PHYCAA: data-driven measurement and removal of physiological noise in BOLD fMRI.

The effects of physiological noise may significantly limit the reproducibility and accuracy of BOLD fMRI. However, physiological noise evidences a complex, undersampled temporal structure and is often non-orthogonal relative to the neuronally-linked BOLD response, which presents a significant challenge for identifying and removing such artifact. This paper presents a multivariate, data-driven method for the characterization and removal of physiological noise in fMRI data, termed PHYCAA (PHYsiological correction using Canonical Autocorrelation Analysis). The method identifies high frequency, autocorrelated physiological noise sources with reproducible spatial structure, using an adaptation of Canonical Correlation Analysis performed in a split-half resampling framework. The technique is able to identify physiological effects with vascular-linked spatial structure, and an intrinsic dimensionality that is task- and subject-dependent. We also demonstrate that increasing dimensionality of such physiological noise is correlated with increasing variability in externally-measured respiratory and cardiac processes. Using PHYCAA as a denoising technique significantly improves simulated signal detection with physiological noise, and real data-driven model prediction and reproducibility, for both block and event-related task designs. This is demonstrated compared to no physiological noise correction, and to the widely used RETROICOR (Glover et al., 2000) physiological denoising algorithm, which uses externally measured cardiac and respiration signals.

Optimizing preprocessing and analysis pipelines for single-subject fMRI. I. Standard temporal motion and physiological noise correction methods.

Subject-specific artifacts caused by head motion and physiological noise are major confounds in BOLD fMRI analyses. However, there is little consensus on the optimal choice of data preprocessing steps to minimize these effects. To evaluate the effects of various preprocessing strategies, we present a framework which comprises a combination of (1) nonparametric testing including reproducibility and prediction metrics of the data-driven NPAIRS framework (Strother et al. [2002]: NeuroImage 15:747-771), and (2) intersubject comparison of SPM effects, using DISTATIS (a three-way version of metric multidimensional scaling (Abdi et al. [2009]: NeuroImage 45:89-95). It is shown that the quality of brain activation maps may be significantly limited by sub-optimal choices of data preprocessing steps (or "pipeline") in a clinical task-design, an fMRI adaptation of the widely used Trail-Making Test. The relative importance of motion correction, physiological noise correction, motion parameter regression, and temporal detrending were examined for fMRI data acquired in young, healthy adults. Analysis performance and the quality of activation maps were evaluated based on Penalized Discriminant Analysis (PDA). The relative importance of different preprocessing steps was assessed by (1) a nonparametric Friedman rank test for fixed sets of preprocessing steps, applied to all subjects; and (2) evaluating pipelines chosen specifically for each subject. Results demonstrate that preprocessing choices have significant, but subject-dependant effects, and that individually-optimized pipelines may significantly improve the reproducibility of fMRI results over fixed pipelines. This was demonstrated by the detection of a significant interaction with motion parameter regression and physiological noise correction, even though the range of subject head motion was small across the group (≪ 1 voxel). Optimizing pipelines on an individual-subject basis also revealed brain activation patterns either weak or absent under fixed pipelines, which has implications for the overall interpretation of fMRI data, and the relative importance of preprocessing methods.

Top-down and bottom-up attention to memory are dissociated in posterior parietal cortex: neuroimagingand and neuropsychological evidence.

Posterior parietal cortex is active during episodic memory retrieval, yet its role remains unclear. According to a recent proposal, dorsal parietal cortex (DPC) allocates top-down attention to memory retrieval, whereas ventral parietal cortex (VPC) mediates the bottom-up attentional capture by retrieved contents, i.e., the Attention-to-Memory (AtoM) hypothesis. Here, for the first time, functional magnetic resonance imaging (fMRI) and lesion techniques were combined in a single study to test the role of parietal cortex in episodic retrieval. Participants studied word pairs and then detected studied (target) words among new words. In some conditions, a studied word cued the upcoming target word, facilitating recognition performance. In line with the AtoM hypothesis, left DPC was engaged when participants searched for/anticipated memory targets upon presentation of relevant memory cues and predicted the ensuing behavioral advantage. In contrast, left VPC predicted efficacy and speed of target detection on noncued trials and was largest for memory targets that were invalidly cued. Consistent with fMRI evidence, patients with lesions in DPC did not benefit from memory cueing, whereas patients with lesions in VPC had problems recognizing unexpected memory targets. These results support the AtoM hypothesis that DPC and VPC mediate top-down and bottom-up attention to memory retrieval, respectively.

