Comparing the Iowa and Soochow Gambling Tasks in Opiate Users

The Iowa Gambling Task (IGT) is in many respects the gold standard for demonstrating decision making in drug using groups. However, it is not clear how basic task properties such as the frequency and magnitude of rewards and losses affect choice behavior in drug users and even in healthy players. In this study, we used a variant of the IGT, the Soochow Gambling Task (SGT), to observe choice behavior in opiate users and healthy decision makers in a task where reward frequency is not confounded with the long-term outcome of each alternative. In both opiate users (n = 26) and healthy controls (n = 27), we show that reward frequency strongly influences choice behavior in the IGT and SGT. Neither group showed a consistent preference across tasks for alternatives with good long-term outcomes, but rather, subjects appeared to prefer alternatives that win most frequently. We interpret this as evidence to suggest that healthy players perform better than opiate users on the IGT because they are able to utilize gain–loss frequencies to guide their choice behavior on the task. This challenges the previous notion that poorer performance on the IGT in drug users is due to an inability to be guided by future consequences

Functional brain imaging studies of youth depression: A systematic review

AbstractBackgroundThere is growing interest in understanding the neurobiology of major depressive disorder (MDD) in youth, particularly in the context of neuroimaging studies. This systematic review provides a timely comprehensive account of the available functional magnetic resonance imaging (fMRI) literature in youth MDD.MethodsA literature search was conducted using PubMED, PsycINFO and Science Direct databases, to identify fMRI studies in younger and older youth with MDD, spanning 13–18 and 19–25years of age, respectively.ResultsTwenty-eight studies focusing on 5 functional imaging domains were identified, namely emotion processing, cognitive control, affective cognition, reward processing and resting-state functional connectivity. Elevated activity in “extended medial network” regions including the anterior cingulate, ventromedial and orbitofrontal cortices, as well as the amygdala was most consistently implicated across these five domains. For the most part, findings in younger adolescents did not differ from those in older youth; however a general comparison of findings in both groups compared to adults indicated differences in the domains of cognitive control and affective cognition.ConclusionsYouth MDD is characterized by abnormal activations in ventromedial frontal regions, the anterior cingulate and amygdala, which are broadly consistent with the implicated role of medial network regions in the pathophysiology of depression. Future longitudinal studies examining the effects of neurodevelopmental changes and pubertal maturation on brain systems implicated in youth MDD will provide a more comprehensive neurobiological model of youth depression

Alterations in dorsal and ventral posterior cingulate connectivity in APOE ε4 carriers at risk of Alzheimer's disease

Background Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns. Aims To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE 4) allele. Method Participants were 22 SMC carrying the APOE ɛ4 allele (ɛ4+; mean age 72.18 years) and 58 SMC non-carriers (ɛ4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored. Results ɛ4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity. Conclusions The results provide the first evidence that ɛ4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity

Can understanding reward help illuminate anhedonia?

Purpose of review: The goal of this paper is to examine how reward processing might help us understand the symptom of anhedonia. Recent findings: There are extensive reviews exploring the relationship between responses to rewarding stimuli and depression. These often include a discussion on anhedonia and how this might be underpinned in particular by dysfunctional reward processing. However, there is no specific consensus on whether studies to date have adequately examined the various sub-components of reward processing or how these might relate in turn to various aspects of anhedonia symptoms. Summary: The approach to understanding the symptom of anhedonia should be to examine all the sub-components of reward processing at the subjective and objective behavioural and neural level, with well validated tasks that can be replicated. Investigating real life experiences of anhedonia and how theses might be predicted by objective lab measures is also needed in future research

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder:a mega-analysis by the ENIGMA-PGC PTSD workgroup

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p -FDR &lt; 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.</p

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder:a mega-analysis by the ENIGMA-PGC PTSD workgroup

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p -FDR &lt; 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.</p

Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study.

