Microstructural Brain Correlates of Inter-individual Differences in Respiratory Interoception.

Imaging of Eating Disorders: Multiple Techniques to Demonstrate the Dynamic Brain

Introduction: Interoception, defined as the sense of the internal state of one’s body, helps motivate goal-directed behavior. Prior work has shown that methamphetamine (METH) use disorder is associated with altered interoception, and that this may contribute to risky behavior. As people with HIV (PWH) may also experience disrupted bodily sensations (e.g., neuropathy), an important question is whether PWH with a history of METH use disorder might exhibit greater impairment of interoceptive processing. Methods: Eighty-three participants stratified by HIV infection and a past history of methamphetamine use disorder experienced a soft touch paradigm that included slow brush strokes on the left forearm and palm during blood-oxygen level-dependent functional MRI acquisition. To assess differences in interoception and reward, voxelwise analyses were constrained to the insula, a hub for the evaluation of interoceptive cues, and the striatum, which is engaged in reward processing. Results: Overall, individuals with a history of METH use disorder had an attenuated neural response to pleasant touch in both the insula and striatum. Longer abstinence was associated with greater neural response to touch in the insula, suggesting some improvement in responsivity. However, only PWH with no METH use disorder history had lower brain activation in the insula relative to non-using seronegative controls. Conclusions: Our findings suggest that while METH use disorder history and HIV infection independently disrupt the neural processes associated with interoception, PWH with METH use disorder histories do not show significant differences relative to non-using seronegative controls. These findings suggest that the effects of HIV infection and past methamphetamine use might not be additive with respect to interoceptive processing impairment.

Maternal love, which may be the core of maternal behavior, is essential for the mother–infant attachment relationship and is important for an infant’s development and mental health. Therefore, maternal love can be considered a vital human emotion. Using video clips, we examined patterns of maternal brain activation in response to infant cues. We performed functional magnetic resonance imaging (fMRI) measurements while 13 mothers viewed video clips of their own infants and other infants (all approximately 16 months of age) who demonstrated two different attachment behaviors. We found that a limited number of the mother’s brain areas were specifically involved in maternal love, namely orbitofrontal cortex (OFC), striatum, anterior insula, and periaqueductal gray (PAG). Then, we proposed a schematic model of maternal love, based on integration of the two systems in the OFC: the dopamine reward system (OFC, striatum) and the interoceptive information processing system (OFC, insula, PAG). Additionally, we found a strong and specific brain response in a mother viewing her distressed infant. The neural activation pattern was found in the dorsal OFC (dOFC), the dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), dorsomedial prefrontal cortex (DMPFC), dorsal anterior cingulate cortex (dACC), posterior cingulate cortex (PCC), caudate nucleus, supplementary motor area (SMA), and posterior superior temporal sulcus/temporoparietal junction (pSTS/TPJ). These results showed a highly elaborate neural mechanism, based on the above neural basis of maternal love, mediating the diverse and complex maternal behaviors that mothers engage in when raising and protecting their own infants.

Mainero C, Boshyan J, Hadjikhani N. Altered functional magnetic resonance imaging resting-state connectivity in periaqueductal gray networks in migraine. Annals of Neurology 2011;70:838-845. Objective: The periaqueductal gray matter (PAG), a known modulator of somatic pain transmission, shows evidence of interictal functional and structural abnormalities in migraineurs, which may contribute to hyperexcitability along spinal and trigeminal nociceptive pathways, and lead to the migraine attack. The aim of this study was to examine functional connectivity of the PAG in migraine. Methods: Using resting-state functional MRI, we compared functional connectivity between PAG and a subset of brain areas involved in nociceptive/somatosensory processing and pain modulation in 17 subjects with migraine, during a pain-free state, versus 17 genderand age-matched controls. We also assessed the relation between intrinsic resting-state correlations within PAG networks and the average monthly frequency of migraine attacks, as well as allodynia. Results: Our findings show stronger connectivity between the PAG and several brain areas within nociceptive and somatosensory processing pathways in migraineurs versus controls. In addition, as the monthly frequency of migraine attacks worsens, the strength of the connectivity in some areas within these pathways increases, whereas a significant decrease in functional resting-state connectivity between the PAG and brain regions with a predominant role in pain modulation (prefrontal cortex, anterior cingulate, amygdala) can be evidenced. Finally, migraineurs with a history of allodynia exhibit significantly reduced connectivity between PAG, prefrontal regions, and anterior cingulate compared to migraineurs without allodynia. Interpretation: These data reveal interictal dysfunctional dynamics within pain pathways in migraine manifested as an impairment of the descending pain modulatory circuits, likely leading to loss of pain inhibition, and hyperexcitability primarily in nociceptive areas. Comments: Functional neuroimaging techniques have helped elucidate the underlying physiology of migraines. Unlike traditional functional magnetic resonance imaging scans done during a task, resting state functional connectivity is a relatively new neuroimaging technique in which participants are scanned at rest, and the lowfrequency spontaneous fluctuations found to be highly correlated are thought to represent brain areas that are functionally connected at baseline. Mainero et al recently conducted this study to assess the functional connectivity of the periaqueductal gray (PAG) (a region previously implicated in the pathogenesis of migraine) to other brain regions in 17 migraineurs interictally compared with 17 age-/gendermatched controls. They found that compared with the controls, the migraineurs had increased resting state functional connectivity between the PAG, and somatosensory and nociceptive processing pathways. The connections between the PAG and the supramarginal gyrus, anterior insula, and hypothalamus were increased in migraineurs with more frequent attacks, while the connections between PAG and the prefrontal cortex, anterior cingulate, amygdala, and medial thalamus were decreased in migraineurs with more frequent attacks. The 5 migraineurs with allodynia also had significantly reduced connectivity between the PAG and the anterior insula, anterior cingulate, and prefrontal cortex vs genderand age-matched migraineurs without allodynia. This study is one of the first to use resting state functional connectivity analyses to compare the intrinsic neural connections in migraineurs vs controls. As expected, many of the connections between the PAG, and nociceptive and sensory processing pathways were increased in the migraineurs, and some of those connections were stronger in those with more frequent attacks. However, unexpectedly, those with more frequent migraines and those with allodynia had decreased connections between the PAG and areas involved in the cognitive modulation of pain. This suggests that From the Graham Headache Center, Faulkner/Brigham and Women’s Hospital, Boston, MA,

