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Working memory (WM) comprises operations whose coordinated action contributes to our ability to maintain focus on goal-relevant information in the presence of distraction. The present study investigated the nature of distraction upon the neural correlates of WM maintenance operations by presenting task-irrelevant distracters during the interval between the memoranda and probes of a delayed-response WM task. The study used a region of interest (ROIs) approach to investigate the role of anterior (e.g., lateral and medial prefrontal cortex--PFC) and posterior (e.g., parietal and fusiform cortices) brain regions that have been previously associated with WM operations. Behavioral results showed that distracters that were confusable with the memorandum impaired WM performance, compared to either the presence of non-confusable distracters or to the absence of distracters. These different levels of distraction led to differences in the regional patterns of delay interval activity measured with event-related functional magnetic resonance imaging (fMRI). In the anterior ROIs, dorsolateral PFC activation was associated with WM encoding and maintenance, and in maintaining a preparatory state, and ventrolateral PFC activation was associated with the inhibition of distraction. In the posterior ROIs, activation of the posterior parietal and fusiform cortices was associated with WM and perceptual processing, respectively. These findings provide novel evidence concerning the neural systems mediating the cognitive and behavioral responses during distraction, and places frontal cortex at the top of the hierarchy of the neural systems responsible for cognitive control.
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Significant progress has been made in our understanding of the neural substrates of emotion and its disorders. Neuroimaging methods have been used to characterize the circuitry underlying disorders of emotion. Particular emphasis has been placed on the prefrontal cortex, anterior cingulate, parietal cortex, and the amygdala as critical components of the circuitry that may be dysfunctional in both depression and anxiety.
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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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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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Four U.S. sites formed a consortium to conduct a multisite study of fMRI methods. The primary purpose of this consortium was to examine the reliability and reproducibility of fMRI results. FMRI data were collected on healthy adults during performance of a spatial working memory task at four different institutions. Two sets of data from each institution were made available. First, data from two subjects were made available from each site and were processed and analyzed as a pooled data set. Second, statistical maps from five to eight subjects per site were made available. These images were aligned in stereotactic space and common regions of activation were examined to address the reproducibility of fMRI results when both image acquisition and analysis vary as a function of site. Our grouped and individual data analyses showed reliable patterns of activation in dorsolateral prefrontal cortex and posterior parietal cortex during performance of the working memory task across all four sites. This multisite study, the first of its kind using fMRI data, demonstrates highly consistent findings across sites.
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Depression has been associated with dysfunctional executive functions and abnormal activity within the anterior cingulate cortex (ACC), a region critically involved in action regulation. Prior research invites the possibility that executive deficits in depression may arise from abnormal responses to negative feedback or errors, but the underlying neural substrates remain unknown. We hypothesized that abnormal reactions to error would be associated with dysfunctional rostral ACC activity, a region previously implicated in error detection and evaluation of the emotional significance of events. To test this hypothesis, subjects with low and high Beck Depression Inventory (BDI) scores performed an Eriksen Flanker task. To assess whether tonic activity within the rostral ACC predicted post-error adjustments, 128-channel resting EEG data were collected before the task and analyzed with low-resolution electromagnetic tomography (LORETA) using a region-of-interest approach. High BDI subjects were uniquely characterized by significantly lower accuracy after incorrect than correct trials. Mirroring the behavioral findings, high BDI subjects had significantly reduced pretask gamma (36.5-44 Hz) current density within the affective (rostral; BA24, BA25, BA32) but not cognitive (dorsal; BA24', BA32') ACC subdivision. For low, but not high, BDI subjects pretask gamma within the affective ACC subdivision predicted post-error adjustments even after controlling for activity within the cognitive ACC subdivision. Abnormal responses to errors may thus arise due to lower activity within regions subserving affective and/or motivational responses to salient cues. Because rostral ACC regions have been implicated in treatment response in depression, our findings provide initial insight into putative mechanisms fostering treatment response.
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Right-handed subjects tend to look to the left when answering affective questions. The relative shift in gaze from right to left is accentuated when the questions also involve spatial manipulation and attenuated when the questions require verbal manipulation. The data support the hypothesis that the right hemisphere has a special role in emotion in the intact brain, and that predictable patterning of hemispheric activity can occur when specific combinations of cognitive and affective processes interact.