peer reviewed[en] BACKGROUND: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non-motor functioning remain to be elucidated. OBJECTIVE: To quantify cross-sectional regional cerebellar lobule volumes using three dimensional T1-weighted anatomical brain magnetic resonance imaging from the global ENIGMA-PD working group. METHODS: Cerebellar parcellation was performed using a deep learning-based approach from 2487 people with PD and 1212 age and sex-matched controls across 22 sites. Linear mixed effects models compared total and regional cerebellar volume in people with PD at each Hoehn and Yahr (HY) disease stage, to an age- and sex- matched control group. Associations with motor symptom severity and Montreal Cognitive Assessment scores were investigated. RESULTS: Overall, people with PD had a regionally smaller posterior lobe (dmax  = -0.15). HY stage-specific analyses revealed a larger anterior lobule V bilaterally (dmax  = 0.28) in people with PD in HY stage 1 compared to controls. In contrast, smaller bilateral lobule VII volume in the posterior lobe was observed in HY stages 3, 4, and 5 (dmax  = -0.76), which was incrementally lower with higher disease stage. Within PD, cognitively impaired individuals had lower total cerebellar volume compared to cognitively normal individuals (d = -0.17). CONCLUSIONS: We provide evidence of a dissociation between anterior "motor" lobe and posterior "non-motor" lobe cerebellar regions in PD. Whereas less severe stages of the disease are associated with larger motor lobe regions, more severe stages of the disease are marked by smaller non-motor regions

Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA‐Epilepsy study

Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross‐sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA‐Epilepsy working group. Methods: A state‐of‐the‐art deep learning‐based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE‐HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Results: Across all epilepsies, reduced total cerebellar volume was observed (d = .42). Maximum volume loss was observed in the corpus medullare (dmax = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB (dmax = .47), crus I/II (dmax = .39), VIIIA (dmax = .45), and VIIIB (dmax = .40). Earlier age at seizure onset ( η ρ max 2 $$\eta {\mathit{\mathsf{\rho}}}_{\mathsf{max}}^{\mathsf{2}}$$ = .05) and longer epilepsy duration ( η ρ max 2 $$\eta {\mathit{\mathsf{\rho}}}_{\mathsf{max}}^{\mathsf{2}}$$ = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE‐HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. Significance: We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy

A functional magnetic resonance imaging investigation of emotion processing in remitted major depressive disorder: towards the identification of neurobiological trait markers and clinical implications for treatment

Emotional dysregulation is a core feature of Major Depressive Disorder (MDD), manifested by perceptual biases in processing positive and negative emotional stimuli. In support, a constellation of neuroimaging studies have consistently reported abnormalities in brain areas during the processing of negative and positive emotional stimuli in acutely depressed patients during a major depressive episode. These areas, which are pivotal for bottom-up emotion generation processes and top-down cognitive control of emotion through reciprocal connections, include lateral prefrontal cortical (PFC) regions (dorsolateral PFC, ventrolateral PFC), medial PFC regions (orbitofrontal cortex) and subcortical regions (amygdala, ventral striatum). However despite considerable progress into identifying the neural circuitry involved in MDD, a neural circuitry marker for the MDD trait has not yet been defined. Studying individuals in remission from MDD who are euthymic and medication-free, allows for the examination of enduring abnormalities in the neural circuitry supporting emotion processing and its regulation that may represent trait markers of the illness. Therefore the aims of this thesis were to examine, by means of two functional magnetic resonance imaging (fMRI) studies, neural activation in key areas subserving emotion processing and higher-order cognitive control processes, to determine whether abnormalities in the circuit persist into remission and thus represent trait-like markers of MDD. Using blood oxygen level dependent (BOLD) fMRI, 19 remitted medication-free individuals with recurrent MDD (rMDD) (mean age 33.6 ± 13.64) and 20 healthy controls (HC) (mean age 35.8 ± 12.10) completed an implicit gender-labelling emotion processing task (study 1), and a working memory task with emotional distracter stimuli (study 2). In each study faces depicting negative (fearful), positive (happy) and neutral emotions were used. Brain imaging data were analyzed in SPM2 using a whole-brain and region-of-interest approach corrected for multiple comparisons using AlphaSim (PFWE<.05) for the following a priori hypothesized regions: DLPFC (BA 9/46), VLPFC (BA 45/47), OFC (BA 11), subgenual ACC (BA 25), ventral striatum and amygdala. Exploratory, post-hoc analyses were performed in each study, to examine the association between brain activation during the processing of negative and positive emotional stimuli and clinical variables in the rMDD group. Findings indicate altered left-sided medial (OFC) (t37= 3.85, P<0.001, PFWE<0.05) and dorsolateral prefrontal (DLPFC) (t37= 2.55, P=0.008, PFWE<0.05) cortical responses to negative emotional stimuli in the rMDD group compared to HC (study 1). Furthermore, during cognitive load, rMDD patients exhibited greater neural activity in DLPFC during performance of the working memory-load condition in the context of negative emotional distracters, (t37= 2.71, p=.005, PFWE<.05) but reduced activity in DLPFC (t37= 2.43, P=.01, PFWE<.05) and VLPFC (t37= 2.82, P=.01, PFWE<.05) in the context of positive emotional stimuli (study 2). Finally, duration of euthymia was significantly associated with right-sided DLPFC functioning such that the longer rMDD individuals were in recovery, the greater DLPFC functioning (r(19)= .69, P<0.001 ) (study 1), although this finding was not replicated in study 2. These findings demonstrate enduring deficits in OFC, DLPFC and VLPFC functioning in response to predominantly negative emotional stimuli in rMDD individuals. These findings may reflect neurobiological trait markers of the illness and have widespread implications for treatment development and prevention of illness onset in at-risk individuals

