Neuronal activity and reward processing in relation to binge eating.

PURPOSE OF REVIEW: Studies increasingly show the importance of reward processing in binge eating and provide evidence of associated changes in the neurobiological reward system. This review gives an up-to-date overview of the neurobiological substrates of reward processing subconstructs in binge eating. Neural findings are linked to different behavioral theories and the clinical relevance is discussed. RECENT FINDINGS: Increased neural responses in the orbitofrontal cortex, anterior cingulate cortex as well as striatum during anticipation and receipt of food rewards are found in association to binge eating. Increased model-free learning is also found and associated with altered brain reward reactivity. Data in rest report reduced striatal dopamine release and lower frontostriatal connectivity. Mechanisms of onset of binge eating are less clear, but specific personality traits, related to frontostriatal dysconnectivity, probably increase the risk of binge eating onset. SUMMARY: Both structural and task-based imaging studies show differences in the neurobiological reward system in binge eating. These changes are linked to specific reward processing, such as altered reward responsiveness to food cues, reinforcement learning, and habitual behavior. Findings are lined with different behavioral theories of binge eating, and a staging model is described, from onset to full illness development. Understanding the specific underlying aberrant reward mechanism in binge eating, associated with different stages of the illness, enables caregivers to focus their treatment more precisely.

Changes in leukoencephalopathy and serum neurofilament after (neo)adjuvant chemotherapy for breast cancer.

BACKGROUND: Previous case studies have provided evidence for chemotherapy-induced leukoencephalopathy in patients with breast cancer. However, prospective research is lacking. Hence, we investigated leukoencephalopathy before and after chemotherapy and its association with a serum neuroaxonal damage marker. METHODS: This prospective cohort study included 40 patients receiving chemotherapy for breast cancer, and two age- and education-matched control groups, recruited between 2018 and 2021 (31-64 years of age). The latter control groups consisted of 39 chemotherapy-naïve patients and 40 healthy women. Fluid-attenuated inversion-recovery magnetic resonance imaging was used for lesion volumetry (total, juxtacortical, periventricular, infratentorial, and deep white matter) and blood serum to measure neurofilament light chain (NfL) levels. Acquisition took place pre-chemotherapy and three months and one-year post-chemotherapy, or at corresponding intervals. Within/between group differences were compared using robust mixed-effects modeling, and associations between total lesion volume and serum-NfL with linear regression. RESULTS: Stronger increases in deep white matter lesion volumes were observed shortly post-chemotherapy, compared with healthy women (ßstandardized=0.09, pFDR<0.001). Increases in total lesion volume could mainly be attributed to enlargement of existing lesions (mean±SD, 0.12±0.16 mL), rather than development of new lesions (0.02±0.02 mL). A stronger increase in serum-NfL concentration was observed shortly post-chemotherapy compared with both control groups (ß>0.70, p<0.004), neither of which showed any changes over time, whereas a decrease was observed compared with healthy women one-year post-chemotherapy (ß=-0.54, p = 0.002). Serum-NfL concentrations were associated with lesion volume one-year post-chemotherapy (or at matched timepoint; ß=0.36, p = 0.010), whereas baseline or short-term post-therapy levels or changes were not. CONCLUSION: These results underscore the possibility of chemotherapy-induced leukoencephalopathy months post-treatment, as well as the added value of serum-NfL as a prognostic marker for peripheral/central neurotoxicity. TRANSLATIONAL RELEVANCE: Previous case studies have provided evidence of chemotherapy-induced leukoencephalopathy in patients with breast cancer. However, prospective studies to estimate longitudinal changes are currently missing. In this study, we used longitudinal fluid-attenuated inversion-recovery magnetic resonance imaging to assess white matter lesion volumes in patients treated for non-metastatic breast cancer and healthy women. Our findings demonstrate that chemotherapy-treated patients exhibit stronger increases in lesion volumes compared with healthy women, specifically in deep white matter, at three months post-chemotherapy. Increases could mainly be attributed to enlargement of existing lesions, rather than development of new lesions. Last, serum concentrations of neurofilament light chain, a neuroaxonal damage marker, increased shortly after chemotherapy and long-term post-chemotherapy levels were associated with lesion volumes. These findings highlight the potential of this non-invasive serum marker as a prognostic marker for peripheral and/or central neurotoxicity. Implementation in clinical practice could aid in therapeutic decisions, assessing disease activity, or monitoring treatment response.

