We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure [email protected]
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Decision making usually involves uncertainty and risk. Understanding which parts of the human brain are activated during decisions under risk and which neural processes underly (risky) investment decisions are important goals in neuroeconomics. Here, we analyze functional magnetic resonance imaging (fMRI) data on 17 subjects who were exposed to an investment decision task from Mohr, Biele, Krugel, Li, and Heekeren (in NeuroImage 49, 2556–2563, 2010b). We obtain a time series of three-dimensional images of the blood-oxygen-level dependent (BOLD) fMRI signals. We apply a panel version of the dynamic semiparametric factor model (DSFM) presented in Park, Mammen, Wolfgang, and Borak (in Journal of the American Statistical Association 104(485), 284–298, 2009) and identify task-related activations in space and dynamics in time. With the panel DSFM (PDSFM) we can capture the dynamic behavior of the specific brain regions common for all subjects and represent the high-dimensional time-series data in easily interpretable low-dimensional dynamic factors without large loss of variability. Further, we classify the risk attitudes of all subjects based on the estimated low-dimensional time series. Our classification analysis successfully confirms the estimated risk attitudes derived directly from subjects’ decision behavior.
Significant heterogeneity in network structures reflecting individuals’ dynamic processes can exist within subgroups of people (e.g., diagnostic category, gender). This makes it difficult to make inferences regarding these predefined subgroups. For this reason, researchers sometimes wish to identify subsets of individuals who have similarities in their dynamic processes regardless of any predefined category. This requires unsupervised classification of individuals based on similarities in their dynamic processes, or equivalently, in this case, similarities in their network structures of edges. The present paper tests a recently developed algorithm, S-GIMME, that takes into account heterogeneity across individuals with the aim of providing subgroup membership and precise information about the specific network structures that differentiate subgroups. The algorithm has previously provided robust and accurate classification when evaluated with large-scale simulation studies but has not yet been validated on empirical data. Here, we investigate S-GIMME’s ability to differentiate, in a purely data-driven manner, between brain states explicitly induced through different tasks in a new fMRI dataset. The results provide new evidence that the algorithm was able to resolve, in an unsupervised data-driven manner, the differences between different active brain states in empirical fMRI data to segregate individuals and arrive at subgroup-specific network structures of edges. The ability to arrive at subgroups that correspond to empirically designed fMRI task conditions, with no biasing or priors, suggests this data-driven approach can be a powerful addition to existing methods for unsupervised classification of individuals based on their dynamic processes.
Blocked designs in functional magnetic resonance imaging (fMRI) are useful to localize functional brain areas. A blocked design consists of different blocks of trials of the same stimulus type and is characterized by three factors: the length of blocks, i.e., number of trials per blocks, the ordering of task and rest blocks, and the time between trials within one block. Optimal design theory was applied to find the optimal combination of these three design factors. Furthermore, different error structures were used within a general linear model for the analysis of fMRI data, and the maximin criterion was applied to find designs which are robust against misspecification of model parameters.
There is increasing use of functional imaging data to understand the macro-connectome of the human brain. Of particular interest is the structure and function of intrinsic networks (regions exhibiting temporally coherent activity both at rest and while a task is being performed), which account for a significant portion of the variance in functional MRI data. While networks are typically estimated based on the temporal similarity between regions (based on temporal correlation, clustering methods, or independent component analysis [ICA]), some recent work has suggested that these intrinsic networks can be extracted from the inter-subject covariation among highly distilled features, such as amplitude maps reflecting regions modulated by a task or even coordinates extracted from large meta analytic studies. In this paper our goal was to explicitly compare the networks obtained from a first-level ICA (ICA on the spatio-temporal functional magnetic resonance imaging (fMRI) data) to those from a second-level ICA (i.e., ICA on computed features rather than on the first-level fMRI data). Convergent results from simulations, task-fMRI data, and rest-fMRI data show that the second-level analysis is slightly noisier than the first-level analysis but yields strikingly similar patterns of intrinsic networks (spatial correlations as high as 0.85 for task data and 0.65 for rest data, well above the empirical null) and also preserves the relationship of these networks with other variables such as age (for example, default mode network regions tended to show decreased low frequency power for first-level analyses and decreased loading parameters for second-level analyses). In addition, the best-estimated second-level results are those which are the most strongly reflected in the input feature. In summary, the use of feature-based ICA appears to be a valid tool for extracting intrinsic networks. We believe it will become a useful and important approach in the study of the macro-connectome, particularly in the context of data fusion.