The relationship between inflammatory markers and post stroke cognitive impairment.

OBJECTIVE: To determine whether there is a relationship between inflammatory markers (serum C-reactive protein (CRP) and cytokines) and post stroke cognitive impairment (PSCI). METHODS: This was a cross-sectional observational study. Patients were recruited from 4 sources: (1) the acute stroke unit of a general hospital, (2) an outpatient stroke prevention clinic, (3) a stroke rehabilitation unit in a specialized geriatric hospital, or (4) a stroke rehabilitation unit of a rehabilitation hospital. Patients meeting National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (WHO-MONICA) project criteria for stroke were invited to participate in this study within the first 5 to 31 days post stroke. Patients with subarachnoid or intracranial hemorrhage, decreased level of consciousness, severe aphasia or dysarthria, or a significant acute medical, neurological, or psychiatric illness were excluded. Clinical assessments included the Mini-Mental State Examination (MMSE) for cognition, the National Institutes of Health Stroke Scale (NIHSS) for stroke severity, and the Center for Epidemiological Studies-Depression Scale (CES-D) for depressive symptoms. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum concentrations of CRP, interleukin 6 (IL-6), and interferon gamma (IFN-gamma). RESULTS: A total of 48 patients with ischemic stroke (age [mean +/- SD] 71.6 +/- 13.2 years, 54.2% male, MMSE 26.4 +/- 3.8, NIHSS 6.8 +/- 4.0) were recruited within their first month post stroke. Backward stepwise elimination linear regression showed that higher concentrations of serum CRP (beta(CRP) = -0.46, p( CRP) = 0.002) predicted lower post stroke global cognition ([MMSE], F1,44 = 11.31, P = .002), with age (P = .92), level of education (P = .22), infarct side (P = 0.49), IL-6 (P = 0.36), and IFN-gamma (P = .57) removed from the final model. CONCLUSIONS: A post stroke inflammatory response may be important in subacute, PSCI.

A citywide prehospital protocol increases access to stroke thrombolysis in Toronto.

BACKGROUND AND PURPOSE: Intravenous tissue plasminogen activator for ischemic stroke is approved for eligible patients who can be treated within a 3-hour window, but treatment rates remain disappointingly low, often <5%. To improve rapid access to stroke thrombolysis in Toronto, Canada, a citywide prehospital acute stroke activation protocol was implemented by the provincial government to transport acute stroke patients directly to one of 3 regional stroke centers, bypassing local hospitals. This comprised a paramedic screening tool, ambulance destination decision rule, and formal memorandum of understanding of system stakeholders. This report describes the initial impact of the activation protocol at our regional stroke center. METHODS: We compared consecutive patients with stroke arriving to our stroke center during the first 4 months of this new triage protocol (February 14 to June 14, 2005) versus the same 4-month period in 2004. RESULTS: The protocol resulted in an immediate doubling in the number of patients with acute stroke arriving to our regional stroke center within 2.5 hours of symptom onset. We observed a 4-fold increase in patients who were eligible for and treated with tissue plasminogen activator. The tissue plasminogen activator treatment rate for ischemic stroke patients increased from 9.5% to 23.4% (P=0.01), and one in 2 patients with ischemic stroke arriving within 2.5 hours received thrombolysis during this period (one in 5 of patients with ischemic stroke overall). The median onset-to-needle time for tissue plasminogen activator-treated patients was significantly reduced. Many implementation challenges were identified and addressed. CONCLUSIONS: This prehospital triage was immediately successful in improving tissue plasminogen activator access for patients with ischemic stroke, enabling our center to achieve one of the highest tissue plasminogen activator treatment rates in North America and underscoring the need for coordinated systems of acute stroke care. Sustainability of such an initiative will be dependent on interdisciplinary teamwork, ongoing paramedic training, adequate hospital staffing, bed availability, and repatriation agreements with community hospitals.

