Low-frequency BOLD fluctuations demonstrate altered thalamocortical connectivity in diabetic neuropathic pain.
Ontology highlight
ABSTRACT: Background
In this paper we explored thalamocortical functional connectivity in a group of eight patients suffering from peripheral neuropathic pain (diabetic pain), and compared it with that of a group of healthy subjects. We hypothesized that functional interconnections between the thalamus and cortex can be altered after years of ongoing chronic neuropathic pain.Results
Functional connectivity was studied through a resting state functional magnetic resonance imaging (fMRI) paradigm: temporal correlations between predefined regions of interest (primary somatosensory cortex, ventral posterior lateral thalamic nucleus, medial dorsal thalamic nucleus) and the rest of the brain were systematically investigated. The patient group showed decreased resting state functional connectivity between the thalamus and the cortex.Conclusion
This supports the idea that chronic pain can alter thalamocortical connections causing a disruption of thalamic feedback, and the view of chronic pain as a thalamocortical dysrhythmia.
SUBMITTER: Cauda F
PROVIDER: S-EPMC2789078 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ObjectiveTo characterize the functional brain changes involved in δ-9-tetrahydrocannabinol (THC) modulation of chronic neuropathic pain.MethodsFifteen patients with chronic radicular neuropathic pain participated in a randomized, double-blind, placebo-controlled trial employing a counterbalanced, within-subjects design. Pain assessments and functional resting state brain scans were performed at baseline and after sublingual THC administration. We examined functional connectivity of the anterior cingulate cortex (ACC) and pain-related network dynamics using graph theory measures.ResultsTHC significantly reduced patients' pain compared to placebo. THC-induced analgesia was correlated with a reduction in functional connectivity between the anterior cingulate cortex (ACC) and the sensorimotor cortex. Moreover, the degree of reduction was predictive of the response to THC. Graph theory analyses of local measures demonstrated reduction in network connectivity in areas involved in pain processing, and specifically in the dorsolateral prefrontal cortex (DLPFC), which were correlated with individual pain reduction.ConclusionThese results suggest that the ACC and DLPFC, 2 major cognitive-emotional modulation areas, and their connections to somatosensory areas, are functionally involved in the analgesic effect of THC in chronic pain. This effect may therefore be mediated through induction of functional disconnection between regulatory high-order affective regions and the sensorimotor cortex. Moreover, baseline functional connectivity between these brain areas may serve as a predictor for the extent of pain relief induced by THC.
| S-EPMC6177269 | biostudies-literature
Project description:Most studies involving spontaneous fluctuations in the BOLD signal extract connectivity patterns that show relationships between brain areas that are maintained over the length of the scanning session. In this study, however, we examine the spatiotemporal dynamics of the BOLD fluctuations to identify common patterns of propagation within a scan. A novel pattern finding algorithm was developed for detecting repeated spatiotemporal patterns in BOLD fMRI data. The algorithm was applied to high temporal resolution T2*-weighted multislice images obtained from rats and humans in the absence of any task or stimulation. In rats, the primary pattern consisted of waves of high signal intensity, propagating in a lateral to medial direction across the cortex, replicating our previous findings (Majeed et al., 2009a). These waves were observed primarily in sensorimotor cortex, but also extended to visual and parietal association areas. A secondary pattern, confined to subcortical regions consisted of an initial increase and subsequent decrease in signal intensity in the caudate-putamen. In humans, the most common spatiotemporal pattern consisted of an alteration between activation of areas comprising the "default-mode" (e.g., posterior cingulate and anterior medial prefrontal cortices) and the "task-positive" (e.g., superior parietal and premotor cortices) networks. Signal propagation from focal starting points was also observed. The pattern finding algorithm was shown to be reasonably insensitive to the variation in user-defined parameters, and the results were consistent within and between subjects. This novel approach for probing the spontaneous network activity of the brain has implications for the interpretation of conventional functional connectivity studies, and may increase the amount of information that can be obtained from neuroimaging data.
| S-EPMC2997178 | biostudies-literature
Project description:Brain networks are commonly defined using correlations between blood oxygen level-dependent (BOLD) signals in different brain areas. Although evidence suggests that gamma-band (30-100 Hz) neural activity contributes to local BOLD signals, the neural basis of interareal BOLD correlations is unclear. We first defined a visual network in monkeys based on converging evidence from interareal BOLD correlations during a fixation task, task-free state, and anesthesia, and then simultaneously recorded local field potentials (LFPs) from the same four network areas in the task-free state. Low-frequency oscillations (<20 Hz), and not gamma activity, predominantly contributed to interareal BOLD correlations. The low-frequency oscillations also influenced local processing by modulating gamma activity within individual areas. We suggest that such cross-frequency coupling links local BOLD signals to BOLD correlations across distributed networks.
