Change in brain activation after transcranial pulsed electromagnetic fields in treatment-resistant depression.

BACKGROUND: Preliminary evidence suggests antidepressant effects of transcranial pulsed electromagnetic fields (tPEMF). However, the precise mechanism of action in the brain is still unknown. The aim of this study was to investigate the influence of tPEMF on brain activation in patients with treatment-resistant depression (TRD) by studying two processes that might be of particular interest in relation to the symptoms of depression: emotional processing and reward processing. METHODS: Eligible participants (n = 50) with TRD in this sham-controlled double-blind multicenter trial [registered at the Dutch Trial Register ( http://www.trialregister.nl ), NTR3702] were randomly assigned to five weeks daily active or sham tPEMF. Pre- and post-treatment functional MR-scans were made during which participants performed a social-emotional task and a reward task. RESULTS: Participants in the active treatment group showed a stronger decrease in activation post-treatment compared to sham during reward-outcome processing in the left inferior frontal gyrus and in a cluster comprising the right lingual gyrus and the posterior part of the middle temporal gyrus. No effect of tPEMF was found on activation during the social-emotional task. Neurostimulation with tPEMF did also not affect behavioral performance for both tasks. CONCLUSIONS: We found a decrease in reward-related activation as a result of tPEMF stimulation, while no effect of tPEMF on social-emotional processing was found. The treatment-related reduction in activation of regulatory regions may reflect normalization and may have implications for anhedonia. These findings suggest that there is an effect of tPEMF on brain activation of relevant circuits, albeit in the absence of a clinical antidepressant effect.

Neural changes following a body-oriented resilience therapy with elements of kickboxing for individuals with a psychotic disorder: a randomized controlled trial.

Individuals with a psychotic disorder are at an increased risk of becoming the victim of a crime. A body-oriented resilience therapy (BEATVIC) aimed at preventing victimization by addressing putatively underlying factors was developed. One of these factors is social cognition, particularly facial affect processing. The current study investigated neural effects of BEATVIC on facial affect processing using two face processing tasks. Participants were randomized to either BEATVIC or a 'Befriending' control group. Twenty-seven patients completed an Emotional Faces task and the Wall of Faces task during fMRI, pre- and post-intervention. General linear model analyses yielded no differences between groups over time. Independent component analyses revealed increased activation of the salience network to angry and fearful faces in BEATVIC compared to Befriending. Increased activation of the salience network may suggest an increased alertness for potentially dangerous faces.

Distinct temporal brain dynamics in bipolar disorder and schizophrenia during emotion regulation.

BACKGROUND: Disturbances in emotion regulation (ER) are characteristic of both patients with bipolar disorder (BD) and schizophrenia (SZ). We investigated the temporal dynamics of brain activation during cognitive ER in BD and SZ to understand the contribution of temporal characteristics of disturbed ER to their unique and shared symptomatology. METHOD: Forty-six participants performed an ER-task (BD, n = 15; SZ, n = 16; controls, n = 15) during functional magnetic resonance imaging, in which they were instructed to use cognitive reappraisal techniques to regulate their emotional responses. Finite impulse response modeling was applied to estimate the temporal dynamics of brain responses during cognitive reappraisal (v. passive attending) of negative pictures. Group, time, and group × time effects were tested using multivariate modeling. RESULTS: We observed a group × time interaction during ER in the ventrolateral prefrontal cortex (VLPFC), supplementary motor area (SMA) and inferior occipital gyrus. Patients with SZ demonstrated initial hyper-activation of the VLPFC and SMA activation that was not sustained in later regulatory phases. Response profiles in the inferior occipital gyrus in SZ showed abnormal activation in the later phases of regulation. BD-patients showed general blunted responsivity in these regions. CONCLUSIONS: These results suggest that ER-disturbances in SZ are characterized by an inefficient initialization and failure to sustain regulatory control, whereas in BD, a failure to recruit regulatory resources may represent initial deficits in formulating adequate representations of the regulatory needs. This may help to further understand how ER-disturbances give rise to symptomatology of BD and SZ.

Longitudinal brain changes in MDD during emotional encoding: effects of presence and persistence of symptomatology.

