Jatin G. Vaidya

Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia.

Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical–subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences.

On the temporal stability of personality: Evidence for differential stability and the role of life experiences.

The authors investigated the stability of personality and trait affect in young adults. In Studies 1 and 2, young adults were retested on a Big Five personality measure and a trait affect inventory over a 2.5-year and a 2-month period, respectively. Results from Study 1 point to positive mean-level changes; participants scored higher on Extraversion, Openness, Agreeableness, and Conscientiousness at Time 2. Affectively, participants experienced less negative affect and more positive affect at Time 2. Results from both retests provide clear evidence of differential stability. Affective traits were consistently less stable than the Big Five. Other analyses suggest that life events influence the stability of affective traits more than the Big Five.

Differential Stability and Individual Growth Trajectories of Big Five and Affective Traits During Young Adulthood

Big Five and affective traits were measured at three assessments when participants were on average 18, 21, and 24 years old. Rank-order stability analyses revealed that stability correlations tended to be higher across the second compared to the first retest interval; however, affective traits consistently were less stable than the Big Five. Median stability coefficients for the Big Five increased from .62 (Time 1 vs. Time 2) to .70 (Time 2 to Time 3); parallel increases also were observed for measures of negative affectivity (median rs=.49 and .55, respectively) and positive affectivity (median rs=.48 and .57, respectively). Growth curve analyses revealed significant change on each of the Big Five and affective traits, although many of the scales also showed significant variability in individual trajectories. Thus, rank-order stability is increasing for a range of personality traits, although there also is significant variability in change trajectories during young adulthood.

Visual Hallucinations Are Associated With Hyperconnectivity Between the Amygdala and Visual Cortex in People With a Diagnosis of Schizophrenia

INTRODUCTION While auditory verbal hallucinations (AH) are a cardinal symptom of schizophrenia, people with a diagnosis of schizophrenia (SZ) may also experience visual hallucinations (VH). In a retrospective analysis of a large sample of SZ and healthy controls (HC) studied as part of the functional magnetic resonance imaging (fMRI) Biomedical Informatics Research Network (FBIRN), we asked if SZ who endorsed experiencing VH during clinical interviews had greater connectivity between visual cortex and limbic structures than SZ who did not endorse experiencing VH. METHODS We analyzed resting state fMRI data from 162 SZ and 178 age- and gender-matched HC. SZ were sorted into groups according to clinical ratings on AH and VH: SZ with VH (VH-SZ; n = 45), SZ with AH but no VH (AH-SZ; n = 50), and SZ with neither AH nor VH (NoH-SZ; n = 67). Our primary analysis was seed based, extracting connectivity between visual cortex and the amygdala (because of its role in fear and negative emotion) and visual cortex and the hippocampus (because of its role in memory). RESULTS Compared with the other groups, VH-SZ showed hyperconnectivity between the amygdala and visual cortex, specifically BA18, with no differences in connectivity among the other groups. In a voxel-wise, whole brain analysis comparing VH-SZ with AH-SZ, the amygdala was hyperconnected to left temporal pole and inferior frontal gyrus in VH-SZ, likely due to their more severe thought broadcasting. CONCLUSIONS VH-SZ have hyperconnectivity between subcortical areas subserving emotion and cortical areas subserving higher order visual processing, providing biological support for distressing VH in schizophrenia.

Aging and alexithymia: association with reduced right rostral cingulate volume.

OBJECTIVES Previous studies have linked alexithymia to an inability to process emotions appropriately. Older persons show changes in emotion processing and have higher alexithymia scores. Because the anterior cingulate cortex (ACC) is one of the regions showing earlier decline in late-life, and alexithymia seems to be related to a dysfunction in right hemisphere regions including the ACC subserving affective processes, the present study sought to test the hypothesis that reduced ACC volume accounts for the association between older age and alexithymia. DESIGN Correlation analyses between functionally distinct ACC subregions, age and alexithymia features. SETTING University of Iowa. PARTICIPANTS Twenty-four healthy volunteers aged between 24 and 79 years. MEASUREMENTS Psychiatric and neuropsychological assessment and assessment of alexithymia using the 20-item Toronto Alexithymia Scale. High-resolution magnetic resonance imaging, and in-house developed methods for ACC parcellation. RESULTS Older age directly correlated with higher overall alexithymia and reduced bilateral rostral and right dorsal ACC gray matter volume. Furthermore, higher alexithymia scores correlated with reduced right rostral ACC volume. This correlation seems to be influenced primarily by Factor 3 of the alexithymia scale measuring diversion of attention to external details in place of internal feelings. CONCLUSIONS These results suggest that alexithymia in older age may be a result of structural changes in the right rostral ACC.

Effects of Chronic Marijuana Use on Brain Activity During Monetary Decision-Making

Marijuana (MJ) acutely acts on cannabinoid receptors that are found in numerous brain regions, including those involved in reward processing and decision-making. However, it remains unclear how long-term, chronic MJ use alters reward-based decision-making. In the present study, using [15O]water PET imaging, we measured brain activity in chronic MJ users, who underwent monitored abstinence from MJ for approximately 24 h before imaging, and control participants, while they took part in the Iowa Gambling Task (IGT), a monetary decision making task that strongly relies on the ventromedial prefrontal cortex (vmPFC). During PET imaging, participants took part in the standard and a variant version of the IGT as well as a control task. Chronic MJ users performed equally well on the standard IGT, but significantly worse than controls on the variant IGT. Chronic MJ users and control subjects showed increased regional cerebral blood flow (rCBF) in the vmPFC on both versions of the IGT compared to the control task. In the two-group comparison, chronic MJ users showed significantly greater rCBF than controls in the vmPFC on the standard IGT and greater activity in the cerebellum on both versions of the IGT. Furthermore, duration of use, but not age of first use, was associated with greater activity in the vmPFC. Thus, chronic MJ users tend to strongly recruit neural circuitry involved in decision-making and reward processing (vmPFC), and probabilistic learning (cerebellum) when performing the IGT.

