<p>We investigated the impact of cognitive behavioral therapy and mindfulness training (CBT/MT) on attentional task performance in incarcerated adolescents. Attention is a cognitive system necessary for managing cognitive demands and regulating emotions. Yet persistent and intensive demands, such as those experienced during high-stress intervals like incarceration and the events leading to incarceration, may deplete attention resulting in cognitive failures, emotional disturbances, and impulsive behavior. We hypothesized that CBT/MT may mitigate these deleterious effects of high stress and protect against degradation in attention over the high-stress interval of incarceration. Using a quasi-experimental, group randomized controlled trial design, we randomly assigned dormitories of incarcerated youth, ages 16–18, to a CBT/MT intervention (youth n = 147) or an active control intervention (youth n = 117). Both arms received approximately 750 min of intervention in a small-group setting over a 3–5 week period. Youth in the CBT/MT arm also logged the amount of out-of-session time spent practicing MT exercises. The Attention Network Test was used to index attentional task performance at baseline and 4 months post-baseline. Overall, task performance degraded over time in all participants. The magnitude of performance degradation was significantly less in the CBT/MT vs. control arm. Further, within the CBT/MT arm, performance degraded over time in those with no outside-of-class practice time, but remained stable over time in those who practiced mindfulness exercises outside of the session meetings. Thus, these findings suggest that sufficient CBT/MT practice may protect against functional attentional impairments associated with high-stress intervals.</p>
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Mindfulness interventions within adult populations are becoming increasingly popular. Research suggests that mindfulness can deliver lasting improvements in self-awareness and emotional stability to adults with severe and chronic conditions. As yet, research within child and adolescent populations is in its initial stages, although mindfulness shows great clinical promise for young people. This article aims to provide an overview of mindfulness to professionals who are working in child or adolescent settings. Initially, it will provide the reader with some orientation to and definitions from the field, before summarizing the current evidence for the utility of the approach. The article recommends specific clinical modifications for mindfulness with children and adolescents, as well as reviewing how to monitor and enhance the development of this skill. Finally, it highlights important differences among mindfulness, relaxation and other meditative techniques.
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In light of a growing interest in contemplative practices such as meditation, the emerging field of contemplative science has been challenged to describe and objectively measure how these practices affect health and well-being. While “mindfulness” itself has been proposed as a measurable outcome of contemplative practices, this concept encompasses multiple components, some of which, as we review here, may be better characterized as equanimity. Equanimity can be defined as an even-minded mental state or dispositional tendency toward all experiences or objects, regardless of their origin or their affective valence (pleasant, unpleasant, or neutral). In this article, we propose that equanimity be used as an outcome measure in contemplative research. We first define and discuss the inter-relationship between mindfulness and equanimity from the perspectives of both classical Buddhism and modern psychology and present existing meditation techniques for cultivating equanimity. We then review psychological, physiological, and neuroimaging methods that have been used to assess equanimity either directly or indirectly. In conclusion, we propose that equanimity captures potentially the most important psychological element in the improvement of well-being, and therefore should be a focus in future research studies.
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A review of behavioral and neurobiological data on mood and mood regulation as they pertain to an understanding of mood disorders is presented. Four approaches are considered: 1) behavioral and cognitive; 2) neurobiological; 3) computational; and 4) developmental. Within each of these four sections, we summarize the current status of the field and present our vision for the future, including particular challenges and opportunities. We conclude with a series of specific recommendations for National Institute of Mental Health priorities. Recommendations are presented for the behavioral domain, the neural domain, the domain of behavioral-neural interaction, for training, and for dissemination. It is in the domain of behavioral-neural interaction, in particular, that new research is required that brings together traditions that have developed relatively independently. Training interdisciplinary clinical scientists who meaningfully draw upon both behavioral and neuroscientific literatures and methods is critically required for the realization of these goals.
