Somatotopic disruption of the functional connectivity of the primary sensorimotor cortex in complex regional pain syndrome type 1.

In complex regional pain syndrome (CRPS), the representation area of the affected limb in the primary sensorimotor cortex (SM1) reacts abnormally during sensory stimulation and motor actions. We recorded 3T functional magnetic resonance imaging resting-state data from 17 upper-limb CRPS type 1 patients and 19 healthy control subjects to identify alterations of patients' SM1 function during spontaneous pain and to find out how the spatial distribution of these alterations were related to peripheral symptoms. Seed-based correlations and independent component analyses indicated that patients' upper-limb SM1 representation areas display (i) reduced interhemispheric connectivity, associated with the combined effect of intensity and spatial extent of limb pain, (ii) increased connectivity with the right anterior insula that positively correlated with the duration of CRPS, (iii) increased connectivity with periaqueductal gray matter, and (iv) disengagement from the other parts of the SM1 network. These findings, now reported for the first time in CRPS, parallel the alterations found in patients suffering from other chronic pain conditions or from limb denervation; they also agree with findings in healthy persons who are exposed to experimental pain or have used their limbs asymmetrically. Our results suggest that CRPS is associated with a sustained and somatotopically specific alteration of SM1 function, that has correspondence to the spatial distribution of the peripheral manifestations and to the duration of the syndrome.

Intelligent digital tools for screening of brain connectivity and dementia risk estimation in people affected by mild cognitive impairment: the AI-Mind clinical study protocol.

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector, enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions.

Symptom reduction and improved function in chronic CRPS type 1 after 12-week integrated, interdisciplinary therapy.

Background and aims Complex Regional Pain Syndrome (CRPS) often recovers spontaneously within the first year, but when it becomes chronic, available rehabilitative therapies (pharmacological management, physiotherapy, and psychological intervention) have limited effectiveness. This study examined the effect of a 12-week intensive outpatient rehabilitation on pain relief and function in chronic CRPS patients. Rehabilitation program included memantine and morphine treatment (added to patient's prior pain medication) and concurrent psychological and physiotherapeutic intervention. Primary outcome measure was a change in CRPS symptom count and secondary outcomes were motor performance, psychological factors, pain intensity, and quality of life. Methods Ten patients with chronic upper limb CRPS I (median 2.9 years, range 8 months to 12 years) were recruited to the study and were assessed before and after the intervention. Hand motor function of the patients was evaluated by an independent physiotherapist. There were standardized questionnaires for depression, pain anxiety, pain acceptance, quality of life, and CRPS symptom count. In addition, psychological factors were evaluated by a semi-structured interview. Severity of experienced pain was rated at movement and at rest. In addition, a video experiment of a hand action observation was conducted pre- and post-intervention to study possible change in neuronal maladaptation. Intervention consisted of pharmacological, psychological and physiotherapeutic treatment. First, 10 mg daily morphine was started and increased gradually to 30 mg daily, if tolerated. After 30 mg/day or tolerated dose of morphine was achieved, 5 mg daily memantine was started and increased gradually to 40 mg, if tolerated. Psychological intervention consisted of weekly group sessions, using cognitive and behavioral methods (relaxation, behavioral activation, and exposure) and acceptance and commitment therapy (ACT) and daily home practice. Physiotherapeutic intervention consisted of graded motor imagery and physiotherapy exercises with weekly group sessions and/or individual guidance by the physiotherapist, and individual exercise of the affected upper limb. Results Multimodal intensive intervention resulted in significant decrease in CRPS symptom count. The effect was strongest in motor and trophic symptoms (19% decrease after intervention) and in sensory symptoms (18% decrease). Additionally, improvement was seen in some, but not all, secondary outcomes (movement pain, motor symptoms, change in perceptions during video experiment of hand actions, and summary index with motor functioning, pain, and psychological factors). There were no dropouts. Conclusions Intensive 12-week multimodal intervention reduced some CRPS symptoms but was not sufficient to alter patients' rest pain, distress, or quality of life. Implications These results support the efficacy of an interdisciplinary rehabilitation program for pain and function in chronic CRPS patients. After intervention, some CRPS symptoms reduced and function improved, but distress and quality of life were unchanged. This may be due to the relatively short duration of this program; to delayed effects; to particular cognitive problems of CPRS patients; and/or to low distress levels at baseline that make statistically significant reduction less likely.

