A speech planning network for interactive language use.

During conversation, people take turns speaking by rapidly responding to their partners while simultaneously avoiding interruption1,2. Such interactions display a remarkable degree of coordination, as gaps between turns are typically about 200 milliseconds3-approximately the duration of an eyeblink4. These latencies are considerably shorter than those observed in simple word-production tasks, which indicates that speakers often plan their responses while listening to their partners2. Although a distributed network of brain regions has been implicated in speech planning5-9, the neural dynamics underlying the specific preparatory processes that enable rapid turn-taking are poorly understood. Here we use intracranial electrocorticography to precisely measure neural activity as participants perform interactive tasks, and we observe a functionally and anatomically distinct class of planning-related cortical dynamics. We localize these responses to a frontotemporal circuit centred on the language-critical caudal inferior frontal cortex10 (Broca's region) and the caudal middle frontal gyrus-a region not normally implicated in speech planning11-13. Using a series of motor tasks, we then show that this planning network is more active when preparing speech as opposed to non-linguistic actions. Finally, we delineate planning-related circuitry during natural conversation that is nearly identical to the network mapped with our interactive tasks, and we find this circuit to be most active before participant speech during unconstrained turn-taking. Therefore, we have identified a speech planning network that is central to natural language generation during social interaction.

Profiling the proximal proteome of the activated µ-opioid receptor.

The µ-opioid receptor (µOR) represents an important target of therapeutic and abused drugs. So far, most understanding of µOR activity has focused on a subset of known signal transducers and regulatory molecules. Yet µOR signaling is coordinated by additional proteins in the interaction network of the activated receptor, which have largely remained invisible given the lack of technologies to interrogate these networks systematically. Here we describe a proteomics and computational approach to map the proximal proteome of the activated µOR and to extract subcellular location, trafficking and functional partners of G-protein-coupled receptor (GPCR) activity. We demonstrate that distinct opioid agonists exert differences in the µOR proximal proteome mediated by endocytosis and endosomal sorting. Moreover, we identify two new µOR network components, EYA4 and KCTD12, which are recruited on the basis of receptor-triggered G-protein activation and might form a previously unrecognized buffering system for G-protein activity broadly modulating cellular GPCR signaling.

Effects of transcranial magnetic stimulation on the human brain recorded with intracranial electrocorticography.

Transcranial magnetic stimulation (TMS) is increasingly used as a noninvasive technique for neuromodulation in research and clinical applications, yet its mechanisms are not well understood. Here, we present the neurophysiological effects of TMS using intracranial electrocorticography (iEEG) in neurosurgical patients. We first evaluated safety in a gel-based phantom. We then performed TMS-iEEG in 22 neurosurgical participants with no adverse events. We next evaluated intracranial responses to single pulses of TMS to the dorsolateral prefrontal cortex (dlPFC) (N = 10, 1414 electrodes). We demonstrate that TMS is capable of inducing evoked potentials both locally within the dlPFC and in downstream regions functionally connected to the dlPFC, including the anterior cingulate and insular cortex. These downstream effects were not observed when stimulating other distant brain regions. Intracranial dlPFC electrical stimulation had similar timing and downstream effects as TMS. These findings support the safety and promise of TMS-iEEG in humans to examine local and network-level effects of TMS with higher spatiotemporal resolution than currently available methods.

Spinal fMRI demonstrates segmental organisation of functionally connected networks in the cervical spinal cord: A test-retest reliability study.

