Quantification of infarct core volume in patients with acute ischemic stroke using cerebral metabolic rate of oxygen (CMRO2) in CT perfusion.

BACKGROUND AND PURPOSE: The cerebral metabolic rate of oxygen (CMRO2) is considered a robust marker of the infarct core in 15°-tracer- based positron emission tomography. We aimed to delineate the infarct core in patients with acute ischemic stroke using commonly used relative cerebral blood flow (rCBF) < 30% and oxygen metabolism parameter of CMRO2 on CT perfusion in comparison with pre-treatment diffusion- weighted imaging (DWI)-derived infarct core volume. MATERIALS AND METHODS: Patients with acute ischemic stroke who met the inclusion criteria were recruited. The CMRO2 and CBF maps in CT perfusion were automatically generated using post-processing software. The infarct core volume was quantified with relative (r) CMRO2 < 20% - 30% and rCBF < 30%. The optimal threshold was defined as those that demonstrated the smallest mean absolute error, lowest mean infarct core volume difference, narrowest 95% limit of agreement, and largest intraclass correlation coefficient (ICC) against the DWI. RESULTS: This study included 76 patients (mean age ± standard deviation, 69.97 ± 12.15 years, 43 males). The optimal thresholds of rCMRO2 < 26% resulted in the lowest mean infarct core volume difference, narrowest 95% limit of agreement, and largest ICC among different thresholds. Bland-Altman analysis demonstrated a volumetric bias of 1.96 mL between DWI and rCMRO2 < 26%, whereas in cases of DWI and rCBF < 30%, the bias was notably larger at 14.10 mL. The highest correlation was observed for rCMRO2 < 26% (ICC=0.936), whereas rCBF < 30% showed a slightly lower ICC of 0.934. CONCLUSIONS: CT perfusion-derived CMRO2 is a promising parameter for estimating the infarct core volume in patients with acute ischemic stroke. ABBREVIATIONS: CMRO2 = cerebral metabolic rate of oxygen.

Erratum: Agreement and Reliability between Clinically Available Software Programs in Measuring Volumes and Normative Percentiles of Segmented Brain Regions.

This corrects the article on p. 959 in vol. 23, PMID: 36175000.

Association of Brain Microstructure and Functional Connectivity With Cognitive Outcomes and Postnatal Growth Among Early School-Aged Children Born With Extremely Low Birth Weight.

Importance: Postnatal growth may be associated with longitudinal brain development in children born preterm. Objective: To compare brain microstructure and functional connectivity strength with cognitive outcomes in association with postnatal growth among early school-aged children born preterm with extremely low birth weight. Design, Setting, and Participants: This single-center cohort study prospectively enrolled 38 children 6 to 8 years of age born preterm with extremely low birth weight: 21 with postnatal growth failure (PGF) and 17 without PGF. Children were enrolled, past records were retrospectively reviewed, and imaging data and cognitive assessments occurred from April 29, 2013, through February 14, 2017. Image processing and statistical analyses were conducted through November 2021. Exposure: Postnatal growth failure in the early neonatal period. Main Outcomes and Measures: Diffusion tensor images and resting-state functional magnetic resonance images were analyzed. Cognitive skills were tested using the Wechsler Intelligence Scale; executive function was assessed based on a composite score calculated from the synthetic composite of the Children's Color Trails Test, STROOP Color and Word Test, and Wisconsin Card Sorting Test; attention function was evaluated using the Advanced Test of Attention (ATA); and the Hollingshead Four Factor Index of Social Status-Child was estimated. Results: Twenty-one children born preterm with PGF (14 girls [66.7%]), 17 children born preterm without PGF (6 girls [35.3%]), and 44 children born full term (24 girls [54.5%]) were recruited. Attention function was less favorable in children with PGF than those without PGF (mean [SD] ATA score: children with PGF, 63.5 [9.4]; children without PGF, 55.7 [8.0]; P = .008). Significantly lower mean (SD) fractional anisotropy in the forceps major of the corpus callosum (0.498 [0.067] vs 0.558 [0.044] vs 0.570 [0.038]) and higher mean (SD) mean diffusivity in the left superior longitudinal fasciculus-parietal bundle (8.312 [0.318] vs 7.902 [0.455] vs 8.083 [0.393]; originally calculated as millimeter squared per second and rescaled 10 000 times as mean diffusivity × 10 000) were seen among children with PGF compared with children without PGF and controls, respectively. Decreased resting-state functional connectivity strength was observed in the children with PGF. The mean diffusivity of the forceps major of the corpus callosum significantly correlated with the attention measures (r = 0.225; P = .047). Functional connectivity strength between the left superior lateral occipital cortex and both superior parietal lobules correlated with cognitive outcomes of intelligence (right superior parietal lobule, r = 0.262; P = .02; and left superior parietal lobule, r = 0.286; P = .01) and executive function (right superior parietal lobule, r = 0.367; P = .002; and left superior parietal lobule, r = 0.324; P = .007). The ATA score was positively correlated with functional connectivity strength between the precuneus and anterior division of the cingulate gyrus (r = 0.225; P = .048); however, it was negatively correlated with functional connectivity strength between the posterior cingulate gyrus and both superior parietal lobules (the right superior parietal lobule [r = -0.269; P = .02] and the left superior parietal lobule [r = -0.338; P = .002]). Conclusions and Relevance: This cohort study suggests that the forceps major of the corpus callosum and the superior parietal lobule were vulnerable regions in preterm infants. Preterm birth and suboptimal postnatal growth could have negative associations with brain maturation, including altered microstructure and functional connectivity. Postnatal growth may be associated with differences in long-term neurodevelopment among children born preterm.