BACKGROUND: The importance of the hippocampus and amygdala for disrupted emotional memory formation in depression is well-recognized, but it remains unclear whether functional abnormalities are state-dependent and whether they are affected by the persistence of depressive symptoms. METHODS: Thirty-nine patients with major depressive disorder and 28 healthy controls were included from the longitudinal functional magnetic resonance imaging (fMRI) sub-study of the Netherlands Study of Depression and Anxiety. Participants performed an emotional word-encoding and -recognition task during fMRI at baseline and 2-year follow-up measurement. At baseline, all patients were in a depressed state. We investigated state-dependency by relating changes in brain activation over time to changes in symptom severity. Furthermore, the effect of time spent with depressive symptoms in the 2-year interval was investigated. RESULTS: Symptom change was linearly associated with higher activation over time of the left anterior hippocampus extending to the amygdala during positive and negative word-encoding. Especially during positive word encoding, this effect was driven by symptomatic improvement. There was no effect of time spent with depression in the 2-year interval on change in brain activation. Results were independent of medication- and psychotherapy-use. CONCLUSION: Using a longitudinal within-subjects design, we showed that hippocampal-amygdalar activation during emotional memory formation is related to depressive symptom severity but not persistence (i.e. time spent with depression or 'load'), suggesting functional activation patterns in depression are not subject to functional 'scarring' although this hypothesis awaits future replication.

Altered frontal-amygdala effective connectivity during effortful emotion regulation in bipolar disorder.

OBJECTIVES: Sufficient prefrontal top-down control of limbic affective areas, especially the amygdala, is essential for successful effortful emotion regulation (ER). Difficulties in effortful ER have been seen in patients with bipolar disorder (BD), which could be suggestive of a disturbed prefrontal-amygdala regulation circuit. The aim of this study was to investigate whether BD patients show abnormal effective connectivity from the prefrontal areas to the amygdala during effortful ER (reappraisal). METHODS: Forty participants (23 BD patients and 17 healthy controls [HC]) performed an ER task during functional magnetic resonance imaging. Using dynamic causal modeling, we investigated effective connectivity from the dorsolateral prefrontal cortex (DLPFC) and ventrolateral prefrontal cortex (VLPFC) to the amygdala, as well as connectivity between the DLPFC and VLPFC during reappraisal. RESULTS: Both BD patients and HC showed decreased negative affect ratings following reappraisal compared to attending negative pictures (P < .001). There were no group differences (P = .10). There was a differential modulatory effect of reappraisal on the connectivity from the DLPFC to amygdala between BD patients and HC (P = .04), with BD patients showing a weaker modulatory effect on this connectivity compared to HC. There were no other group differences. CONCLUSION: The disturbance in BD patients in effective connectivity from the DLPFC to the amygdala while reappraising is indicative of insufficient prefrontal control. This impairment should be studied further in relation to cycling frequency and polarity of switches in BD patients.

[Apathy, depression and cognitive functioning in patients with MCI and dementia]. / De relatie tussen apathie, depressie en cognitief functioneren bij patiënten met MCI en dementie.

BACKGROUND: In dementia, apathy and depression are often seen as one disorder because of the many overlapping symptoms. However, for therapy a correct differentiation is essential. Moreover, apathy and depression are likely both associated with different cognitive deficits and progression of the disease. In this research we give an overview of cognitive domains associated with apathy and depression in MCI patients and report how often both disorders occur in a population sample. METHOD: We administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to 117 cognitively healthy controls (GC), 97 patients with mild cognitive impairment (MCI) and 50 patients with dementia (DEM). In addition, the Apathy Evaluation Scale clinical version (AES-C) and the Geriatric Depression Scale (GDS) were administered. RESULTS: The number of patients with apathy increased with cognitive decline with respectively 3.4%, 10.4% and 41.5% of patients in the GC, MCI and DEM group. The prevalence of isolated depression was highest in the MCI group (18.8%). Correlation analyses in the MCI group showed that apathy and not depression was associated with a deficit in encoding, attention and global cognitive functioning. CONCLUSION: The prevalence of apathy and depressive symptoms is different in patients with MCI, DEM and GC, and within the MCI group apathy and depression are associated with different cognitive domains.