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OBJECTIVE: The purpose of this study was to use functional magnetic resonance imaging (fMRI) to probe the neural circuitry associated with reactivity to negative and positive affective stimuli in patients with major depressive disorder before treatment and after 2 and 8 weeks of treatment with venlafaxine. Relations between baseline neural activation and response to treatment were also evaluated.
METHOD: Patients with major depressive disorder (N=12) and healthy comparison subjects (N=5) were scanned on three occasions, during which trials of alternating blocks of affective and neutral pictorial visual stimuli were presented. Symptoms were evaluated at each testing occasion, and both groups completed self-report measures of mood. Statistical parametric mapping was used to examine the fMRI data with a focus on the group-by-time interactions.
RESULTS: Patients showed a significant reduction in depressive symptoms with treatment. Group-by-time interactions in response to the negative versus neutral stimuli were found in the left insular cortex and the left anterior cingulate. At baseline, both groups showed bilateral activation in the visual cortices, lateral prefrontal cortex, and amygdala in response to the negative versus neutral stimuli, with patients showing greater activation in the visual cortex and less activation in the left lateral prefrontal cortex. Patients with greater relative anterior cingulate activation at baseline in response to the negative versus neutral stimuli showed the most robust treatment response.
CONCLUSIONS: The findings underscore the importance of the neural circuitry activated by negative affect in depression and indicate that components of this circuitry can be changed within 2 weeks of treatment with antidepressant medication.
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Positive affect elicited in a mother toward her newborn infant may be one of the most powerful and evolutionarily preserved forms of positive affect in the emotional landscape of human behavior. This study examined the neurobiology of this form of positive emotion and in so doing, sought to overcome the difficulty of eliciting robust positive affect in response to visual stimuli in the physiological laboratory. Six primiparous human mothers with no indications of postpartum depression brought their infants into the laboratory for a photo shoot. Approximately 6 weeks later, they viewed photographs of their infant, another infant, and adult faces during acquisition of functional magnetic resonance images (fMRI). Mothers exhibited bilateral activation of the orbitofrontal cortex (OFC) while viewing pictures of their own versus unfamiliar infants. While in the scanner, mothers rated their mood more positively for pictures of their own infants than for unfamiliar infants, adults, or at baseline. The orbitofrontal activation correlated positively with pleasant mood ratings. In contrast, areas of visual cortex that also discriminated between own and unfamiliar infants were unrelated to mood ratings. These data implicate the orbitofrontal cortex in a mother's affective responses to her infant, a form of positive emotion that has received scant attention in prior human neurobiological studies. Furthermore, individual variations in orbitofrontal activation to infant stimuli may reflect an important dimension of maternal attachment.
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Parenting preschoolers can be a challenging endeavor. Yet anecdotal observations indicate that parents who are more mindful may have greater ease in contending with the emotional demands of parenting than parents who are less mindful. Therefore, we hypothesized that parenting effort, defined as the energy involved in deciding on the most effective way to respond to a preschooler, would be negatively associated with mothers’ mindfulness. In this study, a new parenting effort scale and an established mindfulness scale were distributed to 50 mothers of preschoolers. Using exploratory factor analysis, the factor structure of the new parenting effort scale was examined and the scale was refined. Bivariate correlations were then conducted on this new Parenting Effort—Preschool scale and the established mindfulness scale. Results confirmed the hypothesis that a negative correlation exists between these two variables. Implications are that mindfulness practices may have the potential to alleviate some of the challenges of parenting preschoolers.
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The purpose of this study was to examine pathways in a model which proposed associations among parent mindfulness, parent depressive symptoms, two types of parenting, and child problem behavior. Participants' data were from the baseline assessment of a NIMH-sponsored family-group cognitive-behavioral intervention program for the prevention of child and adolescent depression (Compas et al., 2009). Participants consisted of 145 mothers and 17 fathers (mean age = 41.89 yrs, SD = 7.73) with a history of depression and 211 children (106 males) (mean age = 11.49 yrs, SD = 2.00). Analyses showed that (a) positive parenting appears to play a significant role in helping explain how parent depressive symptoms relate to child externalizing problems and (b) mindfulness is related to child internalizing and externalizing problems; however, the intervening constructs examined did not appear to help explain the mindfulness-child problem behavior associations. Suggestions for future research on parent mindfulness and child problem outcome are described.