Resting functional magnetic resonance imaging (fMRI) studies have identified intrinsic spinal cord activity, which forms organised motor (ventral) and sensory (dorsal) resting-state networks. However, to facilitate the use of spinal fMRI in, for example, clinical studies, it is crucial to first assess the reliability of the method, particularly given the unique anatomical, physiological, and methodological challenges associated with acquiring the data. Here, we characterise functional connectivity relationships in the cervical cord and assess their between-session test-retest reliability in 23 young healthy volunteers. Resting-state networks were estimated in two ways (1) by estimating seed-to-voxel connectivity maps and (2) by calculating seed-to-seed correlations. Seed regions corresponded to the four grey matter horns (ventral/dorsal and left/right) of C5-C8 segmental levels. Test-retest reliability was assessed using the intraclass correlation coefficient. Spatial overlap of clusters derived from seed-to-voxel analysis between sessions was examined using Dice coefficients. Following seed-to-voxel analysis, we observed distinct unilateral dorsal and ventral organisation of cervical spinal resting-state networks that was largely confined in the rostro-caudal extent to each spinal segmental level, with more sparse connections observed between segments. Additionally, strongest correlations were observed between within-segment ipsilateral dorsal-ventral connections, followed by within-segment dorso-dorsal and ventro-ventral connections. Test-retest reliability of these networks was mixed. Reliability was poor when assessed on a voxelwise level, with more promising indications of reliability when examining the average signal within clusters. Reliability of correlation strength between seeds was highly variable, with the highest reliability achieved in ipsilateral dorsal-ventral and dorso-dorsal/ventro-ventral connectivity. However, the spatial overlap of networks between sessions was excellent. We demonstrate that while test-retest reliability of cervical spinal resting-state networks is mixed, their spatial extent is similar across sessions, suggesting that these networks are characterised by a consistent spatial representation over time.

The amygdala is a chemosensor that detects carbon dioxide and acidosis to elicit fear behavior.

The amygdala processes and directs inputs and outputs that are key to fear behavior. However, whether it directly senses fear-evoking stimuli is unknown. Because the amygdala expresses acid-sensing ion channel-1a (ASIC1a), and ASIC1a is required for normal fear responses, we hypothesized that the amygdala might detect a reduced pH. We found that inhaled CO(2) reduced brain pH and evoked fear behavior in mice. Eliminating or inhibiting ASIC1a markedly impaired this activity, and localized ASIC1a expression in the amygdala rescued the CO(2)-induced fear deficit of ASIC1a null animals. Buffering pH attenuated fear behavior, whereas directly reducing pH with amygdala microinjections reproduced the effect of CO(2). These data identify the amygdala as an important chemosensor that detects hypercarbia and acidosis and initiates behavioral responses. They also give a molecular explanation for how rising CO(2) concentrations elicit intense fear and provide a foundation for dissecting the bases of anxiety and panic disorders.

Distribution of multiunit pitch responses recorded intracranially from human auditory cortex.

The perception of pitch is a fundamental percept, which is mediated by the auditory system, requiring the abstraction of stimulus properties related to the spectro-temporal structure of sound. Despite its importance, there is still debate as to the precise areas responsible for its encoding, which may be due to species differences or differences in the recording measures and choices of stimuli used in previous studies. Moreover, it was unknown whether the human brain contains pitch neurons and how distributed such neurons might be. Here, we present the first study to measure multiunit neural activity in response to pitch stimuli in the auditory cortex of intracranially implanted humans. The stimulus sets were regular-interval noise with a pitch strength that is related to the temporal regularity and a pitch value determined by the repetition rate and harmonic complexes. Specifically, we demonstrate reliable responses to these different pitch-inducing paradigms that are distributed throughout Heschl's gyrus, rather than being localized to a particular region, and this finding was evident regardless of the stimulus presented. These data provide a bridge across animal and human studies and aid our understanding of the processing of a critical percept associated with acoustic stimuli.

Learning nonnative speech sounds changes local encoding in the adult human cortex.

Adults can learn to identify nonnative speech sounds with training, albeit with substantial variability in learning behavior. Increases in behavioral accuracy are associated with increased separability for sound representations in cortical speech areas. However, it remains unclear whether individual auditory neural populations all show the same types of changes with learning, or whether there are heterogeneous encoding patterns. Here, we used high-resolution direct neural recordings to examine local population response patterns, while native English listeners learned to recognize unfamiliar vocal pitch patterns in Mandarin Chinese tones. We found a distributed set of neural populations in bilateral superior temporal gyrus and ventrolateral frontal cortex, where the encoding of Mandarin tones changed throughout training as a function of trial-by-trial accuracy ("learning effect"), including both increases and decreases in the separability of tones. These populations were distinct from populations that showed changes as a function of exposure to the stimuli regardless of trial-by-trial accuracy. These learning effects were driven in part by more variable neural responses to repeated presentations of acoustically identical stimuli. Finally, learning effects could be predicted from speech-evoked activity even before training, suggesting that intrinsic properties of these populations make them amenable to behavior-related changes. Together, these results demonstrate that nonnative speech sound learning involves a wide array of changes in neural representations across a distributed set of brain regions.