Impact of Cerebellar Injury on Neurodevelopmental Outcomes in Preterm Infants With Cerebral Palsy.

OBJECTIVE: We aimed to analyze brain imaging findings and neurodevelopmental outcomes of preterm infants diagnosed with cerebral palsy. DESIGN: Brain magnetic resonance imaging of preterm infants born between 23 and 32 wks' gestation and diagnosed with cerebral palsy at 2 yrs of corrected age were evaluated. Brain lesions were categorized as periventricular leukomalacia, intraventricular hemorrhage, and cerebellar hemorrhage and graded by the severity. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition, at 18-24 mos corrected age, and the Korean Ages and Stages Questionnaire at 18 and 24 mos of corrected age. RESULTS: Cerebral palsy was found in 38 children (6.1%) among 618 survivors. Cerebellar injury of high-grade cerebellar hemorrhage and/or atrophy accounted for 25%. Among patients with supratentorial lesions, those having cerebellar injury showed significantly lower scores on each Korean Ages and Stages Questionnaire domain except gross motor than patients without cerebellar injury. They also revealed a high proportion of patients below the cutoff value of Korean Ages and Stages Questionnaire in language, fine motor, and problem-solving domains ( P < 0.05) and lower Bayley Scales of Infant and Toddler Development, Third Edition, language composite scores ( P = 0.038). CONCLUSIONS: Poor neurodevelopmental outcomes other than motor function were associated with cerebellar injury. Evaluation of the cerebellum may help predict functional outcomes of patients with cerebral palsy.

Poly(arylene ether)s-Based Polymeric Membranes Applied for Water Purification in Harsh Environment Conditions: A Mini-Review.

Confronting the pressing challenge of freshwater scarcity, polymeric membrane-based water treatment technology has emerged as an essential and effective approach. Poly(arylene ether)s (PAEs) polymers, a class of high-performance engineering thermoplastics, have garnered attention in recent decades as promising membrane materials for advanced water treatment approaches. The PAE-Based membranes are employed to resist the shortages of most common polymeric membranes, such as chemical instability, structural damage, membrane fouling, and shortened lifespan when deployed in harsh environments, owing to their excellent comprehensive performance. This article presents the advancements in the research of several typical PAEs, including poly(ether ether ketone) (PEEK), polyethersulfone (PES), and poly(arylene ether nitrile) (PEN). Techniques for membrane formation, modification strategies, and applications in water treatment have been reviewed. The applications encompass processes for oil/water separation, desalination, and wastewater treatment, which involve the removal of heavy metal ions, dyes, oils, and other organic pollutants. The commendable performance of these membranes has been summarized in terms of corrosion resistance, high-temperature resistance, anti-fouling properties, and durability in challenging environments. In addition, several recommendations for further research aimed at developing efficient and robust PAE-based membranes are proposed.