A functional magnetic resonance imaging investigation of emotion processing in remitted major depressive disorder: towards the identification of neurobiological trait markers and clinical implications for treatment

Emotional dysregulation is a core feature of Major Depressive Disorder (MDD), manifested by perceptual biases in processing positive and negative emotional stimuli. In support, a constellation of neuroimaging studies have consistently reported abnormalities in brain areas during the processing of negative and positive emotional stimuli in acutely depressed patients during a major depressive episode. These areas, which are pivotal for bottom-up emotion generation processes and top-down cognitive control of emotion through reciprocal connections, include lateral prefrontal cortical (PFC) regions (dorsolateral PFC, ventrolateral PFC), medial PFC regions (orbitofrontal cortex) and subcortical regions (amygdala, ventral striatum). However despite considerable progress into identifying the neural circuitry involved in MDD, a neural circuitry marker for the MDD trait has not yet been defined. Studying individuals in remission from MDD who are euthymic and medication-free, allows for the examination of enduring abnormalities in the neural circuitry supporting emotion processing and its regulation that may represent trait markers of the illness. Therefore the aims of this thesis were to examine, by means of two functional magnetic resonance imaging (fMRI) studies, neural activation in key areas subserving emotion processing and higher-order cognitive control processes, to determine whether abnormalities in the circuit persist into remission and thus represent trait-like markers of MDD. Using blood oxygen level dependent (BOLD) fMRI, 19 remitted medication-free individuals with recurrent MDD (rMDD) (mean age 33.6 ± 13.64) and 20 healthy controls (HC) (mean age 35.8 ± 12.10) completed an implicit gender-labelling emotion processing task (study 1), and a working memory task with emotional distracter stimuli (study 2). In each study faces depicting negative (fearful), positive (happy) and neutral emotions were used. Brain imaging data were analyzed in SPM2 using a whole-brain and region-of-interest approach corrected for multiple comparisons using AlphaSim (PFWE<.05) for the following a priori hypothesized regions: DLPFC (BA 9/46), VLPFC (BA 45/47), OFC (BA 11), subgenual ACC (BA 25), ventral striatum and amygdala. Exploratory, post-hoc analyses were performed in each study, to examine the association between brain activation during the processing of negative and positive emotional stimuli and clinical variables in the rMDD group. Findings indicate altered left-sided medial (OFC) (t37= 3.85, P<0.001, PFWE<0.05) and dorsolateral prefrontal (DLPFC) (t37= 2.55, P=0.008, PFWE<0.05) cortical responses to negative emotional stimuli in the rMDD group compared to HC (study 1). Furthermore, during cognitive load, rMDD patients exhibited greater neural activity in DLPFC during performance of the working memory-load condition in the context of negative emotional distracters, (t37= 2.71, p=.005, PFWE<.05) but reduced activity in DLPFC (t37= 2.43, P=.01, PFWE<.05) and VLPFC (t37= 2.82, P=.01, PFWE<.05) in the context of positive emotional stimuli (study 2). Finally, duration of euthymia was significantly associated with right-sided DLPFC functioning such that the longer rMDD individuals were in recovery, the greater DLPFC functioning (r(19)= .69, P<0.001 ) (study 1), although this finding was not replicated in study 2. These findings demonstrate enduring deficits in OFC, DLPFC and VLPFC functioning in response to predominantly negative emotional stimuli in rMDD individuals. These findings may reflect neurobiological trait markers of the illness and have widespread implications for treatment development and prevention of illness onset in at-risk individuals