Activity In Anterior Cingulate Cortex Research Articles

Alterations in brain activation patterns in women with functional defecatory disorder: A novel fMRI rectal balloon expulsion study.

Functional defecatory disorders (FDD) are common among women. Despite the extensive research on peripheral mechanisms involved in FDD, the central-neural contribution to its pathophysiology remains poorly understood. We aimed to delineate specific supra-spinal regions involved in defecation and examine whether their activity, as measured by blood-oxygen-level-dependent (BOLD) signals, is different in FDD. We performed functional MRI (fMRI) with concurrent rectal manometry in 15 controls and 18 females with ROME III diagnosis of FDD. A block design was used and brain activation maps based on BOLD effect employing the generalized linear model were calculated for each subject. Statistical significance between groups was assessed by a Student t-test with cluster-based multiple comparisons correction (corrected p<0.01). Simulated defecation was associated with activation of regions of primary and supplementary motor (SMA) and somatosensory cortices, homeostatic afferent (thalamus, mid-cingulate cortex, and insula), and emotional arousal networks (hippocampus and prefrontal cortex), occipital and cerebellum along with deactivation of right anterior cingulate cortex (ACC) in controls. Women with FDD had fewer regions engaged in defecation and BOLD activation was much decreased is areas related to executive-cognitive function (insula, parietal, and prefrontal cortices). Patients unlike controls showed activation in right ACC and otherwise had similar brain activation patterns during anal squeeze. Our results provide evidence that distinct differences exist in supra-spinal control of defecation in key regions of motivational-affective regulation and executive-cognitive function, in patients with FDD as compared to controls.

Forward planning driven by context-dependant conflict processing in anterior cingulate cortex

Cognitive control and forward planning in particular is costly, and therefore must be regulated such that the amount of cognitive resources invested is adequate to the current situation. However, knowing in advance how beneficial forward planning will be in a given situation is hard. A way to know the exact value of planning would be to actually do it, which would ab initio defeat the purpose of regulating planning, i.e. the reduction of computational and time costs. One possible solution to this dilemma is that planning is regulated by learned associations between stimuli and the expected demand for planning. Such learning might be based on generalisation processes that cluster together stimulus states with similar control relevant properties into more general control contexts. In this way, the brain could infer the demand for planning, based on previous experience with situations that share some structural properties with the current situation. Here, we used a novel sequential task to test the hypothesis that people use control contexts to efficiently regulate their forward planning, using behavioural and functional magnetic resonance imaging data. Consistent with our hypothesis, reaction times increased with trial-by-trial conflict, where this increase was more pronounced in a context with a learned high demand for planning. Similarly, we found that fMRI activity in the dorsal anterior cingulate cortex (dACC) increased with conflict, and this increase was more pronounced in a context with generally high demand for planning. Taken together, the results indicate that the dACC integrates representations of planning demand at different levels of abstraction to regulate planning in an efficient and situation-appropriate way.

Neural Mechanisms of Facial Emotion Recognition in Autism: Distinct Roles for Anterior Cingulate and dlPFC

ABSTRACT Objective The present study sought to measure and internally validate neural markers of facial emotion recognition (FER) in adolescents and young adults with ASD to inform targeted intervention. Method We utilized fMRI to measure patterns of brain activity among individuals with ASD (N = 21) and matched controls (CON; N = 20) 2 s prior to judgments about the identity of six distinct facial emotions (happy, sad, angry, surprised, fearful, disgust). Results Predictive modeling of fMRI data (support vector classification; SVC) identified mechanistic roles for brain regions that forecasted correct and incorrect identification of facial emotion as well as sources of errors over these decisions. BOLD signal activation in bilateral insula, anterior cingulate (ACC) and right dorsolateral prefrontal cortex (dlPFC) preceded accurate FER in both controls and ASD. Predictive modeling utilizing SVC confirmed the utility of ACC in forecasting correct decisions in controls but not ASD, and further indicated that a region within the right dlPFC was the source of a type 1 error signal in ASD (i.e. neural marker reflecting an impending correct judgment followed by an incorrect behavioral response) approximately two seconds prior to emotion judgments during fMRI. Conclusions ACC forecasted correct decisions only among control participants. Right dlPFC was the source of a false-positive signal immediately prior to an error about the nature of a facial emotion in adolescents and young adults with ASD, potentially consistent with prior work indicating that dlPFC may play a role in attention to and regulation of emotional experience.

