Biology subjects

Howard, M. A.

Publications and source records attributed to Howard, M. A..

34 records · Page 2Linked to original sources

bioRxiv2023

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

Resting 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 demonstrate a novel implementation for acquiring BOLD-sensitive resting-state spinal fMRI, which was used to characterise functional connectivity relationships in the cervical cord and assess their test-retest reliability in 23 young healthy volunteers. Resting-state networks were estimated in two ways: (1) by extracting the mean timeseries from anatomically constrained seed masks and estimating voxelwise connectivity maps and (2) by calculating seed-to-seed correlations between extracted mean timeseries. 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 (ICC) in the following ways: for each voxel in the cervical spine; each voxel within an activated cluster; the mean signal as a summary estimate within an activated cluster; and correlation strength in the seed-to-seed analysis. Spatial overlap of clusters derived from voxelwise analysis between sessions was examined using Dice coefficients. Following voxelwise 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 (Bonferroni corrected p < 0.003, threshold-free cluster enhancement with 5000 permutations). Additionally, strongest correlations were observed between within-segment ipsilateral dorso-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 highest reliability achieved in ipsilateral dorso-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.

neuroscience↗

bioRxiv2022

Epigenetics of post-operative delirium: A genome-wide DNA methylation study of neurosurgery patients

AimsThere is no previous study demonstrating the differences of genome-wide DNA methylation (DNAm) profiles between patients with and without postoperative delirium (POD). We aimed to discover epigenetic (DNAm) markers that are associated with POD in blood obtained from patients before and after neurosurgery. MethodsPre- and post-surgical blood DNA samples from 37 patients, including 10 POD cases, were analyzed using the Illumina EPIC array genome-wide platform. We examined DNAm differences in blood from patients with and without POD. Enrichment analysis with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms were also conducted. ResultsWhen POD cases were tested for DNAm change before and after surgery, enrichment analyses showed many relevant signals with statistical significance in immune response related-pathways and inflammatory cytokine related-pathways such as "cellular response to cytokine stimulus", "regulation of immune system process", "regulation of cell activation", and "regulation of cytokine production". Furthermore, after excluding the potential effect of common factors related to surgery and anesthesia between POD cases and non-POD controls, the enrichment analyses showed significant signals such as "immune response" and "T cell activation", which are same pathways previously identified from an independent non-surgical inpatient cohort. Conclusions: Our first genome-wide DNAm investigation of POD showed promising signals related to immune response, inflammatory response and other relevant signals considered to be associated with delirium pathophysiology. Our data supports the hypothesis that epigenetics are playing an important role in pathophysiological mechanism of delirium and suggest the potential usefulness of epigenetics based biomarker of POD.

neuroscience↗

bioRxiv2022

Immediate neural network impact after the loss of a semantic hub

The human brain extracts meaning from the world using an extensive neural system for semantic knowledge. Whether such broadly distributed systems1-3 crucially depend on or can compensate for the loss of one of their highly interconnected hubs4-6 is controversial4. The strongest level of causal evidence for the role of a brain hub is to evaluate its acute network-level impact following disconnection and any rapid functional compensation that ensues. We report rare neurophysiological data from two patients who underwent awake intracranial recordings during a speech prediction task immediately before and after neurosurgical treatment that required disconnection of the left anterior temporal lobe (ATL), a crucial hub for semantic knowledge4-6. Informed by a predictive coding framework, we tested three sets of hypotheses including diaschisis causing disruption in interconnected sites7 and incomplete or complete compensation by other language-critical and speech processing sites8-10. Immediately after ATL disconnection, we observed highly specific neurophysiological alterations in the recorded fronto-temporal network, including abnormally magnified high gamma responses to the speech sounds in auditory cortex. We also observed evidence for rapid compensation, seen as focal increases in effective connectivity involving language-critical sites in the inferior frontal gyrus and speech processing sites in auditory cortex. However, compensation was incomplete, in part because after ATL disconnection speech prediction signals were depleted in auditory cortex. This study provides direct causal evidence for a semantic hub in the human brain and shows striking neural impact and a rapid attempt at compensation in a neural network after the loss of one of its hubs.

