal capsule (PLIC) using DTI and corticomotor activity using motor-task fMRI in stroke patients who completed up to 15 sessions of rehabilitation therapy using Brain-Computer Interface (BCI) technology. We hypothesized that (1) the structural integrity of PLIC and corticomotor activity are affected by stroke; (2) changes in structural integrity and corticomotor activity following BCI intervention are related to motor recovery; (3) there is a potential relationship between structural integrity and corticomotor activity. We found that (1) the ipsilesional PLIC showed significantly decreased fractional anisotropy (FA) values when compared to the contralesional PLIC; (2) lower ipsilesional PLIC-FA values were significantly associated with worse motor outcomes (i.e., ipsilesional PLIC-FA and motor outcomes were positively correlated.); (3) lower ipsilesional PLIC-FA values were significantly associated with greater ipsilesional corticomotor activity during impaired-finger-tapping-task fMRI (i.e., ipsilesional PLIC-FA and ipsilesional corticomotor activity were negatively correlated), with an overall bilateral pattern of corticomotor activity observed; and (4) baseline FA values predicted motor recovery assessed after BCI intervention. These findings suggest that (1) greater vs. lesser microstructural integrity of the ipsilesional PLIC may contribute toward better vs. poor motor recovery respectively in the stroke-affected limb and demand lesser vs. greater cortical activity respectively from the ipsilesional motor cortex; and that (2) PLIC-FA is a promising biomarker in tracking and predicting motor functional recovery in stroke patients receiving BCI intervention.

It has been known that stroke constitutes a major source of acquired disability, with nearly 800,000 new strokes each year in the USA alone. While advances in public and preventative health have helped reduce stroke incidence in high-income countries in recent decades, growth of the aging population, increasing stroke rates in low- to middle-income countries and medical advances that have reduced stroke mortality are all contributing to an increase in stroke survivors worldwide. Large numbers of stroke survivors have residual motor deficits. This editorial will provide an introduction to a class of new therapies being investigated with the aim of improving motor outcomes in stroke patients that uses what is known as brain–computer interface technology.

Objective Several neuroimaging studies have examined language reorganization in stroke patients with aphasia. However, few studies have examined language reorganization in stroke patients without aphasia. Here, we investigated functional connectivity (FC) changes after stroke in the language network using resting-state fMRI and performance on a verbal fluency (VF) task in patients without clinically documented language deficits. Methods Early-stage ischemic stroke patients (N = 26) (average 5 days from onset), 14 of whom were tested at a later stage (average 4.5 months from onset), 26 age-matched healthy control subjects (HCs), and 12 patients with cerebrovascular risk factors (patients at risk, PR) participated in this study. We examined FC of the language network with 23 seed regions based on a previous study. We evaluated patients' behavioral performance on a VF task and correlation between brain resting-state FC (rsFC) and behavior. Results Compared to HCs, early stroke patients showed significantly decreased rsFC in the language network but no difference with respect to PR. Early stroke patients showed significant differences in performance on the VF task compared to HCs but not PR. Late-stage patients compared to HCs and PR showed no differences in brain rsFC in the language network and significantly stronger connections compared to early-stage patients. Behavioral differences persisted in the late stage compared to HCs. Change in specific connection strengths correlated with changes in behavior from early to late stage. Conclusions These results show decreased rsFC in the language network and verbal fluency deficits in early stroke patients without clinically documented language deficits.

