Sedation is an essential component of treatment for some patients admitted to the ICU, but it carries a risk of sedation-related delirium. Sedation-related delirium is associated with higher mortality and increased length of stay, but pharmacologic treatments for delirium can lead to oversedation or other adverse effects. Therefore, nonpharmacologic treatments are recommended in the literature; however, these recommendations are quite general and do not provide structured interventions. To establish a structured nonpharmacologic intervention that could improve indications of delirium after sedation, we combined evidence-based interventions including recordings of sensory-rich stories told by the patient's family and patient-specific music into our novel positive stimulation for medically sedated patients (PSMSP) protocol. The positive listening stimulation playlist organized by a board-certified music therapist (MT-BC) within the PSMSP protocol can be used in carefully monitored sessions with the MT-BC potentially to decrease agitation and stabilize arousal, as well as being played by nursing staff throughout the patient's recovery from sedation. Further controlled studies will be necessary, but the PSMSP protocol has the potential to reduce agitation and increase arousal during listening, as highlighted by the case of a patient recovering from sedation during treatment for COVID-19 pneumonia. It is important for the entire critical care team to be aware of nonpharmacologic treatments like PSMSP that are available for delirium mitigation so that, where applicable, these therapies can be incorporated into the patient's treatment regimen.

This note from the field outlines how an integrated arts in health department within a hospital created clinical and non-clinical art experiences for patients and providers during COVID-19. Working with a multi-disciplinary team, the Center for Performing Arts Medicine at Houston Methodist established creative arts therapy and arts integration programmes targeting patient and provider experiences during COVID-19. Emphasis is placed on how programmes respond to both physical health and emotional well-being through accessible, appropriate art experiences. This article outlines those strategies and highlights various entry points for arts experiences in a hospital experience during a pandemic.

Purpose Functional MRI (fMRI) at the mesoscale of cortical layers and columns requires both sensitivity and specificity, the latter of which can be compromised if the imaging method is affected by vascular artifacts, particularly cortical draining veins at the pial surface. Recent studies have shown that cerebral blood volume (CBV) imaging is more specific to the actual laminar locus of neural activity than BOLD imaging using standard gradient-echo EPI sequences. Gradient and spin-echo (GRASE) BOLD imaging has also shown greater specificity when compared with standard gradient-echo EPI BOLD. Here we directly compare CBV and BOLD contrasts in high-resolution imaging of the primary motor cortex for laminar functional MRI in four combinations of signal labeling, CBV using slice-selective slab-inversion vascular space occupancy (VASO) and BOLD, each with 3D gradient-echo EPI and zoomed 3D-GRASE image readouts. Methods Activations were measured using each sequence and contrast combination during a motor task. Activation profiles across cortical depth were measured to assess the sensitivity and specificity (pial bias) of each method. Results Both CBV imaging using gradient-echo 3D-EPI and BOLD imaging using 3D-GRASE show similar specificity and sensitivity and are therefore useful tools for mesoscopic functional MRI in the human cortex. The combination of GRASE and VASO did not demonstrate high levels of sensitivity, nor show increased specificity. Conclusion Three-dimensional EPI with VASO contrast and 3D-GRASE with BOLD contrast both demonstrate sufficient sensitivity and specificity for laminar functional MRI to be used by neuroscientists in a wide range of investigations of depth-dependent neural circuitry in the human brain.

BACKGROUND: Current diagnostic strategy for bipolar disorders relies on symptomological classification. Yet, responses to both pharmacological and psychotherapeutic treatments vary widely, suggesting that underlying neuropathological differences are not well defined by current nosology. Classifying patients with bipolar disorder based on emotion regulation network (ERN) activation may account for some of the heterogeneity within the disorder. METHODS: Euthymic participants diagnosed with bipolar I disorder (n = 86) and healthy subjects (n = 80) underwent functional magnetic resonance imaging scans while engaged in emotional reappraisal of negative stimuli. After determining average regional activations in key network regions, we applied agglomerative hierarchical clustering to identify subtypes of bipolar disorder. Next, we examined relations among neural subtypes, demographic variables, and mood symptoms. RESULTS: Analyses revealed two primary neural subtypes of euthymic bipolar I disorder participants. The first subtype, ERN cluster 1, was characterized by increased amygdala activation and slightly increased ventrolateral prefrontal and subgenual cingulate activation, whereas ERN cluster 2 was defined by decreased amygdala activation with wider-spread prefrontal activation. Cluster 1 was associated with a higher number of hospitalizations for depression (odds ratio = 1.30, 95% confidence interval = 1.02-1.64) and later onset of manic episodes (odds ratio = 1.06, 95% confidence interval = 1.00-21.13) than cluster 2. ERN clusters of healthy subjects differed from bipolar disorder clusters and were defined by differential activation of the prefrontal cortex. ERN clusters of healthy subjects, which differed from bipolar disorder clusters, were defined by differential activation of the prefrontal cortex. CONCLUSIONS: Emotion regulation circuitry can distinguish neurobiological subtypes of bipolar disorder in the euthymic state. These subtypes, which are differentially associated with indices of illness severity and subsyndromal affective symptoms, may help to inform relapse risk and more personalized treatment approaches.