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<p>Subregional analyses of the hippocampus have suggested a selective role for the CA1 subregion in intermediate/long-term spatial memory and consolidation, but not short-term acquisition or encoding processes. It remains unclear how the direct cortical projection to CA1 via the perforant path (pp) contributes to these CA1-dependent processes. It has been suggested that dopamine selectively modulates the pp projection to CA1 while having little to no effect on the Schaffer collateral (SC) projection to CA1. This series of behavioral and electrophysiological experiments takes advantage of this pharmacological dissociation to demonstrate that the direct pp inputs to CA1 are critical in CA1-dependent intermediate-term retention and retrieval function. Here we demonstrate that local infusion of the nonselective dopamine agonist, apomorphine (10, 15 microg), into the CA1 subregion of awake animals produces impairments in between-day retention and retrieval, sparing within-day encoding of a modified Hebb-Williams maze and contextual conditioning of fear. In contrast, apomorphine produces no deficits when infused into the CA3 subregion. To complement the behavioral analyses, electrophysiological data was collected. In anesthetized animals, local infusion of the same doses of apomorphine significantly modifies evoked responses in the distal dendrites of CA1 following angular bundle stimulation, but produces no significant effects in the more proximal dendritic layer following stimulation of the SC. These results support a modulatory role for dopamine in the EC-CA1, but not CA3-CA1 circuitry, and suggest the possibility of a more fundamental role for EC-CA1 synaptic transmission in terms of intermediate-term, but not short-term spatial memory.</p>
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The length polymorphism of the serotonin (5-HT) transporter gene promoter region has been implicated in altered 5-HT function and, in turn, neuropsychiatric illnesses, such as anxiety and depression. The nonhuman primate has been used as a model to study anxiety-related mechanisms in humans based upon similarities in behavior and the presence of a similar 5-HT transporter gene polymorphism. Stressful and threatening contexts in the nonhuman primate model have revealed 5-HT transporter genotype dependent differences in regional glucose metabolism. Using the rhesus monkey, we examined the extent to which serotonin transporter genotype is associated with 5-HT transporter binding in brain regions implicated in emotion-related pathology.
METHODS: Genotype data and high resolution PET scans were acquired in 29 rhesus (Macaca mulatta) monkeys. [C-11]DASB dynamic PET scans were acquired for 90 min in the anesthetized animals and images of distribution volume ratio (DVR) were created to serve as a metric of 5-HT transporter binding for group comparison based on a reference region method of analysis. Regional and voxelwise statistical analysis were performed with corrections for anatomical differences in gray matter probability, sex, age and radioligand mass.
RESULTS: There were no significant differences when comparing l/l homozygotes with s-carriers in the regions of the brain implicated in anxiety and mood related illnesses (amygdala, striatum, thalamus, raphe nuclei, temporal and prefrontal cortex). There was a significant sex difference in 5-HT transporter binding in all regions with females having 18%-28% higher DVR than males.
CONCLUSIONS: Because these findings are consistent with similar genotype findings in humans, this further strengthens the use of the rhesus model for studying anxiety-related neuropathologies.
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A variant allele in the promoter region of the serotonin transporter gene, SLC6A4, the s allele, is associated with increased vulnerability to develop anxiety-related traits and depression. Furthermore, functional magnetic resonance imaging (fMRI) studies reveal that s carriers have increased amygdala reactivity in response to aversive stimuli, which is thought to be an intermediate phenotype mediating the influences of the s allele on emotionality. We used high-resolution microPET [18F]fluoro-2-deoxy-D-glucose (FDG) scanning to assess regional brain metabolic activity in rhesus monkeys to further explore s allele-related intermediate phenotypes. Rhesus monkeys provide an excellent model to understand mechanisms underlying human anxiety, and FDG microPET allows for the assessment of brain activity associated with naturalistic environments outside the scanner. During FDG uptake, monkeys were exposed to different ethologically relevant stressful situations (relocation and threat) as well as to the less stressful familiar environment of their home cage. The s carriers displayed increased orbitofrontal cortex activity in response to both relocation and threat. However, during relocation they displayed increased amygdala reactivity and in response to threat they displayed increased reactivity of the bed nucleus of the stria terminalis. No increase in the activity of any of these regions occurred when the animals were administered FDG in their home cages. These findings demonstrate context-dependent intermediate phenotypes in s carriers that provide a framework for understanding the mechanisms underlying the vulnerabilities of s-allele carriers exposed to different types of stressors.
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This brief commentary highlights seven sins in the study of emotion that are explicitly treated in contemporary affective neuroscience. These sins are (1) Affect and cognition are subserved by separate and independent neural circuits; (2) Affect is subcortical; (3) Emotions are in the head; (4) Emotions can be studied from a purely psychological perspective; (5) Emotions are similar in structure across age and species; (6) Specific emotions are instantiated in discrete locations in the brain; and (7) Emotions are conscious feeling states. Each of these is briefly discussed and evidence from affective neuroscience that bears on these sins is noted. The articles in this Special Issue underscore the vitality of research in affective neuroscience and illustrate how some of these sins can be addressed and rectified using concepts and methods from affective neuroscience.