Decision making can be a complex process requiring the integration of several attributes of choice options. Understanding the neural processes underlying (uncertain) investment decisions is an important topic in neuroeconomics. We analyzed functional magnetic resonance imaging (fMRI) data from an investment decision study for stimulus-related effects. We propose a new technique for identifying activated brain regions: cluster, estimation, activation, and decision method. Our analysis is focused on clusters of voxels rather than voxel units. Thus, we achieve a higher signal-to-noise ratio within the unit tested and a smaller number of hypothesis tests compared with the often used General Linear Model (GLM). We propose to first conduct the brain parcellation by applying spatially constrained spectral clustering. The information within each cluster can then be extracted by the flexible dynamic semiparametric factor model (DSFM) dimension reduction technique and finally be tested for differences in activation between conditions. This sequence of Cluster, Estimation, Activation, and Decision admits a model-free analysis of the local fMRI signal. Applying a GLM on the DSFM-based time series resulted in a significant correlation between the risk of choice options and changes in fMRI signal in the anterior insula and dorsomedial prefrontal cortex. Additionally, individual differences in decision-related reactions within the DSFM time series predicted individual differences in risk attitudes as modeled with the framework of the mean-variance model.
Attention has been shown to modulate the visual evoked potential (VEP) recorded to reversing achromatic patterns. However, the chromatic onset VEP appears to be robust to attentional shifts. Functional magnetic resonance imaging (fMRI) responses to both chromatic and achromatic reversing patterns are also affected by attention. Resolution and comparison of these results is problematic due to differences in presentation mode, stimulus parameters, and the source of the response. Here, we report the results of experiments using comparable perceptual contrasts, pattern reversals, and a co-extensive and highly demanding multiple object tracking (MOT) task while exploring the effects of attentional modulation across both the chromatic (L − M) and (S − (L + M)) and the achromatic visual pathways. Our findings indicate that although achromatic VEPs are modulated by attention, chromatic VEPs are more robust to attentional modulation, even when using comparable stimulus presentation modes and in the presence of a highly demanding distractor task. In addition, we found that the majority of the modulation appears to be from a relative decrease in response due to the distractor task rather than a relative increase in response during heightened attention to the stimulus.
This chapter provides a cross-sectional overview of current neuroimaging techniques and signals used to investigate the processing of linguistically relevant speech units in the bilingual brain. These techniques are reviewed in the light of important contributions to the understanding of perceptual and production processes in different bilingual populations. The chapter is structured as follows. First, we discuss several non-invasive technologies that provide unique insights in the study of bilingual phonetics and phonology. This introductory section is followed by a brief review of the key brain regions and pathways that support the perception and production of speech units. Next, we discuss the neuromodulatory effects of different bilingual experiences on these brain regions from shorter to longer neural latencies and timescales. As we will show, bilingualism can significantly alter the time course, strength, and nature of the neural responses to speech, when compared with monolinguals.
Similar to adults with posttraumatic stress disorder, children with early life adversity show bias in memory for negative emotional stimuli. However, it is not well understood how childhood adversity impacts mechanisms underlying emotional memory. N = 56 children (8–14 years, 48% female) reported on adverse experiences including potentially traumatic events and underwent fMRI while attending to emotionally pleasant, neutral, or negative images. Post-scan, participants completed a cued recall test to assess memory for these images. Emotional difference-in-memory (DM) scores were computed by subtracting negative or positive from neutral recall performance. All children showed enhancing effects of emotion on recall, with no effect of trauma load. However, children with less trauma showed a larger emotional DM for both positive and negative stimuli when amygdala or anterior hippocampal activity was higher. In contrast, highly trauma-exposed children demonstrated a lower emotional DM with greater amygdala or hippocampal activity. This suggested that alternative neural mechanisms might support emotional enhancement of encoding in children with greater trauma load. Whole-brain analyses revealed that right fusiform activity during encoding positively correlated with both trauma load and successful later recall of positive images. Therefore, highly trauma-exposed children may use alternative, potentially adaptive neural pathways via the ventral visual stream to encode positive emotional events.