Agreement and Reliability between Clinically Available Software Programs in Measuring Volumes and Normative Percentiles of Segmented Brain Regions.

OBJECTIVE: To investigate the agreement and reliability of estimating the volumes and normative percentiles (N%) of segmented brain regions among NeuroQuant (NQ), DeepBrain (DB), and FreeSurfer (FS) software programs, focusing on the comparison between NQ and DB. MATERIALS AND METHODS: Three-dimensional T1-weighted images of 145 participants (48 healthy participants, 50 patients with mild cognitive impairment, and 47 patients with Alzheimer's disease) from a single medical center (SMC) dataset and 130 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset were included in this retrospective study. All images were analyzed with DB, NQ, and FS software to obtain volume estimates and N% of various segmented brain regions. We used Bland-Altman analysis, repeated measures ANOVA, reproducibility coefficient, effect size, and intraclass correlation coefficient (ICC) to evaluate inter-method agreement and reliability. RESULTS: Among the three software programs, the Bland-Altman plot showed a substantial bias, the ICC showed a broad range of reliability (0.004-0.97), and repeated-measures ANOVA revealed significant mean volume differences in all brain regions. Similarly, the volume differences of the three software programs had large effect sizes in most regions (0.73-5.51). The effect size was largest in the pallidum in both datasets and smallest in the thalamus and cerebral white matter in the SMC and ADNI datasets, respectively. N% of NQ and DB showed an unacceptably broad Bland-Altman limit of agreement in all brain regions and a very wide range of ICC values (-0.142-0.844) in most brain regions. CONCLUSION: NQ and DB showed significant differences in the measured volume and N%, with limited agreement and reliability for most brain regions. Therefore, users should be aware of the lack of interchangeability between these software programs when they are applied in clinical practice.

Alterations of Power Spectral Density in Salience Network during Thought-action Fusion Induction Paradigm in Obsessive-compulsive Disorder.

Objective: Recent studies highlighted the triple-network model which illustrated the interactions among three large-scale networks including salience network (SN). The functional magnetic resonance imaging used in this study was designed to investigate the characteristics of three large-scale networks associated with the thought-action fusion (TAF) in patients with obsessive-compulsive disorder (OCD) using power spectral density (PSD) analysis. Methods: This study included 32 OCD patients and 38 age-matched healthy controls (HC). The TAF task was modified from the experiment of Rassin. PSD from time courses in large-scale networks of each subject was measured to compare between the groups for both TAF and resting state. Results: In SN, OCD reported lower power in the low-frequency domain of SN compared to HC using the two-sample t test during the TAF task (t = -2.395, p = 0.019) but not in the resting state. The PSD in the low-frequency domain of the SN had a significant negative correlation with state score in the guilty inventory (r = -0.361, p = 0.042) in OCD patients. Conclusion: This study suggests that OCD patients showed reduced SN power which can be prominent in a certain situation, such as TAF. In addition, the PSD alterations in SN cause difficulty in processing ambiguous emotional cues in social situations, and the difficulty can be connected with a negative feeling (e.g., guilt).

Aberrant functional connectivity of neural circuits associated with thought-action fusion in patients with obsessive-compulsive disorder.