| S-EPMC3531830 | biostudies-literature
Project description:PurposeTo examine spatiotemporal dynamics of low frequency fluctuations in rat cortex.Materials and methodsGradient-echo echo-planar imaging images were acquired from anesthetized rats (repetition time = 100 ms). Power spectral analysis was performed to detect different frequency peaks. Functional connectivity maps were obtained for the frequency peaks of interest. The images in the filtered time-series were displayed as a movie to study spatiotemporal patterns in the data for frequency bands of interest.ResultsHigh temporal and spectral resolution allowed separation of primary components of physiological noise and visualization of spectral details. Two low frequency peaks with distinct characteristics were observed. Selective visualization of the second low frequency peak revealed waves of activity that typically began in the secondary somatosensory cortex and propagated to the primary motor cortex.ConclusionTo date, analysis of these fluctuations has focused on the detection of functional networks assuming steady state conditions. These results suggest that detailed examination of the spatiotemporal dynamics of the low frequency fluctuations may provide more insight into brain function, and add a new perspective to the analysis of resting state fMRI data.
| S-EPMC2758521 | biostudies-literature
Project description:Schizophrenia has long been framed as a disorder of altered brain connectivity, with dysfunction in thalamocortical circuity potentially playing a key role in the development of the illness phenotype, including psychotic symptomatology and cognitive impairments. There is emerging evidence for functional and structural hypoconnectivity between thalamus and prefrontal cortex in persons with schizophrenia spectrum disorders, as well as hyperconnectivity between thalamus and sensory and motor cortices. However, it is unclear whether thalamocortical dysconnectivity is a general marker of vulnerability to schizophrenia or a specific mechanism of schizophrenia pathophysiology. This study aimed to answer this question by using diffusion-weighted imaging to examine thalamocortical structural connectivity in 22 persons with schizophrenia or schizoaffective disorder (SZ), 20 siblings of individuals with a schizophrenia spectrum disorder (SIB), and 44 healthy controls (HC) of either sex. Probabilistic tractography was used to quantify structural connectivity between thalamus and six cortical regions of interest. Thalamocortical structural connectivity was compared among the three groups using cross-thalamic and voxel-wise approaches. Thalamo-prefrontal structural connectivity was reduced in both SZ and SIB relative to HC, while SZ and SIB did not differ from each other. Thalamo-motor structural connectivity was increased in SZ relative to SIB and HC, while SIB and HC did not differ from each other. Hemispheric differences also emerged in thalamic connectivity with motor, posterior parietal, and temporal cortices across all groups. The results support the hypothesis that altered thalamo-prefrontal structural connectivity is a general marker of vulnerability to schizophrenia, whereas altered connectivity between thalamus and motor cortex is related to illness expression or illness-related secondary factors.
| S-EPMC7451425 | biostudies-literature
Project description:Spontaneous low-frequency Blood-Oxygenation Level-Dependent (BOLD) signals acquired during resting state are characterized by spatial patterns of synchronous fluctuations, ultimately leading to the identification of robust brain networks. The resting-state brain networks, including the Default Mode Network (DMN), are demonstrated to persist during sustained task execution, but the exact features of task-related changes of network properties are still not well characterized. In this work we sought to examine in a group of 20 healthy volunteers (age 33 ± 6 years, 8 F/12 M) the relationship between changes of spectral and spatiotemporal features of one prominent resting-state network, namely the DMN, during the continuous execution of a working memory n-back task. We found that task execution impacted on both functional connectivity and amplitude of BOLD fluctuations within large parts of the DMN, but these changes correlated between each other only in a small area of the posterior cingulate. We conclude that combined analysis of multiple parameters related to connectivity, and their changes during the transition from resting state to continuous task execution, can contribute to a better understanding of how brain networks rearrange themselves in response to a task.
| S-EPMC5568127 | biostudies-literature
Project description:Prior neuroimaging clinical trials investigating the neural effects of intranasal administration of the neuropeptide oxytocin demonstrated a key role of the amygdala in oxytocin's neuromodulatory effects. These studies mostly demonstrated the acute effects of single-dose administrations, examining task-dependent effects of oxytocin on brain activity elicited during explicit experimental tasks or stimuli presentations. The increased consideration of oxytocin as a potential ameliorating treatment in autism spectrum disorder (ASD) requires a better understanding of how multiple-dose oxytocin administration affects intrinsic, task-free, amygdala function. In this double-blind, randomized, placebo-controlled trial with between-subject design, 38 adult men with ASD underwent resting-state fMRI scanning before and after oxytocin or placebo treatment. Effects were assessed either after a single-dose administration, consisting of 24 international units, or after multiple-dose treatment, consisting of 4 weeks of once-daily nasal spray administrations. Compared to placebo, oxytocin induced a decrease in intrinsic resting-state BOLD signal amplitudes of the bilateral amygdala (fractional amplitudes of low-frequency fluctuations) and modulated cross-frequency interactions between adjacent BOLD frequency components. The right amygdala showed a pattern of reduced cross-frequency harmonicity, while the left amygdala showed a relative increase in harmonic cross-frequency interactions after oxytocin treatment. Notably, the direction and magnitude of BOLD spectral changes induced after a single-dose were qualitatively similar to treatment effects induced after multiple-dose treatment. Furthermore, the identified spectral changes in amygdalar BOLD amplitude and cross-frequency harmonicity were associated with improved feelings of tension, reflecting oxytocin's anxiolytic, stress-reducing neuromodulatory role. The observed effects of oxytocin on amygdalar BOLD spectral characteristics and associated behaviors contribute to a deeper mechanistic understanding of the intrinsic, task-free neuromodulatory dynamics that underlie single- and multiple-dose oxytocin treatment in ASD. European Clinical Trial Registry (Eudract 2014-000586-45).