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<p>The study reported here is seeking to gain enhanced understandings of the acquisition and development of core and generic skills in higher education and employment against a backcloth of continued pressure for their effective delivery from employers, government departments, and those responsible for the management and funding of higher education. This pressure appears to have had little impact so far, in part because of tutors' scepticism of the message, the messenger and its vocabulary, and in part because the skills demanded lack clarity, consistency and a recognisable theoretical base. Any empirical attempt to acquire enhanced understandings of practice thus requires the conceptualisation and development of models of generic skills and of course provision. These models are presented together with evidence of their validity, including exemplars of the patterns of course provision identified.</p>
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Neuroimage phenotyping for psychiatric and neurological disorders is performed using voxelwise analyses also known as voxel based analyses or morphometry (VBM). A typical voxelwise analysis treats measurements at each voxel (e.g., fractional anisotropy, gray matter probability) as outcome measures to study the effects of possible explanatory variables (e.g., age, group) in a linear regression setting. Furthermore, each voxel is treated independently until the stage of correction for multiple comparisons. Recently, multi-voxel pattern analyses (MVPA), such as classification, have arisen as an alternative to VBM. The main advantage of MVPA over VBM is that the former employ multivariate methods which can account for interactions among voxels in identifying significant patterns. They also provide ways for computer-aided diagnosis and prognosis at individual subject level. However, compared to VBM, the results of MVPA are often more difficult to interpret and prone to arbitrary conclusions. In this paper, first we use penalized likelihood modeling to provide a unified framework for understanding both VBM and MVPA. We then utilize statistical learning theory to provide practical methods for interpreting the results of MVPA beyond commonly used performance metrics, such as leave-one-out-cross validation accuracy and area under the receiver operating characteristic (ROC) curve. Additionally, we demonstrate that there are challenges in MVPA when trying to obtain image phenotyping information in the form of statistical parametric maps (SPMs), which are commonly obtained from VBM, and provide a bootstrap strategy as a potential solution for generating SPMs using MVPA. This technique also allows us to maximize the use of available training data. We illustrate the empirical performance of the proposed framework using two different neuroimaging studies that pose different levels of challenge for classification using MVPA.
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OBJECTIVES: To examine whether mindfulness meditation (MM) was associated with changes in objectively measured polysomnographic (PSG) sleep profiles and to relate changes in PSG sleep to subjectively reported changes in sleep and depression within the context of a randomized controlled trial. Previous studies have indicated that mindfulness and other forms of meditation training are associated with improvements in sleep quality. However, none of these studies used objective PSG sleep recordings within longitudinal randomized controlled trials of naïve subjects.
METHODS: Twenty-six individuals with partially remitted depression were randomized into an 8-week Mindfulness-Based Cognitive Therapy (MBCT) course or a waitlist control condition. Pre-post measurements included PSG sleep studies and subjectively reported sleep and depression symptoms.
RESULTS: According to PSG sleep, MM practice was associated with several indices of increased cortical arousal, including more awakenings and stage 1 sleep and less slow-wave sleep relative to controls, in proportion to amount of MM practice. According to sleep diaries, subjectively reported sleep improved post MBCT but not above and beyond controls. Beck Depression Inventory scores decreased more in the MBCT group than controls. Improvements in depression were associated with increased subjective sleep continuity and increased PSG arousal.
CONCLUSIONS: MM is associated with increases in objectively measured arousal during sleep with simultaneous improvements in subjectively reported sleep quality and mood disturbance. This pattern is similar to the profiles of positive responders to common antidepressant medications.
