Functional connectivity between posterior hippocampus and retrosplenial complex predicts individual differences in navigational ability

Individuals vary widely in their ability to orient and navigate within the environment. Previous neuroimaging research has shown that hippocampus (HC) and scene‐responsive regions (retrosplenial complex [RSC] and parahippocampal gyrus/parahippocampal place area [PPA]) were crucial for spatial orienting and navigation. Resting‐state functional connectivity and a self‐reported questionnaire of navigational ability were used to examine the hypothesis that the pattern of reciprocal connections between these regions reflects individual differences in spatial navigation. It was found that the functional connectivity between the posterior HC and RSC was significantly higher in good than in poor navigators. These results confirmed the crucial role of hippocampal and extra‐hippocampal regions in spatial navigation and provided new insight into how spontaneous brain activity may account for individual differences in spatial ability. © 2016 Wiley Periodicals, Inc.     

Quantifying the variability of scene‐selective regions: Interindividual,interhemispheric, and sex differences

Scene‐selective regions (SSRs), including the parahippocampal place area (PPA), retrosplenial cortex (RSC), and transverse occipital sulcus (TOS), are among the most widely characterized functional regions in the human brain. However, previous studies have mostly focused on the commonality within each SSR, providing little information on different aspects of their variability. In a large group of healthy adults (N = 202), we used functional magnetic resonance imaging to investigate different aspects of topographical and functional variability within SSRs, including interindividual, interhemispheric, and sex differences. First, the PPA, RSC, and TOS were delineated manually for each individual. We then demonstrated that SSRs showed substantial interindividual variability in both spatial topography and functional selectivity. We further identified consistent interhemispheric differences in the spatial topography of all three SSRs, but distinct interhemispheric differences in scene selectivity. Moreover, we found that all three SSRs showed stronger scene selectivity in men than in women. In summary, our work thoroughly characterized the interindividual, interhemispheric, and sex variability of the SSRs and invites future work on the origin and functional significance of these variabilities. Additionally, we constructed the first probabilistic atlases for the SSRs, which provide the detailed anatomical reference for further investigations of the scene network. Hum Brain Mapp 38:2260–2275, 2017. © 2017 Wiley Periodicals, Inc.     

Functional connectivity constrains the category‐related organization of human ventral occipitotemporal cortex

One of the most robust and oft‐replicated findings in cognitive neuroscience is that several spatially distinct, functionally dissociable ventral occipitotemporal cortex (VOTC) regions respond preferentially to different categories of concrete entities. However, the determinants of this category‐related organization remain to be fully determined. One recent proposal is that privileged connectivity of these VOTC regions with other regions that store and/or process category‐relevant properties may be a major contributing factor. To test this hypothesis, we used a multicategory functional magnetic resonance imaging (MRI) localizer to individually define category‐related brain regions of interest (ROIs) in a large group of subjects (n = 33). We then used these ROIs in resting‐state functional connectivity MRI analyses to explore spontaneous functional connectivity among these regions. We demonstrate that during rest, distinct category‐preferential VOTC regions show differentially stronger functional connectivity with other regions that have congruent category‐preference, as defined by the functional localizer. Importantly, a “tool”‐preferential region in the left medial fusiform gyrus showed differentially stronger functional connectivity with other left lateralized cortical regions associated with perceiving and knowing about common tools—posterior middle temporal gyrus (involved in perception of nonbiological motion), lateral parietal cortex (critical for reaching, grasping, manipulating), and ventral premotor cortex (involved in storing/executing motor programs)—relative to other category‐related regions in VOTC of both the right and left hemisphere. Our findings support the claim that privileged connectivity with other cortical regions that store and/or process category‐relevant properties constrains the category‐related organization of VOTC. Hum Brain Mapp 36:2187–2206, 2015. © Published 2015. This article is a U.S. Government work and is in the public domain in the USA.     