BACKGROUND: Cognitive theories of obsessive-compulsive disorder (OCD) stress the importance of dysfunctional beliefs in the development and maintenance of the disorder. However, a neurobiological understanding of these cognitive models, including thought-action fusion (TAF), is surprisingly lacking. Thus, this functional magnetic resonance imaging study aimed to investigate whether altered functional connectivity (FC) is associated with the TAF paradigm in OCD patients. METHODS: Forty-one OCD patients and 47 healthy controls (HCs) participated in a functional magnetic resonance imaging study using a TAF task, in which they were asked to read the name of a close or a neutral person in association with positive and negative statements. RESULTS: The conventional TAF condition (negative statements/close person) induced significant FC between the regions of interest (ROIs) identified using multivoxel pattern analysis and the visual association areas, default mode network subregions, affective processing, and several subcortical regions in both groups. Notably, sparser FC was observed in OCD patients. Further analysis confined to the cortico-striato-thalamo-cortical (CSTC) and affective networks demonstrated that OCD patients exhibited reduced ROI FC with affective regions and greater ROI FC with CSTC components in the TAF condition compared to HCs. Within the OCD patients, middle cingulate cortex-insula FC was correlated with TAF and responsibility scores. CONCLUSIONS: Our TAF paradigm revealed altered context-dependent engagement of the CSTC and affective networks in OCD patients. These findings suggest that the neurobiology of cognitive models corresponds to current neuroanatomical models of OCD. Further, they elucidate the underlying neurobiological mechanisms of OCD at the circuit-based level.

The Neural Correlates of Positive Versus Negative Thought-action Fusion in Healthy Young Adults.

OBJECTIVE: Thought-action fusion (TAF), one of the most-studied dysfunctional beliefs in obsessive-compulsive disorder, represents an individual's belief that his/her thoughts directly influence events. TAF belief types are divided into personal thoughts relating to positive (positive TAF) and negative outcomes (negative TAF). However, the neural mechanisms underlying both aspects of the TAF response remain elusive. METHODS: This functional magnetic resonance imaging study aimed to investigate the neural circuits related to positive and negative TAF and their relationships with psychological measures. Thirty-one healthy male volunteers participated in a modified TAF task wherein they were asked to read the name of a close person embedded in positive statements (PS) or negative statements (NS). RESULTS: Conjunction analysis revealed activation of the fusiform and lingual gyri, midcingulate and superior medial frontal gyri, inferior orbitofrontal gyrus, and temporoparietal junction. The NS > PS comparison showed additional activation in the precuneus and medial prefrontal cortex, superior frontal gyrus, insula, globus pallidus, thalamus, and midbrain. Precuneus activity was associated with the TAF score among these areas. Moreover, activity in the inferior orbitofrontal gyrus, insula, superior, middle and medial frontal gyri, globus pallidus, inferior parietal lobule, and precuneus was associated with dimensional obsessive-compulsive scores. In contrast, the PS > NS comparison revealed no significant activation. CONCLUSION: These results suggest that negative TAF, relative to positive TAF, recruits additional regions for self-referential processing, salience, and habitual responding, which may contribute to the activation of the belief that a negative thought increases the probability of that negative outcome.

Believing is seeing: an fMRI study of thought-action fusion in healthy male adults.

Thought-action fusion (TAF) is a tendency of individuals to establish causal relations between their own thoughts and external reality. TAF can lead to maladaptive behaviors typically observed in obsessional thoughts. However, neural mechanisms underlying TAF are still unknown. In this study, 38 healthy men were informed that MR signals were able to detect thoughts of the word 'apple' and that this recognition could result in the administration of electrical shocks to a person outside the scanner. During MR acquisition, they were asked to suppress or not suppress the thought of 'apple' while sham electrical shocks were or were not administered to the other person. The main effect of the sham administration of electrical shock to another person was shown in the bilateral lingual gyri, fusiform gyri, and middle occipital cortices (FDR corrected p < 0.05). Also, fusiform gyrus, lingual gyrus, and middle occipital cortex activity correlated with scores of guilty feeling only when participants consciously tried to think of apple as less as possible. Our study demonstrates that visual association areas may play primary roles in TAF. The simple belief and visual imagery that one's thought may lead to someone's injury activated visual areas of the brain where, in turn, brain activity is associated with feelings of guilt.

Effects of emotional maltreatment on semantic network activity during cognitive reappraisal.

