Perception of family functioning and depressive symptomatology in individuals with anorexia nervosa or bulimia nervosa

This study investigated the relationship between the perception of family functioning and depressive symptomatology in individuals with eating disorders (EDs). Subjects were evaluated by diagnostic clinical interview using DSM-III-R criteria for EDs, the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L), and two self-report measures, the Beck Depression Inventory (BDI) and the Family Assessment Device (FAD). A significant association was found between self-reported depressive symptomatology and perceived poor family functioning. Subjects with bulimia nervosa (BN) reported a significantly more dysfunctional family background than subjects with anorexia nervosa (AN). In our sample, the presence of self-reported depressive symptomatology was a more powerful predictive variable for perceived family dysfunction than the diagnosis of affective disorder. Also, the diagnosis of BN was a more consistent predictor of dysfunctional family interaction than the diagnosis of affective disorder. Depressive symptoms and EDs seem to play different roles in the way in which they contribute to dysfunctional family patterns.     

Neural responses to negative feedback are related to negative emotionality in healthy adults

Prior neuroimaging and electrophysiological evidence suggests that potentiated responses in the anterior cingulate cortex (ACC), particularly the rostral ACC, may contribute to abnormal responses to negative feedback in individuals with elevated negative affect and depressive symptoms. The feedback-related negativity (FRN) represents an electrophysiological index of ACC-related activation in response to performance feedback. The purpose of the present study was to examine the FRN and underlying ACC activation using low resolution electromagnetic tomography source estimation techniques in relation to negative emotionality (a composite index including negative affect and subclinical depressive symptoms). To this end, 29 healthy adults performed a monetary incentive delay task while 128-channel event-related potentials were recorded. We found that enhanced FRNs and increased rostral ACC activation in response to negative-but not positive-feedback was related to greater negative emotionality. These results indicate that individual differences in negative emotionality-a putative risk factor for emotional disorders-modulate ACC-related processes critically implicated in assessing the motivational impact and/or salience of environmental feedback.     

Anterior cingulate subregion volumes and executive function in bipolar disorder

OBJECTIVE: Although research findings suggest a relationship between the function of anterior cingulate cortex (ACC) and both cognitive ability and the pathophysiology of bipolar disorder (BPD), few studies have examined cognitive correlates of specific ACC subregion volumes in BPD. Therefore, the primary aim of this study was to examine the relationship between magnetic resonance imaging (MRI)-derived gray and white matter volumes of ACC subregions (caudal, rostral, and subgenual) and performance on tests of executive function in 27 patients with BPD and 22 healthy subjects. METHODS: 1.5T MRI and neuropsychological assessment were conducted with all participants. RESULTS: MANCOVA revealed statistically significant group differences in performance on executive function measures. However, no group differences were observed in any of the ACC white matter or gray matter regions of interest. Multiple regression analyses revealed that rostral and subgenual gray matter each interacted significantly with group in predicting performance on the Wisconsin Card Sorting Test. In addition, a significant interaction was observed between group and both rostral gray and white matter in predicting performance on the Trail Making Test. CONCLUSIONS: The results of this preliminary study support the extant literature that suggests that patients with BPD perform more poorly than healthy subjects on tests of executive function. Furthermore, the relationship between ACC subregion volumes and cognitive test performance was found to differ between patients with BPD and healthy subjects, despite comparable ACC volumes in the two groups.     

The timing of action-monitoring processes in the anterior cingulate cortex

The anterior cingulate cortex (ACC) has been shown to respond to conflict between simultaneously active, incompatible response tendencies. This area is active during high-conflict correct trials and also when participants make errors. Here, we use the temporal resolution of high-density event-related potentials (ERPs) in combination with source localization to investigate the timing of ACC activity during conflict and error detection. We predicted that the same area of the ACC is active prior to high-conflict correct responses and following erroneous responses. Dipole modeling supported this prediction: The frontocentral N2, occurring prior to the response on correct conflict trials, and the ERN, occurring immediately following error responses, could both be modeled as having a generator in the caudal ACC, suggesting the same process to underlie both peaks. Modeling further suggested that the rostral area of the ACC was also active following errors, but later in time, contributing to the error positivity (P(E)), and peaking at 200-250 msec following the ERN peak. Despite the inherent limitations of source localization, these data may begin to shed light on the timing of action-monitoring processes. First, the time course of caudal ACC activity follows the time course as predicted by the conflict theory of this region. Second, caudal ACC activity might be temporally dissociated from rostral ACC activity during error trials, which possibly reflects a separate, affective component of the evaluative functions of the ACC.     

