Michael C. Brumm

Anterior cingulate cortex: an MRI-based parcellation method.

OBJECTIVE The anterior cingulate cortex (ACC) is an important part of the limbic system involved in emotions, cognition and executive function. The ACC has structurally distinct subregions, both microscopically and functionally, that have been implicated in several major psychiatric disorders. However, a structural analysis of these subregions with magnetic resonance imaging (MRI) has not been done. Our main purpose was to develop an MRI-based parcellation method of the ACC that permits us to explore plausible abnormalities in 4 functionally relevant subregions: dorsal, rostral, subcallosal and subgenual. METHODS The reliability study for gray matter volume and surface area of each subregion was performed on 14 randomly selected MR scans by 3 different raters. Our method posits to conserve the topographic uniqueness of individual brains and is based on our ability to visualize both the 3-dimensional rendered brain and the 3 orthogonal planes simultaneously with BRAINS2 software. We developed rules to hand-trace regions of interest (ROI) to surround contiguous areas of gray matter for dorsal, rostral, subcallosal and subgenual regions. The ACC was then parcellated into these 4 distinct subregions (8 when both right and left hemispheres were measured). RESULTS AND DISCUSSION The intraclass R coefficients for gray matter volume of each subregion ranged between 0.85 and 0.93. The current study describes a new highly reliable and reproducible topography-based parcellation method of the ACC into its dorsal, rostral, subcallosal and subgenual regions. CONCLUSIONS This new parcellation method provides a new means of exploring the role of the functionally and structurally distinct subregions of the ACC in schizophrenia, depression and various other brain illnesses.

Implications of Starvation-Induced Change in Right Dorsal Anterior Cingulate Volume in Anorexia Nervosa

OBJECTIVE Converging evidence suggests a role for the anterior cingulate cortex (ACC) in the pathophysiology of anorexia nervosa (AN). This study sought to determine whether ACC volume was affected by starvation in active AN and, if so, whether this had any clinical significance. METHOD Eighteen patients with active AN and age- and gender-matched normal controls underwent magnetic resonance imaging (MRI). Sixteen patients (89%) with AN had intelligence quotients (IQ) testing at intake, 14 (78%) had repeat MRIs after weight normalization, and 10 (56%) had outcome data at 1-year posthospitalization. RESULTS Right dorsal ACC volume was significantly reduced in active AN patients versus controls and was correlated with lower performance IQ. While ACC normalization occurred with weight restoration, smaller change in right dorsal ACC volume prospectively predicted relapse after treatment. CONCLUSION Reduced right dorsal ACC volume during active AN relates to deficits in perceptual organization and conceptual reasoning. The degree of right dorsal ACC normalization during treatment is related to outcome.

Mirror neuron function, psychosis, and empathy in schizophrenia

Processing of social and emotional information has been shown to be disturbed in schizophrenia. The biological underpinnings of these abnormalities may be explained by an abnormally functioning mirror neuron system. Yet the relationship between mirror neuron system activity in schizophrenia, as measured using an electroencephalography (EEG) paradigm, and socio-emotional functioning has not been assessed. The present research measured empathy and mirror neuron activity using an established EEG paradigm assessing the integrity of the Mu rhythm (8-13Hz) suppression over the sensorimotor cortex during observed and actual hand movement in 16 schizophrenia-spectrum disorder (SSD) participants (n=8 actively psychotic and n=8 in residual illness phase) and 16 age- and gender-matched healthy comparison participants. Actively psychotic SSD participants showed significantly greater mu suppression over the sensorimotor cortex of the left hemisphere than residual phase SSD and healthy comparison individuals. The latter two groups showed similar levels of mu suppression. Greater left-sided mu suppression was positively correlated with psychotic symptoms (i.e., greater mu suppression/mirror neuron activity was highest among subjects with the greater severity of psychotic symptoms). SSD subjects tended to have significantly higher levels of Personal Distress (as measured by the Interpersonal Reactivity Index) than healthy participants. The present study suggests that abnormal mirror neuron activity may exist among patients with schizophrenia during the active (psychotic) phase of the illness, and correlates with severity of psychosis.

Metabolic correlates of antidepressant and antipsychotic response in patients with psychotic depression undergoing electroconvulsive therapy.

