Biology subjects

Schweinhardt, P.

Publications and source records attributed to Schweinhardt, P..

6 recordsLinked to original sources

bioRxiv2025

Stable Somatotopy in Chronic Low Back Pain: Is Cortical Map Reorganization a Myth?

Chronic low back pain (CLBP) has been linked to maladaptive cortical plasticity in sensorimotor regions, which may contribute to pain persistence through less distinct ("smudged") somatotopic maps of afferent input from the back. However, empirical support for such functional reorganization processes, especially in the primary somatosensory cortex (S1), is limited. To delineate precise sensory representations of the back and test for altered somatotopic processing in CLBP, we utilized an MR-compatible pneumatic vibration device and applied frequency-specific vibrotactile stimuli (20 Hz and 80 Hz) at nine thoracolumbar paraspinal sites in 45 patients with CLBP and 41 healthy controls. Representational similarity analysis (RSA) was employed via a whole-brain searchlight method, and the neural representational patterns were contrasted against theoretical models including a segmental (based on anatomical proximity), simple (upper vs. lower back division) and a random model. In addition, a machine learning classifier was trained to predict afferent input from the upper vs lower back in healthy controls and tested in CLBP patients. Both groups displayed well-organized segmental representations spanning somatosensory, motor, and posterior parietal cortices. Posterior parietal regions exhibited the best model fits, followed by S1. No evidence for differences in representational patterns between groups was found. In CLBP patients, these patterns did not show associations with pain duration, severity, fear of movement or self-reported back perception. The classifier, trained on healthy controls, accurately predicted upper vs lower back afferent input in CLBP patients. These findings indicate preserved cortical maps of the back in CLBP, challenging the hypothesis of sensory cortical reorganization in this condition. Significance StatementChronic low back pain (CLBP) is often linked to maladaptive reorganization of somatotopic maps in sensorimotor cortices, providing the mechanistic rationale for therapies like sensory discrimination training to "normalize" these maps and alleviate pain. Using frequency-specific vibrotactile stimulation of the back and multivariate fMRI analysis, we found well-organized, segmental cortical representations in both CLBP patients and healthy controls, with no evidence of group differences. Representational patterns showed no associations with clinical measures such as pain duration or intensity. These findings challenge the cortical reorganization hypothesis in CLBP and suggest sensory training benefits may involve alternative mechanisms.

neuroscience↗

bioRxiv2023

Improving magnetic resonance spectroscopy in the brainstem periaqueductal grey using spectral registration

PurposeFunctional understanding of the periaqueductal grey (PAG), a clinically relevant brainstem region, can be advanced using proton magnetic resonance spectroscopy (1H-MRS). However, the PAGs small size and high levels of physiological noise are methodologically challenging. This study aimed to (1) improve 1H-MRS quality in the PAG using spectral registration for frequency and phase error correction, (2) investigate whether spectral registration is particularly useful in cases of greater head motion and (3) examine metabolite quantification using literature-based or individual-based water relaxation times. MethodsSpectra were acquired in 33 healthy volunteers (50.1 years, SD=17.19, 18 females) on a 3T Philipps MR system using a point-resolved spectroscopy sequence optimized with very selective saturation pulses (OVERPRESS) and voxel-based flip angle calibration (effective volume of interest size: 8.8x10.2x12.2 mm3). Spectra were fitted using LCModel and signal-to-noise ratios (SNR), N-acetylaspartate peak linewidths and Cramer-Rao lower bounds (CRLBs) were measured after spectral registration and after minimal frequency alignment. ResultsSpectral registration improved SNR by 5 % (p=0.026, median value post-correction: 18.0) and spectral linewidth by 23 % (p<0.001, 4.3 Hz), and reduced the metabolites CRLBs by 1-15 % (ps<0.026). Correlational analyses revealed smaller SNR improvements with greater head motion (p=0.010) recorded using a markerless motion tracking system. Higher metabolite concentrations were detected using individual-based compared to literature-based water relaxation times (ps<0.001). ConclusionThis study demonstrates high-quality 1H-MRS acquisition in the PAG using spectral registration. This shows promise for future 1H-MRS studies in the PAG and possibly also other clinically relevant brain regions with similar methodological challenges.

neuroscience↗

bioRxiv2022

Endogenous modulation of pain relief: evidence for dopaminergic but not opioidergic involvement

Relief of ongoing pain is a potent motivator of behavior, directing actions to escape from or reduce potentially harmful stimuli. Whereas endogenous modulation of pain events is well characterized, relatively little is known about the modulation of pain relief and its corresponding neurochemical basis. Here we studied pain modulation during a probabilistic relief-seeking task (a wheel of fortune gambling task), in which people actively or passively received reduction of a tonic thermal pain stimulus. We found that relief perception was enhanced by active decisions and unpredictability, and greater in high novelty-seeking trait individuals, consistent with a model in which relief is tuned by its informational content. We then probed the roles of dopaminergic and opioidergic signaling, both of which are implicated in relief processing, by embedding the task in a double-blinded cross-over design with administration of the dopamine precursor levodopa and the opioid receptor antagonist naltrexone. We found that levodopa, but not naltrexone, enhanced each of these information-specific aspects of relief modulation. These results show that dopaminergic signaling has a key role in modulating the perception of pain relief to optimize motivation and behavior.

neuroscience↗

bioRxiv2021

Do we really understand the role of the prefrontal cortex in placebo analgesia?