Convergence between behavioral, neural, and self-report measures of cognitive control: The Frontal Systems Behavior Scale in bipolar disorder

The Frontal Systems Behavior Scale (FrSBe) is a self-report measure that assesses difficulties with cognitive and emotional control such as apathetic behavior, lack of inhibitory control, and executive dysfunction. Previous neuroimaging studies highlight the involvement of the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex (DLPFC) in these processes. In this study, we investigated whether there was convergence across subjective and objective measures of apathy, disinhibition, and executive dysfunction. Specifically, we studied whether ACC, OFC, and DLPFC activation during a modified version of the Multi-Source Interference Task (MSIT), is associated with FrSBe apathy, disinhibition, and executive dysfunction scores, in healthy controls (HC) and individuals with Bipolar Disorder (BD), who commonly exhibit difficulties in these domains. Individuals with BD (n = 31) and HCs (n = 31) with no current or past psychiatric illness completed the FrSBe and the MSIT during fMRI scanning. We investigated task-specific changes in the ACC, DLPFC, and OFC and their correlations with FrSBe apathy, disinhibition, and executive dysfunction subscale scores, respectively. Individuals with BD and the HC group demonstrated greater ACC, DLPFC, and OFC activation during MSIT interference conditions compared with non-interference conditions. Furthermore, there was a significant negative correlation between OFC activation and disinhibition scores, which remained significant after accounting for medication load. Together, these results demonstrate the FrSBe disinhibition subscale, in particular, can be a self-report measure that converges with behavioral and neural markers of disinhibition in BD.

An increase in spontaneous activity mediates visual habituation.

SUMMARYThe cerebral cortex is spontaneously active, but the function of this ongoing activity remains unclear. To test whether spontaneous activity encodes learned experiences, we measured the response of neuronal populations in mouse primary visual cortex with chronic two-photon calcium imaging during visual habituation to a specific oriented stimulus. We find that, during habituation, spontaneous activity increases in neurons across the full range of orientation selectivity, eventually matching that of evoked levels. This increase in spontaneous activity robustly correlates with the degree of habituation. Moreover, boosting spontaneous activity with two-photon optogenetic stimulation to the levels of visually evoked activity accelerates habituation. Our study shows that cortical spontaneous activity is linked to habituation, and we propose that habituation unfolds by minimizing the difference between spontaneous and stimulus-evoked activity levels. We conclude that baseline spontaneous activity could gate incoming sensory information to the cortex based on the learned experience of the animal.

Structural and Functional Neural Correlates of Treatment Response for Interpersonal Psychotherapy for Depressed Adolescents.

Precision medicine approaches hold tremendous promise to advance current clinical practice by providing information about which individuals will benefit from which treatments. This pilot study evaluated if baseline structure and function of the salience and emotion brain regions implicated in adolescent depression, specifically the amygdala and anterior cingulate cortex (ACC), predict response to Interpersonal Psychotherapy for Depressed Adolescents (IPT-A). Adolescents (n = 15; mean age = 14.5 (1.6); 80.0% female) diagnosed with a depressive disorder completed brain scans before the start of a 16 week trial of IPT-A. Clinical measures assessing depressive symptoms were completed before, during, and after a trial of therapy. Results show that at baseline, greater ACC activation in the context of an emotion-matching task and greater amygdala-ACC resting-state functional connectivity was related to greater improvement in depression symptoms. There was minimal evidence that brain structure predicted changes in depressive symptoms. The present study is the first to evaluate neural predictors of IPT-A response. While the results are preliminary, these findings suggest some avenues for future research to pursue in the hopes that more will benefit from treatment.

Prediction and action in cortical pain processing.