Impairments in prospective and retrospective memory following stroke.

Prospective memory (PM) is the ability to carry out a planned intention at a future time. We studied PM deficits in a group of community-dwelling stroke survivors compared with normal controls. Twelve stroke patients and 12 matched controls performed a series of tests assessing executive function, prospective (PM) and retrospective memory (RM). Patients performed less well than controls on laboratory measures of PM and associative RM; they also showed deficits on standard tests of RM and executive control. The groups did not differ on more structured clinical measures of executive function, RM, PM or self-rated PM and RM. The results are discussed in terms of an impairment in the ability to 'self-initiate' effortful cognitive processes.

Modern stroke unit.

The modern stroke unit is making significant contributions to the care of stroke victims and is proving to be an effective, cost-saving enterprise. The precise factors that contribute to the efficacy of these units have yet to be identified, but a combination of protocolized approaches to patient care, critical paths, a focus of expertise, and heightened index of suspicion for comorbidities all probably play a role. This article outlines the basic features of a modern stroke unit and surveys the literature on stroke unit outcomes.

Influence of specific stroke diagnosis on prognostication, recovery, and early management.

Strokes are focal lesions in the brain and as such bring about deficits and portend a course of recovery depending on the nature of the lesion. Given the large number of possible combinations of locations, sizes, and types of lesions, a clear and reliable formula for predicting outcomes based on these characteristics has been statistically difficult, particularly early in the course of recovery. Severity of deficit and age of the patient accounts for sufficient variability that the influence of other factors becomes statistically harder to illustrate.

Mental status and behavioral changes in the early postacute phase of care.

Neurocognitive sequelae of stroke create a significant impact on the patient and frequently disrupt recovery from the physical manifestations. This article strives to review types of neurocognitive changes after stroke and discuss the underlying pathophysiology. Management options are presented for the diverse changes that may be encountered.

Dynamic working memory performance in individuals with single-domain amnestic mild cognitive impairment.

Previous studies have observed poorer working memory performance in individuals with amnestic mild cognitive impairment than in healthy older adults. It is unclear, however, whether these difficulties are true only of the multiple-domain clinical subtype in whom poorer executive functioning is common. The current study examined working memory, as measured by the self-ordered pointing task (SOPT) and an n-back task, in healthy older adults and adults with single-domain amnestic mild cognitive impairment (aMCI). Individuals with single-domain aMCI committed more errors and required longer to develop an organizational strategy on the SOPT. The single-domain aMCI group did not differ from healthy older adults on the 1-back or 2-back, but had poorer discrimination on the 3-back task. This is, to our knowledge, the first characterization of dynamic working memory performance in a single-domain aMCI group. These results lend support for the idea that clinical amnestic MCI subtypes may reflect different stages on a continuum of progression to dementia and question whether standardized measures of working memory (span tasks) are sensitive enough to capture subtle changes in performance.

Frequency of domain-specific cognitive impairment in sub-acute and chronic stroke.