Several reviews have strongly implicated prefrontal cortical engagement in expectation-based placebo analgesia. We recently found a robust placebo analgesic response and associated decreases in pain-related cortical activations, without observable prefrontal engagement. We hypothesized our substantial conditioning and weak verbal instructions diminished expectation-related prefrontal activation. To test this, we examined the same subjects during a conditioning procedure, in which expectancy of pain relief was high. In two conditioning sessions, noxious heat was applied to a leg region treated with an "analgesic" cream and another treated with a "moisturizing" cream. In reality, both creams were inert, but the temperature applied to the moisturizing-cream area was 2{degrees}C higher than that applied to the analgesic-cream area. Functional MRI was acquired during the second conditioning session. Pain ratings were lower for the low heat than the high heat, with corresponding reduced activations in pain-related regions. Similar to previous studies with strong expectation for pain relief, we observed more prefrontal activations during the "analgesic" than the control condition. Nevertheless, contrary to the idea of active prefrontal engagement, the relative activation was based on differences in negative BOLD signals. A literature review revealed that only a few studies conclusively showed active engagement of prefrontal cortex, i.e. increased positive BOLD signal during high expectation compared to a control, with variable timing and spatial-specificity. We suggest that this variability is due to the heterogeneous influence of cognitive, emotional and motivational factors. Future studies should attempt to unravel the multiple contributions to placebo responsiveness in the prefrontal cortex.

neuroscience↗

bioRxiv2020

Neural effects of placebo analgesia in fibromyalgia patients and healthy individuals

Placebo analgesia is hypothesized to involve top-down engagement of prefrontal regions that access endogenous pain inhibiting opioid pathways. Fibromyalgia (FM) patients have neuroanatomical and neurochemical alterations in pathways relevant to placebo analgesia. Thus, it remains unclear whether placebo analgesic mechanisms would differ in FM patients compared to healthy controls (HCs). Here, using placebo-analgesia-inducing paradigms that included verbal suggestions and conditioning manipulations, we examined whether behavioral and neural placebo analgesic responses differed between 32 FM patients and 46 age- and sex-matched HCs. Participants underwent a manipulation scan, where noxious high and low heat were paired with the control and placebo cream, respectively, and a placebo experimental scan with equal noxious heat temperatures. Before the experimental scan, each participant received saline or naloxone, an opioid receptor antagonist. Across all participants, the placebo condition decreased pain intensity and unpleasantness ratings, decreased activity within the right insula and bilateral secondary somatosensory cortex, and modulated the Neurologic Pain Signature. There were no differences between HCs and FM patients in pain intensity ratings or neural responses during the placebo condition. Despite the perceptual and neural effects of the placebo manipulation, prefrontal circuitry was not activated during the expectation period and the placebo analgesia was unaltered by naloxone, suggesting placebo effects were driven more by conditioning than expectation. Together, these findings suggest that placebo analgesia can occur in both HCs and chronic pain FM patients, without the involvement of opiodergic prefrontal modulatory networks.

neuroscience↗

bioRxiv2018

Pain-related fear - From different fear constructs to dissociable neural sources

Fear of pain demonstrates significant prognostic value regarding the development of persistent musculoskeletal pain and disability. Its assessment often relies on self-report measures of pain-related fear by a variety of questionnaires. However, based either on \"fear of movement/(re)injury/kinesiophobia\", \"fear avoidance beliefs\" or \"pain anxiety\", pain-related fear constructs seemingly differ while the potential overlap of the questionnaires is unclear. Furthermore, the relationship to other anxiety measures such as state or trait anxiety remains ambiguous. Because the neural bases of fearful and anxious states are well described, advances in neuroimaging such as machine learning on brain activity patterns recorded by functional magnetic resonance imaging might help to dissect commonalities or differences across pain-related fear constructs. We applied a pattern regression approach in 20 non-specific chronic low back pain patients to reveal predictive relationships between fear-related neural information and different pain-related fear questionnaires. More specifically, the applied Multiple Kernel Learning approach allowed generating models to predict the questionnaire scores based on a hierarchical ranking of fear-related neural patterns induced by viewing videos of potentially harmful activities for the back. We sought to find evidence for or against overlapping pain-related fear constructs by comparing the questionnaire prediction models according to their predictive abilities and associated neural contributors. The results underpin the diversity of pain-related fear constructs by demonstrating evidence of non-overlapping neural predictors within fear processing regions. This neuroscientific approach might ultimately help to further understand and dissect psychological pain-related fear constructs.\n\nSignificancePain-related fear, often assessed through self-reports such as questionnaires, has shown prognostic value and clinical utility for a variety of musculoskeletal pain disorders. However, it remains difficult to determine a common underlying construct of pain-related fear due to several proposed constructs among questionnaires. The current study describes a novel neuroscientific approach using machine learning of neural patterns within the fear circuit of chronic low back pain patients that has the potential to identify neural commonalities or differences among the various pain-related fear constructs. Ultimately, this approach might afford a deeper understanding of the suggested constructs and might be also applied to other domains where ambiguity exists between different psychological constructs.

neuroscience↗