This study aims to examine the changes in task-related brain activity induced by rehabilitative therapy using brain-computer interface (BCI) technologies and whether these changes are relevant to functional gains achieved through the use of these therapies. Stroke patients with persistent upper-extremity motor deficits received interventional rehabilitation therapy using a closed-loop neurofeedback BCI device (n = 8) or no therapy (n = 6). Behavioral assessments using the Stroke Impact Scale, the Action Research Arm Test (ARAT), and the Nine-Hole Peg Test (9-HPT) as well as task-based fMRI scans were conducted before, during, after, and 1 month after therapy administration or at analogous intervals in the absence of therapy. Laterality Index (LI) values during finger tapping of each hand were calculated for each time point and assessed for correlation with behavioral outcomes. Brain activity during finger tapping of each hand shifted over the course of BCI therapy, but not in the absence of therapy, to greater involvement of the non-lesioned hemisphere (and lesser involvement of the stroke-lesioned hemisphere) as measured by LI. Moreover, changes from baseline LI values during finger tapping of the impaired hand were correlated with gains in both objective and subjective behavioral measures. These findings suggest that the administration of interventional BCI therapy can induce differential changes in brain activity patterns between the lesioned and non-lesioned hemispheres and that these brain changes are associated with changes in specific motor functions.

Brain-computer interface (BCI) technology is being incorporated into new stroke rehabilitation devices, but little is known about brain changes associated with its use. We collected anatomical and functional MRI of nine stroke patients with persistent upper extremity motor impairment before, during, and after therapy using a BCI system. Subjects were asked to perform finger tapping of the impaired hand during fMRI. Action Research Arm Test (ARAT), 9-Hole Peg Test (9-HPT), and Stroke Impact Scale (SIS) domains of Hand Function (HF) and Activities of Daily Living (ADL) were also assessed. Group-level analyses examined changes in whole-brain task-based functional connectivity (FC) to seed regions in the motor network observed during and after BCI therapy. Whole-brain FC analyses seeded in each thalamus showed FC increases from baseline at mid-therapy and post-therapy (p0.05). Changes in FC between seeds at both the network and the connection levels were examined for correlations with changes in behavioral measures. Average motor network FC was increased post-therapy, and changes in average network FC correlated (p0.05) with changes in performance on ARAT (R (2) = 0.21), 9-HPT (R (2) = 0.41), SIS HF (R (2) = 0.27), and SIS ADL (R (2) = 0.40). Multiple individual connections within the motor network were found to correlate in change from baseline with changes in behavioral measures. Many of these connections involved the thalamus, with change in each of four behavioral measures significantly correlating with change from baseline FC of at least one thalamic connection. These preliminary results show changes in FC that occur with the administration of rehabilitative therapy using a BCI system. The correlations noted between changes in FC measures and changes in behavioral outcomes indicate that both adaptive and maladaptive changes in FC may develop with this therapy and also suggest a brain-behavior relationship that may be stimulated by the neuromodulatory component of BCI therapy.

Therapies involving new technologies such as brain-computer interfaces (BCI) are being studied to determine their potential for interventional rehabilitation after acute events such as stroke produce lasting impairments. While studies have examined the use of BCI devices by individuals with disabilities, many such devices are intended to address a specific limitation and have been studied when this limitation or disability is present in isolation. Little is known about the therapeutic potential of these devices for individuals with multiple disabilities with an acquired impairment overlaid on a secondary long-standing disability. We describe a case in which a male patient with congenital deafness suffered a right pontine ischemic stroke, resulting in persistent weakness of his left hand and arm. This patient volunteer completed four baseline assessments beginning at 4 months after stroke onset and subsequently underwent 6 weeks of interventional rehabilitation therapy using a closed-loop neurofeedback BCI device with visual, functional electrical stimulation, and tongue stimulation feedback modalities. Additional assessments were conducted at the midpoint of therapy, upon completion of therapy, and 1 month after completing all BCI therapy. Anatomical and functional MRI scans were obtained at each assessment, along with behavioral measures including the Stroke Impact Scale (SIS) and the Action Research Arm Test (ARAT). Clinically significant improvements in behavioral measures were noted over the course of BCI therapy, with more than 10 point gains in both the ARAT scores and scores for the SIS hand function domain. Neuroimaging during finger tapping of the impaired hand also showed changes in brain activation patterns associated with BCI therapy. This case study demonstrates the potential for individuals who have preexisting disability or possible atypical brain organization to learn to use a BCI system that may confer some rehabilitative benefit.

