Processing of primary and secondary rewards: A quantitative meta-analysis and review of human functional neuroimaging studies

One fundamental question concerning brain reward mechanisms is to determine how reward-related activity is influenced by the nature of rewards. Here, we review the neuroimaging literature and explicitly assess to what extent the representations of primary and secondary rewards overlap in the human brain. To achieve this goal, we performed an activation likelihood estimation (ALE) meta-analysis of 87 studies (1452 subjects) comparing the brain responses to monetary, erotic and food reward outcomes. Those three rewards robustly engaged a common brain network including the ventromedial prefrontal cortex, ventral striatum, amygdala, anterior insula and mediodorsal thalamus, although with some variations in the intensity and location of peak activity. Money-specific responses were further observed in the most anterior portion of the orbitofrontal cortex, supporting the idea that abstract secondary rewards are represented in evolutionary more recent brain regions. In contrast, food and erotic (i.e. primary) rewards were more strongly represented in the anterior insula, while erotic stimuli elicited particularly robust responses in the amygdala. Together, these results indicate that the computation of experienced reward value does not only recruit a core "reward system" but also reward type-dependent brain structures

Allostatic load and executive functions in overweight adults

Background/objective: Overweight is linked to inflammatory and neuroendocrine responses potentially prompting deregulations in biological systems harmful to the brain, particularly to the prefrontal cortex. This structure is crucial for executive performance, ultimately supervising behaviour. Thus, in the present work, we aimed to test the relationship between allostatic load increase, a surrogate of chronic physiological stress, and core executive functions, such as cognitive flexibility, inhibitory control, and working memory. Method Forty-seven healthy-weight and 56 overweight volunteers aged from 21 to 40 underwent medical and neuropsychological examination. Results: Overweight subjects exhibited a greater allostatic load index than healthy-weight individuals. Moreover, the allostatic load index was negatively related to inhibitory control. When separated, the link between allostatic load index and cognitive flexibility was more marked in the overweight group. Conclusions: An overweight status was linked to chronic physiological stress. The inverse relationship between the allostatic load index and cognitive flexibility proved stronger in this group. Set-shifting alterations could sustain rigid-like behaviours and attitudes towards food

Inflammatory agents partially explain associations between cortical thickness, surface area, and body mass in adolescents and young adulthood

Background/objectives Excessive body mass index (BMI) has been linked to a low-grade chronic inflammation state. Unhealthy BMI has also been related to neuroanatomical changes in adults. Research in adolescents is relatively limited and has produced conflicting results. This study aims to address the relationship between BMI and adolescents'brain structure as well as to test the role that inflammatory adipose-related agents might have over this putative link. Methods We studied structural MRI and serum levels of interleukin-6, tumor necrosis factor alpha (TNF-α), C-reactive protein and fibrinogen in 65 adolescents (aged 12-21 years). Relationships between BMI, cortical thickness and surface area were tested with a vertex-wise analysis. Subsequently, we used backward multiple linear regression models to explore the influence of inflammatory parameters in each brain-altered area. Results We found a negative association between cortical thickness and BMI in the left lateral occipital cortex (LOC) and the right precentral gyrus as well as a positive relationship between surface area and BMI in the left rostral middle frontal gyrus and the right superior frontal gyrus. In addition, we found that higher fibrinogen serum concentrations were related to thinning within the left LOC (β=−0.45,p< 0.001), while higher serum levels of TNF-αwere associated to a greater surface area in the right superior frontal gyrus (β=0.32,p=0.045). Besides, we have also identified a trend that negatively correlates the cortical thickness of the left fusiform gyrus with the increases in BMI. It was also associated to fibrinogen(β=−0.33,p=0.035). Conclusions These results suggest that adolescents'body mass increases are related with brain abnormalities in areas that could play a relevant role in some aspects of feeding behavior. Likewise, we have evidenced that these cortical changes were partially explained by inflammatory agents such as fibrinogen and TNF-α

Allostatic Load Is Linked to Cortical Thickness Changes Depending on Body-Weight Status