Purpose: To achieve highly accelerated submillimeter resolution T-2-weighted functional MRI at 7T by developing a three-dimensional gradient and spin echo imaging (GRASE) with inner-volume selection and variable flip angles (VFA). Methods: GRASE imaging has disadvantages in that (a) k-space modulation causes T-2 blurring by limiting the number of slices and (b) a VFA scheme results in partial success with substantial SNR loss. In this work, accelerated GRASE with controlled T-2 blurring is developed to improve a point spread function (PSF) and temporal signal-to-noise ratio (ISNR) with a large number of slices. To this end, the VFA scheme is designed by minimizing a trade-off between SNR and blurring for functional sensitivity, and a new GRASE-optimized random encoding, which takes into account the complex signal decays of T-2 and T-2* weightings, is proposed by achieving incoherent aliasing for constrained reconstruction. Numerical and experimental studies were performed to validate the effectiveness of the proposed method over regular and VFA GRASE (R- and V-GRASE). Results: The proposed method, while achieving 0.8 mm isotropic resolution, functional MRI compared to R- and V-GRASE improves the spatial extent of the excited volume up to 36 slices with 52%-68% full width at half maximum (FWHM) reduction in PSF but approximately 2- to 3-fold mean tSNR improvement, thus resulting in higher BOLD activations. Conclusions: We successfully demonstrated the feasibility of the proposed method in T-2-weighted functional MRI. The proposed method is especially promising for cortical layer-specific functional MRI.

This study aims to explore the similarities in functional connectivity (FC) patterns in individuals when listening to different music genres and, in comparison, to the spoken word, using a novel data-driven approach. Our model and findings can potentially be utilized for evaluating the neurological effects of therapeutic music interventions. Twelve healthy volunteers listened to seven different sound tracks while undergoing functional magnetic resonance imaging (fMRI) scans: music of the volunteer’s choice with positive emotional attachment, two selections of unfamiliar classical music, one classical piece repeated with visual guidance and three spoken language tracks. FC network graphs were created, and selected graph properties were evaluated toward their commonalities across sound tracks. For comparison, FC patterns represented by the graph adjacency matrices were directly compared for high and low BOLD activation during listening. Graph properties averaged across subjects showed similar values for the same sound track compared to different sound tracks (p < 0.003). For high BOLD activation involving most areas in the auditory cortex, FC patterns for the same sound track correlated highly (0.74 ± 0.11), whereas FC patterns for different sound tracks did not (0.09 ± 0.07; p < 6e−5). For low BOLD activation involving additional brain regions, correlation of FC patterns for the sound tracks was still higher (0.43 ± 0.07) than for different sound tracks (0.09 ± 0.05; p < 8e−6). Similar music creates similar functional activation and connectivity patterns in the brain of healthy individuals as does listening to the spoken word. Direct comparison of FC patterns yielded higher correlations than indirect comparisons of graph properties derived from corresponding FC networks.

Background: Music therapy, a nontraditional approach to patient care, has long been used to achieve a wide variety of positive results. To deepen our understanding of the connection and therapeutic potential of music, the effect of music therapy and music medicine (music administered to individuals without an interactive therapeutic relationship) on the brain remains a topic of active research. Objective: This study is aimed at investigating the effect of different music genres and individualized music selection on brain functional connectivity (FC) measured by functional magnetic resonance imaging (fMRI). Methods: Twelve healthy subjects listened to five excerpts: Bach with and without visual guide (unfamiliar), self-selected familiar music, Gagaku (unfamiliar music) and Chaplin (spoken word) while undergoing a block design fMRI study. fMRI datasets were imported into CONN (Matlab toolbox) and graph networks were created for 132 anatomical regions in MNI space. Group connectivity for each soundtrack was quantified and statistically analyzed using the R package. Results: Complex interactions between brain regions, cerebellar regions (713), superior frontal gyrus (178) and parahippocampus (223), were highest for self-selected music. Brain regions involving sound processing, memory retrieval, semantic processing and motor areas were continuously activated for all five excerpts; however, most connections were formed in language processing regions for the Bach excerpt. Conclusion: Functional brain connectivity varied by soundtrack with the largest degree of connectivity found consistently for self-selected and unfamiliar (Bach, Gagaku) music. Incorporating individualized music listening into existing therapy paradigms may positively contribute to standard protocol for stroke rehabilitation and prevention.