The role of Area 10 (BA10) in human multitasking and in social cognition: a lesion study

A role for rostral prefrontal cortex (BA10) has been proposed in multitasking, in particular, the selection and maintenance of higher order internal goals while other sub-goals are being performed. BA10 has also been implicated in the ability to infer someone else's feelings and thoughts, often referred to as theory of mind. While most of the data to support these views come from functional neuroimaging studies, lesion studies are scant. In the present study, we compared the performance of a group of frontal patients whose lesions involved BA10, a group of frontal patients whose lesions did not affect this area (nonBA10), and a group of healthy controls on tests requiring multitasking and complex theory of mind judgments. Only the group with lesions involving BA10 showed deficits on multitasking and theory of mind tasks when compared with control subjects. NonBA10 patients performed more poorly than controls on an executive function screening tool, particularly on measures of response inhibition and abstract reasoning, suggesting that theory of mind and multitasking deficits following lesions to BA10 cannot be explained by a general worsening of executive function. In addition, we searched for correlations between performance and volume of damage within different subregions of BA10. Significant correlations were found between multitasking performance and volume of damage in right lateral BA10, and between theory of mind and total BA10 lesion volume. These findings stress the potential pivotal role of BA10 in higher order cognitive functions.     

Altered affective,executive and sensorimotor resting state networks in patients with pediatric mania

BackgroundThe aim of the present study was to map the pathophysiology of resting state functional connectivity accompanying structural and functional abnormalities in children with bipolar disorder.MethodsChildren with bipolar disorder and demographically matched healthy controls underwent resting-state functional magnetic resonance imaging. A model-free independent component analysis was performed to identify intrinsically interconnected networks.ResultsWe included 34 children with bipolar disorder and 40 controls in our analysis. Three distinct resting state networks corresponding to affective, executive and sensorimotor functions emerged as being significantly different between the pediatric bipolar disorder (PBD) and control groups. All 3 networks showed hyperconnectivity in the PBD relative to the control group. Specifically, the connectivity of the dorsal anterior cingulate cortex (ACC) differentiated the PBD from the control group in both the affective and the executive networks. Exploratory analysis suggests that greater connectivity of the right amygdala within the affective network is associated with better executive function in children with bipolar disorder, but not in controls.LimitationsUnique clinical characteristics of the study sample allowed us to evaluate the pathophysiology of resting state connectivity at an early state of PBD, which led to the lack of generalizability in terms of comorbid disorders existing in a typical PBD population.ConclusionAbnormally engaged resting state affective, executive and sensorimotor networks observed in children with bipolar disorder may reflect a biological context in which abnormal task-based brain activity can occur. Dual engagement of the dorsal ACC in affective and executive networks supports the neuroanatomical interface of these networks, and the amygdala’s engagement in moderating executive function illustrates the intricate interplay of these neural operations at rest.     