neuroscience↗

bioRxiv2022

Effects of transcranial magnetic stimulation on the human brain recorded with intracranial electrocorticography: First-in-human study

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 first in-human study evaluating the 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 20 neurosurgical participants with no adverse events. Next, we evaluated brain-wide intracranial responses to single pulses of TMS to the dorsolateral prefrontal cortex (dlPFC) (N=10, 1414 electrodes). We demonstrate that TMS preferentially induces neuronal responses locally within the dlPFC at sites with higher electric field strength. Evoked responses were also noted downstream in the anterior cingulate and anterior insular cortex, regions functionally connected to the dlPFC. 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.

neuroscience↗

bioRxiv2021

Distribution of multi-unit pitch responses recorded intracranially from human auditory cortex

The perception of pitch requires the abstraction of stimulus properties related to the spectrotemporal structure of sound. Previous studies utilizing both animal electrophysiology and human imaging have indicated the presence of a center for pitch representation in the auditory cortex. Recent data from our own group - examining local field potentials (LFPs) in humans - indicate more widely distributed pitch-associated responses within the auditory cortex (Gander et al., 2019). To probe this with greater spatial resolution, we examined multi-unit activity related to three different auditory stimuli, in seven epilepsy patients who were implanted with high-impedance electrodes in auditory cortex for the clinical purpose of localizing seizures. The stimuli were regular-interval noise (RIN) with a pitch strength that is related to the temporal regularity, and pitch value determined by repetition rate, and harmonic complexes with missing fundamentals. We demonstrated increases in spiking activity in 69 of 104 (66%) responsive multiunit activity in auditory cortex due to pitch-associated stimuli. Importantly, these responses were distributed across the entire extent of Heschls gyrus (HG), in both primary and non-primary areas, rather than isolated to a specific region, and this finding was evident regardless of the stimulus presented. These findings are the first multi-unit pitch responses recorded from humans, and align with a recent study in macaques (Kikuchi et al., 2019) demonstrating that both local field potential and unit responses to pitch-inducing stimuli are distributed throughout auditory cortex. Significance StatementThe perception of pitch is a fundamental acoustic attribute that is mediated by the auditory system. Despite its importance, there is still debate as to the precise areas responsible for its encoding, which may be due to differences in the recording measures and choices of stimuli used in previous studies. Here, we present the first study to measure multi-unit pitch responses in the auditory cortices of intracranially-implanted humans. Importantly, we demonstrate reliable responses to three different pitch-inducing paradigms that are distributed throughout Heschls gyrus, rather than being localized to a particular region. These data provide a bridge across animal and human studies, and aid in our understanding of the processing of a critical attribute of acoustic stimuli.

neuroscience↗

bioRxiv2021

A candidate neuroimaging biomarker for detection of neurotransmission-related functional alterations and prediction of pharmacological analgesic response in chronic pain

BackgroundChronic pain is a world-wide clinical challenge. Response to analgesic treatment is limited and difficult to predict. Functional MRI (fMRI) has been suggested as a potential solution. However, while most analgesics target specific neurotransmission pathways, fMRI-based biomarkers are not specific for any neurotransmitter system, limiting our understanding of how they might contribute to predict treatment response. MethodsHere, we sought to bridge this gap by applying Receptor-Enriched Analysis of Functional Connectivity by Targets (REACT) to investigate whether neurotransmission-enriched functional connectivity (FC) mapping can provide insights into the brain mechanisms underlying chronic pain and inter-individual differences in analgesic response after a placebo or duloxetine. Chronic knee osteoarthritis (OA) pain patients (n=56) underwent pre-treatment brain scans in two clinical trials. Study 1 (n=17) was a 2-week single-blinded placebo pill trial. Study 2 (n=39) was a 3-month double-blinded randomized trial comparing placebo to duloxetine, a dual serotonin-noradrenaline reuptake inhibitor. ResultsAcross two independent studies, we found that chronic pain OA patients present FC alterations in the FC related to the serotonin (SERT) and noradrenaline (NET) transporters, when compared to age-matched healthy controls. Placebo responders presented with higher pre-treatment dopamine transporter (DAT)-enriched FC than non-responders. Duloxetine responders presented with higher pre-treatment SERT and NET-enriched FC than non-responders. Pre-treatment SERT and NET-enriched FC achieved predictive positive values of duloxetine response up to 85.71%. ConclusionNeurotransmission-enriched FC mapping might hold promise as a new mechanistic-informed biomarker for functional brain alterations and prediction of response to pharmacological analgesia in chronic pain.