One in eight children experience early life stress (ELS), which increases risk for psychopathology. ELS, particularly neglect, has been associated with reduced responsivity to reward. However, little work has investigated the computational specifics of this disrupted reward response – particularly with respect to the neural response to Reward Prediction Errors (RPE) – a critical signal for successful instrumental learning – and the extent to which they are augmented to novel stimuli. The goal of the current study was to investigate the associations of abuse and neglect, and neural representation of RPE to novel and non-novel stimuli.
Methods
One hundred and seventy-eight participants (aged 10–18, M = 14.9, s.d. = 2.38) engaged in the Novelty task while undergoing functional magnetic resonance imaging. In this task, participants learn to choose novel or non-novel stimuli to win monetary rewards varying from $0 to $0.30 per trial. Levels of abuse and neglect were measured using the Childhood Trauma Questionnaire.
Results
Adolescents exposed to high levels of neglect showed reduced RPE-modulated blood oxygenation level dependent response within medial and lateral frontal cortices particularly when exploring novel stimuli (p < 0.05, corrected for multiple comparisons) relative to adolescents exposed to lower levels of neglect.
Conclusions
These data expand on previous work by indicating that neglect, but not abuse, is associated with impairments in neural RPE representation within medial and lateral frontal cortices. However, there was no association between neglect and behavioral impairments on the Novelty task, suggesting that these neural differences do not necessarily translate into behavioral differences within the context of the Novelty task.
This study aimed to evaluate a novel rTMS protocol for treatment-resistant depression (TRD), using an EEG 10–20 system guided dual-target accelerated approach of right lateral orbitofrontal cortex (lOFC) inhibition followed by left dorsolateral prefrontal cortex (dlPFC) excitation, along with comparing 20 Hz dlPFC accelerated TMS v. sham.
Methods
Seventy five patients participated in this trial consisting of 20 sessions over 5 consecutive days comparing dual-site (cTBS of right lOFC followed sequentially by 20 Hz rTMS of left dlPFC), active control (sham right lOFC followed by 20 Hz rTMS of left dlPFC) and sham control (sham for both targets). Resting-state fMRI was acquired prior to and following treatment.
Results
Hamilton Rating Scale for Depression (HRSD-24) scores were similarly significantly improved at 4 weeks in both the Dual and Single group relative to Sham. Planned comparisons immediately after treatment highlighted greater HRSD-24 clinical responders (Dual: 47.8% v. Single:18.2% v. Sham:4.3%, χ2 = 13.0, p = 0.002) and in PHQ-9 scores by day 5 in the Dual relative to Sham group. We further showed that accelerated 20 Hz stimulation targeting the left dlPFC (active control) is significantly better than sham at 4 weeks. Dual stimulation decreased lOFC-subcallosal cingulate functional connectivity. Greater baseline lOFC-thalamic connectivity predicted better therapeutic response, while decreased lOFC-thalamic connectivity correlated with better response.
Conclusions
Our novel accelerated dual TMS protocol shows rapid clinically relevant antidepressant efficacy which may be related to state-modulation. This study has implications for community-based accessible TMS without neuronavigation and rapid onset targeting suicidal ideation and accelerated discharge from hospital.
Studies suggest severe mental disorders (SMDs), such as schizophrenia, major depressive disorder and bipolar disorder, are associated with common alterations in brain activity, albeit with a graded level of impairment. However, discrepancies between study findings likely to results from both small sample sizes and the use of different functional magnetic resonance imaging (fMRI) tasks. To address these issues, data-driven meta-analytic approach designed to identify homogeneous brain co-activity patterns across tasks was conducted to better characterize the common and distinct alterations between these disorders.
Methods
A hierarchical clustering analysis was conducted to identify groups of studies reporting similar neuroimaging results, independent of task type and psychiatric diagnosis. A traditional meta-analysis (activation likelihood estimation) was then performed within each of these groups of studies to extract their aberrant activation maps.