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Individuals with fragile X syndrome (FXS) commonly display characteristics of social anxiety, including gaze aversion, increased time to initiate social interaction, and difficulty forming meaningful peer relationships. While neural correlates of face processing, an important component of social interaction, are altered in FXS, studies have not examined whether social anxiety in this population is related to higher cognitive processes, such as memory. This study aimed to determine whether the neural circuitry involved in face encoding was disrupted in individuals with FXS, and whether brain activity during face encoding was related to levels of social anxiety. A group of 11 individuals with FXS (5 M) and 11 age- and gender-matched control participants underwent fMRI scanning while performing a face encoding task with online eye-tracking. Results indicate that compared to the control group, individuals with FXS exhibited decreased activation of prefrontal regions associated with complex social cognition, including the medial and superior frontal cortex, during successful face encoding. Further, the FXS and control groups showed significantly different relationships between measures of social anxiety (including gaze-fixation) and brain activity during face encoding. These data indicate that social anxiety in FXS may be related to the inability to successfully recruit higher level social cognition regions during the initial phases of memory formation.
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Temperamentally anxious individuals can be identified in childhood and are at risk to develop anxiety and depressive disorders. In addition, these individuals tend to have extreme asymmetric right prefrontal brain activity. Although common and clinically important, little is known about the pathophysiology of anxious temperament. Regardless, indirect evidence from rodent studies and difficult to interpret primate studies is used to support the hypothesis that the amygdala plays a central role. In previous studies using rhesus monkeys, we characterized an anxious temperament endophenotype that is associated with excessive anxiety and fear-related responses and increased electrical activity in right frontal brain regions. To examine the role of the amygdala in mediating this endophenotype and other fearful responses, we prepared monkeys with selective fiber sparing ibotenic acid lesions of the amygdala. Unconditioned trait-like anxiety-fear responses remained intact in monkeys with >95% bilateral amygdala destruction. In addition, the lesions did not affect EEG frontal asymmetry. However, acute unconditioned fear responses, such as those elicited by exposure to a snake and to an unfamiliar threatening conspecific were blunted in monkeys with >70% lesions. These findings demonstrate that the primate amygdala is involved in mediating some acute unconditioned fear responses but challenge the notion that the amygdala is the key structure underlying the dispositional behavioral and physiological characteristics of anxious temperament.
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<p>Virtually all developmental neuropsychiatric disorders involve some dysfunction or dysregulation of emotion. Moreover, many psychiatric disorders with adult onset have early subclinical manifestations in children. This essay selectively reviews the literature on the neuroimaging of affect and disorders of affect in children. Some critical definitional and conceptual issues are first addressed, including the distinctions between the perception and production of emotion and between emotional states and traits. Developmental changes in morphometric measures of brain structure are then discussed and the implications of such findings for studies of functional brain activity are considered. Data on functional neuroimaging and childhood depression are then reviewed. While the extant data in this area are meager, they are consistent with studies in adults that have observed decreased left-sided anterolateral prefrontal cortex activation in depression. Studies in children on the recognition of emotion and affective intent in faces using functional magnetic resonance imaging are then reviewed. These findings indicate that the amygdala plays an important role in such affective face processing in children, similar to the patterns of activation observed in adults. Moreover, one study has reported abnormalities in amygdala activation during a task requiring the judgment of affective intent from the eye region of the face in subjects with autism. Some of the methodological complexities of developmental research in this area are discussed, and directions for future research are suggested.</p>
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The authors propose a model of the prosocial classroom that highlights the importance of teachers’ social and emotional competence (SEC) and well-being in the development and maintenance of supportive teacher–student relationships, effective classroom management, and successful social and emotional learning program implementation. This model proposes that these factors contribute to creating a classroom climate that is more conducive to learning and that promotes positive developmental outcomes among students. Furthermore, this article reviews current research suggesting a relationship between SEC and teacher burnout and reviews intervention efforts to support teachers’ SEC through stress reduction and mindfulness programs. Finally, the authors propose a research agenda to address the potential efficacy of intervention strategies designed to promote teacher SEC and improved learning outcomes for students.