Trait anxiety modulates anterior cingulate activation to threat interference

Background: Individuals vary in the degree to which salient threatening stimuli disrupt or distract from goal‐directed cognitive processes. Excessive attention to threat or difficulty resolving the interference created by threat cues could contribute to anxious psychopathology; disruptions in frontal brain regions implicated in attentional control or resolution of emotional interference (e.g. anterior cingulate cortex, “ACC”) might play a role. In this study, we explored the hypothesis that trait anxiety would be associated with ACC activity in an attentional control task with varying levels of threat interference. Methods: During functional magnetic resonance imaging, 20 healthy individuals who varied in trait anxiety levels viewed angry, fearful, and neutral faces superimposed on an indoor or outdoor scene. In a high‐threat interference condition, subjects identified the gender of the face (Attend Face). In a low‐threat interference condition, they identified the scene type (Attend Scene). Whole‐brain analysis was used to compare Attend Face with Attend Scene for angry and fearful (versus neutral) faces. Contrasts were correlated with trait anxiety level. Results: Behavioral data confirmed that Attend Face produced greater threat interference than Attend Scene. Brain imaging results showed that trait anxiety was inversely associated with bilateral rostral ACC activity for Attend Face relative to Attend Scene for angry faces. A similar relationship was not seen for fearful faces. Conclusions: The rostral ACC is implicated in assessing the salience of emotional information and controlling attention to resolve emotional interference. The link between higher trait anxiety and decreased ACC activation for angry faces suggests reduced attentional control for signals of interpersonal threat in healthy anxiety‐prone individuals. Depression and Anxiety 28:194–201, 2011. © 2011 Wiley‐Liss, Inc.     

Covert auditory attention generates activation in the rostral/dorsal anterior cingulate cortex

The anterior cingulate cortex (ACC) is believed to mediate conscious information processing or high-capacity attention. However, previous functional imaging studies have largely relied on tasks that involve motor function as well as attention. The work from our group utilizing an auditory continuous performance task demonstrated increased activity in a caudal division of the ACC that borders the supplementary motor area (SMA). Activity in this region was attributed to motor responding as well as attention. In the present study, we used (15)O H(2)O positron emission tomography (PET) to map brain activation during nonmotor, covert auditory attention. Our hypothesis was that a different region within the ACC, anterior to the SMA, would be active during covert attention (CA). Six men and six women were asked to monitor aurally presented syllables presented at a 1-sec interstimulus interval. During the CA condition, subjects were asked to continuously discriminate target (.19 probability) from nontarget stimuli. Simultaneous recording of event-related potentials (ERPs) confirmed the discrimination of target and nontarget stimuli and the allocation of attention capacity. Comparison of the monitored versus nonmonitored presentation of stimuli demonstrated significant activity in a rostral/dorsal division of the right ACC, anterior to SMA. Other regions of activation included the lateral prefrontal cortex and posterior superior temporal gyrus in the left hemisphere, consistent with neurocognitive models of language and vigilance. We conclude that a rostral/dorsal subdivision of the right ACC is specific for conscious attention during auditory processing, in contrast to premotor response formation.     

Prefrontal cortical dysfunction in abstinent cocaine abusers

The anterior cingulate cortex (ACC) and lateral prefrontal (LPFC) cortex are brain regions important to executive cognitive functions (ECF). We determined ACC and LPFC function in 23-day abstinent cocaine abusers using positron emission tomography (PET H(2)(15)O) during performance of a modified version of the Stroop Task. Cocaine abusers showed less activation than non-drug-using comparison subjects in the left ACC and the right LPFC and greater activation in the right ACC. Average amount of cocaine used per week was negatively correlated with activity in the rostral ACC and right LPFC. Disruption of ECF in substance abusers could interfere with attempts to stop drug use and undermine treatment. Since impairment in ECF may be a common feature of various neuropsychiatric disorders, these findings have applicability beyond the neurobiology of addiction.     

A comparison of the symptoms of medical and psychiatric patients matched on the Beck Depression Inventory

The goals of this study were to examine, in greater detail, the experience of depression in the medically ill, and to compare their experience with that of depressed psychiatric patients. Medical and psychiatric inpatients were matched in terms of total scores on the Beck Depression Inventory (BDI). In addition to the BDI, all patients completed a self-report symptom battery. No difference was found between the two groups in terms of total BDI scores, but psychiatric patients scored significantly higher on the affective BDI items, and medical patients scored significantly higher on the somatic BDI items. Discriminant analysis was used to compare their responses to the symptom battery. Depression in the psychiatric patients was characterized primarily by suicidal ideation and loss of interest, whereas in medical patients a lack of energy and worry were the predominant symptoms. The implications of these findings for assessing depression in the medically ill are discussed.     

