Biology subjects

Hashmi, J. A.

Publications and source records attributed to Hashmi, J. A..

4 recordsLinked to original sources

bioRxiv2026

Distinct contributions of post-traumatic stress and working memory to affective and sensory dimensions of chronic pain, with pain modulation as a shared mechanism

Chronic pain is highly heterogeneous, with individuals varying substantially in symptoms. pain severity, disability, affective distress, cognitive functioning, and trauma-related symptoms. This study examined whether working memory, post-traumatic stress symptoms (PTSS), trauma exposure, and pain modulation explain distinct or shared dimensions of chronic pain variability. Individuals with chronic pain completed clinical, cognitive, trauma-related, and behavioural pain modulation measures, as well as resting-state functional magnetic resonance imaging. Multivariate regressions were used to determine whether working memory, PTSS, trauma exposure, and pain modulation independently predicted chronic pain outcomes. Principal component analysis was used to identify latent dimensions of chronic pain, and mediation analyses tested whether behavioural pain modulation explained relationships between dlPFC to vlPAG resting-state functional connectivity and clinical pain outcomes. PTSS independently predicted affective outcomes, including depression, state anxiety, and trait anxiety, whereas working memory independently predicted pain severity and pain interference. Trauma exposure was associated with greater PTSS and poorer working memory, but did not independently predict core pain outcomes after accounting for these more proximal factors. Principal component analysis identified partially distinct affective and sensory-disability dimensions, while trauma exposure loaded primarily on a separate component characterized by greater PTSS and poorer working memory. Behavioural pain modulation showed broader relationships across symptom dimensions and was associated with dlPFC to vlPAG connectivity. Exploratory mediation analyses demonstrated that pain modulation mediated relationships between dlPFC to vlPAG connectivity and both pain severity and affective distress. These findings support an integrated model where PTSS and working memory are more proximal predictors of affect and severity respectively, and trauma exposure represents a more distal vulnerability factor that predicts both. Thus, pain modulation represents a shared mechanism linking cortico-brainstem connectivity to chronic pain intensity and affect. These variables need further testing for phenotyping people with chronic pain based on their specific clinical needs.

Neuroscience↗

bioRxiv2026

Post-traumatic stress symptoms are associated with altered cognitive circuits and threat pathways in chronic pain

Chronic pain and post-traumatic stress symptoms (PTSS) frequently co-occur. However, how they interact in the brain to influence cognition and emotion is not well understood. Here, we examined how PTSS affects working memory-related networks during an N-back task. In addition, we examined how these networks interact with subcortical threat regions and influence working memory and pain symptoms. Fifty-three chronic low back pain participants completed the N-back task during fMRI. Brain activation was analyzed in relation to PTSS as both a continuous measure and as high-versus-low groups, using whole-brain parcellation across task loads (FDR corrected). We also examined whether abnormally activated regions were functionally connected to periaqueductal gray subregions, the amygdala, or hippocampus, and how these connections related to PTSS. Although higher PTSS did not affect task performance, it was associated with reduced activation in dorsal and inferior lateral frontal regions during the 3-back condition. PTSS was also associated with increased functional connectivity between the dorsolateral prefrontal cortex and periaqueductal gray, but not with the amygdala or hippocampus. Reduced prefrontal activations and high connectivity with periaqueductal gray predicted higher depression and catastrophizing symptoms. Thus, in chronic pain, PTSS selectively disrupts prefrontal circuits, suggesting that greater trauma symptoms interact with prefrontal circuits when cognitive demand is high. PTSS strengthens coupling between prefrontal regions and brainstem threat/pain circuits, suggesting cognitive-affective coupling. These neural alterations occur even when working memory performance is intact and are linked to higher depression and pain catastrophizing. Larger studies are needed to confirm and clarify these mechanisms.

neuroscience↗

bioRxiv2026

Pain-regulation circuitry as a predictor of chronic pain phenotypes

Chronic pain involves sensory, emotional, and functional disruption, yet diagnostic labels rarely capture this variability, limiting individualized care. Multidimensional models, such as fear-avoidance and predictive coding, suggest that high emotional burden may disrupt expectation-based pain modulation and midbrain pain regulatory pathways, particularly within the periaqueductal gray (PAG). We tested whether chronic pain phenotypes defined by pain intensity, disability, and affective distress (PDA) differ in expectation-induced pain modulation, PAG connectivity, and behavioral markers including catastrophizing, hypervigilance, and medication use, and whether these features aid phenotype classification. We studied 159 patients with fibromyalgia or chronic low back pain and 72 controls. Our data-driven clustering approach identified high and low PDA groups. High PDA patients showed impaired modulation when positive expectations were violated and reported greater cognitive and behavioral burden (P<0.05). They also exhibited more negative connectivity between the dorsolateral/lateral PAG (dl/lPAG) and the dorsomedial prefrontal cortex (dmPFC) (corrected). Machine learning models classified PDA subtypes above chance, with accuracy improving when PAG connectivity was included. Findings highlight disrupted expectation-driven regulation and altered PAG pathways as markers for chronic pain stratification.

neuroscience↗

bioRxiv2019

Spontaneous back-pain alters randomness in functional connections in large scale brain networks

We use randomness as a measure to assess the impact of evoked pain on brain networks. Randomness is defined here as the intrinsic correlations that exist between different brain regions when the brain is in a task-free state. We use fMRI data of three brain states in a set of back pain patients monitored over a period of 6 months. We find that randomness in the task-free state closely follows the predictions of Gaussian orthogonal ensemble of random matrices. However, the randomness decreases when the brain is engaged in attending to painful inputs in patients suffering with early stages of back pain. A persistence of this pattern is observed in the patients that develop chronic back pain, while the patients who recover from pain after 6 months, the randomness reverts back to a normal level.\n\nAuthor SummaryBack-pain is a salient percept known to affect brain regions. We studied random correlations in brain networks using random matrix theory. The brain networks were generated by fMRI scans obtained from a longitudinal back-pain study. Without modelling the neuronal interactions, we studied universal and subject-independent properties of brain networks in resting state and two distinct task states. Specifically, we hypothesized that relative to the resting state, random correlations would decrease when the brain is engaged in a task and found that the random correlations showed a maximum decrease when the brain is engaged in detecting back pain than performing a visual task.

biophysics↗