Biological, Psychiatric, Psychosocial, and Cognitive Factors of Poststroke Depression.

BACKGROUND: Depression is the most common psychiatric condition that occurs after cerebrovascular accident, especially within the first year after stroke. Poststroke depression (PSD) may occur due to environmental factors such as functional limitations in daily activities, lower quality of life, or biological factors such as damage to areas in the brain involved in emotion regulation. Although many factors are hypothesized to increase the risk of PSD, the relative contribution of these factors is not well understood. PURPOSE: We evaluated which cross-sectional variables were associated with increased odds of PSD in our adult outpatient stroke neuropsychology clinic population. METHODS: The sample included 325 patients (49.2% female; mean age of 59-years old) evaluated at an average of 8.1 months after an ischemic or hemorrhagic stroke. Variables included in logistic regression were stroke characteristics, demographics, psychosocial factors, comorbid medical problems, comorbid psychiatric conditions, and cognitive status. The Mini International Neuropsychiatric Inventory was used to determine DSM-defined PSD and anxiety disorders. A standard neuropsychological test battery was administered. RESULTS: PSD occurred in 30.8% of the sample. Logistic regression indicated that increased odds of PSD were associated with a comorbid anxiety disorder (5.9 times more likely to suffer from PSD, p < 0.001). Further, increased odds of PSD were associated with a history of depression treatment before stroke (3.0 times more likely to suffer from PSD), fatigue (2.8 times more likely), memory impairment (2.4 times more likely), and younger age at stroke (all p values < 0.006). DISCUSSION: Results suggest that PSD is likely multifactorial and extends the literature by demonstrating that a comorbid anxiety disorder correlated strongest with PSD. Poststroke screening and treatment plans should address not only depression but comorbid anxiety.

Barriers to Enrollment in Post-Stroke Brain Stimulation in a Racially and Ethnically Diverse Population.

BACKGROUND AND PURPOSE: Brain stimulation is an adjuvant strategy to promote rehabilitation after stroke. Here, we evaluated the influence of inclusion/exclusion criteria on enrollment in a transcranial direct current stimulation (tDCS) trial in the context of a racially/ethnically diverse acute stroke service at University of Texas Southwestern (UTSW). METHODS: 3124 (59.7 ± 14.5 years) racially/ethnically diverse (38.4% non-Hispanic white, (W), Hispanic (H) 22%, African American (AA) 33.5%, Asian (A) 2.3%) patients were screened in the acute stroke service at UTSW. Demographics, stroke characteristics, and reasons for exclusion were recorded prospectively. RESULTS: 2327 (74.5%) patients had a verified stroke. Only 44 of them (1.9%) were eligible. Causes for exclusion included in order of importance: (1) magnitude of upper extremity (UE) motor impairment, (2) prior strokes (s), (3) hemorrhagic stroke, (4) psychiatric condition or inability to follow instructions, and (5) old age, of these (2) and (4) were more common in AA patients but not in other minorities. 31 of the 44 eligible individuals were enrolled (W 1.68%, H 1.37%, AA .77%, A 3.774%). 90.5% of verified stroke patients did not exhibit contraindications for stimulation. CONCLUSIONS: 3 main conclusions emerged: (a) The main limitations for inclusion in brain stimulation trials of motor recovery were magnitude of UE motor impairments and stroke lesion characteristics, (b) most stroke patients could be stimulated with tDCS without safety concerns and (c) carefully tailored inclusion criteria could increase diversity in enrollment.Clinical Trial Registration-URL: http://clinicaltrials.gov. Unique identifier: NCT01007136.

Individual variability of cerebral autoregulation, posterior cerebral circulation and white matter hyperintensity.