Introduction: Brain-computer interface (BCI) is an emerging technology for stroke rehabilitation, but little is known about brain changes associated with its use. We examine changes in laterality index (LI) and functional connectivity (FC) during hand movements associated with BCI interventional therapy. Methods: We collected anatomical and functional MRI of 8 stroke patients with upper extremity motor impairment before, during, and after up to 6 weeks of therapy using a BCI system with tongue and functional electrical stimulations. We acquired functional images during imagined (MI) and executed (ME) tapping and squeezing of each hand; not all subjects performed all tasks. Two subjects’ scans were flipped so that as a group the lesion was left (L) and the impaired limb right (R). We computed LI using 3 mask sets: whole brain, motor network, and motor cortex. Group-level analyses examined FC changes to motor network seeds using AFNI and Matlab NBS toolbox. Results: BCI intervention led to decreased average LI during tapping. Overall, R taps shifted L to bilateral; all L taps shifted bilateral to R. Trends were consistent across all masks at thresholds p Conclusions: BCI interventional therapy of the impaired hand leads to more bilateral brain activity, while more lateralized activation was seen of the unimpaired hand to its corresponding contralateral motor regions. With different patterns of change observed during tasks using the impaired or unimpaired hand, lesioned brain areas may respond differently to BCI than unlesioned counterparts.

Stroke remains a major source of disability in the United States as well as in many industrialized countries. Although most patients survive acute stroke and some spontaneous recovery is common, the restoration of function is rarely complete, leaving persistent deficits that affect a patient's activities of daily living. While the structural damage is usually rather localized, the functional damage can be vast, impacting regions physically remote from the area of infarct. Functional magnetic resonance imaging (fMRI) allows us to pursue, noninvasively, the investigation of stroke-related disruptions and brain recovery from such injuries. There is an emerging consensus from these fMRI studies in terms of the recovery process of the brain after a stroke. Task-based motor fMRI studies with patients exhibiting motor deficit have revealed initial recruitment of perilesional areas to the infarcted regions of the primary motor cortex as well as the homologous area in the contralesional hemisphere reaching high levels of activity at the subacute stages of recovery. The recruitment of such activity is thought to provide assistance initially in the execution of the motor functional task. This activity is then reduced in the later stages of recovery, mostly associated with further improvement of motor functions. Similarly, in patients exhibiting language deficit, perilesional areas to the infarcted regions of the language areas as well as the homologous areas in the contralesional hemisphere are recruited, reaching high levels of activity at the subacute stages of recovery and overall improvement of language function. This activity is then reduced in the later stages of recovery, mostly associated with further improvement of language functions. Although there is no clear consensus, most of these studies suggest a benefit of suppression of contralesional activation over time, which has shown promise in therapeutic rehabilitation strategies such as constraint-induced therapy and noninvasive brain stimulation methods. A third type of deficit that is common in stroke patients is hemispatial neglect caused by lesions that affect the directing of attention (the dorsal attention network). There is some fMRI evidence suggesting that recovery mechanisms within such a population involves reestablishment of the weighted activity within the dorsal attention network as well as involvement of a ventral attention network. Moreover, from analysis of networks in patients with stroke injury, interhemispheric connectivity initially disrupted by the onset of the injury is preferentially reestablished in the later stages if possible. Regaining of interhemispheric connectivity does not necessarily translate into increased activity, but rather translates into better communication between the two hemispheres, excitatory or inhibitory. There also exists a reestablishment of greater top-down modulatory control of higher level cortical areas on the lower cortices, such as premotor cortex exerting modulatory influence on the primary motor cortex in the motor system. Although the brain organization of a recovered patient returns to a “normal-like” pattern of activation with better recovery, graph theoretical analyses have demonstrated that neural reorganization after stroke may progress through the establishment of nonoptimal network structures, with the incorporation of previously unrecruited areas. Altogether, fMRI has consistently been proved to be a valuable and pragmatic tool in the investigation of the underlying mechanisms of stroke impairment and recovery. This allows us to hope that better treatment strategies will soon emanate and decrease the persistent burden that the injury of stroke imposes on the patient and society. Additionally, the use of fMRI provides several prospects in rehabilitation strategies such as future use of fMRI in real-time feedback modulation of neural activity in therapeutic protocols.