BACKGROUND: Functional contributions of cognitive impairment may vary by domain and severity. OBJECTIVE: (1) To characterize frequency of cognitive impairment by domain after stroke by severity (mild: -1.5 ≤ z-score < -2; severe: Z ≤ -2) and time (sub-acute: < 90d; chronic: 90d-2yrs); and (2) To assess the association of cognitive impairment with function in chronic stroke. METHODS: Cognitive function was characterized among 215 people with sub-acute or chronic stroke (66.8 years, 43.3% female). Z-scores by cognitive domain were determined from normative data. Function was defined as the number of IADLs minimally independent. RESULTS: 76.3% of sub-acute and 67.3% of chronic stroke participants had cognitive impairment in ≥ 1 domain (p-for-difference = 0.09). Severe impairment was most common in psychomotor speed (sub-acute: 53.5%; chronic: 33.7%). Impairment in executive function was common (sub-acute: 39.5%; chronic: 30.7%) but was usually mild. Severe impairment in psychomotor speed, visuospatial function, and language and any impairment in executive function and memory was associated with IADL impairment (p < 0.03). CONCLUSIONS: Mild cognitive impairment is common after stroke but is not associated with functional disability. Impairment in psychomotor speed, executive function, and visuospatial function is common and associated with functional impairment so should be a focus of screening and rehabilitation post-stroke.

Changes in neuromagnetic beta-band oscillation after music-supported stroke rehabilitation.

Precise timing of sound is crucial in music for both performing and listening. Indeed, listening to rhythmic sound sequences activates not only the auditory system but also the sensorimotor system. Previously, we showed the significance of neural beta-band oscillations (15-30 Hz) for the timing processing that involves such auditory-motor coordination. Thus, we hypothesized that motor rehabilitation training incorporating music playing will stimulate and enhance auditory-motor interaction in stroke patients. We examined three chronic patients who received Music-Supported Therapy following the protocols practiced by Schneider. Neuromagnetic beta-band activity was remarkably alike during passive listening to a metronome and during finger tapping, with or without the metronome, for either the paretic or nonparetic hand, suggesting a shared mechanism of the beta modulation. In the listening task, the magnitude of the beta decrease after the tone onset was more pronounced at the posttraining time point and was accompanied by improved arm and hand skills. The present case data give insight into the neural underpinnings of rehabilitation with music making and rhythmic auditory stimulation.

Functional imaging of stroke recovery: an ecological review from a neural network perspective with an emphasis on motor systems.

Functional imaging is beginning to outline the brain's functional architecture and mechanisms of recovery from injury. I will review primarily the motor-function literature from normal populations, learning trials, stroke recovery, and rehabilitation with a neural network approach that may prove fruitful in further advancing our understanding of brain plasticity in response to focal lesions. A key consideration in this review will be how the development of distributed motor networks might constrain recovery as a function of the altered connectivity between damaged and nondamaged areas. It will be argued that this connectivity is central to both recovery from injury and response to treatment.

Theory of mind and the right cerebral hemisphere: refining the scope of impairment.

The neuropsychological and functional characterisation of mental state attribution ("theory of mind" (ToM)) has been the focus of several recent studies. The literature contains opposing views on the functional specificity of ToM and on the neuroanatomical structures most relevant to ToM. Studies with brain-lesioned patients have consistently found ToM deficits associated with unilateral right hemisphere damage (RHD). Also, functional imaging performed with non-brain-injured adults implicates several specific neural regions, many of which are located in the right hemisphere. The present study examined the separation of ToM impairment from other deficits associated with brain injury. We tested 11 patients with unilateral right hemisphere damage (RHD) and 20 normal controls (NC) on a humour rating task, an emotion rating task, a graded (first-order, second-order) ToM task with non-mentalistic control questions, and two ancillary measures: (1) Trails A and B, in order to assess overall level of impairment and set-shifting abilities associated with executive function, and (2) a homograph reading task to assess central coherence skills. Our findings indicate that RHD can result in a functionally specific deficit in attributing intentional states, particularly those involving second-order attributions. Performance on ToM questions was not reliably related to measures of cognitive impairment; however, performance on non-ToM control questions was reliably predicted by Trails A and B. We also discuss individual RHD patients' performance with attention to lesion locus. Our findings suggest that damage to the areas noted as specialised in neuroimaging studies may not affect ToM performance, and underscore the necessity of combining lesion and imaging studies in determining functional-anatomical relations.