Maltreatment experiences alter brain development associated with emotion processing, and dysregulation of emotion may trigger mental health problems in maltreated people. However, studies revealing alterations in brain networks during cognitive reappraisal in victims of maltreatment are strikingly insufficient. In this study, 27 healthy subjects were recruited. The maltreatment experiences and positive reappraisal abilities were measured using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) and Cognitive Emotion Regulation Questionnaire (CERQ), respectively. A cognitive reappraisal task using the International Affective Picture System (IAPS) was designed for functional magnetic resonance imaging (fMRI) experiments. Cognitive reappraisal induced more activities in the bilateral inferior parietal lobes and bilateral middle temporal gyri compared to the condition of "look" (false discovery rate (FDR) corrected p < 0.05). Furthermore, the left inferior parietal lobe and right middle temporal gyrus functionally interacted with components of the default mode network, including the precuneus and the posterior cingulate cortex. In residual analyses after controlling for age and depressive symptoms, the bilateral inferior parietal and middle temporal activities exhibited positive correlations with cognitive reappraisal abilities (all ps < 0.05), and emotional maltreatment experiences were negatively correlated with the left inferior parietal cortex, bilateral middle temporal cortex activities, and left inferior parietal lobe-posterior cingulate cortex connectivity (all ps < 0.05). We found that semantic networks were significant to cognitive reappraisal, especially reinterpretation, and negative effects of emotional maltreatment experiences on semantic network activities.

Partial and Total Sleep Deprivation Interferes With Neural Correlates of Consolidation of Fear Extinction Memory.

BACKGROUND: We assessed the impact of total and partial sleep loss on neural correlates of fear conditioning, extinction learning, and extinction recall in healthy young adults. METHODS: Participants (56.3% female, age 24.8 ± 3.4 years) were randomized to a night of normal sleep (NS) (n = 48), sleep restriction (SR) (n = 53), or sleep deprivation (SD) (n = 53). All completed fear conditioning and extinction learning phases the following morning. Extinction recall was tested in the evening of the same day. Task-based contrasts were modeled at the beginning of, at the end of, and across the fear conditioning and extinction learning phases, and at the beginning of extinction recall. These contrasts were compared among the 3 groups by means of analysis of variance. Nonparametric permutation corrected analyses using a cluster-determining threshold of p < .005 and a familywise error of p < .05. RESULTS: At the end of fear conditioning, NS activated medial prefrontal regions, SR activated motor areas, and participants in the SD group showed no significant activations. Across extinction learning, only NS activated both salience (fear) and extinction (regulatory) areas. For extinction recall, SD activated similar regions as NS across extinction learning, while SR activated salience and motor areas. During early fear conditioning, compared with NS, SD activated more medial prefrontal and SR activated more salience network areas. For extinction recall, NS activated more prefrontal areas and SD activated more of both salience- and extinction-related areas than SR. CONCLUSIONS: Relative to NS, SR may enhance fear-related and diminish extinction-related activity, whereas SD may delay engagement of extinction learning. Findings may have clinical implications for populations and occupations in which sleep loss is common.

Gadolinium-Based Neuroprognostic Magnetic Resonance Imaging Agents Suppress COX-2 for Prevention of Reperfusion Injury after Stroke.

Advancements in recanalization therapies have rendered reperfusion injury an important challenge for stroke management. It is essential to work toward effective therapeutics that protect the ischemic brain from reperfusion injury. Here, we report a new concept of neuroprognostic agents, which combine molecular diagnostic imaging and targeted neuroprotection for treatment of reperfusion injury after stroke. These neuroprognostic agents are inflammation-targeted gadolinium compounds conjugated with nonsteroidal anti-inflammatory drugs (NSAIDs). Our results demonstrated that gadolinium-based MRI contrast agents conjugated with NSAIDs suppressed the increase in cyclooxygenase-2 (COX-2) levels, ameliorated glial activation, and neuron damage that are phenotypic for stroke by mitigating neuroinflammation, which prevented reperfusion injury. In addition, this study showed that the neuroprognostic agents are promising T1 molecular MRI contrast agents for detecting precise reperfusion injury locations at the molecular level. Our results build on this new concept of neuroprognostics as a novel management strategy for ischemia-reperfusion injury, combining neuroprotection and molecular diagnostics.