Apathy is related to reduced activation in cognitive control regions during set-shifting.

Apathy is a prominent and influential symptom in several neurological and psychiatric disorders, but it also occurs in the healthy population. It has considerable impact on daily life functioning, in clinical as well as healthy samples. Even though cognitive control is thought to be disrupted in people with apathy, the exact neural underpinnings of apathy remain unclear. Because flexible shifting between behaviors (set-shifting) is crucial for goal-directed behavior, disruptions in set-shifting may underlie apathy. In this study, the neural correlates of apathy during set-shifting were studied in 34 healthy participants with varying levels of apathy, measured by the Apathy Evaluation Scale. During functional MRI scanning participants performed a set-shifting task, distinguishing between behavioral switches (a change in response to different stimuli), cognitive switches (a change in response rule), and salience decoupling (detecting a change in relevant stimuli). Regression analysis was used to assess the relationship between apathy and brain activation. Results showed that higher apathy scores were related to reduced activation in the medial superior frontal gyrus and cerebellum (Crus I/II) during cognitive set-shifting, but not behavioral shifting and salience decoupling. No relationship between apathy and accuracy or response time was found. These results support the idea that alterations in the neural basis of cognitive control, especially cognitive set-shifting, may contribute to apathy. Hum Brain Mapp 38:2722-2733, 2017. © 2017 Wiley Periodicals, Inc.

CHANGES IN REGIONAL BRAIN ACTIVATION RELATED TO DEPRESSIVE STATE: A 2-YEAR LONGITUDINAL FUNCTIONAL MRI STUDY.

BACKGROUND: Abnormal brain activations during processing of emotional facial expressions in depressed patients have been demonstrated. We investigated the natural course of brain activation in response to emotional faces in depression, indexed by functional magnetic resonance imaging (fMRI) scans preceding and following change in depressive state. We hypothesized a decrease in activation in the amygdala, anterior cingulate cortex (ACC), and insula with a decrease in depressive pathology. METHODS: A 2-year longitudinal fMRI study was conducted as part of the Netherlands Study of Depression and Anxiety. We included 32 healthy controls and 49 depressed patients. During the second scan, 27 patients were in remission (remitters), the other 22 were not (nonremitters). All participants viewed faces with emotional expressions during scanning. RESULTS: Rostral ACC activation during processing of happy faces was predictive of a decrease in depressive state (PFWE = .003). In addition, remitters showed decreased activation of the insula over time (PFWE = .016), specifically during happy faces. Nonremitters displayed increased abnormalities in emotion recognition circuitry during the second scan compared to the first. No effect of selective serotonin reuptake inhibitor use was observed. CONCLUSIONS: Our results demonstrate that rostral ACC activation may predict changes in depressive state even at 2-year outcome. The association between change in depressed state and change in insula activation provides further evidence for the role of the insula in a network maintaining emotional and motivational states.

Cognitive vulnerability and implicit emotional processing: imbalance in frontolimbic brain areas?

It has been proposed that the neural basis for cognitive vulnerability to depression involves an imbalance in frontolimbic activity during the processing of cues with a negative affective value. Although the question is central to cognitive theory, whether this association is amplified by diagnosis of an affective disorder or recent life stress has not been investigated. A composite cognitive vulnerability score based on questionnaire assessment was used to predict neural responses to negative emotional stimuli in N = 112 participants. Potential moderating effects of psychiatric diagnosis and negative life events were examined. Main and interaction effects were tested against a threshold of p < .05, family-wise error (FWE) corrected at the cluster level, and the results were small-volume corrected in regions of interest. Cognitive vulnerability predicted higher activation of superior parietal areas (p(FWE) < .01) for negative than for positive faces. The association was significantly stronger in healthy participants. For negative versus control stimuli, cognitive vulnerability predicted higher ventrolateral prefrontal and subgenual anterior cingulate activation (p(FWE) < .05) to equal extents in both groups. We found no evidence for an association with amygdala activation. Life events did not moderate the findings. We concluded that cognitive vulnerability was associated with higher activation of frontoparietal areas during an implicit emotional task. These higher levels of activation may potentially reflect increased effort being required to ignore irrelevant negative emotional information in vulnerable populations.