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This paper reports three studies showing sex differences in EEG asymmetry during self-generated cognitive and affective tasks. In the first experiment, bilateral EEG, quantified for alpha on-line, was recorded from right-handed subjects while they either whistled, sang or recited lyrics of familiar songs. The results revealed significant asymmetry between the whistle and talk conditions only for subjects with no familial left-handedness and, within this group, only for females and not for males. In the second experiment, bilateral EEG was recorded while right-handed subjects (with no familial left-handedness) self-induced covert affective and non-affective states. Results revealed significantly greater relative right-hemisphere activation during emotion versus non-emotion trials only in females; males showed no significant task-dependent shifts in asymmetry between conditions. The third experiment was designed to test the hypothesis that females show greater percent time asymmetry than males during biofeedback training for symmetrical and asymmetrical EEG patterns. Results confirmed this prediction as well as indicating that females show better control of such asymmetrical cortical patterning. These findings provide new neuropsychological support for the hypothesis of greater bilateral flexibility in females during self-generation tasks.
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The development of functional neuroimaging of emotion holds the promise to enhance our understanding of the biological bases of affect and improve our knowledge of psychiatric diseases. However, up to this point, researchers have been unable to objectively, continuously and unobtrusively measure the intensity and dynamics of affect concurrently with functional magnetic resonance imaging (fMRI). This has hindered the development and generalizability of our field. Facial electromyography (EMG) is an objective, reliable, valid, sensitive, and unobtrusive measure of emotion. Here, we report the successful development of a method for simultaneously acquiring fMRI and facial EMG. The ability to simultaneously acquire brain activity and facial physiology will allow affective neuroscientists to address theoretical, psychiatric, and individual difference questions in a more rigorous and generalizable way.
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Test-retest reliability of resting regional cerebral metabolic rate of glucose (rCMR) was examined in selected subcortical structures: the amygdala, hippocampus, thalamus, and anterior caudate nucleus. Findings from previous studies examining reliability of rCMR suggest that rCMR in small subcortical structures may be more variable than in larger cortical regions. We chose to study these subcortical regions because of their particular interest to our laboratory in its investigations of the neurocircuitry of emotion and depression. Twelve normal subjects (seven female, mean age = 32.42 years, range 21-48 years) underwent two FDG-PET scans separated by approximately 6 months (mean = 25 weeks, range 17-35 weeks). A region-of-interest approach with PET-MRI coregistration was used for analysis of rCMR reliability. Good test-retest reliability was found in the left amygdala, right and left hippocampus, right and left thalamus, and right and left anterior caudate nucleus. However, rCMR in the right amygdala did not show good test-retest reliability. The implications of these data and their import for studies that include a repeat-test design are considered.
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We present a new sparse shape modeling framework on the Laplace-Beltrami (LB) eigenfunctions. Traditionally, the LB-eigenfunctions are used as a basis for intrinsically representing surface shapes by forming a Fourier series expansion. To reduce high frequency noise, only the first few terms are used in the expansion and higher frequency terms are simply thrown away. However, some lower frequency terms may not necessarily contribute significantly in reconstructing the surfaces. Motivated by this idea, we propose to filter out only the significant eigenfunctions by imposing l1-penalty. The new sparse framework can further avoid additional surface-based smoothing often used in the field. The proposed approach is applied in investigating the influence of age (38-79 years) and gender on amygdala and hippocampus shapes in the normal population. In addition, we show how the emotional response is related to the anatomy of the subcortical structures.
