Longitudinal evolution of diffusion metrics after left hemisphere ischaemic stroke.

White matter is often severely affected after human ischaemic stroke. While animal studies have suggested that various factors may contribute to white matter structural damage after ischaemic stroke, the characterization of damaging processes to the affected hemisphere after human stroke remains poorly understood. Thus, the present study aims to thoroughly describe the longitudinal pattern of evolution of diffusion magnetic resonance imaging metrics in different parts of the ipsilesional white matter after stroke. We acquired diffusion and anatomical images in 17 patients who had suffered from a single left hemisphere ischaemic stroke, at 24-72 h, 8-14 days and 6 months post-stroke. For each patient, we created three regions of interest: (i) the white matter lesion; (ii) the perilesional white matter; and (iii) the remaining white matter of the left hemisphere. We extracted diffusion metrics (fractional anisotropy, mean, axial and radial diffusivities) for each region and conducted two-way repeated measures ANOVAs with stage post-stroke (acute, subacute and chronic) × regions of interest (white matter lesion, perilesional white matter and remaining white matter). Fractional anisotropy values stayed consistent across time-points, with significantly lower values in the white matter lesion compared to the perilesional white matter and remaining white matter tissue. Fractional anisotropy values of the perilesional white matter were also significantly lower than that of the remaining white matter. Mean, axial and radial diffusivities in the white matter lesion were all decreased in the acute stage compared to perilesional white matter and remaining white matter, but significantly increased in both the subacute and chronic stages. Significant increases in mean and radial diffusivities in the perilesional white matter were seen in the later stages of stroke. Our findings suggest that various physiological processes are at play in the acute, subacute and chronic stages following ischaemic stroke, with the infarct territory and perilesional white matter affected by ischaemia at different rates and to different extents throughout the stroke recovery stages. The examination of multiple diffusivity metrics may inform us about the mechanisms occurring at different time-points, i.e. focal swelling, axonal damage or myelin loss.

Treatment-induced neuroplasticity after anomia therapy in post-stroke aphasia: A systematic review of neuroimaging studies.

We systematically reviewed the literature on neural changes following anomia treatment post-stroke. We conducted electronic searches of CINAHL, Cochrane Trials, Embase, Ovid MEDLINE, MEDLINE-in-Process and PsycINFO databases; two independent raters assessed all abstracts and full texts. Accepted studies reported original data on adults with post-stroke aphasia, who received behavioural treatment for anomia, and magnetic resonance brain imaging (MRI) pre- and post-treatment. Search results yielded 2481 citations; 33 studies were accepted. Most studies employed functional MRI and the quality of reporting neuroimaging methodology was variable, particularly for pre-processing steps and statistical analyses. The most methodologically robust data were synthesized, focusing on pre- versus post-treatment contrasts. Studies more commonly reported increases (versus decreases) in activation following naming therapy, primarily in the left supramarginal gyrus, and left/bilateral precunei. Our findings highlight the methodological heterogeneity across MRI studies, and the paucity of robust evidence demonstrating direct links between brain and behaviour in anomia rehabilitation.

Word-finding in confrontation naming and picture descriptions produced by individuals with early post-stroke aphasia.

Objective: The present study aims to assess the relationship between quantitative measures of connected speech production and performance in confrontation naming in early post-stroke aphasia (8-14 days post-stroke). Method: We collected connected speech samples elicited by a picture description task and administered a confrontation naming task to 20 individuals with early post-stroke aphasia and 20 healthy controls. Transcriptions were made in compliance with the CHAT format guidelines. Several micro- (i.e. duration, total number of words, words per minute, mean length of utterances, ratio of open- to closed-class words and noun-to-verb ratio, VOC-D, repetitions, self-corrections, and phonological and semantic errors) and macrolinguistic (i.e. informativeness and efficiency) measures were extracted. Results: We provide evidence for the presence of impairments in an array of micro- and macrolinguistic measures of speech in individuals with early post-stroke aphasia. We show that in the patient group, confrontation naming abilities most strongly relate to informativeness in a picture description task. Conclusion: Our findings contribute to a better understanding of the relationship between performance in confrontation naming and in connected speech production in the first days after stroke onset and also suggest that discourse analysis may provide unique, possibly more complex information.