Predicting that a stimulus is painful facilitates action to avoid harm. But how distinct are the neural processes underlying the prediction of upcoming painful events vis-à-vis those taking action to avoid them? Here, we investigated brain activity as a function of current and predicted painful or nonpainful thermal stimulation, as well as the ability of voluntary action to affect the duration of upcoming stimulation. Participants performed a task which involved the administration of a painful or nonpainful stimulus (S1), which predicted an immediately subsequent very painful or nonpainful stimulus (S2). Pressing a response button within a specified time window during S1 either reduced or did not reduce the duration of the upcoming stimulation. Predicted pain increased activation in several regions, including anterior cingulate cortex (ACC), midcingulate cortex (MCC), and insula; however, activation in ACC and MCC depended on whether a meaningful action was performed, with MCC activation showing a direct relationship with motor output. Insula's responses for predicted pain were also modulated by potential action consequences, albeit without a direct relationship with motor output. These findings suggest that cortical pain processing is not specifically tied to the sensory stimulus, but instead, depends on the consequences of that stimulus for sensorimotor control of behavior.

Neighborhood Socioeconomic Disadvantage and the Neurobiology of Uncertainty in Traumatically Injured Adults

BackgroundIndividuals residing in more socioeconomically disadvantaged neighborhoods experience greater uncertainty through insecurity of basic needs such as food, employment, and housing, compared with more advantaged neighborhoods. Although the neurobiology of uncertainty has been less frequently examined in relation to neighborhood disadvantage, there is evidence that neighborhood disadvantage is associated with widespread neural alterations. MethodsRecently traumatically injured participants (n = 90) completed a picture anticipation task in the magnetic resonance imaging scanner, in which they viewed images presented in a temporally predictable or unpredictable manner. We investigated how neighborhood disadvantage (via area deprivation index [ADI]) was related to neural activation during anticipation and presentation of negative and neutral images after accounting for individual factors (i.e., age, gender, income, acute posttraumatic stress symptoms). ResultsThere was a significant interaction during the anticipation period such that higher ADI rankings were related to greater activation of the right anterior cingulate cortex to predictable versus unpredictable neutral stimuli. Although no other robust interactions emerged related to ADI, we note several novel simple effects of ADI during anticipation and presentation periods in the hippocampus and prefrontal, cingulate, and occipital cortices. ConclusionsTogether, these results may represent an adaptive response to predictable and/or negative stimuli, stemming from chronic exposure to socioeconomic-based uncertainties. Although effects were modest, future work should continue to examine pretrauma context on posttrauma outcomes. To better understand trauma outcomes, it is imperative that researchers consider the broader context in which trauma survivors reside.

A Functional Magnetic Resonance Imaging Study on Activation of Anterior Cingulate Cortex at Episode and Interictal Phases in Migraine

&lt;sec&gt; &lt;title&gt;Objective:&lt;/title&gt; By using amplitude of low-frequency fluctuations (ALFF) we have analyzed activationsin brain regions at different phases in migraineurs. &lt;/sec&gt; &lt;sec&gt; &lt;title&gt;Methods:&lt;/title&gt; Participants included 41 patients with migraine, 19 in episode and 22 in interictal phase, and 22 controls in the healthy condition. To analyze the brain function of patients and controls, ALFF was used for performing the post-processing in the resting state by scores of Montreal Cognitive Assessment (MoCA) scale, Mini-Mental State Examination (MMSE), Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D). &lt;/sec&gt; &lt;sec&gt; &lt;title&gt;Results:&lt;/title&gt; The comparison between groups of patients with migraine in the episode or interictal phases, and healthy controls showed that both episode and interictal migraine groups had the similar HAM-A and HAM-D scores (P &gt; 0.05), but higher than that in controls (P &lt; 0.01). For ALFF values of Episode and Interictal groups, the Montreal Neurological Institute (MNI) coordinates of the decreased ALFF were (−9, 42, 9), the voxel size = 215, including the bilateral anterior cingulate cortex (ACC), T =−4.15, without significant differences. Patients in Interictal group were with a stronger activation at MNI coordinates (12, 51, 12), in the bilateral ACC, voxel size = 90, T =3.87. &lt;/sec&gt; &lt;sec&gt; &lt;title&gt;Conclusion:&lt;/title&gt; ACC plays an adaptive, regulatory role in migraine and is related to multiple brain regions, which may mediate activation through descending anti-nociceptive pathways. ACC is related to opioid receptor and glutamate excitatory regulation. &lt;/sec&gt;

Nx4 attenuated stress-induced activity of the anterior cingulate cortex-A post-hoc analysis of a randomized placebo-controlled crossover trial.