The neural correlates of thought-action fusion in healthy adults: A functional magnetic resonance imaging study.

BACKGROUND: Thought-action fusion (TAF) represents an individual's belief that a thought is like action. Inflated TAF has been considered a central mechanism for developing obsessive thoughts. However, the neural mechanisms underlying TAF are yet unknown. METHODS: We recruited 32 healthy men to participate in a functional magnetic resonance imaging (fMRI) study. Whereas inside the 3T MRI scanner, participants were asked to read negative statements describing the expectation of bad events associated with close persons (CPs condition) or neutral persons (NPs condition). They also completed the assessment of TAF and obsessive-compulsive (OC) symptoms. RESULTS: Both CP and NP conditions commonly activated the lingual gyrus, caudate nucleus, precuneus, and several areas of the frontal cortex. Importantly, many of these regions were positively correlated with measures of OC symptoms, especially for the CP condition. The CP condition showed higher activation in the insula and temporal gyrus than the NP condition. In contrast, the NP condition evoked higher activation in regions associated with mentalizing, such as the medial prefrontal cortex and dorsal anterior cingulate cortex than the CP condition. CONCLUSIONS: We introduced and validated a TAF-induction paradigm suitable for fMRI studies and characterized the neural circuits engaged during this paradigm. Further studies using this task may help us to better understand how dysfunctions in TAF neural processing may contribute to psychiatric conditions such as obsessive-compulsive disorder.

Diffusion tensor imaging and voxel-based morphometry reveal corticospinal tract involvement in the motor dysfunction of adult-onset myotonic dystrophy type 1.

Magnetic resonance imaging (MRI) studies have demonstrated that patients with myotonic dystrophy type 1 (DM1) exhibit gray and white matter abnormalities that are correlated with various genetic and neuropsychological measures. However, few MRI studies have focused on the correlations between brain abnormalities and overall motor function including gait performance. Here, we investigated the correlations between brain abnormalities, as assessed with MRI including diffusion tensor imaging (DTI), and motor performance, as assessed with the Medical Research Council sum score (MRCSS), 6-minute walk test (6MWT), and hand grip power, in patients with DM1. Eighteen patients with DM1 and twenty healthy controls participated in this study. The MRCSS and 6MWT reflect patients' general motor performance, particularly gait, while hand grip reflects the presence of myotonia. We found significant relationships between DTI parameters in the corticospinal tract (CST) and genetic factors and motor performance in patients with DM1. These findings suggest that CST involvement reflecting deterioration of the motor tracts may play a significant role in clinical myotonia. Further, a direct relationship between the cortical gray matter volume and DTI measures in the CST suggests that white matter abnormalities in the CST are strongly associated with volume reductions in the sensorimotor cortex of patients with DM1.

Delayed fear extinction in individuals with insomnia disorder.

Study Objectives: Insomnia increases the risk for anxiety disorders that are also associated with fear-extinction deficits. We compared activation of fear and extinction networks between insomnia disorder (ID) without comorbidity and good sleepers (GS). Methods: Twenty-three ID participants age- and sex-matched to 23 GS participants completed 14 days of actigraphy and diaries, three nights of ambulatory polysomnography and a 2-day fear conditioning and extinction paradigm. Fear conditioning and extinction learning occurred on the first day, followed 24 hours later by extinction recall. Blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) signal and skin conductance responses (SCR) were recorded. Nineteen participants per group produced usable fMRI data. Beta weights from areas where activation differed between groups were regressed against sleep and psychophysiological measures. SCR was compared between groups at various stages of the paradigm. Results: During fear conditioning, both ID (N = 19) and GS (N = 19) activated fear-related structures. Across extinction learning, ID (N = 19) demonstrated little change, whereas GS (N = 16) activated both fear and extinction-related areas, including the hippocampus, insula, dorsal anterior cingulate (dACC), and ventromedial prefrontal (vmPFC) cortices. During extinction recall, while GS (N = 17) demonstrated limited activation, ID (N = 16) activated regions similar to those previously activated in GS (vmPFC, dACC, insula). Sleep quality was predictive of activations seen at various stages of the paradigm. SCR data suggested ID were more physiologically reactive than GS. Conclusions: Across extinction learning, GS but not ID activated both fear and extinction-related networks. At extinction recall, ID engaged similar regions whereas GS no longer did so. Individuals with ID may show a delayed acquisition of fear extinction memories.