Objectives: Although electroconvulsive therapy (ECT) is a very effective treatment of depression and psychosis, the mechanisms by which this occurs are not fully delineated. The objective of this study was to investigate the functional alterations in brain metabolism in response to ECT through the use of positron emission tomography assessment of cerebral glucose metabolism before and after a course of ECT. Methods: Ten subjects with psychotic depression were studied with positron emission tomography using [18F]fluorodeoxyglucose before and between 2 and 3 weeks after a course of ECT. Statistical parametric mapping and region of interest analyses of the anterior cingulate cortex (ACC) subregions (dorsal, rostral, subcallosal, and subgenual) and hippocampus were used to determine glucose metabolic changes from ECT. The Hamilton Depression Rating Scale and the Scale for Assessing Positive Symptoms were the primary measures used for assessing clinical changes from ECT. Results: Electroconvulsive therapy led to significant increases in the left subgenual ACC and hippocampal metabolism, which were directly correlated with each other and to a reduction in depression as measured by total Hamilton Depression Rating Scale scores. Better antidepressant responders had increased, whereas poorer responders had a decreased left subgenual ACC and hippocampal metabolism. The decrease in positive symptoms was also correlated with increased left hippocampal metabolism. Conclusions: The antidepressant effect of ECT was correlated with increased metabolism in the left subgenual ACC and hippocampus, whereas the antipsychotic effect of ECT was only correlated with increased left hippocampal metabolism. This finding has implications to better understand the mechanism of antidepressant and antipsychotic effects of ECT.

Relative ineffectiveness of ultrabrief right unilateral versus bilateral electroconvulsive therapy in depression.

Objective: Bilateral (BL) electrode placement delivered at 2.5 times the initial seizure threshold (ST; 2.5 × ST) is the gold standard method for seizure delivery during electroconvulsive therapy (ECT). However, there is a growing interest in using a high dose (6 × ST) with ultrabrief right unilateral (UB-RUL) electrode placement to reduce the incidence of possible short-term memory problems associated with BL ECT. Although studies have found UB-RUL ECT to have similar effectiveness to BL ECT, the objective of this study was to determine potential differences in efficiency (ie, the number of treatments needed to reach remission). Methods: Electroconvulsive therapeutic data for 56 patients with depression treated during 2006 and 2007 were analyzed via retrospective chart review. A total of 26 patients were started on UB-RUL ECT, whereas 30 patients were started on brief pulse BL ECT. Results: The patients started on high-dose UB-RUL ECT required significantly more treatments than the patients started on BL ECT (9.4 [3.3] vs 7.7 [2.8] treatments). Of the 26 patients started on UB-RUL ECT, 12 (46%) experienced a lack of effectiveness and/or insufficient seizure induction and were thus switched to BL ECT; the 8 patients switched because of lack of effectiveness received a mean (SD) of 12.2 (2.9) treatments, whereas the 4 patients switched because of insufficient seizure induction received a mean (SD) of 11.3 (3.6) treatments. Conclusions: These findings add to an emerging story of reduced efficiency of UB-RUL versus BL electrode placement for an index course of ECT for the treatment of depression.

Longitudinal examination of decision-making performance in anorexia nervosa: Before and after weight restoration

BACKGROUND This study aimed to extend previous work on decision-making deficits in anorexia nervosa (AN) by using a longitudinal design to examine decision-making before and after weight restoration. METHODS Participants were 22 women with AN and 20 healthy comparison participants who completed the Iowa Gambling Task (IGT). Decision-making was assessed both before and after weight restoration in a subset of 14 AN patients. Self-report and interview assessments were used to measure psychological correlates of decision-making performance including depression, anxiety, and eating disorder symptoms, and magnetic resonance imaging (MRI) scans were conducted to explore associations between brain volume in the orbitofrontal cortex (OFC) and decision-making in individuals with AN. RESULTS Currently ill AN patients performed worse on the IGT compared to the control group. Although decision-making performance did not improve significantly with weight restoration in the full AN sample, AN patients who were poor performers at baseline did improve task performance with weight-restoration. When actively ill, lower body mass index (BMI) and decreased left medial OFC volume were significantly associated with worse IGT performance, and these associations were no longer significant after weight restoration. CONCLUSIONS Findings suggest that decision-making deficits in AN in the acute phase of illness are associated with low weight and decreased left medial OFC volume, but increases in brain volume and BMI may not have been sufficient to improve decision-making in all patients. Findings contribute to a model for understanding how some patients may sustain self-starvation, and future work should examine whether decision-making deficits predict relapse.

Antipsychotic effect of electroconvulsive therapy is related to normalization of subgenual cingulate theta activity in psychotic depression

OBJECTIVE Electroconvulsive therapy (ECT) is one of the most effective options available for treating depressive and psychotic symptoms in a variety of disorders. While the exact mechanism of ECT is unclear, it is known to increase metabolism and blood flow specifically in the anterior cingulate cortex (ACC). The ACC is a cortical generator of theta rhythms, which are abnormal in patients with depression and psychotic disorders. Since patients with psychotic depression are known to respond particularly robustly to ECT, we investigated whether the therapeutic effect of ECT in this population was related to normalization of abnormal theta activity in the ACC. METHOD We obtained 19-lead electroencephalography (EEG) data from 17 participants with psychotic depression before and 2-3 weeks after a full course of ECT. EEG data was analyzed with quantitative measures and low-resolution electromagnetic tomography (LORETA) compared to an age-adjusted normative database. RESULTS Quantitative EEG analyses revealed that theta band (4-7 Hz) activity was the only frequency band that changed with ECT. LORETA analyses revealed that the primary site of theta activity change was within the subgenual ACC (Brodmann area 25). There was a positive association between increased subgenual ACC theta activity and decreased psychotic symptoms. The degree of low theta activity in the subgenual ACC prior to ECT predicted the antipsychotic response of ECT. CONCLUSIONS The antipsychotic effect of ECT is related to normalization of subgenual ACC theta hypoactivity.