| S-EPMC9489696 | biostudies-literature
Project description:Neuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system. A frequent cause of peripheral neuropathic pain is diabetic neuropathy. Its complex pathophysiology is not yet fully elucidated, which contributes to underassessment and undertreatment. A mechanism-based treatment of painful diabetic neuropathy is challenging but phenotype-based stratification might be a way to develop individualized therapeutic concepts. Our goal is to review current knowledge of the pathophysiology of peripheral neuropathic pain, particularly painful diabetic neuropathy. We discuss state-of-the-art clinical assessment, validity of diagnostic and screening tools, and recommendations for the management of diabetic neuropathic pain including approaches towards personalized pain management. We also propose a research agenda for translational research including patient stratification for clinical trials and improved preclinical models in relation to current knowledge of underlying mechanisms.
| S-EPMC7148276 | biostudies-literature
Project description:In this study, we aimed to demonstrate whether spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal derived from resting state functional magnetic resonance imaging (fMRI) reflect spontaneous neuronal activity in pathological brain regions as well as in regions spared by epileptiform discharges. This is a crucial issue as coherent fluctuations of fMRI signals between remote brain areas are now widely used to define functional connectivity in physiology and in pathophysiology. We quantified functional connectivity using non-linear measures of cross-correlation between signals obtained from intracerebral EEG (iEEG) and resting-state functional MRI (fMRI) in 5 patients suffering from intractable temporal lobe epilepsy (TLE). Functional connectivity was quantified with both modalities in areas exhibiting different electrophysiological states (epileptic and non affected regions) during the interictal period. Functional connectivity as measured from the iEEG signal was higher in regions affected by electrical epileptiform abnormalities relative to non-affected areas, whereas an opposite pattern was found for functional connectivity measured from the BOLD signal. Significant negative correlations were found between the functional connectivities of iEEG and BOLD signal when considering all pairs of signals (theta, alpha, beta and broadband) and when considering pairs of signals in regions spared by epileptiform discharges (in broadband signal). This suggests differential effects of epileptic phenomena on electrophysiological and hemodynamic signals and/or an alteration of the neurovascular coupling secondary to pathological plasticity in TLE even in regions spared by epileptiform discharges. In addition, indices of directionality calculated from both modalities were consistent showing that the epileptogenic regions exert a significant influence onto the non epileptic areas during the interictal period. This study shows that functional connectivity measured by iEEG and BOLD signals give complementary but sometimes inconsistent information in TLE.
| S-EPMC3098283 | biostudies-literature
Project description:UnlabelledSickle cell disease (SCD) is a hemoglobinopathy that affects more than 100,000 individuals in the United States. The disease is characterized by the presence of sickle hemoglobin and recurrent episodes of pain. Some individuals with SCD experience frequent hospitalizations and a high burden of pain. The role of central mechanisms in SCD pain has not been explored. Twenty-five adolescents and young adults with SCD underwent functional magnetic resonance imaging. Participants were stratified into groups with high pain or low pain based on the number of hospitalizations for pain in the preceding 12 months. Resting state functional connectivity was analyzed using seed-based and dual regression independent component analysis. Intrinsic brain connectivity was compared between the high pain and low pain groups, and association with fetal hemoglobin, a known modifier of SCD, was explored. Patients in the high pain group displayed an excess of pronociceptive connectivity such as between anterior cingulate and default mode network structures, such as the precuneus, whereas patients in the low pain group showed more connectivity to antinociceptive structures such as the perigenual and subgenual cingulate. Although a similar proportion of patients in both groups reported that they were on hydroxyurea, the fetal hemoglobin levels were significantly higher in the low pain group and were associated with greater connectivity to antinociceptive structures. These findings support the role of central mechanisms in SCD pain. Intrinsic brain connectivity should be explored as a complementary and objective outcome measure in SCD pain research.PerspectiveAltered connectivity patterns associated with high pain experience in patients with sickle cell disease suggest a possible role of central mechanisms in sickle cell pain. Resting state brain connectivity studies should be explored as an effective methodology to investigate pain in SCD.
| S-EPMC4986827 | biostudies-literature