Acute kidney injury and liver disease in an American bulldog with suspected leptospirosis.

A 6-year-old spayed female American bulldog was brought to a veterinary clinic with a 3-day history of vomiting, lethargy, anorexia, icterus, hemorrhagic diarrhea, and oliguria. The dog's clinical signs, complete blood (cell) count, serum biochemistry, urinalysis, and diagnostic imaging were indicative of acute kidney injury and acute hepatopathy consistent with leptospirosis. Treatment for leptospirosis was initiated but, due to the dog's lack of response and progression of clinical signs, euthanasia was ultimately elected after 3 d of hospitalization. The dog tested negative for Leptospira spp. on ELISA; urine, blood, and tissue PCRs; and immunohistochemistry. This case demonstrates that confirmation of leptospirosis can be challenging, even in an animal with the expected clinical presentation. Therefore, limitations of the diagnostic tests available, as well as the possibility of other, less likely differential diagnoses such as toxicosis, must be considered.

Lésion rénale aiguë et maladie hépatique chez un bouledogue américain avec leptospirose suspectée. Une femelle bouledogue américain stérilisée âgée de 6 ans a été présenté à une clinique vétérinaire avec une histoire d'une durée de 3 jours de vomissement, léthargie, anorexie, ictère, diarrhée hémorragique et oligurie. Les signes cliniques de la chienne, un comptage cellulaire sanguin complet, une biochimie sérique, une analyse d'urine et de l'imagerie diagnostique étaient indicateur de lésion rénale aiguë et d'hépatopathie aiguë compatibles avec la leptospirose. Un traitement pour la leptospirose a été instauré mais, étant donné l'absence de réponse de l'animal et la progression des signes cliniques, l'euthanasie a finalement été décidée après 3 jours d'hospitalisation. L'animal s'est avéré négatif par ELISA pour Leptospira spp.; l'urine, le sang et les tissus étaient également négatifs par PCR; et par immunohistochime. Ce cas illustre le fait que la confirmation de la leptospirose peut représenter un défi, même chez un animal avec la présentation clinique attendue. Ainsi, les limites des tests diagnostiques disponibles, de même que la possibilité d'autres diagnostics différentiels moins probables, tel qu'une toxicose, doivent être considérés.(Traduit par Dr Serge Messier).

Gamma Activation and Alpha Suppression within Human Auditory Cortex during a Speech Classification Task.

The dynamics of information flow within the auditory cortical hierarchy associated with speech processing and the emergence of hemispheric specialization remain incompletely understood. To study these questions with high spatiotemporal resolution, intracranial recordings in 29 human neurosurgical patients of both sexes were obtained while subjects performed a semantic classification task. Neural activity was recorded from posteromedial portion of Heschl's gyrus (HGPM) and anterolateral portion of Heschl's gyrus (HGAL), planum temporale (PT), planum polare, insula, and superior temporal gyrus (STG). Responses to monosyllabic words exhibited early gamma power increases and a later suppression of alpha power, envisioned to represent feedforward activity and decreased feedback signaling, respectively. Gamma activation and alpha suppression had distinct magnitude and latency profiles. HGPM and PT had the strongest gamma responses with shortest onset latencies, indicating that they are the earliest auditory cortical processing stages. The origin of attenuated top-down influences in auditory cortex, as indexed by alpha suppression, was in STG and HGAL. Gamma responses and alpha suppression were typically larger to nontarget words than tones. Alpha suppression was uniformly greater to target versus nontarget stimuli. Hemispheric bias for words versus tones and for target versus nontarget words, when present, was left lateralized. Better task performance was associated with increased gamma activity in the left PT and greater alpha suppression in HGPM and HGAL bilaterally. The prominence of alpha suppression during semantic classification and its accessibility for noninvasive electrophysiologic studies suggests that this measure is a promising index of auditory cortical speech processing.SIGNIFICANCE STATEMENT Understanding the dynamics of cortical speech processing requires the use of active tasks. This is the first comprehensive intracranial electroencephalography study to examine cortical activity within the superior temporal plane, lateral superior temporal gyrus, and the insula during a semantic classification task. Distinct gamma activation and alpha suppression profiles clarify the functional organization of feedforward and feedback processing within the auditory cortical hierarchy. Asymmetries in cortical speech processing emerge at early processing stages. Relationships between cortical activity and task performance are interpreted in the context of current models of speech processing. Results lay the groundwork for iEEG studies using connectivity measures of the bidirectional information flow within the auditory processing hierarchy.