Effects of right prefrontal theta-burst transcranial magnetic stimulation or transcranial direct current stimulation on apathy in patients with schizophrenia: A multicenter RCT.

Apathy is a core negative symptom associated with an unfavorable functional outcome. Noninvasive brain stimulation has shown promise in the treatment of schizophrenia but has not been tested specifically for apathy. We conducted a randomized controlled trial of intermittent theta-burst (iTBS) transcranial magnetic stimulation and transcranial direct current stimulation (tDCS) targeted at the right dorsolateral prefrontal cortex (DLPFC) in patients diagnosed with a psychotic disorder suffering from apathy. The study was a multicenter, randomized, placebo-controlled, and rater-blinded trial. Patients (N = 88) were randomized into active iTBS, active tDCS, sham iTBS or sham tDCS treatment, daily for two weeks (excluding weekends). Effects were measured post-treatment and at four week and ten week follow-up. Primary outcome was apathy severity (Apathy Evaluation Scale, clinician-rated). Additional measures included assessment of negative symptoms, depression, anhedonia and quality of life. No significant difference in improvement of apathy or negative symptoms was observed for real versus sham treatment with either iTBS or tDCS, though all groups improved to a small extent. We conclude that two weeks of brain stimulation over the right DLPFC with either iTBS or tDCS is not effective for improving apathy or negative symptoms. Longer and more intensive protocols may yield different results.

Planning in amnestic mild cognitive impairment: an fMRI study.

INTRODUCTION: The memory impairment that is characteristic of amnestic mild cognitive impairment (aMCI) is often accompanied by difficulties in executive functioning, including planning. Though planning deficits in aMCI are well documented, their neural correlates are largely unknown, and have not yet been investigated with functional magnetic resonance imaging (fMRI). OBJECTIVES: The aim of this study was to: (1) identify differences in brain activity and connectivity during planning between people with aMCI and cognitively healthy older adults, and (2) find whether planning-related activity and connectivity are associated with cognitive performance and symptoms of apathy. METHODS: Twenty-five people with aMCI and 15 cognitively healthy older adults performed a visuospatial planning task (Tower of London; ToL) during fMRI. Task-related brain activation, spatial maps of task-related independent components, and seed-to-voxel functional connectivity were compared between the two groups and regressed against measures of executive functions (Trail Making Test difference score, TMT B-A; Digit Symbol Substitution Test, DSST), delayed recall (Rey Auditory Verbal Learning Test), and apathy (Apathy Evaluation Scale). RESULTS: People with aMCI scored lower on task-switching (TMT B-A), working memory (DSST), and planning (ToL). During planning, people with aMCI had less activation in the bilateral anterior calcarine sulcus/cuneus, the bilateral temporal cortices, the left precentral gyrus, the thalamus, and the right cerebellum. Across all participants, higher planning-related activity in the supplementary motor area, the retrosplenial cortex and surrounding areas, and the right temporal cortex was related to better delayed recall. There were no between-group differences in functional connectivity, nor were there any associations between connectivity and cognition. We also did not find any associations between brain activity or connectivity and apathy. CONCLUSION: Impaired planning in people with aMCI appears to be accompanied by lower activation in a diffuse cortico-thalamic network. Across all participants, higher planning-related activity in parieto-occipital, temporal, and frontal areas was related to better memory performance. The results point to the relevance of planning deficits for understanding aMCI and extend its clinical and neurobiological signature.

Insight does not come at random: Individual gray matter networks relate to clinical and cognitive insight in schizophrenia.