Objective: Overweight (body mass index or BMI 25 kg/m2) and stress interact with each other in complex ways. Overweight promotes chronic low-inflammation states, while stress is known to mediate caloric intake. Both conditions are linked to several avoidable health problems and to cognitive decline, brain atrophy, and dementia. Since it was proposed as a framework for the onset of mental illness, the allostatic load model has received increasing attention. Although changes in health and cognition related to overweight and stress are well-documented separately, the association between allostatic load and brain integrity has not been addressed in depth, especially among overweight subjects. Method: Thirty-four healthy overweight-to-obese and 29 lean adults underwent blood testing, neuropsychological examination, and magnetic resonance imaging to assess the relationship between cortical thickness and allostatic load, represented as an index of 15 biomarkers (this is, systolic and diastolic arterial tension, glycated hemoglobin, glucose, creatinine, total cholesterol, HDL and LDL cholesterol, triglycerides, c-reactive protein, interleukin-6, insulin, cortisol, fibrinogen, and leptin). Results: Allostatic load indexes showed widespread positive and negative significant correlations (p < 0.01) with cortical thickness values depending on body-weight status. Conclusion: The increase of allostatic load is linked to changes in the gray matter composition of regions monitoring behavior, sensory-reward processing, and general cognitive function

Allostatic load and disordered white matter microstructure in overweight adults

Overweight and stress are both related to brain structural abnormalities. The allostatic load model states that frequent disruption of homeostasis is inherently linked to oxidative stress and inflammatory responses that in turn can damage the brain. However, the effects of the allostatic load on the central nervous system remain largely unknown. The current study aimed to assess the relationship between the allostatic load and the composition of whole-brain white matter tracts in overweight subjects. Additionally, we have also tested for grey matter changes regarding allostatic load increase. Thirty-one overweight-to-obese adults and 21 lean controls participated in the study. Our results showed that overweight participants presented higher allostatic load indexes. Such increases correlated with lower fractional anisotropy in the inferior fronto-occipital fasciculi and the right anterior corona radiata, as well as with grey matter reductions in the left precentral gyrus, the left lateral occipital gyrus, and the right pars opercularis. These results suggest that an otherwise healthy overweight status is linked to long-term biological changes potentially harmful to the brain

COVID-19 severity is related to poor executive function in people with post-COVID conditions

Open Access funding provided thanks to the CRUE-CSIC agreement with Springer NaturePatients with post-coronavirus disease 2019 (COVID-19) conditions typically experience cognitive problems. Some studies have linked COVID-19 severity with long-term cognitive damage, while others did not observe such associations. This discrepancy can be attributed to methodological and sample variations. We aimed to clarify the relationship between COVID-19 severity and long-term cognitive outcomes and determine whether the initial symptomatology can predict long-term cognitive problems. Cognitive evaluations were performed on 109 healthy controls and 319 post-COVID individuals categorized into three groups according to the WHO clinical progression scale: severe-critical (n¿=¿77), moderate-hospitalized (n¿=¿73), and outpatients (n¿=¿169). Principal component analysis was used to identify factors associated with symptoms in the acute-phase and cognitive domains. Analyses of variance and regression linear models were used to study intergroup differences and the relationship between initial symptomatology and long-term cognitive problems. The severe-critical group performed significantly worse than the control group in general cognition (Montreal Cognitive Assessment), executive function (Digit symbol, Trail Making Test B, phonetic fluency), and social cognition (Reading the Mind in the Eyes test). Five components of symptoms emerged from the principal component analysis: the “Neurologic/Pain/Dermatologic” “Digestive/Headache”, “Respiratory/Fever/Fatigue/Psychiatric” and “Smell/ Taste” components were predictors of Montreal Cognitive Assessment scores; the “Neurologic/Pain/Dermatologic” component predicted attention and working memory; the “Neurologic/Pain/Dermatologic” and “Respiratory/Fever/Fatigue/Psychiatric” components predicted verbal memory, and the “Respiratory/Fever/Fatigue/Psychiatric,” “Neurologic/Pain/Dermatologic,” and “Digestive/Headache” components predicted executive function. Patients with severe COVID-19 exhibited persistent deficits in executive function. Several initial symptoms were predictors of long-term sequelae, indicating the role of systemic inflammation and neuroinflammation in the acute-phase symptoms of COVID-19.” Study Registration: www.ClinicalTrials.gov, identifier NCT05307549 and NCT05307575.This research was supported by the Agency for Management of University and Research Grants (AGAUR) from the Generalitat de Catalunya (Pandemies, 202PANDE00053) and La Marató de TV3 Foundation (202111-30-31-32).Peer ReviewedArticle signat per 16 autors/es: Mar Ariza, Neus Cano, Bàrbara Segura, Ana Adan, Núria Bargalló, Xavier Caldú, Anna Campabadal, Maria Angeles Jurado, Maria Mataró, Roser Pueyo, Roser Sala‑Llonch, Cristian Barrué, Javier Bejar, Claudio Ulises Cortés on behalf of NAUTILUS Project Collaborative Group, Maite Garolera Carme JunquéPostprint (published version