Stress-related symptoms are associated with significant health and economic burden. Several studies suggest Nx4 for the pharmacological management of the stress response and investigated the underlying neural processes. Here we hypothesized that Nx4 can directly affect the stress response in a predefined stress network, including the anterior cingulate cortex (ACC), which is linked to various stress-related symptoms in patients. In a randomized, placebo-controlled, double-blind, crossover trial, 39 healthy males took a single dose of placebo or Nx4. Psychosocial stress was induced by the ScanSTRESS paradigm inside an MRI scanner, and stress network activation was analyzed in brain regions defined a priori. Using the placebo data only, we could validate the activation of a distinct neural stress pattern by the ScanSTRESS paradigm. For Nx4, we provide evidence of an attenuating effect on this stress response. A statistically significant reduction in differential stress-induced activation in the right supracallosal ACC was observed for the rotation stress task of the ScanSTRESS paradigm. The results add to previously published results of Nx4 effects on emotion regulation. Our results strengthen the hypothesis that Nx4 modulates the stress response by reducing the activation in parts of the neural stress network, particularly in the ACC. NCT02602275; ClinicalTrials.gov.

Neural Correlates of Attachment Representation in Patients With Borderline Personality Disorder Using a Personalized Functional Magnet Resonance Imaging Task.

BackgroundFear of abandonment and aloneness play a key role in the clinical understanding interpersonal and attachment-specific problems in patients with borderline personality disorder (BPD) and has been investigated in previous functional Magnet Resonance Imaging (fMRI) studies. The aim of the present study was to examine how different aspects of attachment representations are processed in BPD, by using for the first time an fMRI attachment paradigm including personalized core sentences from the participants’ own attachment stories. We hypothesized that BPD patients would show increased functional involvement of limbic brain regions associated with fear and pain (e.g., the amygdala and the anterior cingulate cortex) when presented personalized attachment relevant stimuli representing loneliness compared to healthy controls (HC).MethodsWe examined the attachment classifications of 26 female BPD patients and 26 female HC using the Adult Attachment Projective Picture System (AAP). We used an fMRI-adapted attachment paradigm to investigate the neural correlates of attachment. All participants were presented three personalized (vs. neutral) sentences extracted from their AAP attachment narrative, combined with standardized AAP pictures representing being alone (monadic) or in interactive (dyadic) attachment situations.ResultsAs expected, the classification of unresolved attachment was significantly greater in BPD compared to HC. BPD patients showed increased fMRI-activation in brain areas associated with fear, pain, and hyperarousal than HC when presented with personalized attachment-relevant alone stimuli. In particular, pictures with monadic attachment situations induced greater anterior medial cingulate cortex, anterior insula, amygdala, thalamus and superior temporal gyrus activation in the patient group.ConclusionThe results point to increased fMRI-activation in areas processing emotional distress and painful experiences in BPD patients. In particular, the emotional cascade reflecting attachment distress was evoked by combining monadic pictures, representing abandonment and aloneness, with the patients’ personalized narrative material. Our results confirmed and replicated previous results that illustrate once again the high relevance of aloneness and feelings of abandonment for BPD in the context of attachment trauma. Moreover, our results support the hypothesis of hypermentalization in response to attachment distress as a core feature of social-cognitive impairment in BPD associated with common treatment implications across different therapeutic orientations.

Experimental evidence for a child-to-adolescent switch in human amygdala-prefrontal cortex communication: A cross-sectional pilot study.