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Differences between dyslexics and controls in the unimanual and bimanual conditions of the peg placement section of the Purdue Pegboard Test were examined. Twenty-three disabled and twenty-three normal readers were studied. The groups were carefully screened on a neuropsychological battery. The disabled readers were comprised of a relatively homogeneous language-disordered subgroup exhibiting deficits in naming. Significant Group X Condition interactions were obtained for both raw and percentile scores and indicated that disabled readers performed worse than controls in the unimanual compared to bimanual conditions. The dyslexics performed particularly poorly compared with controls on the left hand condition. The implications of these data for hypotheses which argue for left hemisphere dysfunction, as well as those which posit interhemispheric transfer deficits in reading disabled children, are discussed.
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Mindfulness-based cognitive therapy for children (MBCT-C) is a manualized group psychotherapy for children ages 9–13 years old, which was developed specifically to increase social-emotional resiliency through the enhancement of mindful attention. Program development is described along with results of the initial randomized controlled trial. We tested the hypotheses that children randomized to participate in MBCT-C would show greater reductions in (a) attention problems, (b) anxiety symptoms, and (c) behavior problems than wait-listed age and gender-matched controls. Participants were boys and girls aged 9–13 (N = 25), mostly from low-income, inner-city households. Twenty-one of 25 children were ethnic minorities. A randomized cross-lagged design provided a wait-listed control group, a second trial of MBCT-C, and a 3-month follow-up of children who completed the first trial. Measures included the Child Behavior Checklist, State-Trait Anxiety Inventory for Children, and Multidimensional Anxiety Scale for Children. Participants who completed the program showed fewer attention problems than wait-listed controls and those improvements were maintained at three months following the intervention [F (1, 1, 18) = 5.965, p = .025, Cohen’s d = .42]. A strong relationship was found between attention problems and behavior problems (r = .678, p < .01). Reductions in attention problems accounted for 46% of the variance of changes in behavior problems, although attention changes proved to be a non-significant mediator of behavior problems (p = .053). Significant reductions in anxiety symptoms and behavior problems were found for those children who reported clinically elevated levels of anxiety at pretest (n = 6). Results show that MBCT-C is a promising intervention for attention and behavior problems, and may reduce childhood anxiety symptoms.
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<p>This experiment was designed to test whether reading disabled boys differ from matched controls on behavioral measures of interhemispheric transfer time (IHTT). Specifically, we proposed that language-disordered reading disabled children who had deficits in naming would show either faster or slower IHTTs compared with controls. From an initial group of 118 right-handed males, we selected a group of 25 disabled and 25 normal readers, matched on age. All subjects had to obtain a full scale IQ of 90 or above, a PIQ score of 85 or above, and a scaled score of 7 or above on the Block Design Subtest of the WISC-R. After meeting additional criteria for group assignment, manual reaction time (RT) measures of IHTT were obtained in response to simple visual and tactile stimuli during two laboratory testing sessions. Half the trials were conducted with the hands in an uncrossed orientation and half with the hands crossed in order to examine the effects of spatial compatibility on estimates of IHTT. The results revealed no overall group differences in IHTT for any of the conditions. However, correlations between IHTT measures and indices of cognitive performance indicated that faster IHTTs were significantly correlated with poorer performance on measures of reading and language function in the dyslexic group. These data are discussed within the context of a model of interhemispheric transfer deficits in disabled readers.</p>
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BACKGROUND: Anhedonia, a reduced ability to experience pleasure, is a chief symptom of major depressive disorder and is related to reduced frontostriatal connectivity when attempting to upregulate positive emotion. The present study examined another facet of positive emotion regulation associated with anhedonia-namely, the downregulation of positive affect-and its relation to prefrontal cortex (PFC) activity.