A preliminary study of the neural mechanisms of frustration in pediatric bipolar disorder using magnetoencephalography

Background: Irritability is prevalent and impairing in pediatric bipolar disorder (BD) but has been minimally studied using neuroimaging techniques. We used magnetoencephalography (MEG) to study theta band oscillations in the anterior cingulate cortex (ACC) during frustration in BD youth. ACC theta power is associated with attention to emotional stimuli, and the ACC may mediate responses to frustrating stimuli. Methods: We used the affective Posner task, an attention paradigm that uses rigged feedback to induce frustration, to compare 20 medicated BD youth (14.9±2.0 years; 45% male) and 20 healthy controls (14.7±1.7 years; 45% male). MEG measured neuronal activity after negative and positive feedback; we also compared groups on reaction time, response accuracy, and self‐reported affect. Patients met strict DSM‐IV BD criteria and were euthymic. Controls had no psychiatric history. Results: BD youth reported more negative affective responses than controls. After negative feedback, BD subjects, relative to controls, displayed greater theta power in the right ACC and bilateral parietal lobe. After positive feedback, BD subjects displayed lower theta power in the left ACC than did controls. Correlations between MEG, behavior, and affect were nonsignificant. Conclusion: In this first MEG study of BD youth, BD youth displayed patterns of theta oscillations in the ACC and parietal lobe in response to frustration‐inducing negative feedback that differed from healthy controls. These data suggest that BD youth may display heightened processing of negative feedback and exaggerated self‐monitoring after frustrating emotional stimuli. Future studies are needed with unmedicated bipolar youth, and comparison ADHD and anxiety groups. Depression and Anxiety, 2010. © 2009 Wiley‐Liss, Inc.     

Source localization (LORETA) of the error-related-negativity (ERN/Ne) and positivity (Pe)

We investigated error processing of 39 subjects engaging the Eriksen flanker task. In all 39 subjects a pronounced negative deflection (ERN/Ne) and a later positive component (Pe) were observed after incorrect as compared to correct responses. The neural sources of both components were analyzed using LORETA source localization. For the negative component (ERN/Ne) we found significantly higher brain electrical activity in medial prefrontal areas for incorrect responses, whereas the positive component (Pe) was localized nearby but more rostral within the anterior cingulate cortex (ACC). Thus, different neural generators were found for the ERN/Ne and the Pe, which further supports the notion that both error-related components represent different aspects of error processing.     

The role of the anterior cingulate cortex in emotional response inhibition

Although the involvement of the anterior cingulate cortex (ACC) in emotional response inhibition is well established, there are several outstanding issues about the nature of this involvement that are not well understood. The present study aimed to examine the precise contribution of the ACC to emotion-modulated response inhibition by capitalizing on fine temporal resolution of the event-related potentials (ERPs) and the recent advances in source localization. To this end, participants (N = 30) performed an indirect affective Go/Nogo task (i.e., unrelated to the emotional content of stimulation) that required the inhibition of a motor response to three types of visual stimuli: arousing negative (A-), neutral (N), and arousing positive (A+). Behavioral data revealed that participants made more commission errors to A+ than to N and A-. Electrophysiological data showed that a specific region of the ACC at the intersection of its dorsal and rostral subdivisions was significantly involved in the interaction between emotional processing and motor inhibition. Specifically, activity reflecting this interaction was observed in the P3 (but not in the N2) time range, and was greater during the inhibition of responses to A+ than to N and A-. Additionally, regression analyses showed that inhibition-related activity within this ACC region was associated with the emotional content of the stimuli (its activity increased as stimulus valence was more positive), and also with behavioral performance (both with reaction times and commission errors). The present results provide additional data for understanding how, when, and where emotion interacts with response inhibition within the ACC.     