Complex regional pain syndrome: The matter of white matter?

INTRODUCTION: Many central pathophysiological aspects of complex regional pain syndrome (CRPS) are still unknown. Although brain-imaging studies are increasingly supporting the contribution of the central nervous system to the generation and maintenance of the CRPS pain, the brain's white-matter alterations are seldom investigated. METHODS: In this study, we used diffusion tensor imaging to explore white-matter changes in twelve CRPS-type-1 female patients suffering from chronic right upper-limb pain compared with twelve healthy control subjects. RESULTS: Tract-based spatial-statistics analysis revealed significantly higher mean diffusivity, axial diffusivity, and radial diffusivity in the CRPS patients, suggesting that the structural connectivity is altered in CRPS. All these measures were altered in the genu, body, and splenium of corpus callosum, as well as in the left anterior and posterior and the right superior parts of the corona radiata. Axial diffusivity was significantly correlated with clinical motor symptoms at whole-brain level, supporting the physiological significance of the observed white-matter abnormalities. CONCLUSIONS: Altogether, our findings further corroborate the involvement of the central nervous system in CRPS.

Abnormal Brain Responses to Action Observation in Complex Regional Pain Syndrome.

Patients with complex regional pain syndrome (CRPS) display various abnormalities in central motor function, and their pain is intensified when they perform or just observe motor actions. In this study, we examined the abnormalities of brain responses to action observation in CRPS. We analyzed 3-T functional magnetic resonance images from 13 upper limb CRPS patients (all female, ages 31-58 years) and 13 healthy, age- and sex-matched control subjects. The functional magnetic resonance imaging data were acquired while the subjects viewed brief videos of hand actions shown in the first-person perspective. A pattern-classification analysis was applied to characterize brain areas where the activation pattern differed between CRPS patients and healthy subjects. Brain areas with statistically significant group differences (q < .05, false discovery rate-corrected) included the hand representation area in the sensorimotor cortex, inferior frontal gyrus, secondary somatosensory cortex, inferior parietal lobule, orbitofrontal cortex, and thalamus. Our findings indicate that CRPS impairs action observation by affecting brain areas related to pain processing and motor control. PERSPECTIVE: This article shows that in CRPS, the observation of others' motor actions induces abnormal neural activity in brain areas essential for sensorimotor functions and pain. These results build the cerebral basis for action-observation impairments in CRPS.

Enlargement of choroid plexus in complex regional pain syndrome.

The choroid plexus, located in brain ventricles, has received surprisingly little attention in clinical neuroscience. In morphometric brain analysis, we serendipitously found a 21% increase in choroid plexus volume in 12 patients suffering from complex regional pain syndrome (CRPS) compared with age- and gender-matched healthy subjects. No enlargement was observed in a group of 8 patients suffering from chronic pain of other etiologies. Our findings suggest involvement of the choroid plexus in the pathogenesis of CRPS. Since the choroid plexus can mediate interaction between peripheral and brain inflammation, our findings pinpoint the choroid plexus as an important target for future research of central pain mechanisms.

A correlation-based method for extracting subject-specific components and artifacts from group-fMRI data.

We present a simple but effective correlation-based method (maxCorr) for extracting subject-specific components from group-fMRI data. The method finds signal components that correlate maximally with the data set of one subject and minimally with the data sets of the other subjects. We show that such subject-specific components are often related to movement and physiological noise (e.g. cardiac cycle, respiration). We further demonstrate that removing the most subject-specific components for each subject reduces the overall data variance and improves the statistical identification of true fMRI activations. We compare the performance of maxCorr with CompCor, a commonly used artifact-finding method in fMRI analysis. We show that maxCorr is less likely than CompCor to remove actual stimulus-related activity, especially when no information about the stimulus is available. MaxCorr operates without stimulus information and is therefore well suitable for analyses of fMRI experiments employing naturalistic stimuli, such as movies, where stimulus regressors are difficult to construct, and for brain decoding techniques benefiting from reduced subject-specific variance in each subject's data.