Behavioral and c-fos expression changes induced by nitric oxide donors microinjected into the dorsal periaqueductal gray

Background:Schizophrenia and bipolar disorder have been linked to alterations in the functional activity and grey matter volume of some brain areas, reflected in impaired regional homogeneity and aberrant voxel-based morphometry. However, because of variable findings and methods used across studies, identifying patterns of brain alteration in schizophrenia and bipolar disorder has been difficult.Methods:We conducted a meta-analysis of differences in regional homogeneity and voxel-based morphometry between patients and healthy controls for schizophrenia and bipolar disorder separately, using seed-based d mapping.Results:We included 45 publications on regional homogeneity (26 in schizophrenia and 19 in bipolar disorder) and 190 publications on voxel-based morphometry (120 in schizophrenia and 70 in bipolar disorder). Patients with schizophrenia showed increased regional homogeneity in the frontal cortex and striatum and the supplementary motor area; they showed decreased regional homogeneity in the insula, primary sensory cortex (visual and auditory cortices) and sensorimotor cortex. Patients with bipolar disorder showed increased regional homogeneity in the frontal cortex and striatum; they showed decreased regional homogeneity in the insula. Patients with schizophrenia showed decreased grey matter volume in the superior temporal gyrus, inferior frontal gyrus, cingulate cortex and cerebellum. Patients with bipolar disorder showed decreased grey matter volume in the insula, cingulate cortex, frontal cortex and thalamus. Overlap analysis showed that patients with schizophrenia displayed decreased regional homogeneity and grey matter volume in the left insula and left superior temporal gyrus; patients with bipolar disorder displayed decreased regional homogeneity and grey matter volume in the left insula.Limitations:The small sample size for our subgroup analysis (unmedicated versus medicated patients and substantial heterogeneity in the results for some regions could limit the interpretability and generalizability of the results.Conclusion:Patients with schizophrenia and bipolar disorder shared a common pattern of regional functional and structural alterations in the insula and frontal cortex. Patients with schizophrenia showed more widespread functional and structural impairment, most prominently in the primary sensory motor areas.

The arterial baroreflex is a key mechanism for the homeostatic control of blood pressure (BP). In animals and humans, psychological stressors suppress the capacity of the arterial baroreflex to control short-term fluctuations in BP, reflected by reduced baroreflex sensitivity (BRS). While animal studies have characterized the brain systems that link stressor processing to BRS suppression, comparable human studies are lacking. Here, we measured beat-to-beat BP and heart rate (HR) in 97 adults who performed a multisource interference task that evoked changes in spontaneous BRS, which were quantified by a validated sequence method. The same 97 participants also performed the task during functional magnetic resonance imaging (fMRI) of brain activity. Across participants, task performance (i) increased BP and HR and (ii) reduced BRS. Analyses of fMRI data further demonstrated that a greater task-evoked reduction in BRS covaried with greater activity in brain systems important for central autonomic and cardiovascular control, particularly the cingulate cortex, insula, amygdala, and midbrain periaqueductal gray (PAG). Moreover, task performance increased the functional connectivity of a discrete area of the anterior insula with both the cingulate cortex and amygdala. In parallel, this same insula area showed increased task-evoked functional connectivity with midbrain PAG and pons. These novel findings provide human evidence for the brain systems presumptively involved in suppressing baroreflex functionality, with relevance for understanding the neurobiological mechanisms of stressor-related cardiovascular reactivity and associated risk for essential hypertension and atherosclerotic heart disease.