The Impact of Mindfulness on Functional Brain Connectivity and Peripheral Inflammation in Breast Cancer Survivors with Cognitive Complaints.

BACKGROUND: Cancer-related cognitive impairment (CRCI) has been linked to functional brain changes and inflammatory processes. Hence, interventions targeting these underlying mechanisms are needed. In this study, we investigated the effects of a mindfulness-based intervention on brain function and inflammatory profiles in breast cancer survivors with CRCI. METHODS: Female breast cancer survivors reporting cognitive complaints (n = 117) were randomly assigned to a mindfulness-based intervention (n = 43), physical training (n = 36), or waitlist control condition (n = 38). Region-of-interest (ROI) and graph theory analyses of resting state functional MRI data were performed to study longitudinal group differences in functional connectivity and organization in the default mode, dorsal attention, salience, and frontoparietal network. Additionally, bead-based immunoassays were used to investigate the differences in inflammatory profiles on serum samples. Measures were collected before, immediately after and three months post-intervention. RESULTS: No ROI-to-ROI functional connectivity changes were identified. Compared to no intervention, graph analysis showed a larger decrease in clustering coefficient after mindfulness and physical training. Additionally, a larger increase in global efficiency after physical training was identified. Furthermore, the physical training group showed a larger decrease in an inflammatory profile compared to no intervention (IL-12p70, IFN-γ, IL-1ß, and IL-8). CONCLUSION: Both mindfulness and physical training induced changes in the functional organization of networks related to attention, emotion processing, and executive functioning. While both interventions reduced functional segregation, only physical training increased functional integration of the neural network. In conclusion, physical training had the most pronounced effects on functional network organization and biomarkers of inflammation, two mechanisms that might be involved in CRCI.

How negative affect does and does not lead to binge eating-The importance of craving and negative urgency in bulimia nervosa.

Studies suggest that negative affect (NA) can trigger binge eating (BE) in patients with bulimia nervosa (BN). Important factors in this relation between NA and BE could be craving (an intense desire for a BE episode) and negative urgency (the tendency to act rashly when NA is high). Therefore, this study wants to firstly explore the relations between NA, craving, rash action, and BE in daily life and secondly whether craving and rash action mediate the relationship between NA and BE. A sample of 70 female patients with BN and 76 female healthy controls (HC) took part in an experience sampling study where they reported on momentary NA, craving, rash action, and eating behaviors in daily life in a burst-measurement design over a period of 12 months. Assessments occurred eight times a day on Thursdays, Fridays, and Saturdays in seven bursts of 3 weeks, all separated by 5-week periods of no assessment. First, NA predicted subsequent rash action in the whole sample but this was more pronounced in patients with BN. Second, NA predicted subsequent craving in patients with BN, but not in HC. Third, rash action and craving predicted subsequent BE in patients with BN. Fourth, NA had competing effects on eating in patients with BN, predicting subsequent BE through rash action and craving, but also predicting subsequent not eating. These results suggest that NA can lead to BE in daily life through rash action and craving, but that NA can also lead to dietary restriction. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Exploring structural connectomes in children with unilateral cerebral palsy using graph theory.