Object Functional MRI (fMRI) has proven to be an effective component of pretreatment planning in patients harboring a variety of different brain lesions. The authors have recently reported significant relationships concerning distances between brain tumor borders and areas of functional activation (lesion-to-activation distance; LAD) with regard to patient morbidity and mortality. This study further examines the relationship between LAD, focusing on a host of vascular lesions and pre- and posttreatment morbidity. Methods This study included a sample population of patients with vascular lesions (n = 106), primarily arteriovenous malformations (AVMs) and cavernomas. These patients underwent pretreatment fMRI-based motor mapping (n = 72) or language mapping (n = 84). The impact of LAD and other variables derived from the patient medical record were analyzed with respect to functional deficits in terms of morbidity (weakness and/or aphasia). Results In patients with no pretreatment deficits, there was trend for a significant relationship between the Wernicke area LAD and posttreatment language deficits. In patients with or without pretreatment deficits, a trend toward significance was observed between sensorimotor LAD and posttreatment motor deficits. Additionally, lesion type (AVMs or cavernomas) affected posttreatment deficits, with more patients with cavernomas showing posttreatment language deficits than patients with AVMs. However, this difference was not observed for posttreatment motor deficits. Conclusions These findings suggest that the proximity of a vascular lesion to sensorimotor and language areas is a relevant parameter in estimating patient prognosis in the perioperative period. Additionally, vascular lesion type and existence of pretreatment deficits play a significant role in outcomes.

Governmental agencies serve individuals with Intellectual Disabilities (ID) and Psychiatric Disabilities (PD) and must consequently communicate with these individuals at multiple points, from interviews with claims representatives to written notices sent to applicants and beneficiaries about highly complex material. We review the social scientific, survey research-based, cognitive testing-based and other relevant literatures regarding effective communication with these individuals. Given the nature of governmental contact with individuals with ID and PD, particular interest falls upon formal written communication, but other modes of communicating factual information (e.g., telephone, in-person) are also within the scope of this literature review. We evaluate what is known regarding the receptive and expressive communicative capacities of these individuals. We attempt to evaluate what is known about the communicative strategies to determine how the literature may inform a set of evidence-based best practices regarding for effective and efficient communication with individuals with ID and PD.

Background: Vascular lesion patients may have atypical language networks (Vikingstad et al. 2000). When evaluating language function in vascular lesion patients, the threshold of significance at which functional activations are analyzed may lead to differences in the lateralization index (LI) calculated. We examine the effect of various thresholds on language LIs in vascular lesion patients and control subjects. We further aim to compare language LIs in these two groups and to analyze patient LIs for correlations with lesion activation distance (LAD). Methods: Structural and functional images were collected from 29 vascular lesion patients and 14 normal controls while they performed language tasks in the scanner such as word generation and text comprehension. Left Hemisphere, frontal lobe (Broca’s), and temporal lobe (Wernicke’s) masks as well as masks of their homologous counterparts were created based on the language network identified in a meta-analysis of language studies by Vigneau et al. 2006. LI was calculated for each subject for each task on which data was acquired using each of the six masks at four different thresholds of statistical significance. Patient LIs were further analyzed for correlations with LAD to Broca’s and Wernicke’s areas. Results: Vascular lesion patients tend to display bilateral or left-lateralized language functions. At the group level, increasing threshold value tended to shift LIs toward left-lateralization. Relative to controls, patients with vascular lesions appear to lateralize language functions necessary for word generation to a lesser degree, which was trending toward significance. Pooled data from visual receptive language tasks shows association between computed LI values for the frontal lobe and Wernicke's LAD, which was significant at lower thresholds. Conclusions: Variable thresholding may cause reclassification of some patients based on LI, and higher thresholds tend to shift LI towards left-lateralization. The association observed between frontal lobe LI values and LAD to Wernicke’s area suggest that for these patients LAD to Wernicke’s may be a significant factor in lateralization at lower thresholds. These factors may be important if using LI in presurgical planning. Differences in the degree of lateralization between vascular lesion patients and controls may be due to long-term brain reorganization.