Data‐driven approaches for tau‐PET imaging biomarkers in Alzheimer's disease

Previous positron emission tomography (PET) studies have quantified filamentous tau pathology using regions‐of‐interest (ROIs) based on observations of the topographical distribution of neurofibrillary tangles in post‐mortem tissue. However, such approaches may not take full advantage of information contained in neuroimaging data. The present study employs an unsupervised data‐driven method to identify spatial patterns of tau‐PET distribution, and to compare these patterns to previously published “pathology‐driven” ROIs. Tau‐PET patterns were identified from a discovery sample comprised of 123 normal controls and patients with mild cognitive impairment or Alzheimer's disease (AD) dementia from the Swedish BioFINDER cohort, who underwent [¹⁸F]AV1451 PET scanning. Associations with cognition were tested in a separate sample of 90 individuals from ADNI. BioFINDER [¹⁸F]AV1451 images were entered into a robust voxelwise stable clustering algorithm, which resulted in five clusters. Mean [¹⁸F]AV1451 uptake in the data‐driven clusters, and in 35 previously published pathology‐driven ROIs, was extracted from ADNI [¹⁸F]AV1451 scans. We performed linear models comparing [¹⁸F]AV1451 signal across all 40 ROIs to tests of global cognition and episodic memory, adjusting for age, sex, and education. Two data‐driven ROIs consistently demonstrated the strongest or near‐strongest effect sizes across all cognitive tests. Inputting all regions plus demographics into a feature selection routine resulted in selection of two ROIs (one data‐driven, one pathology‐driven) and education, which together explained 28% of the variance of a global cognitive composite score. Our findings suggest that [¹⁸F]AV1451‐PET data naturally clusters into spatial patterns that are biologically meaningful and that may offer advantages as clinical tools.     

Immediate memory for “when,where and what”: Short‐delay retrieval using dynamic naturalistic material

We investigated the neural correlates supporting three kinds of memory judgments after very short delays using naturalistic material. In two functional magnetic resonance imaging (fMRI) experiments, subjects watched short movie clips, and after a short retention (1.5–2.5 s), made mnemonic judgments about specific aspects of the clips. In Experiment 1, subjects were presented with two scenes and required to either choose the scene that happened earlier in the clip (“scene‐chronology”), or with a correct spatial arrangement (“scene‐layout”), or that had been shown (“scene‐recognition”). To segregate activity specific to seen versus unseen stimuli, in Experiment 2 only one probe image was presented (either target or foil). Across the two experiments, we replicated three patterns underlying the three specific forms of memory judgment. The precuneus was activated during temporal‐order retrieval, the superior parietal cortex was activated bilaterally for spatial‐related configuration judgments, whereas the medial frontal cortex during scene recognition. Conjunction analyses with a previous study that used analogous retrieval tasks, but a much longer delay (>1 day), demonstrated that this dissociation pattern is independent of retention delay. We conclude that analogous brain regions mediate task‐specific retrieval across vastly different delays, consistent with the proposal of scale‐invariance in episodic memory retrieval. Hum Brain Mapp 36:2495–2513, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

A majority rule approach for region-of-interest-guided streamline fiber tractography

Hand-drawn gray matter regions of interest (ROI) are often used to guide the estimation of white matter tractography, obtained from diffusion-weighted magnetic resonance imaging (DWI), in healthy and in patient populations. However, such ROIs are vulnerable to rater bias of the individual segmenting the ROIs, scan variability, and individual differences in neuroanatomy. In this report, a “majority rule” approach is introduced for ROI segmentation used to guide streamline tractography in white matter structures. DWI of one healthy participant was acquired in ten separate sessions using a 3 T scanner over the course of a month. Four raters identified ROIs within the left hemisphere [Cerebral Peduncle (CPED); Internal Capsule (IC); Hand Portion of the Motor Cortex, or Hand Bump, (HB)] using a group-established standard operating procedure for ROI definition to guide the estimation of streamline tracts within the corticospinal tract (CST). Each rater traced the ROIs twice for each scan session. The overlap of each rater’s two ROIs was used to define a representative ROI for each rater. These ROIs were combined to create a “majority rules” ROI, in which the rule requires that each voxel is selected by at least three of four raters. Reproducibility for ROIs and CST segmentations were analyzed with the Dice Similarity Coefficient (DSC). Intra-rater reliability for each ROI was high (DSCs ≥ 0.83). Inter-rater reliability was moderate to adequate (DSC range 0.54–0.75; lowest for IC). Using intersected majority rules ROIs, the resulting CST showed improved overlap (DSC = 0.82) in the estimated streamline tracks for the ten sessions. Despite high intra-rater reliability, there was lower inter-rater reliability consistent with the expectation of rater bias. Employing the majority rules method improved reliability in the overlap of the CST.     