METHODS: Neuroimaging data were collected from 27 individuals meeting criteria for major depressive disorder as they attempted to suppress positive emotion during a positive emotion regulation task. Their PFC activation pattern was compared with the PFC activation pattern exhibited by 19 healthy control subjects during the same task. Anhedonia scores were collected at three time points: at baseline (time 1), 8 weeks after time 1 (i.e., time 2), and 6 months after time 1 (i.e., time 3). Prefrontal cortex activity at time 1 was used to predict change in anhedonia over time. Analyses were conducted utilizing hierarchical linear modeling software.
RESULTS: Depressed individuals who could not inhibit positive emotion-evinced by reduced right ventrolateral prefrontal cortex activity during attempts to dampen their experience of positive emotion in response to positive visual stimuli-exhibited a steeper anhedonia reduction slope between baseline and 8 weeks of treatment with antidepressant medication (p < .05). Control subjects showed a similar trend between baseline and time 3.
CONCLUSIONS: To reduce anhedonia, it may be necessary to teach individuals how to counteract the functioning of an overactive pleasure-dampening prefrontal inhibitory system.
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High rates of child abuse and neglect occur in many families in which either or both parents abuse illicit drugs. This study reports on the results of a randomized controlled trial with families having a parent on methadone maintenance (N = 64), in which an intensive, home-based intervention, the Parents Under Pressure (PUP) program, was compared to standard care. A second brief intervention control group of families received a two-session parenting education intervention. The PUP intervention draws from the ecological model of child development by targeting multiple domains of family functioning including the psychological functioning of individuals in the family, parent–child relationships, and social contextual factors. Mindfulness skills were included to address parental affect regulation, a significant problem for this group of parents. At 3- and 6-month follow-up, PUP families showed significant reductions in problems across multiple domains of family functioning, including a reduction in child abuse potential, rigid parenting attitudes, and child behavior problems. Families in the brief intervention group showed a modest reduction in child abuse potential but no other changes in family function. There were no improvements found in the standard care group and some significant worsening was observed. Results are discussed in terms of their implications for improved treatment.
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Baseline resting electroencephalogram (EEG) activity was recorded from 6 normothymic depressives and 8 controls using three different reference montages. Power in all frequency bands was extracted by Fourier transformation. Significant Group X Region X Hemisphere interactions were found consistently for alpha band power only. Previously depressed subjects had less left-sided anterior and less right-sided posterior activation (i.e., more alpha activity) than did never depressed subjects. Previously depressed subjects had no history of pharmacological treatment and did not differ from controls in emotional state at the time of testing. The pattern of anterior and posterior asymmetry in the previously depressed subjects is similar to that found in acutely depressed subjects and suggests that this may be a state-independent marker for depression.
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Electroencephalogram (EEG) alpha power has been demonstrated to be inversely related to mental activity and has subsequently been used as an indirect measure of brain activation. The thalamus has been proposed as an important site for modulation of rhythmic alpha activity. Studies in animals have suggested that cortical alpha rhythms are correlated with alpha rhythms in the thalamus. However, little empirical evidence exists for this relation in humans. In the current study, resting EEG and a fluorodeoxyglucose positron emission tomography scan were measured during the same experimental session. Over a 30-min period, average EEG alpha power across 28 electrodes from 27 participants was robustly inversely correlated with glucose metabolic activity in the thalamus. These data provide the first evidence for a relation between alpha EEG power and thalamic activity in humans.