neuroscience↗

bioRxiv2020

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. 30 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. Low frequency HRV (LF-HRV) and the CPM score were negatively correlated; individuals with higher LF-HRV during pain reported reductions in pain during CPM. PAG-frontal medial cortex (FMC) and PAG-rostral ventro-medial medulla (RVM) functional connectivity correlated negatively with the CPM. Importantly, PAG-FMC functional connectivity mediated the strength of HRV-CPM association. CPM response magnitude was also negatively associated with PAG and positively associated with FMC grey matter volumes. Our multi-modal approach, using behavioral, 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.

neuroscience↗

bioRxiv2020

Oscillatory correlates of auditory working memory examined with human electrocorticography

This work examines how sounds are held in auditory working memory (AWM) in humans by examining oscillatory local field potentials (LFPs) in candidate brain regions. Previous fMRI studies by our group demonstrated blood oxygenation level-dependent (BOLD) response increases during maintenance in auditory cortex, inferior frontal cortex and the hippocampus using a paradigm with a delay period greater than 10s. The relationship between such BOLD changes and ensemble activity in different frequency bands is complex, and the long delay period raised the possibility that long-term memory mechanisms were engaged. Here we assessed LFPs in different frequency bands in six subjects with recordings from all candidate brain regions using a paradigm with a short delay period of 3 s. Sustained delay activity was demonstrated in all areas, with different patterns in the different areas. Enhancement in low frequency (delta) power and suppression across higher frequencies (beta/gamma) were demonstrated in primary auditory cortex in medial Heschls gyrus (HG) whilst non-primary cortex showed patterns of enhancement and suppression that altered at different levels of the auditory hierarchy from lateral HG to superior- and middle-temporal gyrus. Inferior frontal cortex showed increasing suppression with increasing frequency. The hippocampus and parahippocampal gyrus showed low frequency increases and high frequency decreases in oscillatory activity. The work demonstrates sustained activity patterns that can only be explained by AWM maintenance, with prominent low-frequency increases in medial temporal lobe regions.

neuroscience↗

bioRxiv2020

Differential causal involvement of human auditory and frontal cortices in vocal motor control

Speech motor control requires integration of sensory and motor information. Bidirectional communication between frontal and auditory cortices is crucial for speech production, self-monitoring and motor control. We used cortical direct electrical stimulation (DES) to functionally dissect audio-motor interactions underlying speech production and motor control. Eleven neurosurgical patients performed a visually cued vocal task in which a short auditory feedback perturbation was introduced during vocalization. We evaluated the effect of DES on vocal initiation, voice fundamental frequency (F0) and feedback-dependent motor control. DES of frontal sites modulated vocal onset latencies. Stimulation of different inferior frontal gyrus sites elicited either shortening or prolongation of vocal latencies. DES distinctly modulated voice F0 at different vocalization stages. Frontal and temporal areas played an important role in setting voice F0 in the first 250 ms of an utterance, while Heschls gyrus was involved later when auditory input is available for self-monitoring. Vocal responses to pitch-shifted auditory feedback were mostly reduced by DES of non-core auditory cortices. Overall, we demonstrate that vocal planning and initiation are driven by frontal cortices, while feedback-dependent control relies predominantly on non-core auditory cortices. Our findings represent direct evidence of the role played by different auditory and frontal regions in vocal motor control.