We explored structural brain connectomes in children with spastic unilateral cerebral palsy (uCP) and its relation to sensory-motor function using graph theory. In 46 children with uCP (mean age = 10 years 7 months ± 2 years 9 months; Manual Ability Classification System I = 15, II = 16, III = 15) we assessed upper limb somatosensory and motor function. We collected multi-shell diffusion-weighted, T1-weighted and T2-FLAIR MRI and identified the corticospinal tract (CST) wiring pattern using transcranial magnetic stimulation. Structural connectomes were constructed using Virtual Brain Grafting-modified FreeSurfer parcellations and multi-shell multi-tissue constrained spherical deconvolution-based anatomically-constrained tractography. Graph metrics (characteristic path length, global/local efficiency and clustering coefficient) of the whole brain, the ipsilesional/contralesional hemisphere, and the full/ipsilesional/contralesional sensory-motor network were compared between lesion types (periventricular white matter (PWM) = 28, cortical and deep gray matter (CDGM) = 18) and CST-wiring patterns (ipsilateral = 14, bilateral = 14, contralateral = 12, unknown = 6) using ANCOVA with age as covariate. Using elastic-net regularized regression we investigated how graph metrics, lesion volume, lesion type, CST-wiring pattern and age predicted sensory-motor function. In both the whole brain and subnetworks, we observed a hyperconnectivity pattern in children with CDGM-lesions compared with PWM-lesions, with higher clustering coefficient (p = [<.001-.047], η p 2 =[0.09-0.27]), characteristic path length (p = .003, η p 2 =0.19) and local efficiency (p = [.001-.02], η p 2 =[0.11-0.21]), and a lower global efficiency with age (p = [.01-.04], η p 2 =[0.09-0.15]). No differences were found between CST-wiring groups. Overall, good predictions of sensory-motor function were obtained with elastic-net regression (R2  = .40-.87). CST-wiring pattern was the strongest predictor for motor function. For somatosensory function, all independent variables contributed equally to the model. In conclusion, we demonstrated the potential of structural connectomics in understanding disease severity and brain development in children with uCP.

The impact of mindfulness on cancer-related cognitive impairment in breast cancer survivors with cognitive complaints.

BACKGROUND: Interventions that target cancer-related cognitive impairment (CRCI) to improve the quality of life of cancer survivors are needed. In this study, the potential of a mindfulness-based intervention to reduce CRCI in breast cancer survivors, compared with physical training and a wait list control group, was investigated. METHODS: Breast cancer survivors with cognitive complaints (N = 117) were randomly allocated to a mindfulness (n = 43), physical training (n = 36), or wait list control condition (n = 38). Participants completed neuropsychological tests and questionnaires before the intervention, immediately after, and 3 months after intervention. The primary outcome measure was the change in cognitive complaints over time. Secondary outcomes were objective cognitive impairment and psychological well-being. All outcomes were compared between groups over time using linear mixed models, including participants with missing values. RESULTS: Of the 117 included participants, 96 completed the three assessments. Participants in the three groups reported decreased cognitive complaints after intervention, without group differences. There were no between-group differences in objective cognitive impairment after intervention compared with baseline. Compared with the wait list control group, participants reported increased mindfulness skills and reduced emotional distress after mindfulness and reduced emotional distress and fatigue after physical training. CONCLUSION: Contrary to the hypothesis, all groups reported an improvement in cognitive complaints over time. It is suggested that priming and acknowledgment of CRCI might alter the experience of cognitive impairment. Additionally, both mindfulness-based intervention and physical training can improve psychological well-being of breast cancer survivors with cognitive complaints.

Cerebral glucose changes after chemotherapy and their relation to long-term cognitive complaints and fatigue.