Spinal and supraspinal modulation of pain responses by hypnosis, suggestions, and distraction.

The mechanisms underlying pain modulation by hypnosis and the contribution of hypnotic induction to the efficacy of suggestions being still under debate, our study aimed, (1) to assess the effects of identical hypoalgesia suggestions given with and without hypnotic induction, (2) to compare hypnotic hypoalgesia to distraction hypoalgesia and (3) to evaluate whether hypnotic suggestions of increased and decreased pain share common psychophysiological mechanisms. To this end, pain ratings, nociceptive flexion reflex amplitude, autonomic responses and electroencephalographic activity were measured in response to noxious electrical stimulation of the sural nerve in 20 healthy participants, who were subjected to four conditions: suggestions of hypoalgesia delivered with and without hypnosis induction (i.e. hypnotic-hypoalgesia and suggested-hypoalgesia), distraction by a mental calculation task and hypnotic suggestions of hyperalgesia. As a result, pain ratings decreased in distraction, suggested-hypoalgesia and hypnotic-hypoalgesia, while it increased in hypnotic-hyperalgesia. Nociceptive flexion reflex amplitude and autonomic activity decreased during suggested-hypoalgesia and hypnotic-hypoalgesia but increased during distraction and hypnotic-hyperalgesia. Hypnosis did not enhance the effects of suggestions significantly in any measurement. No somatosensory-evoked potential was modulated by the four conditions according to strict statistical criteria. The absence of a significant difference between the hypnotic hypoalgesia and hyperalgesia conditions suggests that brain processes as evidenced by evoked potentials are not invariably related to pain modulation. Time-frequency analysis of electroencephalographic activity showed a significant differentiation between distraction and hypnotic hypoalgesia in the theta domain. These results highlight the diversity of neurophysiological processes underlying pain modulation through different psychological interventions.

Brain Responses to Hypnotic Verbal Suggestions Predict Pain Modulation.

Background: The effectiveness of hypnosis in reducing pain is well supported by the scientific literature. Hypnosis typically involves verbal suggestions but the mechanisms by which verbal contents are transformed into predictive signals to modulate perceptual processes remain unclear. We hypothesized that brain activity during verbal suggestions would predict the modulation of responses to acute nociceptive stimuli. Methods: Brain activity was measured using BOLD-fMRI in healthy participants while they listened to verbal suggestions of HYPERALGESIA, HYPOALGESIA, or NORMAL sensation (control) following a standardized hypnosis induction. Immediately after the suggestions, series of noxious electrical stimuli were administered to assess pain-related responses. Brain responses measured during the suggestions were then used to predict changes in pain-related responses using delayed regression analyses. Results: Listening to suggestions of HYPERALGESIA and HYPOALGESIA produced BOLD decreases (vs. control) in the parietal operculum (PO) and in the anterior midcingulate cortex (aMCC), and increases in the left parahippocampal gyrus (lPHG). Changes in activity in PO, aMCC and PHG during the suggestions predicted larger pain-evoked responses following the HYPERALGESIA suggestions in the anterior cingulate cortex (ACC) and the anterior insula (aINS), and smaller pain-evoked responses following the HYPOALGESIA suggestions in the ACC, aMCC, posterior insula (pINS) and thalamus. These changes in pain-evoked brain responses are consistent with the changes in pain perception reported by the participants in HYPERALGESIA and HYPOALGESIA, respectively. Conclusions: The fronto-parietal network (supracallosal ACC and PO) has been associated with self-regulation and perceived self-agency. Deactivation of these regions during suggestions is predictive of the modulation of brain responses to noxious stimuli in areas previously associated with pain perception and pain modulation. The response of the hippocampal complex may reflect its role in contextual learning, memory and pain anticipation/expectations induced by verbal suggestions of pain modulation. This study provides a basis to further explore the transformation of verbal suggestions into perceptual modulatory processes fundamental to hypnosis neurophenomenology. These findings are discussed in relation to predictive coding models.

Predicting Early Post-stroke Aphasia Outcome From Initial Aphasia Severity.