neuroscience↗

bioRxiv2020

Focal cortical surface cooling is a novel and safe method for intraoperative functional brain mapping

ObjectiveElectrical cortical stimulation (ECS) has been the gold standard for intraoperative functional mapping in neurosurgery, yet it carries the risk of induced seizures. Here we assess the safety of focal cortical cooling (CC) as a potential alternative to ECS for functional brain mapping. MethodsWe retrospectively reviewed 40 consecutive subjects (n=13 tumor, 27 mesial temporal lobe epilepsy (MTLE) resection) who underwent intraoperative CC during craniotomy at the University of Iowa Hospital and Clinics from 2007 through 2019 (CC group). Thirty-eight of the 40 subjects had ECS performed along with CC during the same procedure. To assess the safety of CC, intra- and post-operative seizure incidence and post-operative neurological deficits were collected together with new post-operative radiographic findings not related to the surgical procedure itself (i.e. non-mapping portions). As a control cohort, we collected 55 consecutive subjects (n=21 MTLE, 34 tumor/vascular pathology) who underwent awake ECS mapping without CC between 2006 and 2019 (ECS-alone group). To evaluate potential long term effects of mapping techniques (CC and/or ECS), we separately collected another 25 consecutive subjects who underwent anterior temporal lobectomy(ATL) without CC nor ECS between 2007 and 2019 (No ECS/No CC-ATL group). ResultsA total of 79 brain sites were cooled in the 40 CC subjects, including inferior frontal gyrus (44%), precentral gyrus (39%), postcentral gyrus (6%), subcentral gyrus (4%) and superior temporal gyrus (6%). No intraoperative seizures were reported in the CC group, whereas 3.6% of ECS-alone group had intraoperative seizures. The incidence of seizure(s) within the first post-operative week did not significantly differ amongst CC (7.9%), ECS-alone (9.0%) and No ECS/No CC-ATL groups (12%). There was no significante difference in the incidence of postoperative radiographic change between CC (7.5%) and ECS-alone groups (5.5 %). The long term seizure outcome for MTLE subjects did not statistically differ regarding good outcomes (Engel I+II): CC group (80%), ECS-alone (83.3%) and No ECS/No CC-ATL group (83.3%). ConclusionsCortical cooling when used as an intraoperative mapping technique is safe, and may complement traditional electrical cortical stimulation.

neuroscience↗

bioRxiv2020

Common Fronto-temporal Effective Connectivity in Humans and Monkeys

Cognitive pathways supporting human language and declarative memory are thought to have uniquely evolutionarily differentiated in our species. However, cross-species comparisons are missing on site-specific effective connectivity between regions important for cognition. We harnessed a new approach using functional imaging to visualize the impact of direct electrical brain stimulation in human neurosurgery patients. Applying the same approach with macaque monkeys, we found remarkably comparable patterns of effective connectivity between auditory cortex and ventro-lateral prefrontal cortex (vlPFC) and parahippocampal cortex in both species. Moreover, in humans electrical tractography revealed rapid evoked potentials in vlPFC from stimulating auditory cortex and speech sounds drove vlPFC, consistent with prior evidence in monkeys of direct projections from auditory cortex to vocalization responsive regions in vlPFC. The results identify a common effective connectivity signature that from auditory cortex is equally direct to vlPFC and indirect to the hippocampus (via parahippocampal cortex) in human and nonhuman primates. HighlightsO_LIPrivileged human auditory to inferior frontal connectivity, linked to monkeys C_LIO_LICommon auditory to parahippocampal effective connectivity in both species C_LIO_LIGreater lateralization in human effective connectivity, more symmetrical in monkeys C_LIO_LIHuman fronto-temporal network function rooted in evolutionarily conserved signature C_LI eTOC short summaryFunctional connectivity between regions crucial for language and declarative memory is thought to have substantially differentiated in humans. Using a new technique to similarly visualize directional effective connectivity in humans and monkeys, we found remarkably comparable connectivity patterns in both species between fronto-temporal regions crucial for cognition.