Adaptive control deficits in attention-deficit/hyperactivity disorder (ADHD): the role of error processing

Cognitive performance of children with attention-deficit hyperactivity disorder (ADHD) is characterized by large moment-to-moment fluctuations in cognitive control reflected by a highly inconsistent and inaccurate response style. It has been suggested that abnormal error processing underlies this failure to implement adequate control. We investigated the error-related negativity (ERN), a negative deflection in the event-related potential (ERP) time-locked to erroneous responses in 16 rigorously screened ADHD boys aged 8-12 years and 16 age-matched normal control boys during a modified Eriksen flanker paradigm with two levels of time pressure. Children with ADHD responded as fast and regularly as controls, but committed significantly more errors, particularly when facing time pressure and response conflict. ADHD children produced shorter runs of correct responses than controls. In addition, with high time pressure, error runs were prolonged relative to control children, suggesting an increase in both frequency and magnitude of temporary lapses of control. ERP amplitude differences between correct and incorrect responses were diminished in ADHD children, whereas post-error slowing remained unaffected. This pattern of results indicates that a specific deficit in monitoring ongoing behaviour, rather than insufficient strategic adjustments, gave rise to performance limitations in ADHD. Findings are discussed in terms of anterior cingulate cortex (ACC) dysfunction, leading to a failure to predict the likelihood that an error occurs in a given context.     

Anterior cingulate cortex and the Stroop task: neuropsychological evidence for topographic specificity

Neuroimaging studies have implicated the anterior cingulate cortex (ACC) in many aspects of attention and cognition. Major theories of ACC function have proposed a role in conflict monitoring, executive control, response selection, and general arousal. Although the ACC is often treated as a unitary structure, extensive evidence suggests it exhibits anatomical and functional specificity. ACC activity during the Stroop color word interference task has been of particular interest. The purpose of the present study was to determine whether two different ACC subregions are necessary for intact color naming performance in the Stroop task. One experiment utilized blocked trial and mixed trial designs to emulate neuroimaging studies and to compare interference and facilitation effects, respectively. A third variant manipulated the probabilities of congruent and incongruent trials to alter levels of interference and cognitive control, or engagement of strategic processes, on a block by block basis. Two patients with focal lesions in either right mid-caudal (patient D.L.) or left rostral to mid-dorsal ACC (patient R.N.) exhibited distinctive performance profiles in these three versions of the Stroop task, providing further support for topographic specificity of function within the human ACC. Contrary to predictions from some neuroimaging experiments, damage to right mid-caudal ACC was associated with normal levels of interference and accurate performance on incongruent trials. Instead, D.L. showed reduced levels of facilitation relative to controls. Further, interference was not modulated by the probability manipulation in D.L., suggesting equivalently high levels of cognitive control in both conditions. Conversely, damage to left mid-dorsal ACC resulted in consistently lower accuracy on incongruent trials, indicating deficits in maintaining task set and inhibiting the automatic response. These results can help to constrain interpretations of ACC activations in functional imaging experiments of the Stroop task.     

Neural basis of the Stroop interference task: response competition or selective attention?

Previous neuroimaging studies of the Stroop task have postulated that the anterior cingulate cortex (ACC) plays a critical role in resolution of the Stroop interference condition. However, activation of the ACC is not invariably seen and appears to depend on a variety of methodological factors, including the degree of response conflict and response expectancies. The present functional MRI study was designed to identify those brain areas critically involved in the interference condition. Healthy subjects underwent a blocked-trial design fMRI experiment while responding to 1 of 3 stimulus conditions: (1) incongruent color words, (2) congruent color words, and (3) color-neutral words. Subjects responded to the printed color of the word via a manual response. Compared to the congruent and neutral conditions, the incongruent condition produced significant activation within the left inferior precentral sulcus (IpreCS) located on the border between the inferior frontal gyrus, pars opercularis (BA 44) and the ventral premotor region (BA 6). Significant deactivations in the rostral component of the ACC and the posterior cingulate gyrus were also observed. Selective activation of the left IpreCS is compatible with findings from previous neuroimaging, lesion, electrophysiological, and behavioral studies and is presumably related to the mediation of competing articulatory demands during the interference condition.     