Study protocol of a randomized controlled trial of home-based computerized executive function training for children with cerebral palsy

Background: Cerebral palsy (CP) is frequently associated with specific cognitive impairments, such as executive dysfunction which are related to participation and quality of life (QOL). The proposed study will examine whether a computerized executive function (EF) training programme could provide superior benefits for executive functioning, participation, QOL and brain plasticity, as compared to usual care. Methods: A single-blind randomized controlled trial (RCT) design will be performed. Thirty children with CP aged 8 to 12 years will participate in a home-based computerized multi-modal executive training programme (12 weeks, 5 days a week, 30 min a day training, total dose = 30 h). Thirty children with CP matched by age, sex, motor and intelligence quotient (IQ) will compose the waitlist group. Cognitive, behavioural, emotional, participation and QOL measures will be obtained at three time points: before, immediately after and 9 months after completing the training. Additionally, structural and functional (resting state) magnetic resonance images (MRI) will be obtained in a subsample of 15 children from each group. Outcomes between groups will be compared following standard principles for RCTs. Discussion: The study will test whether the cognitive training programme exerts a positive effect not only on neuropsychological and daily functioning of children with CP but also on other measures such as participation and QOL. We will also use brain MRI to test brain functional and structural changes after the intervention. If this on-line and home-based training programme proves effective, it could be a cost-effective intervention with short- and long-term effects on EF, participation or QOL in CP

Neuropsychological Impairment in Post-COVID condition individuals with and without cognitive complaints

One of the most prevalent symptoms of post-COVID condition is cognitive impairment, which results in a significant degree of disability and low quality of life. In studies with large sample sizes, attention, memory, and executive function were reported as long-term cognitive symptoms. This study aims to describe cognitive dysfunction in large post-COVID condition individuals, compare objective neuropsychological performance in those post-COVID condition individuals with and without cognitive complaints, and identify short cognitive exams that can differentiate individuals with post-COVID symptoms from controls. To address these aims, the Nautilus project was started in June 2021. During the first year, we collected 428 participants' data, including 319 post-COVID and 109 healthy controls (18-65 years old) from those who underwent a comprehensive neuropsychological battery for cognitive assessment. Scores on tests assessing global cognition, learning and long-term memory, processing speed, language and executive functions were significantly worse in the post-COVID condition group than in healthy controls. Montreal Cognitive Assessment, digit symbol test, and phonetic verbal fluency were significant in the binomial logistic regression model and could effectively distinguish patients from controls with good overall sensitivity and accuracy. Neuropsychological test results did not differ between those with and without cognitive complaints. Our research suggests that patients with post-COVID conditions experience significant cognitive impairment and that routine tests like the Montreal Cognitive Assessment, digit symbol, and phonetic verbal fluency test might identify cognitive impairment. Thus, the administration of these tests would be helpful for all patients with post-COVID-19 symptoms, regardless of whether cognitive complaints are present or absent

Influència de les variants genètiques de la COMT i el DAT en l'activació cerebral i en el processament cognitiu i emocional