Results
A total of 762 fMRI study contrasts were targeted, comprising 13 991 patients with SMDs. Hierarchical clustering analysis identified 5 groups of studies (meta-analytic groupings; MAGs) being characterized by distinct aberrant activation patterns across SMDs: (1) emotion processing; (2) cognitive processing; (3) motor processes, (4) reward processing, and (5) visual processing. While MAG1 was mostly commonly impaired, MAG2 was more impaired in schizophrenia, while MAG3 and MAG5 revealed no differences between disorder. MAG4 showed the strongest between-diagnoses differences, particularly in the striatum, posterior cingulate cortex, and ventromedial prefrontal cortex.
Conclusions
SMDs are characterized mostly by common deficits in brain networks, although differences between disorders are also present. This study highlights the importance of studying SMDs simultaneously rather than independently.
Neural predictors underlying variability in depression outcomes are poorly understood. Functional MRI measures of subgenual cortex connectivity, self-blaming and negative perceptual biases have shown prognostic potential in treatment-naïve, medication-free and fully remitting forms of major depressive disorder (MDD). However, their role in more chronic, difficult-to-treat forms of MDD is unknown.
Methods:
Forty-five participants (n = 38 meeting minimum data quality thresholds) fulfilled criteria for difficult-to-treat MDD. Clinical outcome was determined by computing percentage change at follow-up from baseline (four months) on the self-reported Quick Inventory of Depressive Symptomatology (16-item). Baseline measures included self-blame-selective connectivity of the right superior anterior temporal lobe with an a priori Brodmann Area 25 region-of-interest, blood-oxygen-level-dependent a priori bilateral amygdala activation for subliminal sad vs happy faces, and resting-state connectivity of the subgenual cortex with an a priori defined ventrolateral prefrontal cortex/insula region-of-interest.
Findings:
A linear regression model showed that baseline severity of depressive symptoms explained 3% of the variance in outcomes at follow-up (F[3,34] = .33, p = .81). In contrast, our three pre-registered neural measures combined, explained 32% of the variance in clinical outcomes (F[4,33] = 3.86, p = .01).
Conclusion:
These findings corroborate the pathophysiological relevance of neural signatures of emotional biases and their potential as predictors of outcomes in difficult-to-treat depression.
Attitudes toward risk and ambiguity significantly influence how individuals assess and value rewards. This fMRI study examines the reward valuation process under conditions of uncertainty and investigates the associated neural mechanisms in individuals who engage in nonsuicidal self-injury (NSSI) as a coping mechanism for psychological pain.
Methods
The study involved 44 unmedicated individuals who reported five or more NSSI episodes in the past year, along with 42 age-, sex-, handedness-, IQ-, and socioeconomic status-matched controls. During the fMRI scans, all participants were presented with decision-making scenarios involving uncertainty, both in terms of risk (known probabilities) and ambiguity (unknown probabilities).
Results
In the NSSI group, aversive attitudes toward ambiguity were correlated with increased emotion reactivity and greater method versatility. Whole-brain analysis revealed notable group-by-condition interactions in the right middle cingulate cortex and left hippocampus. Specifically, the NSSI group showed decreased neural activation under ambiguity v. risk compared to the control group. Moreover, reduced hippocampal activation under ambiguity in the NSSI group was associated with increased emotion regulation problems.
Conclusions
This study presents the first evidence of reduced brain activity in specific regions during value-based decision-making under conditions of ambiguity in individuals with NSSI. These findings have important clinical implications, particularly concerning emotion dysregulation in this population. This study indicates the need for interventions that support and guide individuals with NSSI to promote adaptive decision-making in the face of ambiguous uncertainty.
This chapter highlights some of the tools used for imaging features of the nervous system. The introduction defines the concepts of temporal and spatial resolution, the anatomical language used to describe structures in relation to one another, and planes of imaging, all of which are knowledge essential to understanding imaging figures. The chapter then describes both structural and functional imaging techniques and the figures that may accompany these scanning methods, including dissection; CT scans; PET scans; various applications of MRI scanning including arterial spin labeling, functional MRI, and diffusion tensor imaging for tract tracing; SPECT scans; and electroencephalography imaging, including a description of event-related potentials.