Interactions between the amygdala and prefrontal cortex are fundamental to human emotion. Despite the central role of frontoamygdala communication in adult emotional learning and regulation, little is known about how top-down control emerges during human development. In the present cross-sectional pilot study, we experimentally manipulated prefrontal engagement to test its effects on the amygdala during development. Inducing dorsal anterior cingulate cortex (dACC) activation resulted in developmentally-opposite effects on amygdala reactivity during childhood versus adolescence, such that dACC activation was followed by increased amygdala reactivity in childhood but reduced amygdala reactivity in adolescence. Bayesian network analyses revealed an age-related switch between childhood and adolescence in the nature of amygdala connectivity with the dACC and ventromedial PFC (vmPFC). Whereas adolescence was marked by information flow from dACC and vmPFC to amygdala (consistent with that observed in adults), the reverse information flow, from the amygdala to dACC and vmPFC, was dominant in childhood. The age-related switch in information flow suggests a potential shift from bottom-up co-excitatory to top-down regulatory frontoamygdala connectivity and may indicate a profound change in the circuitry supporting maturation of emotional behavior. These findings provide novel insight into the developmental construction of amygdala-cortical connections and implications for the ways in which childhood experiences may influence subsequent prefrontal function.

Altered reward and effort processing in children with maltreatment experience: a potential indicator of mental health vulnerability

In this longitudinal study of children and adolescents with a documented history of maltreatment, we investigated the impact of maltreatment on behavioral and neural indices of effort-based decision making for reward and examined their associations with future internalizing symptoms. Thirty-seven children with a documented history of maltreatment (MT group) and a carefully matched group of 33 non-maltreated children (NMT group) aged 10–16, completed an effort-based decision-making task during functional magnetic resonance imaging (fMRI). Internalizing symptoms were assessed at baseline and again 18 months later. Computational models were implemented to extract individual estimates of reward and effort sensitivity, and neural signals during decision-making about different levels of reward and effort were analyzed. These were used to predict internalizing symptoms at follow-up. We identified lower effort-related activation in the anterior cingulate cortex (ACC), a prespecified region-of-interest, in the MT relative to the NMT group. No group differences were observed in the striatum, or in behavioral indices of reward and effort processing. Lower effort-related ACC activation significantly predicted elevated internalizing symptoms at follow-up in the MT group. These findings suggest that disrupted effort-related activation may index latent vulnerability to mental illness in children who have experienced maltreatment.

Relationship between infantile mother preference and neural regions activated by maternal contact in C57BL/6 mice

Mutual attachment between mother and pup is important to enable the mother to care for her pup and for the pup to receive care from its mother. Pups eventually leave their mothers, which is also very important to their growth. The mechanism of preference by which pups transfer attachment from their mother to others remains unknown. In this study, we assessed mother/novel dam preferences and examined the brain regions associated with the regulation of this preference in C57BL/6 mice pups. We found that C57BL/6 mice pups had variety in their mother/novel dam preferences at 16 days old. This variety was not related to the sex of the pups, their weight, or the litter size. In order to clarify the brain mechanisms responsible for this variety, we examined the relationship between mother/novel dam preference and neuronal activation induced by contact with the mother. We found that pups exhibiting novel dam preference had higher neural activity in the anterior cingulate cortex (ACC) and bed nucleus of the stria terminalis (BNST) when exposed to their mother. These results suggest that ACC and/or BNST neural activity may be associated with mother/novel dam preferences in infant mice.

Brain activity during pursuit and goal-conflict threat avoidance in major depressive disorder.

