Biology subjects

Seminowicz, D. A.

Publications and source records attributed to Seminowicz, D. A..

26 records · Page 2Linked to original sources

bioRxiv2022

The mouse claustrum synaptically connects cortical network motifs

Spatially distant areas of cerebral cortex coordinate their activity into networks that are integral to cognitive processing. A common structural motif of cortical networks is co-activated frontal and posterior cortical regions. Knowledge of the neural circuit mechanisms underlying such widespread inter-areal cortical coordination is lacking. Using anesthetized mouse functional magnetic resonance imaging (fMRI) we discovered that mouse frontal cortical functional connectivity reflects the common cortical network motif in its functional connectivity to posterior cortices, but also demonstrates significant functional connectivity with the claustrum. Exploring whether the claustrum may synaptically support such network architecture, we used a channelrhodopsin-assisted electrophysiological circuit mapping approach to assess the strength of synaptic connectivity of 35 unique frontal cortico-claustral-cortical connections through 1,050 subtype-identified claustrum projection neurons. We observed significant trans-claustral synaptic connectivity from the anterior cingulate cortex and prelimbic prefrontal cortex back to originating frontal cortical regions as well as to posteriorly-lying visual and parietal association cortices contralaterally. The infralimbic prefrontal cortex possessed significant trans-claustral synaptic connectivity with the posteriorly-lying retrosplenial cortex, but to a far lesser degree with visual and parietal association cortices. These data reveal discrete extended cortical pathways through the claustrum that are positioned to support cortical network motifs central to cognitive control functions.

neuroscience↗

bioRxiv2021

The influence of somatosensory and auditory evoked potentials on concurrent transcranial-magnetic stimulation electroencephalography recordings

BackgroundTranscranial magnetic stimulation (TMS) evoked potentials (TEPs) can be used to index cortical excitability. However, it remains unclear to what extent TEPs reflect somatosensory and auditory-evoked potentials which arise from the scalp sensation and click of the TMS coil, as opposed to transcranial stimulation of cortical circuits. ObjectivesThe present study had two aims; a) to determine the extent to which sensory potentials contaminate TEPs using a spatially matched sham condition, and b) to determine whether sensory potentials reflect auditory or somatosensory potentials alone, or a combination of the two. MethodsTwenty healthy participants received active or sham stimulation, with the latter consisting of the click of a sham coil combined with scalp electrical stimulation. Earplugs/headphones were used to suppress the TMS click noise. Two additional control conditions i) electrical stimulation alone and ii) auditory stimulation alone were included in a subset of 13 participants. ResultsSignals from active and sham stimulation were correlated in spatial and temporal domains, especially >70ms post-stimulation. Relative to auditory or electrical stimulation alone, combined (sham) stimulation resulted in a) larger evoked responses b) stronger correlations with active stimulation and c) a signal that could not be explained by the linear sum of electrical and auditory stimulation alone. ConclusionsSensory potentials can confound data interpretations of TEPs at timepoints >70ms post-TMS, while earlier timepoints appear reflective of cortical excitability. Furthermore, contamination of TEPs cannot be explained by auditory or somatosensory potentials alone, but instead reflects a non-linear interaction between both sources. Future studies may benefit from controlling for sensory contamination using sham conditions that are spatially matched to active TMS, and which consist of combined auditory and somatosensory stimulation.

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bioRxiv2021

Prolonged tonic pain in healthy humans enhances functional connectivity of descending pain modulation networks involving the amygdala, periaqueductal gray and parabrachial nucleus to cortical sensory-discriminative areas