Background: The greatest degree of language recovery in post-stroke aphasia takes place within the first weeks. Aphasia severity and lesion measures have been shown to be good predictors of long-term outcomes. However, little is known about their implications in early spontaneous recovery. The present study sought to determine which factors better predict early language outcomes in individuals with post-stroke aphasia. Methods: Twenty individuals with post-stroke aphasia were assessed <72 h (acute) and 10-14 days (subacute) after stroke onset. We developed a composite score (CS) consisting of several linguistic sub-tests: repetition, oral comprehension and naming. Lesion volume, lesion load and diffusion measures [fractional anisotropy (FA) and axial diffusivity (AD)] from both arcuate fasciculi (AF) were also extracted using MRI scans performed at the same time points. A series of regression analyses were performed to predict the CS at the second assessment. Results: Among the diffusion measures, only FA from right AF was found to be a significant predictor of early subacute aphasia outcome. However, when combined in two hierarchical models with FA, age and either lesion load or lesion size, the initial aphasia severity was found to account for most of the variance (R 2 = 0.678), similarly to the complete models (R 2 = 0.703 and R 2 = 0.73, respectively). Conclusions: Initial aphasia severity was the best predictor of early post-stroke aphasia outcome, whereas lesion measures, though highly correlated, show less influence on the prediction model. We suggest that factors predicting early recovery may differ from those involved in long-term recovery.

HYPNOTIC AUTOMATICITY IN THE BRAIN AT REST: An Arterial Spin Labelling Study.

The feeling of automaticity reported by individuals undergoing a hypnotic procedure is an essential dimension of hypnosis phenomenology. In the present study, healthy participants rated their subjective experience of automaticity and resting-state arterial spin labelling (ASL) scans were acquired before and after a standard hypnotic induction (i.e., "neutral hypnosis"). The increase in perceived automaticity was positively associated with activity in the parietal operculum (PO) and seed-based coactivation analysis revealed additional associations in the anterior part of the supracallosal cingulate cortex (aMCC). This is consistent with the role of these regions in perceived self-agency and volition and demonstrates that these effects can be evidenced at rest, in the absence of overt motor challenges. Future studies should further examine if/how these changes in brain activity associated with automaticity might facilitate the responses to suggestions and contribute to clinical benefits of hypnosis.

Chronic Central Pain Among Community-Dwelling Survivors of Moderate-to-Severe Traumatic Brain Injury: A Quantitative Sensory Testing Study.

BACKGROUND: Central pain associated with changes in sensory thresholds is one of the most enduring consequences of major trauma. Yet it remains sparsely studied among community-dwelling survivors of moderate-to-severe traumatic brain injury (TBI). PURPOSE: To describe and compare thermal and mechanical sensory thresholds in home-based patients with and without central pain after moderate-to-severe TBI with a cohort of healthy controls. DESIGN: Cross-sectional. METHOD: Thresholds for cold/heat detection, thermal pain, touch, and distorted sensation were gathered using quantitative sensory testing (QST). QST was performed on the painful and contralateral pain-free body regions in TBI participants with pain (TBI-P) and on both forearms in TBI participants without pain (TBI-NP) and healthy controls (HC). Central pain was characterized using the Brief Pain Inventory-Short Form. RESULTS: We tested 16 TBI-P patients, 17 TBI-NP patients, and 16 HC. Mean time since injury for TBI patients was 24 ± 15 months. TBI-P and TBI-NP patients showed significant loss in innocuous mechanical sensitivity compared to HC (F = 18.929; Bonferroni-adjusted p ≤ .001). Right-left differences in cold pain sensations were significantly larger in TBI-P than in TBI-NP and HC participants (F = 14.352; Bonferroni-adjusted p ≤ .001). Elevated heat sensitivity thresholds were also observed in TBI-P participants but remained within normal range. CONCLUSION: Damage to cutaneous mechanoreceptors is a necessary, but not sufficient, condition for the development of chronic central pain following TBI. Damage or incomplete recovery of cutaneous thermoreceptors may be a contributing factor to chronic pain after TBI.

Reprint of: Efficacy, tolerability, and safety of non-pharmacological therapies for chronic pain: An umbrella review on various CAM approaches.