Resting-state connectivity and spontaneous activity of ventromedial prefrontal cortex predict depressive symptomology and peripheral inflammation in HIV

Depression and chronic inflammation are common in persons infected with the human immunodeficiency virus (HIV+). Although depression and response to inflammatory challenge are shown to reflect activity in common neural networks, little is known regarding sub-clinical presentation in persons chronically infected with HIV. The relationship of resting-state functional connectivity (rsFC) between the subgenual anterior cingulate cortex (sgACC) and bilateral amygdala to Beck Depression Inventory-1 (BDI) scores were compared within a group of 23 HIV+ and 23 HIV-negative comparison adults. An interaction was found wherein lower rsFC between the sgACC and both right and left amygdala was associated with higher BDI scores in HIV+ individuals. Total BDI scores and plasma levels of IL-6, IL-8, TNF-α, and IL-10 made available from 10 of the HIV+ patients were regressed upon an index of spontaneous whole-brain activity at rest; i.e., the amplitude of low-frequency fluctuations (ALFFs). Elevated levels of depression and IL-6 were associated with increased ALFF in a cluster of voxels on the medial portion of the ventral surface of the frontal lobe (Brodmann Area 11). Within this sample of HIV+ individuals lower rsFC of the sgACC with subcortical limbic regions predicts greater burden of depressive symptomology whereas elevated activity in the adjacent BA 11 may reflect sickness, indexed by elevated IL-6, and associated depressive behaviors.     

Error-related hyperactivity of the anterior cingulate cortex in obsessive-compulsive disorder.

BACKGROUND: Hyperactivity of the anterior cingulate cortex (ACC) in patients with obsessive-compulsive disorder (OCD) has been shown to increase with symptom provocation and to normalize with treatment-induced symptom reduction. Although the functional significance of anterior cingulate involvement in OCD remains unknown, electrophysiological evidence has linked this region to error-processing abnormalities in patients with OCD. In this functional magnetic resonance imaging (fMRI) study, we sought to further localize error-processing differences within the ACC of OCD patients compared with healthy subjects. METHODS: Event-related fMRI data were collected for eight OCD patients and seven healthy subjects during the performance of a simple cognitive task designed to elicit errors but not OCD symptoms. RESULTS: Both OCD patients and healthy subjects demonstrated dorsal ACC activation during error commission. The OCD patients exhibited significantly greater error-related activation of the rostral ACC than comparison subjects. Activity in this region was positively correlated with symptom severity in the patients. CONCLUSIONS: Error-processing abnormalities within the rostral anterior cingulate occur in the absence of symptom expression in patients with OCD.     

Neural systems supporting the control of affective and cognitive conflicts

Although many studies have examined the neural bases of controlling cognitive responses, the neural systems for controlling conflicts between competing affective responses remain unclear. To address the neural correlates of affective conflict and their relationship to cognitive conflict, the present study collected whole-brain fMRI data during two versions of the Eriksen flanker task. For these tasks, participants indicated either the valence (affective task) or the semantic category (cognitive task) of a central target word while ignoring flanking words that mapped onto either the same (congruent) or a different (incongruent) response as the target. Overall, contrasts of incongruent > congruent trials showed that bilateral dorsal ACC, posterior medial frontal cortex, and dorsolateral pFC were active during both kinds of conflict, whereas rostral medial pFC and left ventrolateral pFC were differentially active during affective or cognitive conflict, respectively. Individual difference analyses showed that separate regions of rostral cingulate/ventromedial pFC and left ventrolateral pFC were positively correlated with the magnitude of response time interference. Taken together, the findings that controlling affective and cognitive conflicts depends upon both common and distinct systems have important implications for understanding the organization of control systems in general and their potential dysfunction in clinical disorders.     

Anterior cingulate epilepsy in an 18-year-old woman

Anterior cingulate epilepsy is a diagnostic and therapeutic challenge, with a broad range of nonspecific symptoms. Seizures can arise from any region of the anterior cingulate cortex (ACC) and manifest distinctive features based on the area of onset and pattern of spread. These features may provide insight as to the origin of the seizures, but because the ACC integrates information from several networks involving emotional and executive functions and has a diverse cytoarchitecture, functional-structural correlates are complex. Further, the location of the ACC within the interhemispheric fissure limits the capacity of scalp electrodes to record seizure activity from this region. This case review illustrates one part of the spectrum of cingulate epilepsy and discusses clinical features of the disorder.