Altered power spectral density in the resting-state sensorimotor network in patients with myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a multisystemic disease that involves the brain with several neurological symptoms. Although there were few imaging studies on DM1, no studies have investigated functional alterations in the sensorimotor network at rest in patients with DM1. In the current study, a power spectral density (PSD) analysis of resting-state fMRI data was performed to assess possible alteration in spontaneous neural activity of the sensorimotor network in patients with DM1. Compared to healthy controls, patients with DM1 showed higher PSD responses in the orbitofrontal cortex, parahippocampus and basal ganglia (corrected P < 0.05). Patients with DM1 showed higher PSD responses in white matter structures associated with motor function (corrected P < 0.05). Furthermore, correlation analysis indicated that the brain regions showing PSD differences were correlated with measures of motor performance (P < 0.05). In gray matter, our findings suggest that motor disability in DM1 is not an isolated deterioration of the motor power but a multimodal dysfunction that also involves the visual system. In addition, the widespread PSD alteration in white matter structures suggest that motor deficits in DM1 involve motor movement structures as well as structures important for its coordination and regulation.

Skin Conductance Responses and Neural Activations During Fear Conditioning and Extinction Recall Across Anxiety Disorders.

Importance: The fear conditioning and extinction neurocircuitry has been extensively studied in healthy and clinical populations, with a particular focus on posttraumatic stress disorder. Despite significant overlap of symptoms between posttraumatic stress disorder and anxiety disorders, the latter has received less attention. Given that dysregulated fear levels characterize anxiety disorders, examining the neural correlates of fear and extinction learning may shed light on the pathogenesis of underlying anxiety disorders. Objectives: To investigate the psychophysiological and neural correlates of fear conditioning and extinction recall in anxiety disorders and to document how these features differ as a function of multiple diagnoses or anxiety severity. Design, Setting, and Participants: This investigation was a cross-sectional, case-control, functional magnetic resonance imaging study at an academic medical center. Participants were healthy controls and individuals with at least 1 of the following anxiety disorders: generalized anxiety disorder, social anxiety disorder, specific phobia, and panic disorder. The study dates were between March 2013 and May 2015. Exposures: Two-day fear conditioning and extinction paradigm. Main Outcomes and Measures: Skin conductance responses, blood oxygenation level-dependent responses, trait anxiety scores from the State Trait Anxiety Inventory-Trait Form, and functional connectivity. Results: This study included 21 healthy controls (10 women) and 61 individuals with anxiety disorders (36 women). P values reported for the neuroimaging results are all familywise error corrected. Skin conductance responses during extinction recall did not differ between individuals with anxiety disorders and healthy controls (ηp2 = 0.001, P = .79), where ηp2 is partial eta squared. The anxiety group had lower activation of the ventromedial prefrontal cortex (vmPFC) during extinction recall (ηp2 = 0.178, P = .02). A similar hypoactive pattern was found during early conditioning (ηp2 = 0.106, P = .009). The vmPFC hypoactivation was associated with anxiety symptom severity (r = -0.420, P = .01 for conditioning and r = -0.464, P = .004 for extinction recall) and the number of co-occuring anxiety disorders diagnosed (ηp2 = 0.137, P = .009 for conditioning and ηp2 = 0.227, P = .004 for extinction recall). Psychophysiological interaction analyses revealed that the fear network connectivity differed between healthy controls and the anxiety group during fear learning (ηp2 range between 0.088 and 0.176 and P range between 0.02 and 0.003) and extinction recall (ηp2 range between 0.111 and 0.235 and P range between 0.02 and 0.002). Conclusions and Relevance: Despite no skin conductance response group differences during extinction recall, brain activation patterns between anxious and healthy individuals differed. These findings encourage future studies to examine the conditions longitudinally and in the context of treatment trials to improve and guide therapeutics via advanced neurobiological understanding of each disorder.