This work develops a novel, simultaneous multi-VENC and simultaneous multi-slice (SMV+SMS) imaging in a single acquisition for robust phase contrast (PC) MRI. To this end, the pulse sequence was designed to permit concurrent acquisition of multiple VENCs as well as multiple slices on a shared frequency encoding gradient, in which each effective echo time for multiple VENCs was controlled by adjusting net gradient area while multiple slices were simultaneously excited by employing multiband resonance frequency (RF) pulses. For VENC and slice separation, RF phase cycling and gradient blip were applied to create both inter-VENC and inter-slice shifts along phase encoding direction, respectively. With an alternating RF phase cycling that generates oscillating steady-state with low and high signal amplitude, the acquired multi-VENC k-space was reformulated into 3D undersampled k-space by generating a virtual dimension along VENC direction for modulation induced artifact reduction. In vivo studies were conducted to validate the feasibility of the proposed method in comparison with conventional PC MRI. The proposed method shows comparable performance to the conventional method in delineating both low and high flow velocities across cardiac phases with high spatial coverage without apparent artifacts. In the presence of high flow velocity that is above the VENC value, the proposed method exhibits clear depiction of flow signals over conventional method, thereby leading to high VNR image with improved velocity dynamic range.

Background: Error detection is a critical part of the self-monitoring functions that guide efficient, goal-directed behaviors. Error-monitoring deficits are well described in schizophrenia, but the extent to which error processing deficits and their associated functional neuroanatomy are evident in individuals at clinical high risk (CHR) for developing schizophrenia is not well characterized. Methods: We studied youth (ages 11–30) meeting CHR for psychosis criteria (n = 30), individuals early in their schizophrenia illness (ESZ; n = 22), and healthy adolescents and young adults (HC; n = 72). Functional magnetic resonance imaging was collected during Go/NoGo response inhibition task performance. Voxelwise main effects of Group (p<.001 height threshold, family-wise error corrected P < .05) for incorrect NoGo versus correct Go activations were examined, and correlated with the signal detection measure d’. Results: Error rates and error-related activations in anterior cingulate and dorsolateral prefrontal cortex were equivalent across the three groups. A significant main effect of Group for the contrast of NoGo errors relative to correct Go responses was detected in the left cerebellum. This main effect of Group was explained by the ESZ group showing significantly less error-related activation, relative to the HC group (with the CHR group differing from neither). In HC individuals, higher error-related contrast values in this cerebellar region significantly related to better d’, a relationship that was not present in either of the clinical groups (group slopes difference, P < .05). Conclusion: ESZ patients showed significantly less cerebellar activation during error processing, relative to HC participants. In HCs, cerebellar activation in this region was significantly related to better signal detection. A role for the cerebellum in performance monitoring is increasingly recognized, and these data suggest that the normal relationship between cerebellar error-related responses and task performance breaks down in both CHR and ESZ groups.

BACKGROUND:Performance during cognitive control functional magnetic resonance imaging (fMRI) tasks are associated with frontal lobe hypoactivation in patients with bipolar disorder, even while euthymic. Here, we study the structural underpinnings for this functional abnormality simultaneously with brain activation data. METHODS:In a sample of ninety adults (45 with inter-episode Bipolar I disorder and 45 healthy controls), we explored whether abnormal functional activation patterns in bipolar euthymic subjects during a Go-NoGo fMRI task are associated with regional deficits in cortical gray matter thickness in the same regions. Cross-sectional differences in fMRI activation were used to form a-priori hypotheses for region-of-interest cortical gray matter thickness analyses. fMRI BOLD to structural magnetic resonance imaging (sMRI) thickness correlations were conducted across the sample and within patients and controls separately. RESULTS:During response inhibition (NoGo minus Go), bipolar subjects showed significant hypoactivation and reduced thickness in the inferior frontal cortex (IFC), superior frontal gyrus and cingulate compared to controls. Cingulate hypoactivation corresponded with reduced regional thickness. A significant activation by disease state interaction was observed with thickness in left prefrontal areas. CONCLUSIONS:Reduced cingulate fMRI activation is associated with reduced cortical thickness. In the left frontal lobe, a thinner cortex was associated with increased fMRI activation in patients, but showed a reverse trend in controls. These findings suggest that reduced activation in the IFC and cingulate during a response inhibition task may have an underlying structural etiology, which may explain task-related functional hypoactivation that persists even when patients are euthymic.