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OBJECTIVE Deficits in positive affect and their neural bases have been associated with major depression. However, whether reductions in positive affect result solely from an overall reduction in nucleus accumbens activity and fronto-striatal connectivity or the additional inability to sustain engagement of this network over time is unknown. The authors sought to determine whether treatment-induced changes in the ability to sustain nucleus accumbens activity and fronto-striatal connectivity during the regulation of positive affect are associated with gains in positive affect. METHOD Using fMRI, the authors assessed the ability to sustain activity in reward-related networks when attempting to increase positive emotion during performance of an emotion regulation paradigm in 21 depressed patients before and after 2 months of antidepressant treatment. Over the same interval, 14 healthy comparison subjects underwent scanning as well. RESULTS After 2 months of treatment, self-reported positive affect increased. The patients who demonstrated the largest increases in sustained nucleus accumbens activity over the 2 months were those who demonstrated the largest increases in positive affect. In addition, the patients who demonstrated the largest increases in sustained fronto-striatal connectivity were also those who demonstrated the largest increases in positive affect when controlling for negative affect. None of these associations were observed in healthy comparison subjects. CONCLUSIONS Treatment-induced change in the sustained engagement of fronto-striatal circuitry tracks the experience of positive emotion in daily life. Studies examining reduced positive affect in a variety of psychiatric disorders might benefit from examining the temporal dynamics of brain activity when attempting to understand changes in daily positive affect.
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<p>OBJECTIVES: The study objectives were to develop and objectively assess the therapeutic effect of a novel movement-based complementary and alternative medicine approach for children with an autism-spectrum disorder (ASD). DESIGN: A within-subject analysis comparing pre- to post-treatment scores on two standard measures of childhood behavioral problems was used. SETTINGS AND LOCATION: The intervention and data analysis occurred at a tertiary care, medical school teaching hospital. SUBJECTS: Twenty-four (24) children aged 3-16 years with a diagnosis of an ASD comprised the study group. INTERVENTION: The efficacy of an 8-week multimodal yoga, dance, and music therapy program based on the relaxation response (RR) was developed and examined. OUTCOME MEASURES: The study outcome was measured using The Behavioral Assessment System for Children, Second Edition (BASC-2) and the Aberrant Behavioral Checklist (ABC). RESULTS: Robust changes were found on the BASC-2, primarily for 5-12-year-old children. Unexpectedly, the post-treatment scores on the Atypicality scale of the BASC-2, which measures some of the core features of autism, changed significantly (p=0.003). CONCLUSIONS: A movement-based, modified RR program, involving yoga and dance, showed efficacy in treating behavioral and some core features of autism, particularly for latency-age children.</p>
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Given the central role of the amygdala in fear perception and expression and its likely abnormality in affective disorders and autism, there is great demand for a technique to measure differences in neurochemistry of the human amygdala. Unfortunately, it is also a technically complex target for magnetic resonance spectroscopy (MRS) due to a small volume, high field inhomogeneity and a shared boundary with hippocampus, which can undergo opposite changes in response to stress. We attempted to achieve reliable PRESS-localized single-voxel MRS at 3T of the isolated human amygdala by using anatomy to guide voxel size and location. We present data from 106 amygdala-MRS sessions from 58 volunteers aged 10 to 52 years, including two tests of one-week stability and a feasibility study in an adolescent sample. Our main outcomes were indices of spectral quality, repeated measurement variability (within- and between-subject standard deviations), and sensitivity to stable individual differences measured by intra-class correlation (ICC). We present metrics of amygdala-MRS reliability for n-acetyl-aspartate, creatine, choline, myo-Inositol, and glutamate+glutamine (Glx). We found that scan quality suffers an age-related difference in field homogeneity and modified our protocol to compensate. We further identified an effect of anatomical inclusion near the endorhinal sulcus, a region of high synaptic density, that contributes up to 29% of within-subject variability across 4 sessions (n=14). Remaining variability in line width but not signal-to-noise also detracts from reliability. Statistical correction for partial inclusion of these strong neurochemical gradients decreases n-acetyl-aspartate reliability from an intraclass correlation of 0.84 to 0.56 for 7-minute acquisitions. This suggests that systematic differences in anatomical inclusion can contribute greatly to apparent neurochemical concentrations and could produce false group differences in experimental studies. Precise, anatomically-based prescriptions that avoid age-related sources of inhomogeneity and use longer scan times may permit study of individual differences in neurochemistry throughout development in this late-maturing structure.
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