KEY POINTS: Cerebral autoregulation (CA) is a key mechanism to protect brain perfusion in the face of changes in arterial blood pressure, but little is known about individual variability of CA and its relationship to the presence of brain white matter hyperintensity (WMH) in older adults, a type of white matter lesion related to cerebral small vessel disease (SVD). This study demonstrated the presence of large individual variability of CA in healthy older adults during vasoactive drug-induced changes in arterial pressure assessed at the internal carotid and vertebral arteries. We also observed, unexpectedly, that it was the 'over-' rather than the 'less-reactive' CA measured at the vertebral artery that was associated with WMH severity. These findings challenge the traditional concept of CA and suggest that the presence of cerebral SVD, manifested as WMH, is associated with posterior brain hypoperfusion during acute increase in arterial pressure. ABSTRACT: This study measured the individual variability of static cerebral autoregulation (CA) and determined its associations with brain white matter hyperintensity (WMH) in older adults. Twenty-seven healthy older adults (13 females, 66 ± 6 years) underwent assessment of CA during steady-state changes in mean arterial pressure (MAP) induced by intravenous infusion of sodium nitroprusside (SNP) and phenylephrine. Cerebral blood flow (CBF) was measured using colour-coded duplex ultrasonography at the internal carotid (ICA) and vertebral arteries (VA). CA was quantified by a linear regression slope (CA slope) between percentage changes in cerebrovascular resistance (CVR = MAP/CBF) and MAP relative to baseline values. Periventricular and deep WMH volumes were measured with T2-weighted magnetic resonance imaging. MAP was reduced by -11 ± 7% during SNP, and increased by 21 ± 8% during phenylephrine infusion. CA demonstrated large individual variability with the CA slopes ranging from 0.37 to 2.20 at the ICA and from 0.17 to 3.18 at the VA; no differences in CA were found between the ICA and VA. CA slopes measured at the VA had positive correlations with the total and periventricular WMH volume (r = 0.55 and 0.59, P < 0.01). Collectively, these findings demonstrated the presence of large individual variability of CA in older adults, and that, when measured in the posterior cerebral circulation, it is the higher rather than lower CA reactivity that is associated with WMH severity.

Functional near-infrared spectroscopy maps cortical plasticity underlying altered motor performance induced by transcranial direct current stimulation.

Transcranial direct current stimulation (tDCS) of the human sensorimotor cortex during physical rehabilitation induces plasticity in the injured brain that improves motor performance. Bi-hemispheric tDCS is a noninvasive technique that modulates cortical activation by delivering weak current through a pair of anodal-cathodal (excitation-suppression) electrodes, placed on the scalp and centered over the primary motor cortex of each hemisphere. To quantify tDCS-induced plasticity during motor performance, sensorimotor cortical activity was mapped during an event-related, wrist flexion task by functional near-infrared spectroscopy (fNIRS) before, during, and after applying both possible bi-hemispheric tDCS montages in eight healthy adults. Additionally, torque applied to a lever device during isometric wrist flexion and surface electromyography measurements of major muscle group activity in both arms were acquired concurrently with fNIRS. This multiparameter approach found that hemispheric suppression contralateral to wrist flexion changed resting-state connectivity from intra-hemispheric to inter-hemispheric and increased flexion speed (p<0.05). Conversely, exciting this hemisphere increased opposing muscle output resulting in a decrease in speed but an increase in accuracy (p<0.05 for both). The findings of this work suggest that tDCS with fNIRS and concurrent multimotor measurements can provide insights into how neuroplasticity changes muscle output, which could find future use in guiding motor rehabilitation.

Cerebral autoregulation of blood velocity and volumetric flow during steady-state changes in arterial pressure.

The validity of using transcranial Doppler measurement of cerebral blood flow velocity (CBFV) to assess cerebral autoregulation (CA) still is a concern. This study measured CBFV in the middle cerebral artery using transcranial Doppler and volumetric cerebral blood flow (CBF) in the internal carotid artery (ICA) using color-coded duplex ultrasonography to assess CA during steady-state changes in mean arterial pressure (MAP). Twenty-one healthy adults participated. MAP was changed stepwise by intravenous infusion of sodium nitroprusside and phenylephrine. Changes in CBFV, CBF, cerebrovascular resistance (CVR=MAP/CBF), or cerebrovascular resistance index (CVRi=MAP/CBFV) were measured to assess CA by linear regression analysis. The relationship between changes in ICA diameter and MAP was assessed. All values were normalized as percentage changes from baseline. Drug-induced changes in MAP were from -26% to 31%. Changes in CBFV and CVRi in response to MAP were linear, and the regression slopes were similar between middle cerebral artery and ICA. However, CBF in ICA remained unchanged despite large changes in MAP. Consistently, a steeper slope of changes in CVR relative to CVRi was observed (0.991 versus 0.804; P<0.05). The ICA diameter changed inversely in response to MAP (r=-0.418; P<0.05). These findings indicate that CA can be assessed with transcranial Doppler measurements of CBFV and CVRi in middle cerebral artery. However, it is likely to be underestimated when compared with the measurements of CBF and CVR in ICA. The inverse relationship between changes in ICA diameter and MAP suggests that large cerebral arteries are involved in CA.