Acute psychological stress elicits a typical response characterized in the short term by elevated sympathetic nerve activity and increases in heart rate and blood pressure. While the primary neural circuitry that underpins these responses is still uncertain, the dorsomedial hypothalamus (DMH) is known to play a major role.1 However, the antecedent inputs responsible for DMH activation in response to stress are unknown. In the present study, retrograde tracing was combined with Fos immunohistochemistry following air jet stress (AJS) to identify neurons that both project to the DMH and are activated by stress.Sprague Dawley rats received a unilateral injection of 15–30 nl of retrograde tracer choleratoxin B subunit‐AlexaFluor 555 into the DMH. One week later rats were exposed to a 15 minute AJS protocol (n=4), while controls (n=2) were left undisturbed. Following perfusion, brain sections were processed for Fos immunohistochemistry and photographed. The distribution of retrogradely and/or Fos‐labeled neurons was mapped using a rat brain atlas.2 The number of labeled cells in key regions was counted. Data are expressed as mean ± SE cells per section.Retrogradely labeled neurons were found throughout the brainstem and forebrain (Table 1). The majority of labeled cells were located in the forebrain, in particular in the medial prefrontal cortex, lateral septal nucleus, claustrum and amygdala. Following AJS, Fos‐positive neurons were located in many, but not all, of the regions in which retrogradely labeled neurons were found. There was a significant increase in the number of Fos‐positive neurons in the Kolliker Fuse nucleus (KF) in the pons, the dorsomedial, dorsolateral and ventrolateral midbrain periaqueductal gray (PAG), amygdala, the cingulate cortex, lateral septal nucleus and the claustrum. Double‐labeled neurons were found in the brainstem in the KF and ventrolateral PAG, and in the forebrain in the amygdala, cingulate cortex, lateral septal nucleus and claustrum. However, overall there were very few double‐labeled neurons seen throughout the brain.Neurons that both project to the DMH and are activated by AJS were identified in several brain regions, particularly in the forebrain. The number of such neurons was very small, suggesting that these neurons may play a minor role in stress‐induced activation of the DMH. An alternate hypothesis is that recruitment of DMH in response to stress may be dependent upon disinhibition. Number of labeled cells in key nuclei Region CTb Fos CTb + Fos RVLM 0.7±0.4 9.2±5.1 0.0±0 RVMM 0.3±0.2 6.1±4 0.0±0 PBC 27.6±14.2 14.4±5.9 1.5±0.8 KF 20.2±14.8 11.0±4.0* 0.6±0.4* dmPAG 4.4±2.1 7.3±1* 0.2±0.2 dIPAG 4.2±1.5 10.7±0.6* 0.5±0.4 IPAG 8.6±2.7 19.9±2.4 0.3±0.1 vIPAG 12.0±1.6 18.4±3.2* 1.0±0.5* Amy 124.4±22.7 55.9±18.3* 2.4±0.7* Cingular Cor 88.8±32.1 17.0±0.3* 3.2±0.8* Lat SN 177.9±62.1 38.5±5.5* 4.9±1.8* Claustrum 148.3±55.2 35.8±11* 2.1±0.4* mPFC 192.0±79 42.4±21.1 3.3±0.8 Values are mean ± SE

Exercise modulates neuronal activation in the micturition circuit of chronically stressed rats: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome (MAPP) research network study

Redux: Do Little Bellyachers Grow up to Become Big Bellyachers?

Frozen samples of postmortem human brain tissue from patients with Parkinson's disease (n = 25) and control patients who died without neurological disease (n = 25) were assayed for neurotensin and bombesin by specific radioimmunoassay. Twelve brain regions were examined: substantia nigra, ventral tegmental area, periaqueductal gray matter, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, nucleus accumbens, frontal cortex, cingulate cortex, and entorhinal cortex. In patients with Parkinson's disease, the concentration of bombesin was significantly decreased in the caudate nucleus and globus pallidus, and the concentration of neurotensin was significantly reduced in the hippocampus. The concentration of neither peptide was significantly altered in the substantia nigra or ventral tegmental area, two regions known to exhibit reductions in other neurotransmitter substances.