BACKGROUND: Complementary and alternative medicine (CAM) therapies may be used as a non-pharmacological approach to chronic pain management. While hundreds of trials about individual CAM modality have been conducted, a comprehensive overview of their results is currently lacking for pain clinicians and researchers. AIM: This umbrella review synthesized the quality of meta-analytic evidence supporting the efficacy, tolerability and safety of CAM therapies for the management of chronic pain. MATERIALS & METHODS: MEDLINE, EMBASE, CINAHL, and CENTRAL were searched from October 1991 to November 2016. Reviews of clinical trials (randomized and non-randomized) with meta-analysis investigating the utility of any CAM modality for chronic pain were eligible. Pain relief post-intervention was the main outcome and secondary outcomes included patients' adherence and incidence of adverse effects during CAM protocol. RESULTS: Twenty-six reviews (207 clinical trials, >12,000 participants) about 18 CAM modalities, falling under natural products, mind and body practices or other complementary health approaches were included. Inhaled cannabis, graded motor imagery, and Compound Kushen injection (a form of Chinese medicine) were found the most efficient (with moderate-to-high effect sizes and low heterogeneity) and tolerable (≥80% of adherence to study protocols) for chronic pain relief. When reported, adverse effects related to these CAM were minor. CONCLUSION: Although several CAM were found effective for chronic pain relief, it remains unclear when these modalities are a reasonable choice against or in conjunction with mainstream treatments. In that sense, future research with a clear emphasis on concurrent evaluation of CAM overall efficacy and patient adherence/tolerance is needed.

Efficacy, tolerability, and safety of non-pharmacological therapies for chronic pain: An umbrella review on various CAM approaches.

BACKGROUND: Complementary and alternative medicine (CAM) therapies may be used as a non-pharmacological approach to chronic pain management. While hundreds of trials about individual CAM modality have been conducted, a comprehensive overview of their results is currently lacking for pain clinicians and researchers. AIM: This umbrella review synthesized the quality of meta-analytic evidence supporting the efficacy, tolerability and safety of CAM therapies for the management of chronic pain. MATERIALS & METHODS: MEDLINE, EMBASE, CINAHL, and CENTRAL were searched from October 1991 to November 2016. Reviews of clinical trials (randomized and non-randomized) with meta-analysis investigating the utility of any CAM modality for chronic pain were eligible. Pain relief post-intervention was the main outcome and secondary outcomes included patients' adherence and incidence of adverse effects during CAM protocol. RESULTS: Twenty-six reviews (207 clinical trials, >12,000 participants) about 18 CAM modalities, falling under natural products, mind and body practices or other complementary health approaches were included. Inhaled cannabis, graded motor imagery, and Compound Kushen injection (a form of Chinese medicine) were found the most efficient (with moderate-to-high effect sizes and low heterogeneity) and tolerable (≥80% of adherence to study protocols) for chronic pain relief. When reported, adverse effects related to these CAM were minor. CONCLUSION: Although several CAM were found effective for chronic pain relief, it remains unclear when these modalities are a reasonable choice against or in conjunction with mainstream treatments. In that sense, future research with a clear emphasis on concurrent evaluation of CAM overall efficacy and patient adherence/tolerance is needed.

Changes in sensory hand representation and pain thresholds induced by motor cortex stimulation in humans.

Shrinking of deafferented somatosensory regions after neural damage is thought to participate to the emergence of neuropathic pain, and pain-relieving procedures have been reported to induce the normalization of altered cortical maps. While repetitive magnetic stimulation (rTMS) of the motor cortex can lessen neuropathic pain, no evidence has been provided that this is concomitant to changes in sensory maps. Here, we assessed in healthy volunteers the ability of 2 modes of motor cortex rTMS commonly used in pain patients to induce changes in pain thresholds and plastic phenomena in the S1 cortex. Twenty minutes of high-frequency (20 Hz) rTMS significantly increased pain thresholds in the contralateral hand, and this was associated with the expansion of the cortical representation of the hand on high-density electroencephalogram source analysis. Neither of these effects were observed after sham rTMS, nor following intermittent theta-burst stimulation (iTBS). The superiority of 20-Hz rTMS over iTBS to induce sensory plasticity may reflect its better match with intrinsic cortical motor frequencies, which oscillate at around 20 Hz. rTMS-induced changes might partly counterbalance the plasticity induced by a nerve lesion, and thus substantiate the use of rTMS to treat human pain. However, a mechanistic relation between S1 plasticity and pain-relieving effects is far from being established.

Neural basis of semantic priming in schizophrenia during a lexical decision task: a magneto-encephalography study.