A Comparative Developmental Study of Impulsivity in Rats and Humans: The Role of Reward Sensitivity

Abstract: The present study was conducted to test the hypothesis that differences in reward sensitivity between adolescents and adults account for differences in impulsivity. In a comparative study, we examined preferences for various concentrations of sucrose solutions as an operational measure of reward sensitivity in adolescent and adult rats and humans. Humans also completed self‐report measures of impulsivity and reward sensitivity. There was some indication that adolescents preferred sweeter solutions compared to adults. Also, adolescents scored substantially higher on impulsivity. However, adolescents and adults did not differ in self‐ratings of reward sensitivity and personality scores were not consistently related to sucrose preferences. The data highlight some of the benefits and issues that arise with developing comparative measures in humans and animals. Future comparative research using alternative behavioral paradigms is necessary to determine if and how changes in reward sensitivity influence developmental shifts in impulsivity.

Aging, grey matter, and blood flow in the anterior cingulate cortex.

The anterior cingulate cortex (ACC) is thought to be the neuroanatomical interface between emotion and cognition. Because effective emotion-cognition interactions are essential to optimal decision making, clarifying how the functionality of the ACC changes in older age using functional imaging holds great promise for ultimately understanding what contributes to the psychological changes occurring in late life. However, the interpretation of functional imaging studies is complicated by the fact that aging is associated with changes in grey matter volume and in the cerebral vasculature. In the present study, we obtained high-resolution structural magnetic resonance (MR) imaging data and quantitative blood flow images to examine the association between aging, blood flow, and grey matter volume in the ACC. Twenty-six healthy individuals between 25 and 79 years of age underwent quantitative [15O]water positron emission tomography (PET) imaging. The ACC was traced onto tissue-classified images derived from T1- and T2-weighted MRIs using previously defined methods. The ACC was divided into dorsal, rostral, and subgenual regions. Age was negatively correlated with blood flow in dorsal and rostral ACC regions. Effects were weaker but in a similar direction for the subgenual ACC. While older age and lower blood flow were both associated with smaller rostral ACC grey matter volumes, mediation analysis revealed that grey matter volume only partially mediated the effect of age on blood flow in the rostral ACC. Neural alterations not detectable on MR images may lead to reduced blood flow due to fewer and/or less metabolically active neurons. Alternatively, lower blood flow may be a cause, rather than a consequence, of smaller grey matter volume in the ACC.

Age-group differences in facets of positive and negative affect

Objectives: The higher order structure of Positive Affect (PA) and Negative Affect (NA) is comparable in self-report affect data from younger and older adults. The current study advances this work by comparing the factor structure of facets of PA and NA in older and younger adults using exploratory and confirmatory factor analyses. Method: Older (N = 203; M age = 73.5 years, range 65–92) and younger (N = 349; M age = 19.1 years, range 18–30) adults completed the Positive and Negative Affect Schedule–Expanded Form (PANAS-X) (Watson, D., & Clark, L.A. (1999). Manual for the Positive and Negative Affect Schedule -- Expanded Form. Iowa City, IA: The University of Iowa), which measures General PA and NA as well as three facets of PA (Joviality, Self-Assurance, and Attentiveness) and four facets of NA (Fear, Sadness, Guilt, and Hostility). Results: Item-level exploratory factor analyses of the facet scales revealed structures that were similar in older and younger adults; however, older adult solutions were more diffuse and diverged more from the PANAS-X scale structure. The facet of Sadness exhibited the largest age-group difference, relating more to guilt and anxiety in older than younger adults. Conclusion: Older adults may discriminate less amongst specific affect terms or may experience greater affective heterogeneity. Further, Sadness may manifest in age-specific ways. The construct variance of Sadness, and how this issue might be related to the assessment of depression in older adults, is discussed.

Prefrontal cortex white matter tracts in prodromal Huntington disease

Huntington disease (HD) is most widely known for its selective degeneration of striatal neurons but there is also growing evidence for white matter (WM) deterioration. The primary objective of this research was to conduct a large‐scale analysis using multisite diffusion‐weighted imaging (DWI) tractography data to quantify diffusivity properties along major prefrontal cortex WM tracts in prodromal HD. Fifteen international sites participating in the PREDICT‐HD study collected imaging and neuropsychological data on gene‐positive HD participants without a clinical diagnosis (i.e., prodromal) and gene‐negative control participants. The anatomical prefrontal WM tracts of the corpus callosum (PFCC), anterior thalamic radiations (ATRs), inferior fronto‐occipital fasciculi (IFO), and uncinate fasciculi (UNC) were identified using streamline tractography of DWI. Within each of these tracts, tensor scalars for fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity coefficients were calculated. We divided prodromal HD subjects into three CAG‐age product (CAP) groups having Low, Medium, or High probabilities of onset indexed by genetic exposure. We observed significant differences in WM properties for each of the four anatomical tracts for the High CAP group in comparison to controls. Additionally, the Medium CAP group presented differences in the ATR and IFO in comparison to controls. Furthermore, WM alterations in the PFCC, ATR, and IFO showed robust associations with neuropsychological measures of executive functioning. These results suggest long‐range tracts essential for cross‐region information transfer show early vulnerability in HD and may explain cognitive problems often present in the prodromal stage. Hum Brain Mapp 36:3717–3732, 2015.