The effects of propofol anaesthesia on molecular-enriched networks during resting-state and naturalistic listening.

Placing a patient in a state of anaesthesia is crucial for modern surgical practice. However, the mechanisms by which anaesthetic drugs, such as propofol, impart their effects on consciousness remain poorly understood. Propofol potentiates GABAergic transmission, which purportedly has direct actions on cortex as well as indirect actions via ascending neuromodulatory systems. Functional imaging studies to date have been limited in their ability to unravel how these effects on neurotransmission impact the system-level dynamics of the brain. Here, we leveraged advances in multi-modal imaging, Receptor-Enriched Analysis of functional Connectivity by Targets (REACT), to investigate how different levels of propofol-induced sedation alter neurotransmission-related functional connectivity (FC), both at rest and when individuals are exposed to naturalistic auditory stimulation. Propofol increased GABA-A- and noradrenaline transporter-enriched FC within occipital and somatosensory regions respectively. Additionally, during auditory stimulation, the network related to the dopamine transporter showed reduced FC within bilateral regions of temporal and mid/posterior cingulate cortices, with the right temporal cluster showing an interaction between auditory stimulation and level of consciousness. In bringing together these micro- and macro-scale systems, we provide support for both direct GABAergic and indirect noradrenergic and dopaminergic-related network changes under propofol sedation. Further, we delineate a cognition-related reconfiguration of the dopaminergic network, highlighting the utility of REACT to explore the molecular substrates of consciousness and cognition.

Electrocorticography reveals the dynamics of famous voice responses in human fusiform gyrus.

Voice and face processing occur through convergent neural systems that facilitate speaker recognition. Neuroimaging studies suggest that familiar voice processing engages early visual cortex, including the bilateral fusiform gyrus (FG) on the basal temporal lobe. However, what role the FG plays in voice processing and whether it is driven by bottom-up or top-down mechanisms is unresolved. In this study we directly examined neural responses to famous voices and faces in human FG with direct cortical surface recordings (electrocorticography) in epilepsy surgery patients. We tested the hypothesis that neural populations in human FG respond to famous voices and investigated the temporal properties of voice responses in FG. Recordings were acquired from five adult participants during a person identification task using visual and auditory stimuli from famous speakers (U.S. Presidents Barack Obama, George W. Bush, and Bill Clinton). Patients were presented with images of presidents or clips of their voices and asked to identify the portrait/speaker. Our results demonstrate that a subset of face-responsive sites in and near FG also exhibit voice responses that are both lower in magnitude and delayed (300-600 ms) compared with visual responses. The dynamics of voice processing revealed by direct cortical recordings suggests a top-down feedback-mediated response to famous voices in FG that may facilitate speaker identification.NEW & NOTEWORTHY Interactions between auditory and visual cortices play an important role in person identification, but the dynamics of these interactions remain poorly understood. We performed direct brain recordings of fusiform face cortex in human epilepsy patients performing a famous voice naming task, revealing the dynamics of famous voice processing in human fusiform face cortex. The findings support a model of top-down interactions from auditory to visual cortex to facilitate famous voice recognition.