IntroductionResting state functional connectivity (FC) is widely used to assess functional brain alterations in patients with chronic pain. However, reports of FC changes accompanying tonic pain in pain-free persons is rare. A brain network disrupted during chronic pain is a network we term the Descending Pain Modulatory Network (DPMN). Here, we evaluate the effect of tonic pain on FC of this network: anterior cingulate cortex (ACC), amygdala (AMYG), periaqueductal gray (PAG), and parabrachial nuclei (PBN). MethodsIn 50 pain-free participants (30F), we induced tonic pain using a capsaicin-heat pain model. We used functional MRI to measure resting BOLD signal during pain-free rest where participants experienced warmth and tonic pain where participants experienced the same temperature thermode combined with capsaicin. We evaluated FC from ACC, AMYG, PAG, and PBN with correlation of self-report pain intensity with FC during both states. We hypothesized tonic pain would disrupt FC dyads within the DPMN. We used partial correlation to determine FC correlated with pain intensity and BOLD signal. ResultsOf hypothesized FC dyads, PAG and subgenual ACC was weakly disrupted during tonic pain (F=3.34; p=0.074; pain-free>pain d=0.25). sgACC-PAG FC became positively related to pain intensity (R=0.38; t=2.81; p=0.007). Right PBN-PAG FC during pain-free rest positively correlated with subsequently experienced pain (R=0.44; t=3.43; p=0.001). During tonic pain, FC of this connection was abolished (paired t=-3.17; p=0.0026). During pain-free rest, FC between left AMYG and right superior parietal lobule and caudate nucleus were positively correlated with subsequent pain. During tonic pain, FC between left AMYG and right inferior temporal and superior frontal gyri negatively correlated with pain. Subsequent pain positively correlated with right AMYG FC and right claustrum; left and right primary visual cortex; right middle temporal gyrus and right temporo-occipitoparietal junction. Finally, subsequent pain positively correlated with PAG FC and left cerebellum, left dorsolateral prefrontal, right posterior cingulate cortex and paracentral lobule, inferior parietal lobule, medial precuneus and PBN. ConclusionWe demonstrate 1) tonic pain weakly disrupts of sgACC-PAG FC; 2) sgACC-PAG tonic pain FC positively correlates with pain; 3) right PBN-PAG FC predicts subsequent pain and is abolished during tonic pain. Finally, we reveal PAG- and right AMYG-anchored networks which predict intensity of tonic pain. Our findings suggest specific connectivity patterns within the DPMN at rest predict experienced pain and are modulated by tonic pain. These nodes and their functional modulation may reveal new therapeutic targets for neuromodulation and biomarkers to guide interventions. HighlightsO_LIParabrachial-periaqueductal gray (PAG) functional connectivity (FC) predicts pain C_LIO_LISubgenual anterior cingulate cortex-PAG FC correlates with pain during tonic pain C_LIO_LIPAG- and amydalocortical networks at rest predict tonic pain intensity C_LIO_LIResting FC of PAG supports cortical targets of neuromodulation to control pain C_LI

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bioRxiv2021

Prolonged Pain Reliably Slows Peak Alpha Frequency by Reducing Fast Alpha Power

The relationship between the 8-12 Hz "alpha: rhythm, the predominant oscillatory activity of the brain, and pain remains unclear. In healthy individuals, acute, noxious stimuli suppress alpha power while patients with chronic pain demonstrate both enhanced alpha power and slowing of the peak alpha frequency (PAF). To investigate these apparent differences, EEG was recorded from healthy individuals while they completed two models of prolonged pain, Phasic Heat Pain and Capsaicin Heat Pain, at two testing visits occurring roughly 8 weeks apart. We report that PAF is reliably slowed and that alpha power is reliably decreased in response to prolonged pain. Furthermore, we show that alpha power changes, but not PAF changes, are fully reversed with stimulus removal suggesting that PAF slowing reflects pain associated states such as sensitization rather than the presence of ongoing pain. Finally, we provide evidence that changes to alpha power and PAF are due to power decreases in the "fast" (10-12 Hz) range of the alpha rhythm. This frequency dependent pain response aligns with the hypothesis that the alpha rhythm is composed of multiple, independent oscillators, and suggest that modulation of a putative "fast" oscillator may represent a promising therapeutic target for treating ongoing pain. In sum, we provide strong evidence that PAF is reliably slowed during prolonged pain and additionally identify a mechanism, "fast" alpha Power, which is responsible for these PAF changes.

neuroscience↗

bioRxiv2021

Three Dimensions of Association Link Migraine Symptoms and Functional Connectivity

Migraine is a heterogeneous disorder with variable symptoms and responsiveness to therapy. Due to previous analytic shortcomings, variance in migraine symptoms has been weakly and inconsistently related to brain function. Taking advantage of neural network organization measured through resting-state functional connectivity (RSFC) and advanced statistical analysis, sophisticated symptom-brain mapping can now be performed. In the current analysis we used data from two sites (n=102 and 41), and performed Canonical Correlation Analysis (CCA), relating RSFC with a broad range of migraine symptoms ranging from headache characteristics to sleep abnormalities. This identified three dimensions of covariance between symptoms and RSFC. Importantly, none of these dimensions bore any relationship with subject motion. The first dimension was related to headache intensity, headache frequency, pain catastrophizing, affect, sleep disturbances, and somatic abnormalities, and was associated with frontoparietal and dorsal attention network connectivity, both of which are major cognitive networks. Additionally, RSFC scores from this dimension - both the baseline value and the change from baseline to post-intervention - were associated with clinical responsiveness to mind-body therapy. The second dimension was related to an inverse association between pain and anxiety, and to default mode network connectivity. The final dimension was related to pain catastrophizing, and salience, sensorimotor and default mode network connectivity. These unique symptom/brain-mappings over three dimensions provide novel network targets to modify specific ensembles of symptoms. In addition to performing CCA, we evaluated the current clustering of migraine patients into episodic and chronic subtypes, and found no evidence to support this clustering. However, when using RSFC scores from the three significant dimensions, we identified a novel clustering of migraine patients into four biotypes with unique functional connectivity patterns. These findings provide new insight into individual variability in migraine, and could serve as the foundation for novel therapies that take advantage of migraine heterogeneity.