BACKGROUND: Impaired clinical and cognitive insight are prevalent in schizophrenia and relate to poorer outcome. Good insight has been suggested to depend on social cognitive and metacognitive abilities requiring global integration of brain signals. Impaired insight has been related to numerous focal gray matter (GM) abnormalities distributed across the brain suggesting dysconnectivity at the global level. In this study, we test whether global integration deficiencies reflected in gray matter network connectivity underlie individual variations in insight. METHODS: We used graph theory to examine whether individual GM-network metrics relate to insight in patients with a psychotic disorder (n = 114). Clinical insight was measured with the Schedule for the Assessment of Insight-Expanded and item G12 of the Positive and Negative Syndrome Scale, and cognitive insight with the Beck Cognitive Insight Scale. Individual GM-similarity networks were created from GM-segmentations of T1-weighted MRI-scans. Graph metrics were calculated using the Brain Connectivity Toolbox. RESULTS: Networks of schizophrenia patients with poorer clinical insight showed less segregation (i.e. clustering coefficient) into specialized subnetworks at the global level. Schizophrenia patients with poorer cognitive insight showed both less segregation and higher connectedness (i.e. lower path length) of their brain networks, making their network topology more "random". CONCLUSIONS: Our findings suggest less segregated processing of information in patients with poorer cognitive and clinical insight, in addition to higher connectedness in patients with poorer cognitive insight. The ability to take a critical perspective on one's symptoms (clinical insight) or views (cognitive insight) might depend especially on segregated specialized processing within distinct subnetworks.

Widespread white matter aberration is associated with the severity of apathy in amnestic Mild Cognitive Impairment: Tract-based spatial statistics analysis.

Apathy is recognized as a prevalent behavioral symptom of amnestic Mild Cognitive Impairment (aMCI). In aMCI, apathy is associated with an increased risk and increases the risk of progression to Alzheimer's Disease (AD). Previous DTI study in aMCI showed that apathy has been associated with white matter alterations in the cingulum, middle and inferior longitudinal fasciculus, fornix, and uncinate fasciculus. However, the underlying white matter correlates associated with apathy in aMCI are still unclear. We investigated this relationship using whole-brain diffusion tensor imaging (DTI). Twenty-nine aMCI patients and 20 matched cognitively healthy controls were included. Apathy severity was assessed using the Apathy Evaluation Scale Clinician version. We applied the tract-based spatial statistics analyses to DTI parameters: fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity to investigate changes in white matter pathways associated with the severity of apathy. No significant difference was found in any of the DTI parameters between aMCI and the control group. In aMCI, higher severity of apathy was associated with lower FA in various white matter pathways including the left anterior part of inferior fronto-occipital fasciculus/uncinate fasciculus, genu and body of the corpus callosum, superior and anterior corona radiata, anterior thalamic radiation of both hemispheres and in the right superior longitudinal fasciculus/anterior segment of arcuate fasciculus (p < .05, TFCE-corrected) after controlling for age, gender and GDS non-apathy. A trend association was observed in the right posterior corona radiata and corticospinal tract/internal capsule, and bilateral forceps minor (p < .065, TFCE-corrected). In conclusion, in aMCI, severity of apathy is associated with aberrant white matter integrity in widely distributed pathways, within and between hemispheres.

No antidepressant effects of low intensity transcranial pulsed electromagnetic fields for treatment resistant depression.

BACKGROUND: Noninvasive neurostimulation with transcranial Pulsed Electromagnetic Fields (tPEMF) may be a promising method for treatment resistant depression (TRD). Studies shown substantial improvement of depressive symptoms in patients with TRD, but there is no information on long-term antidepressant effects. The aim of this study was to investigate the short- and long-term efficacy of tPEMF in participants with TRD. METHODS: Eligible participants with TRD in this sham-controlled double-blind multicenter trial were randomly assigned to five weeks either daily active or sham tPEMF. Severity of depression and anxiety was assessed pre- and directly post-treatment and five and fifteen weeks post-treatment. Primary outcome was change on the 17-item Hamilton depression rating scale directly post-treatment. Secondary outcome was change on the Hamilton-17 during follow-up and change on the Inventory of Depressive Symptomatology Self-Report and the Beck Anxiety Index. RESULTS: Of the 55 included participants, 50 completed the treatment protocol. Depressive symptoms improved over time in both groups. The improvement continued until the last follow-up measure. There was no difference in outcome between the active and the sham group on change in depression post-treatment or on any secondary measure. CONCLUSION: Treatment with this type of active tPEMF was not superior to sham in patients with TRD. This is in contrast to a previous study using a similar design and power calculation, but a higher magnetic field strength, that reported improvement of depression after treatment with tPEMF compared to sham. An important limitation of our study was the fact that no different dosing regimens were tried.