Purpose: To investigate the short-term cerebral metabolic effects of intravenous chemotherapy and their association with long-term fatigue/cognitive complaints. Experimental design: Using [18F]-FDG-PET/CT whole-body scans, we retrospectively quantified relative cerebral glucose metabolism before and after neoadjuvant chemotherapy in a cohort of patients treated for non-metastatic breast cancer (2009-2019). Self-report of cognitive complaints and fatigue were prospectively assessed 7 ± 3 years after therapy. Metabolic changes were estimated with i) robust mixed-effects modelling in regions-of-interest (frontal, parietal, temporal, occipital, and insular cortex) and ii) general-linear modelling of whole-brain voxel-wise outcomes. iii) The association between metabolic changes and self-reported outcomes was evaluated using linear regression-analysis. Results: Of the 667 screened patients, 263 underwent PET/CT before and after chemotherapy and 183 (48 ± 9 years) met the inclusion criteria. After chemotherapy, decreased frontal and increased parietal and insular metabolism were observed (|ß|>0.273, pFDR <0.008). Separately, additional increased occipital metabolism after epiribucin+ cyclophosphamide (EC) and temporal metabolism after EC+ fluorouracil chemotherapy were observed (ß>0.244, pFDR ≤0.048). Voxel-based analysis (pcluster-FWE <0.001) showed decreased metabolism in the paracingulate gyrus (-3.2 ± 3.9%) and putamen (3.1 ± 4.1%) and increased metabolism in the lateral cortex (L=2.9 ± 3.1%) and pericentral gyri (3.0 ± 4.4%). Except for the central sulcus, the same regions showed changes in EC, but not in FEC patients. Of the 97 self-reported responders, 23% and 27% experienced extreme fatigue and long-term cognitive complaints, respectively, which were not associated with metabolic changes. Conclusion: Both hyper- and hypometabolism were observed after chemotherapy for breast cancer. Combined with earlier findings, this study could support inflammatory mechanisms resulting in relative hypermetabolism, mainly in the parietal/occipital cortices. As early metabolic changes did not precede long-term complaints, further research is necessary to identify vulnerable patients.

The neurobiological reward system and binge eating: A critical systematic review of neuroimaging studies.

OBJECTIVE: Changes in reward processing are hypothesized to play a role in the onset and maintenance of binge eating (BE). However, despite an increasing number of studies investigating the neurobiological reward system in individuals who binge eat, no comprehensive systematic review exists on this topic. Therefore, this review has the following objectives: (1) identify structural and functional changes in the brain reward system, either during rest or while performing a task; and (2) formulate directions for future research. METHODS: A search was conducted of articles published until March 31, 2022. Neuroimaging studies were eligible if they wanted to study the reward system and included a group of individuals who binge eat together with a comparator group. Their results were summarized in a narrative synthesis. RESULTS: A total of 58 articles were included. At rest, individuals who binge eat displayed a lower striatal dopamine release, a change in the volume of the striatum, frontal cortex, and insula, as well as a lower frontostriatal connectivity. While performing a task, there was a higher activity of the brain reward system when anticipating or receiving food, more model-free reinforcement learning, and more habitual behavior. Most studies only included one patient group, used general reward-related measures, and did not evaluate the impact of comorbidities, illness duration, race, or sex. DISCUSSION: Confirming previous hypotheses, this review finds structural and functional changes in the neurobiological reward system in BE. Future studies should compare disorders, use measures that are specific to BE, and investigate the impact of confounding factors. PUBLIC SIGNIFICANCE STATEMENT: This systematic review finds that individuals who binge eat display structural and functional changes in the brain reward system. These changes could be related to a higher sensitivity to food, relying more on previous experiences when making decisions, and more habitual behavior. Future studies should use a task that is specific to binge eating, look across different patient groups, and investigate the impact of comorbidities, illness duration, race, and sex.