Wolf Motor Function Test for characterizing moderate to severe hemiparesis in stroke patients.

OBJECTIVE: To extend the applicability of the Wolf Motor Function Test (WMFT) to describe the residual functional abilities of moderate to severely affected stroke patients. DESIGN: Data were collected as part of 2 double-blind, sham-controlled, randomized interventional studies: the Transcranial Direct Current Stimulation (tDCS) in Chronic Stroke Recovery and the tDCS Enhanced Stroke Recovery and Cortical Reorganization. Stroke patients were evaluated with the upper extremity Fugl-Meyer (UFM) and the WMFT in the same setting before treatment. SETTING: University inpatient rehabilitation and outpatient clinic. PARTICIPANTS: Stroke patients (N=32) with moderate to severe hemiparesis enrolled in the tDCS in Chronic Stroke Recovery and the tDCS Enhanced Stroke Recovery and Cortical Reorganization studies. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: WMFT scores were calculated using (1) median performance times and (2) a new calculation using the mean rate of performance. We compared the distribution of values from the 2 methods and examined the WMFT-UFM correlation for the traditional and the new calculation. RESULTS: WMFT rate values were more evenly distributed across their range than median WMFT time scores. The association between the WMFT rate and UFM was as good as the association between the median WMFT time scores and UFM (Spearman ρ, .84 vs -.79). CONCLUSIONS: The new WMFT mean rate of performance is valid and a more sensitive measure in describing the functional activities of the moderate to severely affected upper extremity of stroke subjects and avoids the pitfalls of the median WMFT time calculations.

Functional imaging of intervention effects in stroke motor rehabilitation.

OBJECTIVE: To assess intervention-specific effects on cortical reorganization after stroke as shown by available functional neuroimaging studies. DATA SOURCES: We searched Medline for clinical trials that contained the terms stroke, reorganization, and recovery, as well as either positron-emission tomography and PET, near-infrared spectroscopy and NIRS, single-photon emission tomography and SPECT, or functional magnetic resonance imaging and functional MRI; we reviewed primary and secondary references. STUDY SELECTION: Articles that reported neuroimaging findings as a result of a specific treatment involving more than 1 subject were included. DATA EXTRACTION: We included clinical trials that contained the terms stroke, reorganization, and recovery, as well as functional neuroimaging data findings as a result of a specific treatment involving more than 1 subject. DATA SYNTHESIS: Included studies differed clearly from one another with regard to patient characteristics, intervention protocol, and outcome measures. Most studies used functional magnetic resonance imaging and a motor paradigm. Studies were limited in size. CONCLUSIONS: Despite the methodologic differences, several common features can be identified based on the reviewed studies. Clinical improvements occurred even late after injury, after subjects were deemed to have reached a recovery plateau. This clinical improvement was accompanied by cortical reorganization that depended on the type of intervention as well as other factors. This review also suggests direction for future research studies.

MR compatible force sensing system for real-time monitoring of wrist moments during fMRI testing.

Functional magnetic resonance imaging (fMRI) of brain function is used in neurorehabilitation to gain insight into the mechanisms of neural recovery following neurological injuries such as stroke. The behavioral paradigms involving the use of force motor tasks utilized in the scanner often lack the ability to control details of motor performance. They are often limited by subjectiveness, lack of repeatability, and complexity that may exclude evaluation of patients with poor function. In this paper we describe a novel MR compatible wrist device that is capable of measuring isometric forces generated at the hand and joint moments along wrist flexion-extension and wrist ulnar-radial deviation axes. Joint moments measured by the system can be visually displayed to the individual and used during target matching block or event related paradigms. Through a small set of pilot testing both inside and outside the MR environment, we have found that the force tracking tasks and performance in the scanner are reproducible, and that high quality force and moment recordings can be made during fMRI studies without compromising the fMRI images. Furthermore, the device recordings are extremely sensitive making it possible for individuals with poor hand and wrist function to be tested.

Functional neuroimaging in motor recovery after stroke.

Neuroimaging techniques provide information on the neural substrates underlying functional recovery after stroke, the number one cause of long-term disability. Despite the methodological difficulties, they promise to offer insight into the mechanisms by which therapeutic interventions can modulate human cortical plasticity. This information should lead to the development of new, targeted interventions to maximize recovery.