Threat avoidance is a prominent symptom of affective disorders, yet its biological basis remains poorly understood. Here, we used a validated task, the Joystick Operated Runway Task (JORT), combined with fMRI, to explore whether abnormal function in neural circuits responsible for avoidance underlies these symptoms. Eighteen individuals with major depressive disorder (MDD) and 17 unaffected controls underwent the task, which involved using physical effort to avoid threatening stimuli, paired with mild electric shocks on certain trials. Activity during anticipation and avoidance of threats was explored and compared between groups. Anticipation of aversive stimuli was associated with significant activation in the dorsal anterior cingulate cortex, superior frontal gyrus, and striatum, while active avoidance of aversive stimuli was associated with activity in dorsal anterior cingulate cortex, insula, and prefrontal cortex. There were no significant group differences in neural activity or behavioral performance on the JORT; however, participants with depression reported more dread while being chased on the task. The JORT effectively identified neural systems involved in avoidance and anticipation of aversive stimuli. However, the absence of significant differences in behavioral performance and activation between depressed and non-depressed groups suggests that MDD is not associated with abnormal function in these networks. Future research should investigate the basis of passive avoidance in major depression. Further, the JORT should be explored in patients with anxiety disorders, where threat avoidance may be a more prominent characteristic of the disorder.

Hemodynamic activity in the limbic system predicts reoffending in women

Previous research (Aharoni et al., 2013, 2014) found that hemodynamic activity in the dorsal anterior cingulate cortex (dACC) during error monitoring predicted non-violent felony rearrest in men released from prison. This article reports an extension of the Aharoni et al. (2013, 2014) model in a sample of women released from state prison (n = 248). Replicating aspects of prior work, error monitoring activity in the dACC, as well as psychopathy scores and age at release, predicted non-violent felony rearrest in women. Sex differences in the directionality of dACC activity were observed—high error monitoring activity predicted rearrest in women, whereas prior work found low error monitoring activity predicted rearrest in men. As in prior analyses, the ability of the dACC to predict rearrest outcomes declines with more generalized outcomes (i.e., general felony). Implications for future research and clinical and forensic risk assessment are discussed.

Electrophysiological correlates and predictors of the antidepressant response to repeated ketamine infusions in treatment-resistant depression

BackgroundSub-anesthetic ketamine doses rapidly reduce depressive symptoms, although additional investigations of the underlying neural mechanisms and the prediction of response outcomes are needed. Electroencephalographic (EEG)-derived measures have shown promise in predicting antidepressant response to a variety of treatments, and are sensitive to ketamine administration. This study examined their utility in characterizing changes in depressive symptoms following single and repeated ketamine infusions. MethodsRecordings were obtained from patients with treatment-resistant major depressive disorder (MDD) (N = 24) enrolled in a multi-phase clinical ketamine trial. During the randomized, double-blind, crossover phase (Phase 1), patients received intravenous ketamine (0.5 mg/kg) and midazolam (30 μg/kg), at least 1 week apart. For each medication, three resting, eyes-closed recordings were obtained per session (pre-infusion, immediately post-infusion, 2 h post-infusion), and changes in power (delta, theta1/2/total, alpha1/2/total, beta, gamma), alpha asymmetry, theta cordance, and theta source-localized anterior cingulate cortex activity were quantified. The relationships between ketamine-induced changes with early (Phase 1) and sustained (Phases 2,3: open-label repeated infusions) decreases in depressive symptoms (Montgomery-Åsberg Depression Rating Score, MADRS) and suicidal ideation (MADRS item 10) were examined. ResultsBoth medications decreased alpha and theta immediately post-infusion, however, only midazolam increased delta (post-infusion), and only ketamine increased gamma (immediately post- and 2 h post-infusion). Regional- and frequency-specific ketamine-induced EEG changes were related to and predictive of decreases in depressive symptoms (theta, gamma) and suicidal ideation (alpha). Early and sustained treatment responders differed at baseline in surface-level and source-localized theta. ConclusionsKetamine exerts frequency-specific changes on EEG-derived measures, which are related to depressive symptom decreases in treatment-resistant MDD and provide information regarding early and sustained individual response to ketamine.Clinical Trial Registration: ClinicalTrials.gov: Action of Ketamine in Treatment-Resistant Depression, NCT01945047

Neural processing associated with cognitive empathy in pedophilia and child sexual offending.