GFR estimated with creatinine rather than cystatin C is more reflective of the true risk of adverse outcomes with low GFR in kidney transplant recipients.

BACKGROUND: Serum cystatin C-based estimated glomerular filtration rate (eGFRcys) generally associates with clinical outcomes better than serum creatinine-based eGFR (eGFRcr) despite similar precision in estimating measured GFR (mGFR). We sought to determine whether the risk of adverse outcomes with eGFRcr or eGFRcys was via GFR alone or also via non-GFR determinants among kidney transplant recipients. METHODS: Consecutive adult kidney transplant recipients underwent a standardized GFR assessment during a routine follow-up clinic visit between 2011 and 2013. Patients were followed for graft failure or the composite outcome of cardiovascular (CV) events or mortality through 2020. The risk of these events by baseline mGFR, eGFRcr and eGFRcys was assessed unadjusted, adjusted for mGFR and adjusted for CV risk factors. RESULTS: There were 1135 recipients with a mean baseline mGFR of 55.6, eGFRcr of 54.8 and eGFRcys of 46.8 ml/min/1.73 m2 and a median follow-up of 6 years. Each 10 ml/min/1.73 m2 decrease in mGFR, eGFRcr or eGFRcys associated with graft failure [hazard ratio (HR) 1.79, 1.68 and 2.07, respectively; P < .001 for all) and CV events or mortality outcome (HR 1.28, 1.19 and 1.43, respectively; P < .001 for all). After adjusting for mGFR, eGFRcys associated with graft failure (HR 1.57, P < .001) and CV events or mortality (HR 1.49, P < .001), but eGFRcr did not associate with either. After further adjusting for CV risk factors, risk of these outcomes with lower eGFRcys was attenuated. CONCLUSION: eGFRcr better represents the true relationship between GFR and outcomes after kidney transplantation because it has less non-GFR residual association. Cystatin C is better interpreted as a nonspecific prognostic biomarker than is eGFR in the kidney transplant setting.

Delirium, confusion, or altered mental status as a risk for abnormal head CT in older adults in the emergency department: A systematic review and meta-analysis.

BACKGROUND: Altered mental status (including delirium) is a common presentations among older adults to the emergency department (ED). We aimed to report the association between altered mental status in older ED patients and acute abnormal findings on head computed tomogram (CT). METHODS: A systematic review was conducted using Ovid Medline, Embase, Clinicaltrials.gov, Web of Science, and Cochrane Central from conception to April 8th, 2021. We included citations if they described patients aged 65 years or older who received head imaging at the time of ED assessment, and reported whether patients had delirium, confusion, or altered mental status. Screening, data extraction, and bias assessment were performed in duplicate. We estimated the odds ratios (OR) for abnormal neuroimaging in patients with altered mental status. RESULTS: The search strategy identified 3031 unique citations, of which two studies reporting on 909 patients with delirium, confusion or altered mental status were included. No identified study formally assessed for delirium. The OR for abnormal head CT findings in patients with delirium, confusion or altered mental status was 0.35 (95% CI 0.031 to 3.97) compared to patients without delirium, confusion or altered mental status. CONCLUSION: We did not find a statistically significant association between delirium, confusion or altered mental status and abnormal head CT findings in older ED patients.

A Probabilistic Model of Human Activity Recognition with Loose Clothing.

Human activity recognition has become an attractive research area with the development of on-body wearable sensing technology. Textiles-based sensors have recently been used for activity recognition. With the latest electronic textile technology, sensors can be incorporated into garments so that users can enjoy long-term human motion recording worn comfortably. However, recent empirical findings suggest, surprisingly, that clothing-attached sensors can actually achieve higher activity recognition accuracy than rigid-attached sensors, particularly when predicting from short time windows. This work presents a probabilistic model that explains improved responsiveness and accuracy with fabric sensing from the increased statistical distance between movements recorded. The accuracy of the comfortable fabric-attached sensor can be increased by 67% more than rigid-attached sensors when the window size is 0.5s. Simulated and real human motion capture experiments with several participants confirm the model's predictions, demonstrating that this counterintuitive effect is accurately captured.