[cat] D'entre totes les catecolamines, la dopamina és la més important del sistema nerviós central, on regula funcions com la conducta motora, les emocions i la cognició. Donada la implicació del sistema dopaminèrgic en diverses disfuncions cerebrals, com ara l'esquizofrènia, la malaltia de Parkinson o el trastorn per dèficit d'atenció amb hiperactivitat, l'estudi d'aquest sistema ha esdevingut de gran importància. Els dos mecanismes més importants de terminació de l'activitat dopaminèrgica a nivell sinàptic són la recaptació mitjançant el transportador de la dopamina (DAT) i la degradació a través de la catecol-o-metiltransferasa (COMT). El gen del DAT presenta un polimorfisme consistent en un número variable de repeticions en tàndem (VNTR) de 40 parells de bases (bp). Aquest polimorfisme es troba en una regió no codificant del gen i, per tant, no està associat a mutacions en la seqüència d'aminoàcids de la proteïna, però sí s'han observat diferències en la disponibilitat de la proteïna associades al VNTR. Tot i que els estudis in vivo han estat poc concloents, els estudis in vitro suggereixen una major expressió de la proteïna associada a l'al·lel de 10 repeticions, la qual conduiria a menors nivells de dopamina sinàptica. La COMT és un enzim que pot catalitzar la metilació de petites molècules com fàrmacs, hormones i neurotransmissors o de macromolècules com les proteïnes, l'ARN o l'ADN. El gen de la COMT mostra un polimorfisme funcional causat per la transició d'una guanina a una adenina que suposa un canvi de l'aminoàcid valina per l'aminoàcid metionina al codó 108/158, depenent de si la forma de l'enzim codificada és la citosòlica (codó 108) o la membranal (codó 158). L'enzim que conté l'aminoàcid metionina és termolàbil a 37 ºC, mentre que l'enzim que conté l'aminoàcid valina mostra major estabilitat a temperatures entre els 37 i els 56 ºC. La major estabilitat comporta uns majors nivells d'activitat enzimàtica i, en conseqüència, una menor disponibilitat dopaminèrgica a nivell sinàptic. En els dos estudis que formen aquesta tesi vàrem avaluar l'efecte de les variants genètiques de la COMT i del DAT sobre l'activació cerebral relacionada amb la memòria de treball i el processament d'emocions, així com el seu impacte sobre les funcions cognitives prefrontals. A tal efecte, es va estudiar, mitjançant la tècnica de ressonància magnètica funcional (RMf) i l'administració de proves prefrontals, una mostra de subjectes sans dels quals s'havien obtingut prèviament el genotip per als polimorfismes Val108/158 Met de la COMT i 40 bp VNTR del DAT. Les anàlisis van mostrar una relació entre el genotip de la COMT i l'execució en el Wisconsin Card Sorting Tests (WCST). Concretament, el nombre d'al·lels Val estava relacionat amb un pitjor rendiment en aquest test, reflectit pel major nombre d'errors perseveratius. Pel que fa al genotip del DAT, es va observar un efecte sobre la variable temps de reacció del Continuous Performance Test (CPT). Els subjectes homozigots per a l'al·lel de 9 repeticions van ser els que van mostrar els temps de reacció més elevats, mentre que els subjectes homozigots per a l'al·lel de 10 repeticions van mostrar els temps de reacció més baixos. Tots dos genotips es van relacionar amb el nombre d'errors de comissió en el CPT. El nombre d'al·lels Val de la COMT i el nombre d'al·lels de 10 repeticions del DAT estaven relacionats amb un major nombre d'errors de comissió. Pel que fa a les dades de RMf no es va observar cap efecte dels genotips de la COMT i del DAT independentment, però sí un efecte additiu dels dos genotips sobre l'activació cerebral a la circumvolució frontal mitja (BA 9) durant la realització de l'N-back. Durant el processament d'emocions es va observar un efecte principal del genotip de la COMT en l'activació de l'amígdala dreta. Anàlisis posteriors van revelar una major activació de l'amígdala dreta en els subjectes homozigots per a l'al·lel Met en relació als portadors de l'al·lel Val. Els nostres resultats mostren, per tant, que les variacions genètiques que afecten la transmissió dopaminèrgica tenen un impacte sobre la fisiologia cerebral i sobre el rendiment cognitiu

Is cognitive training an effective tool for improving cognitive function and real-life behaviour in healthy children and adolescents? A systematic review

Computerised cognitive training (CCT) has been applied to improve cognitive function in pathological conditions and in healthy populations. Studies suggest that CCT produces near-transfer effects to cognitive functions, with less evidence for far transfer. Newer applications of CTT in adults seem to produce certain far-transfer effects by influencing eating behaviour and weight loss. However, this is more unexplored in children and adolescents. We conducted a systematic review of 16 studies with randomised controlled design to assess the impact of CCT on cognitive functioning and real-life outcomes, including eating behaviour, in children and adolescents with typical development (PROSPERO registration number: CRD42019123889). Results show near transfer effects to working memory, with inconsistent results regarding far-transfer effects to other cognitive functions and real-life measures. Long-term effects show the same trend. Far-transfer effects occurred after cue related inhibitory control and attentional training, although effects seem not to last. CCT may be a potential weight-loss treatment option but more research is needed to determine the specific characteristics to enhance treatment outcomes