neuroscience↗

bioRxiv2019

Sustained perturbation in functional connectivity induced by cold pain

Functional connectivity (FC) perturbations have been reported in multiple chronic pain phenotypes, but the nature of reported changes is varied and inconsistent between cohorts. Increases and decreases in connectivity strength in task negative and positive networks, for example, the default mode and salience networks (DMN/SN), respectively, have been described, but how other networks are effected, for example, descending pain control networks, remains unknown. Whether connectivity changes relate to peripherally-mediated nociceptive afferent input, represent coping strategies or are sequelae of chronic pain, e.g. anxiety/depression, is also unknown. Here, we examined FC changes in response to experimentally-administered tonic cold pain in healthy volunteers as a means of disambiguating the nature of connectivity changes. We assessed FC prior to, during, and following tonic cold painful stimulation in four seed regions: ventromedial prefrontal cortex (vmPFC), rostral anterior insula (rAI), subgenual anterior cingulate cortex (ACC) and periaqueductal grey (PAG) and recorded subjectively reported pain using a computerised visual analogue scale. We saw DMN FC changes during painful stimulation and that inter-network communication between the rAI and sgACC seeds with the vmPFC became less anti-correlated during pain, whereas PAG-precuneus FC decreased. Pain-induced FC alterations largely persisted during a 6-minute recovery period following cessation of the painful stimulus. Observed FC changes related to the magnitude of individuals subjectively reported pain. We provide new insights into FC changes during and following tonic cold-pain and suggest that some FC changes observed in chronic pain patients may relate to the presence of an ongoing afferent peripheral drive.

neuroscience↗

bioRxiv2019

A sound-sensitive source of alpha oscillations in human non-primary auditory cortex

The functional organization of human auditory cortex can be probed by characterizing responses to various classes of sound at different anatomical locations. Along with histological studies this approach has revealed a primary field in posteromedial Heschls gyrus (HG) with pronounced induced high-frequency (70-150 Hz) activity and short-latency responses that phase-lock to rapid transient sounds. Low-frequency neural oscillations are also relevant to stimulus processing and information flow, however their distribution within auditory cortex has not been established. Alpha activity (7-14 Hz) in particular has been associated with processes that may differentially engage earlier versus later levels of the cortical hierarchy, including functional inhibition and the communication of sensory predictions. These theories derive largely from the study of occipitoparietal sources readily detectable in scalp electroencephalography. To characterize the anatomical basis and functional significance of less accessible temporal-lobe alpha activity we analyzed responses to sentences in seven human adults (four female) with epilepsy who had been implanted with electrodes in superior temporal cortex. In contrast to primary cortex in posteromedial HG, a non-primary field in anterolateral HG was characterized by high spontaneous alpha activity that was strongly suppressed during auditory stimulation. Alpha-power suppression decreased with distance from anterolateral HG throughout superior temporal cortex, and was more pronounced for clear compared to degraded speech. This suppression could not be accounted for solely by a change in the slope of the power spectrum. The differential manifestation and stimulus-sensitivity of alpha oscillations across auditory fields should be accounted for in theories of their generation and function.\n\nSignificance StatementTo understand how auditory cortex is organized in support of perception, we recorded from patients implanted with electrodes for clinical reasons. This allowed measurement of activity in brain regions at different levels of sensory processing. Oscillations in the alpha range (7-14 Hz) have been associated with functions including sensory prediction and inhibition of regions handling irrelevant information, but their distribution within auditory cortex is not known. A key finding was that these oscillations dominated in one particular non-primary field, anterolateral Heschls gyrus, and were suppressed when subjects listened to sentences. These results build on our knowledge of the functional organization of auditory cortex and provide anatomical constraints on theories of the generation and function of alpha oscillations.

neuroscience↗

bioRxiv2018

Processing of Auditory Novelty Across the Cortical Hierarchy: An Intracranial Electrophysiology Study