Recent theories suggest that for youth highly sensitive to incentives, perceiving more social threat may contribute to social anxiety (SA) symptoms. In 129 girls (ages 11–13) oversampled for shy/fearful temperament, we thus examined how interactions between neural responses to social reward (vs. neutral) cues (measured during anticipation of peer feedback) and perceived social threat in daily peer interactions (measured using ecological momentary assessment) predict SA symptoms two years later. No significant interactions emerged when neural reward function was modeled as a latent factor. Secondary analyses showed that higher perceived social threat was associated with more severe SA symptoms two years later only for girls with higher basolateral amygdala (BLA) activation to social reward cues at baseline. Interaction effects were specific to BLA activation to social reward (not threat) cues, though a main effect of BLA activation to social threat (vs. neutral) cues on SA emerged. Unexpectedly, interactions between social threat and BLA activation to social reward cues also predicted generalized anxiety and depression symptoms two years later, suggesting possible transdiagnostic risk pathways. Perceiving high social threat may be particularly detrimental for youth highly sensitive to reward incentives, potentially due to mediating reward learning processes, though this remains to be tested.
Major depressive disorder (MDD) is characterized by deficient reward functions in the brain. However, existing findings on functional alterations during reward anticipation, reward processing, and learning among MDD patients are inconsistent, and it was unclear whether a common reward system implicated in multiple reward functions is altered in MDD. Here we meta-analyzed 18 past studies that compared brain reward functions between adult MDD patients (N = 477, mean age = 26.50 years, female = 59.40%) and healthy controls (N = 506, mean age = 28.11 years, females = 55.58%), and particularly examined group differences across multiple reward functions. Jack-knife sensitivity and subgroup meta-analyses were conducted to test robustness of findings across patient comorbidity, task paradigm, and reward nature. Meta-regression analyses assessed the moderating effect of patient symptom severity and anhedonia scores. We found during reward anticipation, MDD patients showed lower activities in the lateral prefrontal-thalamus circuitry. During reward processing, patients displayed reduced activities in the right striatum and prefrontal cortex, but increased activities in the left temporal cortex. During reward learning, patients showed reduced activity in the lateral prefrontal–thalamic–striatal circuitry and the right parahippocampal–occipital circuitry but higher activities in bilateral cerebellum and the left visual cortex. MDD patients showed decreased activity in the right thalamus during both reward anticipation and learning, and in the right caudate during both reward processing and learning. Larger functional changes in MDD were observed among patients with more severe symptoms and higher anhedonia levels. The thalamic-striatal circuitry functional alterations could be the key neural mechanism underlying MDD patients overarching reward function deficiencies.
Cognitive behavioral therapy (CBT) is an effective treatment for patients with social anxiety disorder (SAD) or major depressive disorder (MDD), yet there is variability in clinical improvement. Though prior research suggests pre-treatment engagement of brain regions supporting cognitive reappraisal (e.g. dorsolateral prefrontal cortex [dlPFC]) foretells CBT response in SAD, it remains unknown if this extends to MDD or is specific to CBT. The current study examined associations between pre-treatment neural activity during reappraisal and clinical improvement in patients with SAD or MDD following a trial of CBT or supportive therapy (ST), a common-factors comparator arm.
Methods
Participants were 75 treatment-seeking patients with SAD (n = 34) or MDD (n = 41) randomized to CBT (n = 40) or ST (n = 35). Before randomization, patients completed a cognitive reappraisal task during functional magnetic resonance imaging. Additionally, patients completed clinician-administered symptom measures and a self-report cognitive reappraisal measure before treatment and every 2 weeks throughout treatment.
Results
Results indicated that pre-treatment neural activity during reappraisal differentially predicted CBT and ST response. Specifically, greater trajectories of symptom improvement throughout treatment were associated with less ventrolateral prefrontal cortex (vlPFC) activity for CBT patients, but more vlPFC activity for ST patients. Also, less baseline dlPFC activity corresponded with greater trajectories of self-reported reappraisal improvement, regardless of treatment arm.