OBJETIVO: Se plantea la hipótesis de que los cambios en el procesamiento de la recompensa desempeñan un papel en el inicio y mantenimiento de los atracones (BE). Sin embargo, a pesar de un número creciente de estudios que investigan el sistema de recompensa neurobiológica en individuos que comen en atracones, no existe una revisión sistemática exhaustiva sobre este tema. Por lo tanto, esta revisión tiene los siguientes objetivos: (1) identificar cambios estructurales y funcionales en el sistema de recompensa cerebral, ya sea en reposo o mientras se realiza una tarea; (2) formular direcciones para futuras investigaciones. MÉTODOS: Se realizó una búsqueda de artículos publicados hasta el 31 de marzo de 2022. Los estudios de neuroimagen eran elegibles si querían estudiar el sistema de recompensa e incluían a un grupo de individuos que comían en atracón junto con un grupo de comparación. Sus resultados se resumieron en una síntesis narrativa. RESULTADOS: Se incluyeron un total de 58 artículos. En reposo, los individuos que comen en atracón mostraron una menor liberación de dopamina estriatal, un cambio en el volumen del cuerpo estriado, la corteza frontal y la ínsula, así como una menor conectividad frontostriatal. Al realizar una tarea, hubo una mayor actividad del sistema de recompensa cerebral al anticipar o recibir alimentos, más aprendizaje de refuerzo sin modelos y un comportamiento más habitual. La mayoría de los estudios sólo incluyeron un grupo de pacientes, utilizaron medidas generales relacionadas con la recompensa y no evaluaron el impacto de las comorbilidades, la duración de la enfermedad, la raza o el sexo. DISCUSIÓN: Confirmando hipótesis anteriores, esta revisión encuentra cambios estructurales y funcionales del sistema de recompensa neurobiológica en BE. Los estudios futuros deben comparar los trastornos, utilizar medidas que sean específicas para el comer en atracones e investigar el impacto de los factores de confusión.

Disentangling the symptoms of schizophrenia: Network analysis in acute phase patients and in patients with predominant negative symptoms.

BACKGROUND: The Positive and Negative Syndrome Scale (PANSS) is widely used in schizophrenia and has been divided into distinct factors (5-factor models) and subfactors. Network analyses are newer in psychiatry and can help to better understand the relationships and interactions between the symptoms of a psychiatric disorder. The aim of this study was threefold: (a) to evaluate connections between schizophrenia symptoms in two populations of patients (patients in the acutely exacerbated phase of schizophrenia and patients with predominant negative symptoms [PNS]), (b) to test whether network analyses support the Mohr 5 factor model of the PANSS and the Kahn 2 factor model of negative symptoms, and finally (c) to identify the most central symptoms in the two populations. METHODS: Using pooled baseline data from four cariprazine clinical trials in patients with acute exacerbation of schizophrenia (n = 2193) and the cariprazine-risperidone study in patients with PNS (n = 460), separate network analyses were performed. Network structures were estimated for all 30 items of the PANSS. RESULTS: While negative symptoms in patients with an acute exacerbation of schizophrenia are correlated with other PANSS symptoms, these negative symptoms are not correlated with other PANSS symptoms in patients with PNS. The Mohr factors were partially reflected in the network analyses. The two most central symptoms (largest node strength) were delusions and uncooperativeness in acute phase patients and hostility and delusions in patients with PNS. CONCLUSIONS: This network analysis suggests that symptoms of schizophrenia are differently structured in acute and PNS patients. While in the former, negative symptoms are mainly secondary, in patients with PNS, they are mainly primary. Further, primary negative symptoms are better conceptualized as distinct negative symptom dimensions of the PANSS.

How COVID-19 lockdown measures could impact patients with bulimia nervosa: Exploratory results from an ongoing experience sampling method study.

OBJECTIVE: The impact of COVID-19 lockdown measures on patients with an eating disorder remains unclear, but preliminary results indicate that some patients could be more vulnerable to experience an increase in eating disorder pathology than others. To provide possible directions for future research, this report explored the impact of the Belgian COVID-19 lockdown measures on patients with bulimia nervosa (BN). METHODS: The data of 15 female patients with BN from an ongoing experience sampling method study were analyzed. Mixed effects models compared surroundings, social context, negative affect (NA), positive affect (PA) and binge eating before and after the implementation of the lockdown measures. RESULTS: After the implementation of the lockdown measures, significant changes in surroundings and social context were found as well as an increase in NA and decrease in PA. Patients who experienced a higher binge eating frequency during the lockdown also experienced a stronger change in NA and PA. CONCLUSIONS: Future research should also look at changes in surroundings, social context, affect and how these interact with factors such as personality traits and coping styles when investigating why some patients are more susceptible to the negative effects of lockdown measures than others.