Semantically defined subdomains of functional neuroimaging literature and their corresponding brain regions

The functional neuroimaging literature has become increasingly complex and thus difficult to navigate. This complexity arises from the rate at which new studies are published and from the terminology that varies widely from study‐to‐study and even more so from discipline‐to‐discipline. One way to investigate and manage this problem is to build a “semantic space” that maps the different vocabulary used in functional neuroimaging literature. Such a semantic space will also help identify the primary research domains of neuroimaging and their most commonly reported brain regions. In this work, we analyzed the multivariate semantic structure of abstracts in Neurosynth and found that there are six primary domains of the functional neuroimaging literature, each with their own preferred reported brain regions. Our analyses also highlight possible semantic sources of reported brain regions within and across domains because some research topics (e.g., memory disorders, substance use disorder) use heterogeneous terminology. Furthermore, we highlight the growth and decline of the primary domains over time. Finally, we note that our techniques and results form the basis of a “recommendation engine” that could help readers better navigate the neuroimaging literature.     

Scene-selective cortical regions in human and nonhuman primates

fMRI studies have revealed three scene-selective regions in human visual cortex [the parahippocampal place area (PPA), transverse occipital sulcus (TOS), and retrosplenial cortex (RSC)], which have been linked to higher-order functions such as navigation, scene perception/recognition, and contextual association. Here, we document corresponding (presumptively homologous) scene-selective regions in the awake macaque monkey, based on direct comparison to human maps, using identical stimuli and largely overlapping fMRI procedures. In humans, our results showed that the three scene-selective regions are centered near-but distinct from-the gyri/sulci for which they were originally named. In addition, all these regions are located within or adjacent to known retinotopic areas. Human RSC and PPA are located adjacent to the peripheral representation of primary and secondary visual cortex, respectively. Human TOS is located immediately anterior/ventral to retinotopic area V3A, within retinotopic regions LO-1, V3B, and/or V7. Mirroring the arrangement of human regions fusiform face area (FFA) and PPA (which are adjacent to each other in cortex), the presumptive monkey homolog of human PPA is located adjacent to the monkey homolog of human FFA, near the posterior superior temporal sulcus. Monkey TOS includes the region predicted from the human maps (macaque V4d), extending into retinotopically defined V3A. A possible monkey homolog of human RSC lies in the medial bank, near peripheral V1. Overall, our findings suggest a homologous neural architecture for scene-selective regions in visual cortex of humans and nonhuman primates, analogous to the face-selective regions demonstrated earlier in these two species.     

Different duration of at-risk mental state associated with neurofunctional abnormalities. A multimodal imaging study

Objectives: Neurofunctional alterations are correlates of vulnerability to psychosis, as well as of the disorder itself. How these abnormalities relate to different probabilities for later transition to psychosis is unclear. We investigated vulnerability‐ versus disease‐related versus resilience biomarkers of psychosis during working memory (WM) processing in individuals with an at‐risk mental state (ARMS). Experimental design: Patients with “first‐episode psychosis” (FEP, n = 21), short‐term ARMS (ARMS‐ST, n = 17), long‐term ARMS (ARMS‐LT, n = 16), and healthy controls (HC, n = 20) were investigated with an n‐back WM task. We examined functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging (sMRI) data in conjunction using biological parametric mapping (BPM) toolbox. Principal observations: There were no differences in accuracy, but the FEP and the ARMS‐ST group had longer reaction times compared with the HC and the ARMS‐LT group. With the 2‐back > 0‐back contrast, we found reduced functional activation in ARMS‐ST and FEP compared with the HC group in parietal and middle frontal regions. Relative to ARMS‐LT individuals, FEP patients showed decreased activation in the bilateral inferior frontal gyrus and insula, and in the left prefrontal cortex. Compared with the ARMS‐LT, the ARMS‐ST subjects showed reduced activation in the right inferior frontal gyrus and insula. Reduced insular and prefrontal activation was associated with gray matter volume reduction in the same area in the ARMS‐LT group. Conclusions: These findings suggest that vulnerability to psychosis was associated with neurofunctional alterations in fronto‐temporo‐parietal networks in a WM task. Neurofunctional differences within the ARMS were related to different duration of the prodromal state and resilience factors. Hum Brain Mapp 33:2281–2294, 2012. © 2011 Wiley Periodicals, Inc.     