In clinical settings, computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) are commonly employed in brain imaging to assist clinicians in determining the type of stroke in patients. However, these modalities are associated with potential hazards or limitations. In contrast, microwave imaging emerges as a promising technique, offering advantages such as non-ionizing radiation, low cost, lightweight, and portability. The primary challenges faced by microwave tomography include the severe ill-posedness of the electromagnetic inverse scattering problem and the time-consuming nature and unsatisfactory resolution of iterative quantitative algorithms. This paper proposes a learning electric field enhancement imaging method (LEFEIM) to achieve quantitative brain imaging based on a microwave tomography system. LEFEIM comprises two cascaded networks. The first, based on a convolutional neural network, utilizes the electric field from the receiving antenna to predict the electric field distribution within the imaging domain. The second network employs the electric field distribution as input to learn the dielectric constant distribution, thereby realizing quantitative brain imaging. Compared to the Born Iterative Method (BIM), LEFEIM significantly improves imaging time, while enhancing imaging quality and goodness-of-fit to a certain extent. Simultaneously, LEFEIM exhibits anti-noise capabilities.

Over the past decade, there has been an increasing focus on quantitative imaging (QI), which, according to one definition, is “the extraction of quantifiable features from medical images for the assessment of normal or the severity, degree of change, or status of a disease, injury, or chronic condition relative to normal” (www.rsna.org/QIBA). To achieve the goals of QI requires the development and standardization of data acquisition, data analysis, and data display techniques, as well as appropriate reporting structures. As such, successful implementation of QI relies heavily on expertise from the fields of medical physics, radiology, statistics, and informatics as well as collaboration from vendors of imaging acquisition, analysis, and reporting systems. When successfully implemented, QI techniques will provide image‐derived metrics with known bias and variance that can be validated with anatomically and physiologically relevant measures, including treatment response, and the heterogeneity of that response, and outcome. Such non‐invasive measures can then be used effectively in clinical and translational research as well as patient care. In addition to modality‐specific QI efforts implemented by individual scientific organizations, national and international organizations, including the NCI, RSNA, FDA, and NIST, appreciating the tremendous potential of QI but also understanding the associated challenges, have become increasingly involved. This symposium session will focus on 1) introducing QI and illustrating why it is important, even though challenging, in both research and clinical applications, and 2) providing overviews of QI efforts from national and international organizations, including the RSNA, NCI, FDA, and NIST.Learning Objectives: Understand the importance and potential of QI in research and clinical applications. Understand key challenges of QI and current barriers to implementation. Understand the current QI efforts of several national and international agencies and organizations, including the FDA, NCI, NIST, and RSNA.

Background and Purpose:Neuropathic pain (NP) is a debilitating condition following spinal cord injury (SCI). The role of periaqueductal gray (PAG) in NP development following SCI remains underexplored. Using resting-state functional MRI (rsfMRI), our study aimed to demonstrate the alterations in functional connectivity (FC) of PAG in NP following SCI.Methods:Ten SCI patients (SCI + NP, n = 7, and SCI − NP, n = 3), alongside 10 healthy controls (HCs), were enrolled. rsfMRI was conducted followed by seed-to-voxel analysis using PAG as the seed region and then group-based analysis comprising three groups (SCI + NP, SCI − NP, and HC). Age and gender were considered as confounding variables.Results:Compared to HCs, SCI + NP demonstrated decreased FC between PAG and right insula, right frontal orbital cortex, right pallidum, dorsal raphe nucleus (DRN), red nuclei (RN), substantia nigra (SN), and ventral posterolateral (VPL) thalamic nuclei. Compared to SCI − NP, SCI + NP demonstrated increased FC between PAG and posterior cingulate cortex (PCC), hippocampus, cerebellar vermis lobules IV and V, and thalamic structures (posterior and lateral pulvinar, the mediodorsal nuclei, and the ventral lateral nuclei). Additionally, decreased FC between the PAG and VPL, geniculate bodies, intralaminar nuclei of thalamus, DRN, RN, SN, and prefrontal cortex was observed in this comparison.Conclusions:Altered FC between PAG and right anterior insula, VPL, DRN, RN, SN, cerebellar vermis lobules IV and V, frontal cortex, and PCC was associated with NP sequelae of SCI. Additionally, SCI was independently associated with decreased FC between PAG and right posterior insula, cerebellar lobules IV and V, and cerebellar vermis lobules III, IV, and V.

A couple of decision-making models with different ingredients have successfully interpreted choices, confidence, and related neural activities. However, empirical and theoretical evidence is currently lacking to distinguish these models clearly. Here, we investigated the decision-congruent confidence bias, where confidence favors evidence from the chosen option, yet the choice and its correctness or optimality are determined equally by alternative evidence strengths across both perceptual and value-based decision-making tasks. This confidence bias is manifested by confidence-coding neural activities, particularly in the dorsal anterior cingulate cortex. Further analyses on an array of neurocomputational models show that only the decision-making model equipped with mutual inhibition and an urgency signal can produce such a selective bias across almost all parameter regimes. These findings suggest that mutual inhibition and an urgency signal are two indispensable features embedded in the decision-making process, while confidence bias might be its consequence.