Pre- and post-electroconvulsive therapy multidomain cognitive assessment in psychotic depression: relationship to premorbid abilities and symptom improvement.

Objectives: Cognitive changes have been reported in patients after electroconvulsive therapy (ECT), but few studies have investigated post-ECT changes across multiple cognitive domains. Because cognitive dysfunction is presumed to be more salient in psychotic depression, we propose a brief pre-ECT multidomain cognitive assessment battery, assessing neurocognitive function in this population before and after ECT. We also compared performance to estimated premorbid levels and determined if neuropsychological functioning was related to symptom improvement. Methods: Twenty participants with psychotic depression (12 females, 8 males) undergoing ECT for severe depression received the repeatable battery for the assessment of neuropsychological status (RBANS) and additional tasks. The wide range achievement test reading test provided an estimate of premorbid intellectual functioning. Depressive symptoms were assessed with the Hamilton Depression Scale-28, whereas negative and positive symptoms were assessed with the Scale for Assessing Negative and Positive Symptoms. Results: There was a significant improvement in depressive symptoms with most measures of cognitive function showing net gains. When cognitive performances were compared with estimated premorbid abilities, findings indicated significant movement toward normalization in overall RBANS score, particularly involving the language index and attention index. Considered individually, 6 (30%) participants showed pre-ECT cognitive dysfunction (RBANS total score ≤80), with only 2 (10%) showing such impairment posttreatment associated with inadequate response to ECT. A linear regression analysis revealed that the changes in RBANS and executive functioning were directly related to change in negative symptoms, but not to change in depression, anxiety or psychotic symptoms. Conclusions: Multidomain pre-ECT cognitive assessment is feasible and well-tolerated in most patients. Cognitive performance did not worsen after ECT in people with psychotic depression and improved on some measures. The degree of cognitive improvement seems to be directly related to the improvement in negative symptoms.

Hippocampal and Left Subcallosal Anterior Cingulate Atrophy in Psychotic Depression

Background Psychotic depression is arguably the most diagnostically stable subtype of major depressive disorder, and an attractive target of study in a famously heterogeneous mental illness. Previous imaging studies have identified abnormal volumes of the hippocampus, amygdala, and subcallosal region of the anterior cingulate cortex (scACC) in psychotic depression, though studies have not yet examined the role of family history of depression in these relationships. Methods 20 participants with psychotic depression preparing to undergo electroconvulsive therapy and 20 healthy comparison participants (13 women and 7 men in each group) underwent structural brain imaging in a 1.5 T MRI scanner. 15 of the psychotic depression group had a first-degree relative with diagnosed affective disorders, while the healthy control group had no first-degree relatives with affective disorders. Depression severity was assessed with the Hamilton Depression Rating Scale and duration of illness was assessed in all patients. Automated neural nets were used to isolate the hippocampi and amygdalae in each scan, and an established manual method was used to parcellate the anterior cingulate cortex into dorsal, rostral, subcallosal, and subgenual regions. The volumes of these regions were compared between groups. Effects of laterality and family history of affective disorders were examined as well. Results Patients with psychotic depression had significantly smaller left scACC and bilateral hippocampal volumes, while no group differences in other anterior cingulate cortex subregions or amygdala volumes were present. Hippocampal atrophy was found in all patients with psychotic depression, but reduced left scACC volume was found only in the patients with a family history of depression. Conclusions Patients with psychotic depression showed significant reduction in hippocampal volume bilaterally, perhaps due to high cortisol states associated with this illness. Reduced left scACC volume may be a vulnerability factor related to family history of depression.

Larger hippocampus size in women with anorexia nervosa who exercise excessively than healthy women

Exercise has been shown to increase hippocampal volume in healthy older adults. Observations from animal models of diabetes and hypertension suggest that the combination of exercise and caloric restriction may exert greater neuroprotection in the hippocampus than either behavior alone. Yet, in humans, the effects of exercise and caloric restriction on the hippocampus are not known. We measured the volume of the hippocampus prior to clinical treatment in women with anorexia nervosa (AN) who were restricting calories and engaging in excessive exercise, women with AN who did not exercise excessively, and healthy women who did not engage in either behavior. Women with AN were also examined longitudinally (once weight was restored and 6 months later). In the present report, we found that women with AN engaged in caloric restriction and excessive exercising prior to clinical treatment had larger hippocampal volumes than healthy comparison women. After weight restoration, women with AN who had engaged in food restriction and excessive exercise prior to treatment had hippocampal volumes similar to that of women with AN who only engaged in caloric restriction. These results advance the field by showing for the first time that hippocampal volume may be increased by exercise alone or exercise interacting with food restriction in AN.