Methods for identifying subject‐specific abnormalities in neuroimaging data

Algorithms that are capable of capturing subject‐specific abnormalities (SSA) in neuroimaging data have long been an area of focus for diverse neuropsychiatric conditions such as multiple sclerosis, schizophrenia, and traumatic brain injury. Several algorithms have been proposed that define SSA in patients (i.e., comparison group) relative to image intensity levels derived from healthy controls (HC) (i.e., reference group) based on extreme values. However, the assumptions underlying these approaches have not always been fully validated, and may be dependent on the statistical distributions of the transformed data. The current study evaluated variations of two commonly used techniques (“pothole” method and standardization with an independent reference group) for identifying SSA using simulated data (derived from normal, t and chi‐square distributions) and fractional anisotropy maps derived from 50 HC. Results indicated substantial group‐wise bias in the estimation of extreme data points using the pothole method, with the degree of bias being inversely related to sample size. Statistical theory was utilized to develop a distribution‐corrected z‐score (DisCo‐Z) threshold, with additional simulations demonstrating elimination of the bias and a more consistent estimation of extremes based on expected distributional properties. Data from previously published studies examining SSA in mild traumatic brain injury were then re‐analyzed using the DisCo‐Z method, with results confirming the evidence of group‐wise bias. We conclude that the benefits of identifying SSA in neuropsychiatric research are substantial, but that proposed SSA approaches require careful implementation under the different distributional properties that characterize neuroimaging data. Hum Brain Mapp 35:5457–5470, 2014. © 2014 Wiley Periodicals, Inc.     

Perceived communicative intent in gesture and language modulates the superior temporal sulcus

Behavioral evidence and theory suggest gesture and language processing may be part of a shared cognitive system for communication. While much research demonstrates both gesture and language recruit regions along perisylvian cortex, relatively less work has tested functional segregation within these regions on an individual level. Additionally, while most work has focused on a shared semantic network, less has examined shared regions for processing communicative intent. To address these questions, functional and structural MRI data were collected from 24 adult participants while viewing videos of an experimenter producing communicative, Participant‐Directed Gestures (PDG) (e.g., “Hello, come here”), noncommunicative Self‐adaptor Gestures (SG) (e.g., smoothing hair), and three written text conditions: (1) Participant‐Directed Sentences (PDS), matched in content to PDG, (2) Third‐person Sentences (3PS), describing a character's actions from a third‐person perspective, and (3) meaningless sentences, Jabberwocky (JW). Surface‐based conjunction and individual functional region of interest analyses identified shared neural activation between gesture (PDGvsSG) and language processing using two different language contrasts. Conjunction analyses of gesture (PDGvsSG) and Third‐person Sentences versus Jabberwocky revealed overlap within left anterior and posterior superior temporal sulcus (STS). Conjunction analyses of gesture and Participant‐Directed Sentences to Third‐person Sentences revealed regions sensitive to communicative intent, including the left middle and posterior STS and left inferior frontal gyrus. Further, parametric modulation using participants' ratings of stimuli revealed sensitivity of left posterior STS to individual perceptions of communicative intent in gesture. These data highlight an important role of the STS in processing participant‐directed communicative intent through gesture and language. Hum Brain Mapp 37:3444–3461, 2016. © 2016 Wiley Periodicals, Inc .     