The miR-17 family of microRNAs has recently been recognized for its importance during lung development. The transgenic overexpression of the entire miR-17–92 cluster in the lung epithelium led to elevated cellular proliferation and inhibition of differentiation, while targeted deletion of miR-17–92 and miR-106b–25 clusters showed embryonic or early post-natal lethality. Herein we demonstrate that miR-17 and its paralogs, miR-20a, and miR-106b, are highly expressed during the pseudoglandular stage and identify their critical functional role during embryonic lung development. Simultaneous downregulation of these three miRNAs in explants of isolated lung epithelium altered FGF10 induced budding morphogenesis, an effect that was rescued by synthetic miR-17. E-Cadherin levels were reduced, and its distribution was altered by miR-17, miR-20a and miR-106b downregulation, while conversely, beta-catenin activity was augmented, and expression of its downstream targets, including Bmp4 as well as Fgfr2b, increased. Finally, we identified Stat3 and Mapk14 as key direct targets of miR-17, miR-20a, and miR-106b and showed that simultaneous overexpression of Stat3 and Mapk14 mimics the alteration of E-Cadherin distribution observed after miR-17, miR-20a, and miR-106b downregulation. We conclude that the mir-17 family of miRNA modulates FGF10–FGFR2b downstream signaling by specifically targeting Stat3 and Mapk14, hence regulating E-Cadherin expression, which in turn modulates epithelial bud morphogenesis in response to FGF10 signaling.

Introduction: Recent neuroimaging studies have suggested changes in composition of brain grey and white matter in patients with inflammatory bowel disease (IBD). In particular, regional cortical thickening has been reported in patients with ulcerative colitis and white matter abnormalities have been reported in patients with Crohn's disease compared to agematched controls. The full range of brain abnormalities in IBD patients and the associated cognitive and affective impairments, however, remain poorly characterized. Here we report preliminary findings from an ongoing study investigating brain cortical thickness changes in patients with Crohn's disease compared to age-matched healthy controls and its relationship with behavior. Methods: Adult patients with Crohn's disease in remission as defined by a Harvey-Bradshaw of 3 or below were recruited from the IBD clinic at the University of Wisconsin School of Medicine and Public Health. Patients with co-morbid chronic pain disorders, taking scheduled medications for pain control, or with contraindications to MRI were excluded. On a 3T MRI scanner, high-resolution T1 weighted structural images were obtained from all subjects and surface based regional cortical thickness measurements were generated using FreeSurfer. Letter fluency task was performed outside the scanner. Four patients with Crohn's disease (age range 20-63 yrs, mean = 38, 2 males) were compared to 7 age-matched healthy controls (age range 22-61 yrs, mean=40, 2 males). All subjects' cortical thickness and performance on the letter fluency task were analyzed.We also examined correlation between cortical thickness and performance on the letter fluency task. Results: We found a statistically significant difference between patients and controls in cortical thickness in the cingulate (p < 0.05, corrected for multiple comparisons) and postcentral (p < 0.005, uncorrected) regions. Furthermore, cortical thickening in the cingulate region correlated with behavioral performance on the letter fluency task (Spearman's rho, p=0.05) in patients. Conclusions: Given that the cingulate region is heavily implicated in various processes such as attention, executive function, and emotional processing, these early findings suggest that patients with Crohn's disease may undergo structural brain changes that may be associated with clinically relevant behaviors. Further investigations of such changes using advanced neuroimaging techniques will likely improve our understanding of brain-gut interactions in patients with IBD and may reveal mechanisms by which observed impairments in cognitive performance and emotional processing develop in this population.