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bioRxiv2018

Decreased grey matter volume in mTBI patients with post-traumatic headache compared to headache-free mTBI patients and healthy controls: a longitudinal MRI study

BackgroundTraumatic brain injury (TBI) occurs in 1.7 million people annually and many patients go on to develop persistent disorders including post-traumatic headache (PTH). PTH is considered chronic if it continues past 3 months. In this study we aimed to identify changes in cerebral grey matter volume (GMV) associated with PTH in mild TBI patients.\n\nMethods50 mTBI patients (31 Non-PTH; 19 PTH) underwent MRI scans: within 10 days post-injury, 1 month, 6 months and 18 months. PTH was assessed at visit 4 by a post-TBI headache questionnaire. Healthy controls (n=21) were scanned twice 6 months apart.\n\nResultsCompared to non-PTH, PTH patients had decreased GMV across two large clusters described as the right anterior-parietal (p=0.012) and left temporal-opercular (p=0.027). Compared to healthy controls non-PTH patients had decreased GMV in the left thalamus (p=0.047); PTH patients had decreased GMV in several extensive clusters: left temporal-opercular (p=0.003), temporal-parietal (p=0.041), superior frontal gyrus (p=0.008) and right middle frontal/superior frontal gyrus (0.004) and anterior-parietal (p=0.003).\n\nConclusionDifferences between PTH and non-PTH patients were most striking at early time points. These early changes may be associated with an increased risk of PTH. Patients with these changes should be monitored for chronic PTH.

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bioRxiv2018

The human claustrum is functionally connected to cognitive networks and involved in cognitive control

The claustrum is among the most highly connected structures in the mammalian brain. However, the function of the claustrum is unknown, which is due to its peculiar anatomical arrangement. Here, we use resting state and task functional magnetic resonance imaging (fMRI) to elucidate claustrum function in human subjects. We first describe a method to reveal claustrum signal with no linear relationship with adjacent regions. We applied this approach to resting state functional connectivity (RSFC) analysis of the claustrum at high resolution (1.5 mm isotropic voxels) using a 7T dataset (n=20) and a separate 3T dataset for replication (n=35). We then assessed claustrum activation during performance of a cognitive task, the multi-source interference task, at 3T (n=33). Extensive functional connectivity was observed between claustrum and cortical regions associated with cognitive control, including anterior cingulate, prefrontal and parietal cortices. Cognitive task performance was associated with widespread activation and deactivation that overlapped with the cortical areas showing functional connectivity to the claustrum. Furthermore, the claustrum was significantly activated at the onset of the difficult condition of the task, but not during the remainder of the difficult condition. These data suggest that the claustrum can be functionally isolated with fMRI, and that it is involved in cognitive control in humans independent of sensorimotor processing.\n\nHighlightsO_LIRemoving signal from neighboring structures isolates claustrum BOLD signal at 7T and 3T field strength\nC_LIO_LIClaustrum is extensively functionally connected with cortex, including cognitive networks\nC_LIO_LIClaustrum is activated at the onset of a cognitive conflict task\nC_LIO_LIClaustrum may be involved in cognition independent of sensorimotor processing\nC_LI

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bioRxiv2018

Slow peak alpha frequency and corticomotor depression linked to high pain susceptibility in transition to sustained pain

Mechanisms that predict an individuals susceptibility to pain, before pain is present or in the first few days following pain onset, are unknown. We utilised a clinically-relevant human transitional pain model (intramuscular injections of nerve growth factor) to examine brain mechanisms that predict pain susceptibility. Resting state EEG and corticomotor excitability measured by TMS were evaluated longitudinally in healthy individuals as pain developed and resolved over 21 days. Whereas pre-pain central peak alpha frequency (PAF) correlated with peak pain occurring 4-6 days later, altered corticomotor excitability developed several days after pain onset and showed two distinct patterns (facilitation, depression). Individuals with combined slow PAF and corticomotor depression developed more severe pain. These data provide the first evidence of the temporal profile of key brain mechanisms as pain progressively develops. PAF and corticomotor excitability could represent biomarkers for susceptibility to high pain severity and subsequently, the development of chronic pain.

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