The cerebellum after trauma: Resting‐state functional connectivity of the cerebellum in posttraumatic stress disorder and its dissociative subtype

The cerebellum plays a key role not only in motor function but also in affect and cognition. Although several psychopathological disorders have been associated with overall cerebellar dysfunction, it remains unclear whether different regions of the cerebellum contribute uniquely to psychopathology. Accordingly, we compared seed‐based resting‐state functional connectivity of the anterior cerebellum (lobule IV–V), of the posterior cerebellum (Crus I), and of the anterior vermis across posttraumatic stress disorder (PTSD; n = 65), its dissociative subtype (PTSD + DS; n = 37), and non‐trauma‐exposed healthy controls (HC; n = 47). Here, we observed decreased functional connectivity of the anterior cerebellum and anterior vermis with brain regions involved in somatosensory processing, multisensory integration, and bodily self‐consciousness (temporo‐parietal junction, postcentral gyrus, and superior parietal lobule) in PTSD + DS as compared to PTSD and HC. Moreover, the PTSD + DS group showed increased functional connectivity of the posterior cerebellum with cortical areas related to emotion regulation (ventromedial prefrontal and orbito‐frontal cortex, subgenual anterior cingulum) as compared to PTSD. By contrast, PTSD showed increased functional connectivity of the anterior cerebellum with cortical areas associated with visual processing (fusiform gyrus), interoceptive awareness (posterior insula), memory retrieval, and contextual processing (hippocampus) as compared to HC. Finally, we observed decreased functional connectivity between the posterior cerebellum and prefrontal regions involved in emotion regulation, in PTSD as compared to HC. These findings not only highlight the crucial role of each cerebellar region examined in the psychopathology of PTSD but also reveal unique alterations in functional connectivity distinguishing the dissociative subtype of PTSD versus PTSD.     

Chronnectome fingerprinting: Identifying individuals and predicting higher cognitive functions using dynamic brain connectivity patterns

The human brain is a large, interacting dynamic network, and its architecture of coupling among brain regions varies across time (termed the “chronnectome”). However, very little is known about whether and how the dynamic properties of the chronnectome can characterize individual uniqueness, such as identifying individuals as a “fingerprint” of the brain. Here, we employed multiband resting‐state functional magnetic resonance imaging data from the Human Connectome Project (N = 105) and a sliding time‐window dynamic network analysis approach to systematically examine individual time‐varying properties of the chronnectome. We revealed stable and remarkable individual variability in three dynamic characteristics of brain connectivity (i.e., strength, stability, and variability), which was mainly distributed in three higher order cognitive systems (i.e., default mode, dorsal attention, and fronto‐parietal) and in two primary systems (i.e., visual and sensorimotor). Intriguingly, the spatial patterns of these dynamic characteristics of brain connectivity could successfully identify individuals with high accuracy and could further significantly predict individual higher cognitive performance (e.g., fluid intelligence and executive function), which was primarily contributed by the higher order cognitive systems. Together, our findings highlight that the chronnectome captures inherent functional dynamics of individual brain networks and provides implications for individualized characterization of health and disease.     

Analysis of a distributed neural system involved in spatial information, novelty, and memory processing

Perceiving a complex visual scene and encoding it into memory involves a hierarchical distributed network of brain regions, most notably the hippocampus (HIPP), parahippocampal gyrus (PHG), lingual gyrus (LNG), and inferior frontal gyrus (IFG). Lesion and imaging studies in humans have suggested that these regions are involved in spatial information processing as well as novelty and memory encoding; however, the relative contributions of these regions of interest (ROIs) are poorly understood. This study investigated regional dissociations in spatial information and novelty processing in the context of memory encoding using a 2 x 2 factorial design with factors Novelty (novel vs. repeated) and Stimulus (viewing scenes with rich vs. poor spatial information). Greater activation was observed in the right than left hemisphere; however, hemispheric effects did not differ across regions, novelty, or stimulus type. Significant novelty effects were observed in all four regions. A significant ROI x Stimulus interaction was observed - spatial information processing effects were largest effects in the LNG, significant in the PHG and HIPP and nonsignificant in the IFG. Novelty processing was stimulus dependent in the LNG and stimulus independent in the PHG, HIPP, and IFG. Analysis of the profile of Novelty x Stimulus interaction across ROIs provided evidence for a hierarchical independence in novelty processing characterized by increased dissociation from spatial information processing. Despite these differences in spatial information processing, memory performance for novel scenes with rich and poor spatial information was not significantly different. Memory performance was inversely correlated with right IFG activation, suggesting the involvement of this region in strategically flawed encoding effort. Stepwise regression analysis revealed that memory encoding accounted for only a small fraction of the variance (< 16%) in medial temporal lobe activation. The implications of these results for spatial information, novelty, and memory processing in each stage of the distributed network are discussed.     