Conclusions
If replicated, findings suggest individual differences in brain response during reappraisal may be transdiagnostically associated with treatment-dependent improvement in symptom severity, but improvement in subjective reappraisal following psychotherapy, more broadly.
Amygdala and dorsal anterior cingulate cortex responses to facial emotions have shown promise in predicting treatment response in medication-free major depressive disorder (MDD). Here, we examined their role in the pathophysiology of clinical outcomes in more chronic, difficult-to-treat forms of MDD.
Methods
Forty-five people with current MDD who had not responded to ⩾2 serotonergic antidepressants (n = 42, meeting pre-defined fMRI minimum quality thresholds) were enrolled and followed up over four months of standard primary care. Prior to medication review, subliminal facial emotion fMRI was used to extract blood-oxygen level-dependent effects for sad v. happy faces from two pre-registered a priori defined regions: bilateral amygdala and dorsal/pregenual anterior cingulate cortex. Clinical outcome was the percentage change on the self-reported Quick Inventory of Depressive Symptomatology (16-item).
Results
We corroborated our pre-registered hypothesis (NCT04342299) that lower bilateral amygdala activation for sad v. happy faces predicted favorable clinical outcomes (rs[38] = 0.40, p = 0.01). In contrast, there was no effect for dorsal/pregenual anterior cingulate cortex activation (rs[38] = 0.18, p = 0.29), nor when using voxel-based whole-brain analyses (voxel-based Family-Wise Error-corrected p < 0.05). Predictive effects were mainly driven by the right amygdala whose response to happy faces was reduced in patients with higher anxiety levels.
Conclusions
We confirmed the prediction that a lower amygdala response to negative v. positive facial expressions might be an adaptive neural signature, which predicts subsequent symptom improvement also in difficult-to-treat MDD. Anxiety reduced adaptive amygdala responses.
Bilinguals may choose to speak a language either at their own will or in response to an external demand, but the underlying neural mechanisms in the two contexts is poorly understood. In the present study, Chinese–English bilinguals named pairs of pictures in three conditions: during forced-switch, the naming language altered between pictures 1 and 2. During non-switch, the naming language used was the same. During free-naming, either the same or different languages were used at participants' own will. While behavioural switching costs were observed during free-naming and forced-switching, neuroimaging results showed that forced language selection (i.e., forced-switch and non-switch) is associated with left-lateralized frontal activations, which have been implicated in inhibitory control. Free language selection (i.e., free-naming), however, was associated with fronto-parietal activations, which have been implicated in self-initiated behaviours. These findings offer new insights into the neural differentiation of language control in forced and free language selection contexts.
Anorexia nervosa (AN) is a serious psychiatric illness that remains difficult to treat. Elucidating the neural mechanisms of AN is necessary to identify novel treatment targets and improve outcomes. A growing body of literature points to a role for dorsal fronto-striatal circuitry in the pathophysiology of AN, with increasing evidence of abnormal task-based fMRI activation within this network among patients with AN. Whether these abnormalities are present at rest and reflect fundamental differences in brain organization is unclear.
Methods
The current study combined resting-state fMRI data from patients with AN (n = 89) and healthy controls (HC; n = 92) across four studies, removing site effects using ComBat harmonization. First, the a priori hypothesis that dorsal fronto-striatal connectivity strength – specifically between the anterior caudate and dlPFC – differed between patients and HC was tested using seed-based functional connectivity analysis with small-volume correction. To assess specificity of effects, exploratory analyses examined anterior caudate whole-brain connectivity, amplitude of low-frequency fluctuations (ALFF), and node centrality.
Results
Compared to HC, patients showed significantly reduced right, but not left, anterior caudate-dlPFC connectivity (p = 0.002) in small-volume corrected analyses. Whole-brain analyses also identified reduced connectivity between the right anterior caudate and left superior frontal and middle frontal gyri (p = 0.028) and increased connectivity between the right anterior caudate and right occipital cortex (p = 0.038). No group differences were found in analyses of anterior caudate ALFF and node centrality.
Conclusions
Decreased coupling of dorsal fronto-striatal regions indicates that circuit-based abnormalities persist at rest and suggests this network may be a potential treatment target.