Relationship between social cognition, general cognition, and risk for suicide in individuals with a psychotic disorder.

OBJECTIVE: Cognitive alterations putatively contribute to the risk for suicide in individuals with psychosis. Yet, a comprehensive assessment of social- and general-cognitive abilities in a large sample is lacking. METHODS: Seven-hundred-fifteen individuals diagnosed with a psychotic disorder performed tasks of facial emotion recognition, Theory of Mind, and general cognitive functioning (sustained attention, set-shifting, IQ-tests and verbal learning) as part of the Genetic-Risk-and-Outcome-of-Psychosis (GROUP) study. Presence of past suicide attempt/s and/or current suicidal ideation was reported by 261 individuals and 454 individuals reported no suicide attempt or ideation. We used general linear models to investigate group differences in task performance. All analysis were controlled for age, sex, education, and psychotic symptom severity. RESULTS: Individuals with suicide attempt and/or ideation showed better performance on the facial emotion recognition task and lower performance on tasks of sustained attention and verbal learning, compared to individuals without suicide attempt and/or ideation, without a clear effect of attempt or ideation. Theory of Mind performance was also better for individuals with suicide attempt and/or ideation, with largest differences between individuals who reported both attempts and ideation compared to individuals without suicide attempt and/or ideation. No effect of suicide attempt and/or ideation was found on misperception of facial emotions, IQ and set-shifting. Overall, effect sizes were small. CONCLUSION: Higher sensitivity to social-emotional cues together with weakened attentional control and learning capacity was observed in individuals with psychosis and suicide attempt and/or ideation. This may suggest that insufficient capacity for regulating perceived social stress contributes to suicidal thoughts and behavior.

The Cognitive-Functional Composite is sensitive to clinical progression in early dementia: Longitudinal findings from the Catch-Cog study cohort.

INTRODUCTION: In an attempt to capture clinically meaningful cognitive decline in early dementia, we developed the Cognitive-Functional Composite (CFC). We investigated the CFC's sensitivity to decline in comparison to traditional clinical endpoints. METHODS: This longitudinal construct validation study included 148 participants with subjective cognitive decline, mild cognitive impairment, or mild dementia. The CFC and traditional tests were administered at baseline, 3, 6, and 12 months. Sensitivity to change was investigated using linear mixed models and r 2 effect sizes. RESULTS: CFC scores declined over time (ß = -.16, P < .001), with steepest decline observed in mild Alzheimer's dementia (ß = -.25, P < .001). The CFC showed medium-to-large effect sizes at succeeding follow-up points (r 2 = .08-.42), exhibiting greater change than the Clinical Dementia Rating scale (r 2 = .02-.12). Moreover, change on the CFC was significantly associated with informant reports of cognitive decline (ß = .38, P < .001). DISCUSSION: By showing sensitivity to decline, the CFC could enhance the monitoring of disease progression in dementia research and clinical practice.

Neural correlates of victimization in psychosis: differences in brain response to angry faces.

Individuals with psychosis are at an increased risk of victimization. Processing of facial expressions has been suggested to be associated with victimization in this patient group. Especially processing of angry expressions may be relevant in the context of victimization. Therefore, differences in brain activation and connectivity between victimized and nonvictimized patients during processing of angry faces were investigated. Thirty-nine patients, of whom nineteen had experienced threats, assaults, or sexual violence in the past 5 years, underwent fMRI scanning, during which they viewed angry and neutral facial expressions. Using general linear model (GLM) analyses, generalized psychophysiological (gPPI) analysis and independent component analyses (ICA) differences in brain activation and connectivity between groups in response to angry faces were investigated. Whereas differences in regional brain activation GLM and gPPI analyses yielded no differences between groups, ICA revealed more deactivation of the sensorimotor network in victimized participants. Deactivation of the sensorimotor network in response to angry faces in victimized patients, might indicate a freeze reaction to threatening stimuli, previously observed in traumatized individuals.

Intrinsic mesocorticolimbic connectivity is negatively associated with social amotivation in people with schizophrenia.