Behavioral studies found evidence for superior cognitive empathy (CE) in pedophilic men without a history of child sexual offending (P − CSO) compared to pedophilic men with a history of child sexual offending (P + CSO). Functional magnetic resonance imaging (fMRI) studies also point to differences between P − CSO and P + CSO. Neural processing associated with CE has not yet been investigated. Therefore, the present study aimed to explore the neural correlates of CE in subjects with pedophilia with (P + CSO) and without (P − CSO) child sexual offending. 15 P + CSO, 15 P − CSO and 24 teleiophilic male controls (TC) performed a CE task during fMRI. We observed reduced activation in the left precuneus (Pcu) and increased activation in the left anterior cingulate cortex (ACC) in P − CSO compared to P + CSO. P − CSO also showed stronger connectivity between these regions, which might reflect a top-down modulation of the Pcu by the ACC toward an increased self-focused emotional reaction in social situations. There was also evidence for increased right superior temporal gyrus activation in P − CSO that might constitute a potentially compensatory recruitment due to the dampened Pcu activation. These findings provide first evidence for altered neural processing of CE in P − CSO and underline the importance of addressing CE in pedophilia and CSO in order to uncover processes relevant to effective prevention of child sexual abuse.

Suppressed activity of the rostral anterior cingulate cortex as a biomarker for depression remission.

Suppression of the rostral anterior cingulate cortex (rACC) has shown promise as a prognostic biomarker for depression. We aimed to use machine learning to characterise its ability to predict depression remission. Data were obtained from 81 15- to 25-year-olds with a major depressive disorder who had participated in the YoDA-C trial, in which they had been randomised to receive cognitive behavioural therapy plus either fluoxetine or placebo. Prior to commencing treatment patients performed a functional magnetic resonance imaging (fMRI) task to assess rACC suppression. Support vector machines were trained on the fMRI data using nested cross-validation, and were similarly trained on clinical data. We further tested our fMRI model on data from the YoDA-A trial, in which participants had completed the same fMRI paradigm. Thirty-six of 81 (44%) participants in the YoDA-C trial achieved remission. Our fMRI model was able to predict remission status (AUC = 0.777 [95% confidence interval (CI) 0.638-0.916], balanced accuracy = 67%, negative predictive value = 74%, p < 0.0001). Clinical models failed to predict remission status at better than chance levels. Testing the model on the alternative YoDA-A dataset confirmed its ability to predict remission (AUC = 0.776, balanced accuracy = 64%, negative predictive value = 70%, p < 0.0001). We confirm that rACC activity acts as a prognostic biomarker for depression. The machine learning model can identify patients who are likely to have difficult-to-treat depression, which might direct the earlier provision of enhanced support and more intensive therapies.

Investigating the Roles of Anterior Cingulate in Behavioral Variant Frontotemporal Dementia: A PET/MRI Study.

Background:The anterior cingulate cortex (ACC) seems to play an important role in behavioral deficits and executive dysfunctions in patients with behavioral variant frontotemporal dementia (bvFTD), while its specific and independent contribution requires clarification.Objective:To identify whether ACC abnormalities in gray matter (GM) volume and standardized uptake value ratio (SUVR) images are associated with disease severity of bvFTD, by analyzing hybrid T1 and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET).Methods:We enrolled 21 bvFTD patients and 21 healthy controls in the study. Each subject underwent a hybrid PET/MRI study and a standardized neuropsychologic assessment battery. GM volume and SUVR are voxel-wise calculated and compared. Then we estimate the mean value inside ACC for further partial Pearson’s correlation to explore the association between GM volume/SUVR of the ACC and severity of behavioral deficit as well as executive dysfunction.Results:ACC was shown to be involved in both atrophy and hypometabolism patterns. The partial Pearson’s correlation analysis showed that the SUVR of the ACC was strongly correlated with frontal behavior inventory total score (left r = –0.85, right r = –0.85, p < 0.0001), disinhibition subscale score (left r = –0.72, p = 0.002; right = –0.75, p < 0.0001), and apathy subscale score (left = –0.87, right = –0.85, p < 0.0001).Conclusion:These findings demonstrated decreased ACC activity contributes to behavioral disturbances of both apathetic and disinhibition syndromes of bvFTD, which can be sensitively detected using 18F-FDG PET.