Numerous behavioral and electrophysiological studies have provided evidence of abnormal semantic processing in schizophrenia. However, the neural basis of these deficits is poorly understood. We investigated magnetic cortical responses elicited by a word-pair lexical decision task in 20 patients with schizophrenia and 12 healthy control subjects. The task involved presentation of a prime word (200 ms), followed by a blank (250 ms), and then a target stimulus (1200 ms); the subject had to decide whether the target was a real word or not. During this task, bilateral temporal and left prefrontal activations were observed in both groups. However, in contrast to controls, patients with schizophrenia did not show increased activation in the left temporal and anterior cingulate cortices between 200 and 450 ms in response to semantic incongruity. These results suggested that schizophrenia was associated with a functional disturbance in some semantic regions that gave rise to the N400 component. Moreover, a significant modulation in the right temporal cortex was observed in patients, but not in controls. This suggested the existence of alternative processes in patients because both groups showed similar behavioral priming. Finally, we elucidated some functional abnormalities in the semantic network during prime word processing in patients, indicated by prolonged activation compared to healthy controls. Thus, in addition to context integration impairment, abnormal activations during the prime word provided new evidence of context processing deficits in schizophrenia.

Cortical representation of the human hand assessed by two levels of high-resolution EEG recordings.

Increasing interest in cortical plasticity has prompted the growing use of somatosensory evoked potentials (SEPs) to estimate changes in the cortical representation of body regions. Here, we tested the effect of different sites of hand stimulation and of the density of spatial sampling in the quality of estimation of somatosensory sources. Sources of two SEP components from the primary somatosensory cortex (N20/P20 and P45) were estimated using two levels of spatial sampling (64- vs. 128-channel) and stimulation of four distal sites in the upper limbs, including single digits (first vs. fifth) and distal nerves with comparable cortical projection (superficial branch of the radial nerve and distal ulnar nerve). The most robust separation of somatosensory sources was achieved by comparing the cortical representations of the first digit and the distal ulnar nerve territories on the N20/P20 component of SEPs. Although both the 64- and the 128-electrode montages correctly discriminated these two areas, only the 128-electrode montage was able to significantly separate sources in the other cases, notably when using first versus fifth digit stimulation. Trustworthy distinction of cortical representations was not obtainable when using the P45 component, probably because of greater activation volume, radial orientation of sources in areas 1-2 and increased variability with attention and vigilance. Assessment of tangential SEP components to stimulation of first digit versus ulnar nerve appears the best option to assess plastic somatosensory changes, especially when using relatively low-electrode sampling.

Methylphenidate reduces impulsive behaviour in juvenile Wistar rats, but not in adult Wistar, SHR and WKY rats.

RATIONALE: Impulsivity is a core symptom of attention deficit/hyperactivity disorder (ADHD). The spontaneously hypertensive rats (SHR) is a strain commonly used as an animal model of ADHD. However, there is no clear evidence that psychostimulants, which are used for treatment of ADHD, reduce impulsivity in SHR. Because ADHD mainly affects children, it may be relevant to study psychostimulants on juvenile animals. OBJECTIVES: Using tolerance to delay of reward as index of impulsivity, the effects of methylphenidate were assessed in adult SHR, Wistar Kyoto (WKY) and Wistar rats and in juvenile Wistar rats. MATERIALS AND METHODS: Animals were trained in a T-maze to choose between a small-but-immediate and a large-but-delayed reward. Adult SHR, WKY and Wistar rats were compared for their ability to tolerate a 15-s delay. The effect of methylphenidate on the tolerance to a 30-s delay was studied in adult rats of the three strains and in juvenile (4.5 to 6.5-week-old) Wistar rats. RESULTS: In adult rats, the waiting ability was lower in SHR than in control strains. Waiting ability was improved by methylphenidate (3 and 5 mg/kg) in juveniles, but not by methylphenidate (3 mg/kg) in adults. CONCLUSIONS: These data support the idea that SHR are more impulsive than control strains. However, at the dose studied, methylphenidate fails to improve tolerance to delay in adult rats whatever the strain used. The reduction of impulsivity induced by methylphenidate in juvenile Wistar rats indicates that juvenile animals may be suitable for testing the therapeutic potential of drugs intended to the treatment of ADHD in children.