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<p>Social cognition, including complex social judgments and attitudes, is shaped by individual learning experiences, where affect often plays a critical role. Aversive classical conditioning-a form of associative learning involving a relationship between a neutral event (conditioned stimulus, CS) and an aversive event (unconditioned stimulus, US)-represents a well-controlled paradigm to study how the acquisition of socially relevant knowledge influences behavior and the brain. Unraveling the temporal unfolding of brain mechanisms involved appears critical for an initial understanding about how social cognition operates. Here, 128-channel ERPs were recorded in 50 subjects during the acquisition phase of a differential aversive classical conditioning paradigm. The CS+ (two fearful faces) were paired 50% of the time with an aversive noise (CS upward arrow + /Paired), whereas in the remaining 50% they were not (CS upward arrow + /Unpaired); the CS- (two different fearful faces) were never paired with the noise. Scalp ERP analyses revealed differences between CS upward arrow + /Unpaired and CS- as early as approximately 120 ms post-stimulus. Tomographic source localization analyses revealed early activation modulated by the CS+ in the ventral visual pathway (e.g. fusiform gyrus, approximately 120 ms), right middle frontal gyrus (approximately 176 ms), and precuneus (approximately 240 ms). At approximately 120 ms, the CS- elicited increased activation in the left insula and left middle frontal gyrus. These findings not only confirm a critical role of prefrontal, insular, and precuneus regions in aversive conditioning, but they also suggest that biologically and socially salient information modulates activation at early stages of the information processing flow, and thus furnish initial insight about how affect and social judgments operate.</p>
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The tensor-based morphometry (TBM) has been widely used in characterizing tissue volume difference between populations at voxel level. We present a novel computational framework for investigating the white matter connectivity using TBM. Unlike other diffusion tensor imaging (DTI) based white matter connectivity studies, we do not use DTI but only T1-weighted magnetic resonance imaging (MRI). To construct brain network graphs, we have developed a new data-driven approach called the e-neighbor method that does not need any predetermined parcellation. The proposed pipeline is applied in detecting the topological alteration of the white matter connectivity in maltreated children.
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BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) system activation is adaptive in response to stress, and HPA dysregulation occurs in stress-related psychopathology. It is important to understand the mechanisms that modulate HPA output, yet few studies have addressed the neural circuitry associated with HPA regulation in primates and humans. Using high-resolution F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in rhesus monkeys, we assessed the relation between individual differences in brain activity and HPA function across multiple contexts that varied in stressfulness.
METHODS: Using a logical AND conjunctions analysis, we assessed cortisol and brain metabolic activity with FDG-PET in 35 adolescent rhesus monkeys exposed to two threat and two home-cage conditions. To test the robustness of our findings, we used similar methods in an archival data set. In this data set, brain metabolic activity and cortisol were assessed in 17 adolescent male rhesus monkeys that were exposed to three stress-related contexts.
RESULTS: Results from the two studies revealed that subgenual prefrontal cortex (PFC) metabolism (Brodmann's area 25/24) consistently predicted individual differences in plasma cortisol concentrations regardless of the context in which brain activity and cortisol were assessed.
CONCLUSIONS: These findings suggest that activation in subgenual PFC may be related to HPA output across a variety of contexts (including familiar settings and novel or threatening situations). Individuals prone to elevated subgenual PFC activity across multiple contexts may be individuals who consistently show heightened cortisol and may be at risk for stress-related HPA dysregulation.
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We present a new tensor-based morphometric framework that quantifies cortical shape variations using a local area element. The local area element is computed from the Riemannian metric tensors, which are obtained from the smooth functional parametrization of a cortical mesh. For the smooth parametrization, we have developed a novel weighted spherical harmonic (SPHARM) representation, which generalizes the traditional SPHARM as a special case. For a specific choice of weights, the weighted-SPHARM is shown to be the least squares approximation to the solution of an isotropic heat diffusion on a unit sphere. The main aims of this paper are to present the weighted-SPHARM and to show how it can be used in the tensor-based morphometry. As an illustration, the methodology has been applied in the problem of detecting abnormal cortical regions in the group of high functioning autistic subjects.
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The information processing capacity of the human mind is limited, as is evidenced by the attentional blink-a deficit in identifying the second of two targets (T1 and T2) presented in close succession. This deficit is thought to result from an overinvestment of limited resources in T1 processing. We previously reported that intensive mental training in a style of meditation aimed at reducing elaborate object processing, reduced brain resource allocation to T1, and improved T2 accuracy [Slagter, H. A., Lutz, A., Greischar, L. L., Francis, A. D., Nieuwenhuis, S., Davis, J., et al. Mental training affects distribution of limited brain resources. PloS Biology, 5, e138, 2007]. Here we report EEG spectral analyses to examine the possibility that this reduction in elaborate T1 processing rendered the system more available to process new target information, as indexed by T2-locked phase variability. Intensive mental training was associated with decreased cross-trial variability in the phase of oscillatory theta activity after successfully detected T2s, in particular, for those individuals who showed the greatest reduction in brain resource allocation to T1. These data implicate theta phase locking in conscious target perception, and suggest that after mental training the cognitive system is more rapidly available to process new target information. Mental training was not associated with changes in the amplitude of T2-induced responses or oscillatory activity before task onset. In combination, these findings illustrate the usefulness of systematic mental training in the study of the human mind by revealing the neural mechanisms that enable the brain to successfully represent target information.
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