Neurotransmitter receptor densities are associated with changes in regional Cerebral blood flow during clinical ongoing pain.

Arterial spin labelling (ASL) plays an increasingly important role in neuroimaging pain research but does not provide molecular insights regarding how regional cerebral blood flow (rCBF) relates to underlying neurotransmission. Here, we integrate ASL with positron emission tomography (PET) and brain transcriptome data to investigate the molecular substrates of rCBF underlying clinically relevant pain states. Two data sets, representing acute and chronic ongoing pain respectively, were utilised to quantify changes in rCBF; one examining pre-surgical versus post-surgical pain, and the second comparing patients with painful hand Osteoarthritis to a group of matched controls. We implemented a whole-brain spatial correlation analysis to explore associations between change in rCBF (ΔCBF) and neurotransmitter receptor distributions derived from normative PET templates. Additionally, we utilised transcriptomic data from the Allen Brain Atlas to inform distributions of receptor expression. Both datasets presented significant correlations of ΔCBF with the µ-opioid and dopamine-D2 receptor expressions, which play fundamental roles in brain activity associated with pain experiences. ΔCBF also correlated with the gene expression distributions of several receptors involved in pain processing. Overall, this is the first study illustrating the molecular basis of ongoing pain ASL indices and emphasises the potential of rCBF as a biomarker in pain research.

Brain-Computer Interfaces for Treatment of Focal Dystonia.

Task-specificity in isolated focal dystonias is a powerful feature that may successfully be targeted with therapeutic brain-computer interfaces. While performing a symptomatic task, the patient actively modulates momentary brain activity (disorder signature) to match activity during an asymptomatic task (target signature), which is expected to translate into symptom reduction.

Electrophysiology of the Human Superior Temporal Sulcus during Speech Processing.

The superior temporal sulcus (STS) is a crucial hub for speech perception and can be studied with high spatiotemporal resolution using electrodes targeting mesial temporal structures in epilepsy patients. Goals of the current study were to clarify functional distinctions between the upper (STSU) and the lower (STSL) bank, hemispheric asymmetries, and activity during self-initiated speech. Electrophysiologic properties were characterized using semantic categorization and dialog-based tasks. Gamma-band activity and alpha-band suppression were used as complementary measures of STS activation. Gamma responses to auditory stimuli were weaker in STSL compared with STSU and had longer onset latencies. Activity in anterior STS was larger during speaking than listening; the opposite pattern was observed more posteriorly. Opposite hemispheric asymmetries were found for alpha suppression in STSU and STSL. Alpha suppression in the STS emerged earlier than in core auditory cortex, suggesting feedback signaling within the auditory cortical hierarchy. STSL was the only region where gamma responses to words presented in the semantic categorization tasks were larger in subjects with superior task performance. More pronounced alpha suppression was associated with better task performance in Heschl's gyrus, superior temporal gyrus, and STS. Functional differences between STSU and STSL warrant their separate assessment in future studies.

The impact of sexual victimization on substance use disorder treatment completion: A systematic review and meta-analysis.

Background:A significant proportion of individuals seeking treatment for substance use disorders (SUDs) have experienced sexual victimization, which has been shown to disrupt the efficacy of SUD treatment services. Objective: To evaluate the relationship between lifetime sexual victimization and SUD treatment completion. Methods: Relevant literature was identified through a systematic, computerized search of nine electronic databases (May 2018) and reference harvesting, yielding 15 peer-reviewed articles published between 1992 and 2017. Two authors independently conducted title and abstract screens, full-text reviews, data abstraction, and methodological appraisals. Risk of bias was assessed using a modified mixed-methods appraisal tool. Only nine studies met criteria for the meta-analysis, which used a random-effects model. Results: Included studies yielded mixed results regarding the impact of sexual victimization on treatment completion. The meta-analysis yielded a non-significant trend of survivors of sexual victimization having slightly lower odds of completing treatment. Conclusions: Findings from this systematic review and meta-analysis did not support the impact of sexual victimization on treatment completion. Methodological limitations of the extant literature limit cross-study comparisons. Future studies should document program-related factors to improve the ability to understand relationships affecting treatment completion.