Functional connectome fingerprinting accuracy in youths and adults is similar when examined on the same day and 1.5‐years apart

Pioneering studies have shown that individual correlation measures from resting‐state functional magnetic resonance imaging studies can identify another scan from that same individual. This method is known as “connectotyping” or functional connectome “fingerprinting.” We analyzed a unique dataset of 12–30 years old (N = 140) individuals who had two distinct resting state scans on the same day and again 12–18 months later to assess the sensitivity and specificity of fingerprinting accuracy across different time scales (same day, ~1.5 years apart) and developmental periods (youths, adults). Sensitivity and specificity to identify one's own scan was high (average AUC = 0.94), although it was significantly higher in the same day (average AUC = 0.97) than 1.5‐years later (average AUC = 0.91). Accuracy in youths (average AUC = 0.93) was not significantly different from adults (average AUC = 0.96). Multiple statistical methods revealed select connections from the Frontoparietal, Default, and Dorsal Attention networks enhanced the ability to identify an individual. Identification of these features generalized across datasets and improved fingerprinting accuracy in a longitudinal replication data set (N = 208). These results provide a framework for understanding the sensitivity and specificity of fingerprinting accuracy in adolescents and adults at multiple time scales. Importantly, distinct features of one's “fingerprint” contribute to one's uniqueness, suggesting that cognitive and default networks play a primary role in the individualization of one's connectome.     

Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease

Alzheimer's disease (AD) can present with distinct clinical variants. Identifying the earliest neurodegenerative changes associated with each variant has implications for early diagnosis, and for understanding the mechanisms that underlie regional vulnerability and disease progression in AD. We performed voxel‐based morphometry to detect atrophy patterns in early clinical stages of four AD phenotypes: Posterior cortical atrophy (PCA, “visual variant,” n = 93), logopenic variant primary progressive aphasia (lvPPA, “language variant,” n = 74), and memory‐predominant AD categorized as early age‐of‐onset (EOAD, <65 years, n = 114) and late age‐of‐onset (LOAD, >65 years, n = 114). Patients with each syndrome were stratified based on: (1) degree of functional impairment, as measured by the clinical dementia rating (CDR) scale, and (2) overall extent of brain atrophy, as measured by a neuroimaging approach that sums the number of brain voxels showing significantly lower gray matter volume than cognitively normal controls (n = 80). Even at the earliest clinical stage (CDR = 0.5 or bottom quartile of overall atrophy), patients with each syndrome showed both common and variant‐specific atrophy. Common atrophy across variants was found in temporoparietal regions that comprise the posterior default mode network (DMN). Early syndrome‐specific atrophy mirrored functional brain networks underlying functions that are uniquely affected in each variant: Language network in lvPPA, posterior cingulate cortex‐hippocampal circuit in amnestic EOAD and LOAD, and visual networks in PCA. At more advanced stages, atrophy patterns largely converged across AD variants. These findings support a model in which neurodegeneration selectively targets both the DMN and syndrome‐specific vulnerable networks at the earliest clinical stages of AD. Hum Brain Mapp 36:4421–4437, 2015. © 2015 Wiley Periodicals, Inc .     

