Biology subjects

Apkarian, A. V.

Publications and source records attributed to Apkarian, A. V..

3 recordsLinked to original sources

bioRxiv2018

Identification of traits and functional connectivity-based neuropsychotypes of chronic pain

Psychological and personality factors, socioeconomic status, and brain properties all contribute to chronic pain but have essentially been studied independently. Here, we administered a broad battery of questionnaires to patients with chronic back pain (CBP). Clustering and network analyses revealed four orthogonal dimensions accounting for 60% of the variance, and defining chronic pain traits. Two of these traits - Pain-trait and Emote-trait - were related to back pain characteristics and could be predicted from distinct distributed functional networks in a cross-validation procedure, identifying neurotraits. These neurotraits were relatively stable in time and segregated CBP patients into subtypes showing distinct traits, pain affect, pain qualities, and socioeconomic status (neuropsychotypes). The results unravel the trait space of chronic pain leading to reliable categorization of patients into distinct types. The approach provides metrics aiming at unifying the psychology and the neurophysiology of chronic pain across diverse clinical conditions, and promotes prognostics and individualized therapeutics.

neuroscience↗

bioRxiv2018

Dorsal Hippocampal Activation Suppresses Neuropathic Pain Behaviors: Chronic pain as extinction-resistant pain-related memory traces

Accumulating evidence suggests the hippocampus being involved in, and modified with, chronic neuropathic pain. However, it is still not clear whether hippocampal activity has direct control over neuropathic behaviors. Here we show that activation of the dorsal, but not ventral, hippocampus, by glutamate microinjection or by chemogenetically increasing excitability (PSAM/PSEM), completely or partially reversed neuropathic behaviors: tactile allodynia and thermal hyperalgesia in the models of spared nerve injury and lumbar spinal nerve ligation. Using a new methodology (chemo-fMRI), where we combine awake resting state brain imaging with viral vector mediated chemogenetic activation (PSAM/PSEM), we could demonstrate that increased excitability of dorsal hippocampus neurons altered resting state functional connectivity within circuitry specifically related to the extent of diminution of neuropathic behavior (tactile allodynia). The identified circuitry most reliably (survived a validation procedure) identified dorsal hippocampal connections to the somatosensory cortex and the thalamus. Moreover, anterograde tracing indicated non-overlapping projections from dorsal and ventral hippocampus. Thus, the present study exhibits a novel causal role for the dorsal hippocampus, and mediating circuitry, controlling neuropathic pain-related behaviors. Altogether, these results imply downregulation of dorsal hippocampus circuitry in chronic neuropathic pain; the activation of which reverses pain behaviors either through disruption of accumulated memories and/or by enhancing extinction circuitry.

neuroscience↗

bioRxiv2017

Brain and psychological determinants of placebo pill response in chronic pain patients

Placebo response is universally observed in randomized controlled trials (RCTs), yet these effects are commonly dismissed as consequences of uncontrollable confounds. In this prospective neuroimaging-based RCT performed in chronic back pain patients, we demonstrate that the intensity, but not quality, of pain is diminished with placebo pill ingestion. The response to placebo pills depended on brain: subcortical limbic volume asymmetry, sensorimotor cortical thickness, and functional coupling of the dorsolateral prefrontal cortex (DLPFC) with the periaqueductal grey (PAG), the rostral anterior cingulate cortex (rACC), and the precentral gyrus (PreCG); and psychological factors. All features were present before exposure to the pill; most remained stable across treatment and washout periods, although specific functional coupling between DLPFC and PAG dissipated with repeated exposure. These brain properties and specific psychological factors, such as interoceptive awareness and openness, were also predictive of the magnitude of response (continuous variable). We used machine learning in a fully cross-validated procedure and demonstrated that psychological factors were sufficient for classifying and predicting response magnitude; and response magnitude could also be predicted from a functional network (nodes mainly located in the limbic community, the DLPFC, the orbitofrontal cortex, and the temporo-parietal junction); the combined model explained 36% of the variance. Together, our results demonstrate that placebo pill analgesia observed in clinical trials depends on a combination of brain properties and specific psychological factors.

neuroscience↗