Under the predictive coding hypothesis, specific spatiotemporal patterns of cortical activation are postulated to occur during sensory processing as expectations generate feedback predictions and prediction errors generate feedforward signals. Establishing experimental evidence for this information flow within cortical hierarchy has been difficult, especially in humans, due to spatial and temporal limitations of non-invasive measures of cortical activity. This study investigated cortical responses to auditory novelty using the local/global deviant paradigm, which engages the hierarchical network underlying auditory predictive coding over short ( local deviance; LD) and long ( global deviance; GD) time scales. Electrocorticographic responses to auditory stimuli were obtained in neurosurgical patients from regions of interest (ROIs) including auditory, auditory-related and prefrontal cortex. LD and GD effects were assayed in averaged evoked potential (AEP) and high gamma (70-150 Hz) signals, the former likely dominated by local synaptic currents and the latter largely reflecting local spiking activity. AEP LD effects were distributed across all ROIs, with greatest percentage of significant sites in core and non-core auditory cortex. High gamma LD effects were localized primarily to auditory cortex in the superior temporal plane and on the lateral surface of the superior temporal gyrus (STG). LD effects exhibited progressively longer latencies in core, non-core, auditory-related and prefrontal cortices, consistent with feedforward signaling. The spatial distribution of AEP GD effects overlapped that of LD effects, but high gamma GD effects were more restricted to non-core areas. High gamma GD effects had shortest latencies in STG and preceded AEP GD effects in most ROIs. This latency profile, along with the paucity of high gamma GD effects in the superior temporal plane, suggest that the STG plays a prominent role in initiating novelty detection signals over long time scales. Thus, the data demonstrate distinct patterns of information flow in human cortex associated with auditory novelty detection over multiple time scales.

neuroscience↗

bioRxiv2018

In Vivo Measurements of the Frequency-Dependent Impedance of the Spinal Cord

Improved knowledge of the electrode-tissue impedance will be useful in optimizing the clinical protocols and resulting efficacy of the existing and emerging approaches to spinal cord stimulation. Toward that end, the complex impedance (amplitude and phase) of in vivo ovine spinal cord tissue was measured at the electrode-pial subdural surface interface from 5 Hz to 1 MHz, and with the bi-polar electrodes oriented both parallel and perpendicular to the rostral-caudal axis of the spinal cord. At stimulation frequencies above 10 kHz, most of the impedance then becomes resistive in nature and the phase diference between the stimulation signal and the resulting current drops to {approx} 10{ring}, thus maximizing power transfer to the tissues. Also, at these higher frequencies, the current pulse maintains significantly greater fidelity to the shape of the stimulation signal applied across the electrodes. Lastly, there were lower impedances associated with parallel as opposed to perpendicular orientation of the electrodes, thus reflecting the effects of fiber orientation within the spinal cord. Impedance differences of this kind have not been reported with epidural stimulation because of the electrical shunting effects of the intervening layer of relatively high conductivity cerebrospinal fluid. These observations provide a quantitative basis for improved models of spinal cord stimulation and suggest certain advantages for direct intradural stimulation relative to the standard epidural approaches. (Some figures in this article are in colour only in the electronic version)

biophysics↗

bioRxiv2017

Surgically disconnected temporal pole exhibits resting functional connectivity with remote brain regions

Functional connectivity, as measured by resting-state fMRI, has proven a powerful method for studying brain systems in the context of behavior, development, and disease states. However, the relationship of functional connectivity to structural connectivity remains unclear. If functional connectivity relies on structural connectivity, then anatomical isolation of a brain region should eliminate functional connectivity with other brain regions. We tested this by measuring functional connectivity of the surgically disconnected temporal pole in resection patients (N=5; mean age 37; 2F, 3M). Functional connectivity was evaluated based on coactivation of whole-brain fMRI data with the average low-frequency BOLD signal from disconnected tissue in each patient. In sharp contrast to our prediction, we observed significant functional connectivity between the disconnected temporal pole and remote brain regions in each disconnection case. These findings raise important questions about the neural bases of functional connectivity measures derived from the fMRI BOLD signal.

neuroscience↗