BACKGROUND: Social amotivation is a core element of the negative symptoms of schizophrenia. However, it is still largely unknown which neural substrates underpin social amotivation in people with schizophrenia, though deficiencies in the mesocorticolimbic dopamine system have been proposed. METHODS: We examined the association between social amotivation and substantia nigra/ventral tegmental area-seeded intrinsic connectivity in 84 people with schizophrenia using resting state functional magnetic resonance imaging. RESULTS: Spontaneous fluctuations of midbrain dopaminergic regions were positively associated with striatal and prefrontal fluctuations in people with schizophrenia. Most importantly, social amotivation was negatively associated with functional connectivity between the midbrain's substantia nigra/ventral tegmental area and medial- and lateral prefrontal cortex, the temporoparietal junction, and dorsal and ventral striatum. These associations were observed independently of depressive and positive symptoms. CONCLUSIONS: Our findings suggest that social amotivation in people with schizophrenia is associated with altered intrinsic connectivity of mesocorticolimbic pathways linked to cognitive control and reward processing. Dysconnectivity of dopaminergic neuronal ensembles that are fundamental to approach behavior and motivation may help explain the lack of initiative social behavior in people with social amotivation.

Assessing cognition and daily function in early dementia using the cognitive-functional composite: findings from the Catch-Cog study cohort.

BACKGROUND: The cognitive-functional composite (CFC) was designed to improve the measurement of clinically relevant changes in predementia and early dementia stages. We have previously demonstrated its good test-retest reliability and feasibility of use. The current study aimed to evaluate several quality aspects of the CFC, including construct validity, clinical relevance, and suitability for the target population. METHODS: Baseline data of the Capturing Changes in Cognition study was used: an international, prospective cohort study including participants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer's disease (AD) dementia, and dementia with Lewy bodies (DLB). The CFC comprises seven existing cognitive tests focusing on memory and executive functions (EF) and the informant-based Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q). Construct validity and clinical relevance were assessed by (1) confirmatory factor analyses (CFA) using all CFC subtests and (2) linear regression analyses relating the CFC score (independent) to reference measures of disease severity (dependent), correcting for age, sex, and education. To assess the suitability for the target population, we compared score distributions of the CFC to those of traditional tests (Alzheimer's Disease Assessment Scale-Cognitive subscale, Alzheimer's Disease Cooperative Study-Activities of Daily Living scale, and Clinical Dementia Rating scale). RESULTS: A total of 184 participants were included (age 71.8 ± 8.4; 42% female; n = 14 SCD, n = 80 MCI, n = 78 AD, and n = 12 DLB). CFA showed that the hypothesized three-factor model (memory, EF, and IADL) had adequate fit (CFI = .931, RMSEA = .091, SRMR = .06). Moreover, worse CFC performance was associated with more cognitive decline as reported by the informant (ß = .61, p < .001), poorer quality of life (ß = .51, p < .001), higher caregiver burden (ß = - .51, p < .001), more apathy (ß = - .36, p < .001), and less cortical volume (ß = .34, p = .02). Whilst correlations between the CFC and traditional measures were moderate to strong (ranging from - .65 to .83, all p < .001), histograms showed floor and ceiling effects for the traditional tests as compared to the CFC. CONCLUSIONS: Our findings illustrate that the CFC has good construct validity, captures clinically relevant aspects of disease severity, and shows no range restrictions in scoring. It therefore provides a more useful outcome measure than traditional tests to evaluate cognition and function in MCI and mild AD.

Structure of the alexithymic brain: A parametric coordinate-based meta-analysis.

Alexithymia refers to deficiencies in identifying and expressing emotions. This might be related to changes in structural brain volumes, but its neuroanatomical basis remains uncertain as studies have shown heterogeneous findings. Therefore, we conducted a parametric coordinate-based meta-analysis. We identified seventeen structural neuroimaging studies (including a total of 2586 individuals with different levels of alexithymia) investigating the association between gray matter volume and alexithymia. Volumes of the left insula, left amygdala, orbital frontal cortex and striatum were consistently smaller in people with high levels of alexithymia. These areas are important for emotion perception and emotional experience. Smaller volumes in these areas might lead to deficiencies in appropriately identifying and expressing emotions. These findings provide the first quantitative integration of results pertaining to the structural neuroanatomical basis of alexithymia.