Association of Resting Metabolism in the Fear Neural Network With Extinction Recall Activations and Clinical Measures in Trauma-Exposed Individuals.

OBJECTIVE: Exposure-based therapy, an effective treatment for posttraumatic stress disorder (PTSD), relies on extinction learning principles. In PTSD patients, dysfunctional patterns in the neural circuitry underlying fear extinction have been observed using resting-state or functional activation measures. It remains undetermined whether resting activity predicts activations during extinction recall or PTSD symptom severity. Moreover, it remains unclear whether trauma exposure per se affects resting activity in this circuitry. The authors employed a multimodal approach to examine the relationships among resting metabolism, clinical symptoms, and activations during extinction recall. METHOD: Three cohorts were recruited: PTSD patients (N=24), trauma-exposed individuals with no PTSD (TENP) (N=20), and trauma-unexposed healthy comparison subjects (N=21). Participants underwent a resting positron emission tomography scan 4 days before a functional MRI fear conditioning and extinction paradigm. RESULTS: Amygdala resting metabolism negatively correlated with clinical functioning (as measured by the Global Assessment of Functioning Scale) in the TENP group, and hippocampal resting metabolism negatively correlated with clinical functioning in the PTSD group. In the PTSD group, dorsal anterior cingulate cortex (dACC) resting metabolism positively correlated with PTSD symptom severity, and it predicted increased dACC activations but decreased hippocampal and ventromedial prefrontal cortex activations during extinction recall. The TENP group had lower amygdala resting metabolism compared with the PTSD and healthy comparison groups, and it exhibited lower hippocampus resting metabolism relative to the healthy comparison group. CONCLUSIONS: Resting metabolism in the fear circuitry correlated with functioning, PTSD symptoms, and extinction recall activations, further supporting the relevance of this network to the pathophysiology of PTSD. The study findings also highlight the fact that chronic dysfunction in the amygdala and hippocampus is demonstrable in PTSD and other trauma-exposed individuals, even without exposure to an evocative stimulus.

Contribution of estradiol levels and hormonal contraceptives to sex differences within the fear network during fear conditioning and extinction.

BACKGROUND: Findings about sex differences in the field of fear conditioning and fear extinction have been mixed. At the psychophysiological level, sex differences emerge only when taking estradiol levels of women into consideration. This suggests that this hormone may also influence sex differences with regards to activations of brain regions involved in fear conditioning and its extinction. Importantly, the neurobiological correlates associated with the use of hormonal oral contraceptives in women have not been fully contrasted against men and against naturally cycling women with different levels of estradiol. In this study, we begin to fill these scientific gaps. METHODS: We recruited 37 healthy men and 48 healthy women. Of these women, 16 were using oral contraceptives (OC) and 32 were naturally cycling. For these naturally cycling women, a median split was performed on their serum estradiol levels to create a high estradiol (HE) group (n = 16) and a low estradiol (LE) group (n = 16). All participants underwent a 2-day fear conditioning and extinction paradigm in a 3 T MR scanner. Using the 4 groups (men, HE women, LE women, and OC users) and controlling for age and coil type, one-way ANCOVAs were performed to look at significant activations within the nodes of the fear circuit. Using post-hoc analyses, beta-weights were extracted in brain regions showing significant effects in order to unveil the differences based on hormonal status (men, HE, LE, OC). RESULTS: Significant main effect of hormonal status group was found across the different phases of the experiment and in different sub-regions of the insular and cingulate cortices, amygdala, hippocampus, and hypothalamus. During conditioning, extinction and recall, most of the observed differences suggested higher activations among HE women relative to men. During the unconditioned response, however, a different pattern was observed with men showing significantly higher brain activations. CONCLUSIONS: Our data further support the important contribution of estradiol levels in the activation of brain regions underlying fear learning and extinction. The results highlight the need to document gonadal hormonal levels, menstrual cycle phase as well as oral contraceptive use in women in order to avoid overlooking sex differences when investigating the neurobiology of emotional regulation.