In executive function, specifically in response inhibition, numerous studies support the essential role for the inferior frontal cortex (IFC). Hypoactivation of the IFC during response-inhibition tasks has been found consistently in subjects with bipolar disorder during manic and euthymic states. The aim of this study was to examine whether reduced IFC activation also exists in unmedicated subjects with bipolar disorder during the depressed phase of the disorder. Participants comprised 19 medication-free bipolar II (BP II) depressed patients and 20 healthy control subjects who underwent functional magnetic resonance imaging (fMRI) while performing a Go/NoGo response-inhibition task. Whole-brain analyses were conducted to assess activation differences within and between groups. The BP II depressed group, compared with the control group, showed significantly reduced activation in right frontal regions, including the IFC (Brodmann's area (BA) 47), middle frontal gyrus (BA 10), as well as other frontal and temporal regions. IFC hypoactivation may be a persistent deficit in subjects with bipolar disorder in both acute mood states as well as euthymia, thus representing a trait feature of bipolar disorder.

BACKGROUND:Patterns of abnormal neural activation have been observed during working memory tasks in bipolar I depression, yet the neural changes associated with bipolar II depression have yet to be explored.METHOD:An n-back working memory task was administered during a 3T functional magnetic resonance imaging scan in age- and gender-matched groups of 19 unmedicated, bipolar II depressed subjects and 19 healthy comparison subjects. Whole-brain and region-of-interest analyses were performed to determine regions of differential activation across memory-load conditions (0-, 1- and 2-back).RESULTS:Accuracy for all subjects decreased with higher memory load, but there was no significant group × memory load interaction. Random-effects analyses of memory load indicated that subjects with bipolar II depression exhibited significantly less activation than healthy subjects in left hemispheric regions of the middle frontal gyrus [Brodmann area (BA) 11], superior frontal gyrus (BA 10), inferior parietal lobule (BA 40), middle temporal gyrus (BA 39) and bilateral occipital regions. There was no evidence of differential activation related to increasing memory load in the dorsolateral prefrontal or anterior cingulate cortex.CONCLUSIONS:Bipolar II depression is associated with hypoactivation of the left medio-frontal and parietal cortex during working memory performance. Our findings suggest that bipolar II depression is associated with disruption of the fronto-parietal circuit that is engaged in working memory tasks, which is a finding reported across bipolar subtypes and mood states.

Background: The inferior frontal cortical (IFC)-striatal network plays an integral role in response inhibition and is compromised in patients with Bipolar Disorder (BP) or Attention-Deficit/Hyperactivity Disorder (ADHD). Prior BP functional neuroimaging studies have not accounted for ADHD comorbidity despite its high prevalence.Methods: The authors conducted an fMRI study using a response inhibition task (Go-NoGo) in 32 euthymic adults with BP, half with comorbid ADHD (BP/ADHD); 16 adults with ADHD alone; and 30 healthy controls. Within- and between-group whole-brain analyses were performed to assess for significant neural function differences.Results: All groups activated frontal and striatal regions involved in response inhibition. ANOVA results demonstrated significant interaction effects of BP and ADHD in the anterior and posterior cingulate, left superior and middle frontal gyri and left inferior parietal lobule. Follow-up comparisons showed significant differences between BP subjects with and without ADHD. Other regions demonstrated main effects of BP (left inferior frontal gyms, left middle frontal gyms, right superior frontal gyrus and left insula) and ADHD (left inferior frontal gyms, left precentral gyrus and right anterior cingulate).Limitations: This study, as the first of its kind, requires replication using large sample sizes and controlling for potential effects of medication.Conclusions: Euthymic bipolar adults with comorbid ADHD have significantly different neural activation patterns from BP patients without this comorbidity. If understanding of the neurobiology of bipolar disorder is to be achieved, it is critical to control for this potential confound, something not done by most prior fMRI studies of adults with BP. Published by Elsevier B.V.