Gray matter alterations in early aging: A diffusion magnetic resonance imaging study

Many studies have observed altered neurofunctional and structural organization in the aging brain. These observations from functional neuroimaging studies show a shift in brain activity from the posterior to the anterior regions with aging (PASA model), as well as a decrease in cortical thickness, which is more pronounced in the frontal lobe followed by the parietal, occipital, and temporal lobes (retrogenesis model). However, very little work has been done using diffusion MRI (dMRI) with respect to examining the structural tissue alterations underlying these neurofunctional changes in the gray matter. Thus, for the first time, we propose to examine gray matter changes using diffusion MRI in the context of aging. In this work, we propose a novel dMRI based measure of gray matter “heterogeneity” that elucidates these functional and structural models (PASA and retrogenesis) of aging from the viewpoint of diffusion MRI. In a cohort of 85 subjects (all males, ages 15–55 years), we show very high correlation between age and “heterogeneity” (a measure of structural layout of tissue in a region‐of‐interest) in specific brain regions. We examine gray matter alterations by grouping brain regions into anatomical lobes as well as functional zones. Our findings from dMRI data connects the functional and structural domains and confirms the “retrogenesis” hypothesis of gray matter alterations while lending support to the neurofunctional PASA model of aging in addition to showing the preservation of paralimbic areas during healthy aging. Hum Brain Mapp 35:3841–3856, 2014. © 2013 Wiley Periodicals, Inc.     

What does the beck depression inventory measure in myocardial infarction patients? a psychometric approach using item response theory and person‐fit

Observed associations between depression following myocardial infarction (MI) and adverse cardiac outcomes could be overestimated due to patients’ tendency to over report somatic depressive symptoms. This study was aimed to investigate this issue with modern psychometrics, using item response theory (IRT) and person‐fit statistics to investigate if the Beck Depression Inventory (BDI) measures depression or something else among MI‐patients. An IRT‐model was fit to BDI‐data of 1135 MI patients. Patients’ adherence to this IRT‐model was investigated with person‐fit statistics. Subgroups of “atypical” (low person‐fit) and “prototypical” (high person‐fit) responders were identified and compared in terms of item‐response patterns, psychiatric diagnoses, socio‐demographics and somatic factors. In the IRT model, somatic items had lower thresholds compared to depressive mood/cognition items. Empirically identified “atypical” responders (n = 113) had more depressive mood/cognitions, scored lower on somatic items and more often had a Comprehensive International Diagnostic Interview (CIDI) depressive diagnosis than “prototypical” responders (n = 147). Additionally, “atypical” responders were younger and more likely to smoke. In conclusion, the BDI measures somatic symptoms in most MI patients, but measures depression in a subgroup of patients with atypical response patterns. The presented approach to account for interpersonal differences in item responding could help improve the validity of depression assessments in somatic patients. Copyright © 2015 John Wiley & Sons, Ltd.     

Vulnerabilities in sequencing and task switching in healthy youth offspring of parents with mood disorders

Introduction: Visuospatial processing and task switching are impaired in individuals with mood disorders. It is unknown whether early deficits are present before mood symptom on set or are related to risk for a specific type of mood disorder. To investigate, we compared visual attention and task switching during sequencing among never-disordered youth with parental family histories of bipolar (BD) and major depressive disorders (MDD) and healthy controls (HC) with no personal or family history of psychopathology.

Method: 8–17-year-old youth of parents with BD (n = 31, “BD-risk”), youth of parents with MDD (n = 49, “MDD-risk”), and demographically similar HC (n = 31, “HC”) were examined using the Delis–Kaplan Executive Functioning System Trail Making Test. Seed-based resting-state functional connectivity (RSFC) was collected from a subset of 88 participants (25 BD-risk, 37 MDD-risk, 26 HC) to investigate group differences in RSFC related to visuospatial processing.

Results: BD-risk and MDD-risk offspring had impaired sequencing and task switching, demonstrated by reduced scores on visual scanning, F(2, 108) = 4.12, p = .02, number sequencing, F(2, 88) = 4.75, p = .01, letter sequencing, F(2, 108) = 4.24, p = .02, and number–letter sequencing, F(2, 108) = 4.66, p = .01, compared to scores in HC. RSFC between the posterior cingulate (PCC) and clusters in the subcallosal cortex, amygdala, and hippocampus significantly differed among HC, BD-risk, and MDD-risk groups. PCC-subcallosal/limbic RSFC was positively coupled in the MDD-risk and BD-risk groups and negatively coupled in HCs.

Conclusions: Youth at familial risk for mood disorders demonstrate visuospatial deficits early in the processing stream. Improved methods for identifying at-risk children with the earliest possible neurocognitive impairments may inform remediation strategies that could prevent mood disorders.