Evaluation of Sagittal Spinopelvic Balance in Spinal Cord Stimulator Patients.

OBJECTIVE: Spinal cord stimulation (SCS) has become a popular nonopioid pain intervention. However, the treatment failure rate for SCS remains significantly high and many of these patients have poor sagittal spinopelvic balance, which has been found to correlate with increased pain and decreased quality of life. The purpose of this study was to determine if poor sagittal alignment is correlated with SCS treatment failure. MATERIALS AND METHODS: Comparative retrospective analysis was performed between two cohorts of patients who had undergone SCS placement, those who had either subsequent removal of their SCS system (representing a treatment failure cohort) and those that underwent generator replacement (representing a successful treatment cohort). The electronic medical record was used to collect demographic and surgical characteristics, which included radiographic measurements of lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Also included were data on pain medication usage including opioid and nonopioid therapies. RESULTS: Eighty-one patients met inclusion criteria, 31 had complete removal, and 50 had generator replacements. Measurement of sagittal balance parameters demonstrated that many patients had poor alignment, with 34 outside normal range for LL (10 vs 24 in removal and replacement cohorts, respectively), 30 for PI (12 [38.7%] vs 18 [36.0%]), 46 for PT (18 [58.1%] vs 28 [56.0%]), 38 for SS (18 [58.1%] vs 20 [40.0%]), and 39 for PI-LL mismatch (14 [45.2%] vs 25 [50.0%]). There were no significant differences in sagittal alignment parameters between the two cohorts. CONCLUSIONS: This retrospective cohort analysis of SCS patients did not demonstrate any relationship between poor sagittal alignment and failure of SCS therapy. Further studies of larger databases should be performed to determine how many patients ultimately go on to have additional structural spinal surgery after failure of SCS and whether or not those patients go on to have positive outcomes.

The association between pain-induced autonomic reactivity and descending pain control is mediated by the periaqueductal grey.

There is a strict interaction between the autonomic nervous system (ANS) and pain, which might involve descending pain modulatory mechanisms. The periaqueductal grey (PAG) is involved both in descending pain modulation and ANS, but its role in mediating this relationship has not yet been explored. Here, we sought to determine brain regions mediating ANS and descending pain control associations. Thirty participants underwent conditioned pain modulation (CPM) assessments, in which they rated painful pressure stimuli applied to their thumbnail, either alone or with a painful cold contralateral stimulation. Differences in pain ratings between 'pressure-only' and 'pressure + cold' stimuli provided a measure of descending pain control. In 18 of the 30 participants, structural scans and two functional MRI assessments, one pain-free and one during cold-pain were acquired. Heart rate variability (HRV) was simultaneously recorded. Normalised low-frequency HRV (LF-HRVnu) and the CPM score were negatively correlated; individuals with higher LF-HRVnu during pain reported reductions in pain during CPM. PAG-ventro-medial prefrontal cortex (vmPFC) and PAG-rostral ventromedial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG-vmPFC functional connectivity mediated the strength of the LF-HRVnu-CPM association. CPM response magnitude was also negatively correlated with vmPFC GM volume. Our multi-modal approach, using behavioural, physiological and MRI measures, provides important new evidence of interactions between ANS and descending pain mechanisms. ANS dysregulation and dysfunctional descending pain modulation are characteristics of chronic pain. We suggest that further investigation of body-brain interactions in chronic pain patients may catalyse the development of new treatments. KEY POINTS: Heart rate variability (HRV) is associated with descending pain modulation as measured by the conditioned pain modulation protocol (CPM). There is an association between CPM scores and the functional connectivity between the periaqueductal grey (PAG) and ventro-medial prefrontal cortex (vmPFC). CPM scores are also associated with vmPFC grey matter volume. The strength of functional connectivity between the PAG and vmPFC mediates the association between HRV and CPM. Our data provide new evidence of interactions between the autonomic nervous system and descending pain mechanisms.