Background: The symptoms of bipolar disorder suggest dysfunction of emotion regulatory networks. In healthy control populations, downregulation of emotional responses activates the ventral lateral prefrontal cortex (vlPFC) and dampens amygdala activation. This study investigated frontal and limbic function and connectivity during emotion downregulation in euthymic subjects with bipolar I disorder (BPI) and healthy control subjects.Methods: Thirty BPI and 26 control subjects underwent functional magnetic resonance imaging scanning while performing an emotion processing task with passive viewing and emotion downregulation conditions. Contrasts were made for each group comparing the downregulation and passive viewing conditions, and these were entered into a between-group random effects analysis to assess group differences in activation. Psychophysiological interaction analyses were conducted to test for significant group differences in functional connectivity between the amygdala and inhibitory frontal regions (i.e., vlPFC).Results: Control subjects showed the expected robust bilateral activation of frontal and limbic regions during passive viewing and emotion downregulation tasks. Between-group analyses revealed similar activation of BPI and control subjects during passive viewing but significantly decreased activation in bilateral vlPFC, bilateral anterior and posterior cingulate, medial frontal gyrus, and bilateral dorsal lateral prefrontal cortex during emotion downregulation in subjects with BPI. Connectivity analysis demonstrated that control subjects had significantly greater negative functional connectivity between the left amygdala and bilateral vlPFC compared with subjects with BPI.Conclusions: This study provides evidence that dysfunction in the neural networks responsible for emotion regulation, including the prefrontal cortex, cingulate, and subcortical structures, are present in BPI subjects, even while euthymic.

OBJECTIVE:We examined resting state functional connectivity in the brain between key emotion regulation regions in bipolar I disorder to delineate differences in coupling from healthy subjects.METHODS:Euthymic subjects with bipolar I disorder (n = 20) and matched healthy subjects (n = 20) participated in a resting state functional magnetic resonance imaging scan. Low-frequency fluctuations in blood oxygen level-dependent (BOLD) signal were correlated in the six connections between four anatomically defined nodes: left and right amygdala and left and right ventrolateral prefrontal cortex (vlPFC). Seed-to-voxel connectivity results were probed for commonly coupled regions. Following this, an identified region was included in a mediation analysis to determine the potential of mediation.RESULTS:The bipolar I disorder group exhibited significant hyperconnectivity between right amygdala and right vlPFC relative to healthy subjects. The connectivity between these regions in the bipolar I disorder group was partially mediated by activity in the anterior cingulate cortex (ACC).CONCLUSIONS:Greater coupling between right amygdala and right vlPFC and their partial mediation by the ACC were found in bipolar I disorder subjects in remission and in the absence of a psychological task. These findings have implications for a trait-related and clinically important imaging biomarker.

Structural neuroimaging studies of the amygdala and hippocampus in bipolar disorder have been largely inconsistent. This may be due in part to differences in the proportion of subjects taking lithium or experiencing an acute mood state, as both factors have recently been shown to influence gray matter structure. To avoid these problems, we evaluated euthymic subjects not currently taking lithium. Thirty-two subjects with bipolar type I disorder and 32 healthy subjects were scanned using magnetic resonance imaging. Subcortical regions were manually traced, and converted to three-dimensional meshes to evaluate the main effect of bipolar illness on radial distance. Statistical analyses found no evidence for a main effect of bipolar illness in either region, although exploratory analyses found a significant age by diagnosis interaction in the right amygdala, as well as positive associations between radial distance of the left amygdala and both prior hospitalizations for mania and current medication status. These findings suggest that, when not treated with lithium or in an acute mood state, patients with bipolar disorder exhibit no structural abnormalities of the amygdala or hippocampus. Future studies, nevertheless, that further elucidate the impact of age, course of illness, and medication on amygdala structure in bipolar disorder are warranted.

Functional neuroimaging studies have implicated the involvement of the amygdala and ventrolateral prefrontal cortex (vlPFC) in the pathophysiology of bipolar disorder. Hyperactivity in the amygdala and hypoactivity in the vlPFC have been reported in manic bipolar patients scanned during the performance of an affective faces task. Whether this pattern of dysfunction persists during euthymia is unclear. Using functional magnetic resonance imaging (fMRI), 24 euthymic bipolar and 26 demographically matched healthy control subjects were scanned while performing an affective task paradigm involving the matching and labeling of emotional facial expressions. Neuroimaging results showed that, while amygdala activation did not differ significantly between groups, euthymic patients showed a significant decrease in activation of the right vlPFC (BA47) compared to healthy controls during emotion labeling. Additionally, significant decreases in activation of the right insula, putamen, thalamus and lingual gyrus were observed in euthymic bipolar relative to healthy control subjects during the emotion labeling condition. These data, taken in context with prior studies of bipolar mania using the same emotion recognition task, could suggest that amygdala dysfunction may be a state-related abnormality in bipolar disorder, whereas vlPFC dysfunction may represent a trait-related abnormality of the illness. Characterizing these patterns of activation is likely to help in understanding the neural changes related to the different mood states in bipolar disorder, as well as changes that represent more sustained abnormalities. Future studies that assess mood-state related changes in brain activation in longitudinal bipolar samples would be of interest.