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OBJECTIVE: Bariatric surgery reduces sweet-liking, but mechanisms remain unclear. We examined related brain responses. METHODS: A total of 24 nondiabetic bariatric surgery and 21 control participants with normal weight to overweight were recruited for an observational controlled cohort study. They underwent sucrose taste testing outside the scanner followed by stimulation with 0.40M and 0.10M sucrose compared with water during functional magnetic resonance imaging. A total of 21 bariatric participants repeated these procedures after surgery. RESULTS: Perceived sweet intensity was not different among the control, presurgery, or postsurgery groups. Bariatric participants' preferred sweet concentration decreased after surgery (0.52M to 0.29M; p = 0.008). Brain reward system (ventral tegmental area, ventral striatum, and orbitofrontal cortex) region of interest analysis showed that 0.40M sucrose activation (but not 0.10M) decreased after surgery. Sensory region (primary somatosensory and primary taste cortex) 0.40M sucrose activation was unchanged by surgery and did not differ between control and bariatric participants. Primary taste cortex activation to 0.10M sucrose solution was greater in postsurgical bariatric participants compared with control participants. CONCLUSIONS: Bariatric surgery reduces the reward system response to sweet taste in women with obesity without affecting activity in sensory regions, which is consistent with reduced drive to consume sweet foods.
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Cirugía Bariátrica , Imagen por Resonancia Magnética , Recompensa , Sacarosa , Gusto , Humanos , Femenino , Adulto , Cirugía Bariátrica/métodos , Gusto/fisiología , Percepción del Gusto/fisiología , Persona de Mediana Edad , Obesidad/cirugía , Obesidad/fisiopatología , Obesidad/psicología , Área Tegmental Ventral/fisiopatología , Área Tegmental Ventral/fisiología , Estriado Ventral , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Encéfalo/fisiopatología , Preferencias Alimentarias/fisiología , Estudios de Cohortes , Corteza Prefrontal , Obesidad Mórbida/cirugía , Obesidad Mórbida/psicología , Obesidad Mórbida/fisiopatologíaRESUMEN
OBJECTIVES: Alcohol use disorder (AUD) is a global health problem with significant negative consequences, including preventable deaths. Although olfactory dysfunction is associated with chronic alcohol drinking, the relationship among specific types of olfactory deficits, depressive symptoms, and problematic drinking remains to be explored. Here, we examined the prevalence of olfactory distortion (parosmia) and hallucination (phantosmia) and assessed their associations with problematic drinking and depressive symptoms. METHODS: In April-June 2022, 250 participants across the spectrum of AUD were recruited for assessment in the National Institute on Alcohol Abuse and Alcoholism COVID-19 Pandemic Impact on Alcohol study. Surveys covered self-reported olfactory function, depressive symptoms, and problematic drinking, with key measures assessed, including the Alcohol Use Disorders Identification Test and the Patient Health Questionnaire. Predictors in the analysis included parosmia and phantosmia, with covariates comprising age, sex, socioeconomic status, race, ethnicity, COVID-19 infection status, and smoking status. RESULTS: Among 250 individuals, 5.2% experienced parosmia and 4.4% reported phantosmia. Parosmia was associated with higher Alcohol Use Disorders Identification Test scores (ß = 7.14; 95% confidence interval = 3.31, 10.96; P < 0.001), whereas phantosmia was linked to higher Patient Health Questionnaire scores (ß = 3.32; 95% confidence interval = 0.22, 6.42; P = 0.03). These associations persisted in both the full sample and the subset of participants without COVID-19. CONCLUSIONS: Our study highlights strong existing links among olfactory deficits, problem drinking, and depressive symptoms, underscoring the need to assess smell impairments in clinical settings. Future research should explore these connections further to develop new treatments for individuals with AUD and depression.
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High-intensity sweet-liking has been linked to alcohol use disorder (AUD) risk. However, the neural underpinning of this association is poorly understood. To find a biomarker predictive of AUD, 140 participants (social and heavy drinkers, ages 21-26) underwent functional magnetic resonance imaging (fMRI) during a monetary incentive delay (MID) task and stimulation with high (SucroseHigh)- and low-concentration sucrose, as well as viscosity-matched water. On another day after imaging, and just before free-access intravenous alcohol self-administration, participants experienced a 30 mg% alcohol prime (10 min ascent) using the Computerized Alcohol Infusion System. Principal component analysis (PCA) of subjective responses (SR) to the prime's ascending limb generated enjoyable (SRenjoy) and sedative (SRsed) intoxication components. Another PCA created one component reflective of self-administered alcohol exposure (AE) over 90 min. Component loadings were entered as regressors in a voxel-wise general linear fMRI model, with reward type as a fixed factor. By design, peak prime breath alcohol concentration was similar across participants (29 ± 3.4 mg%). SRenjoy on the prime's ascending limb correlated positively with [SucroseHigh > Water] in the supplementary motor area and right dorsal anterior insula, implicating the salience network. Neither SR component correlated with the brain's response to MID. AE was unrelated to brain reward activation. While these findings do not support a relationship between alcohol self-administration and (1) subjective liking of or (2) regional brain response to an intensely sweet taste, they show that alcohol's enjoyable intoxicating effects on the rising limb correspond with anterior insular and supplementary motor area responses to high-concentration sucrose taste. No such associations were observed with MID despite robust activation in those regions. Insula and supplementary motor area responses to intense sensations relate to a known risk factor for AUD in a way that is not apparent with a secondary (monetary) reward.
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Alcoholismo , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Gusto/fisiología , Etanol , Alcoholismo/diagnóstico por imagen , Recompensa , Sacarosa , AguaRESUMEN
Poor inhibitory control and heightened feelings of stimulation after alcohol are two well-established risk factors for alcohol use disorder (AUD). Although these risk factors have traditionally been viewed as orthogonal, recent evidence suggests that the two are related and may share common neurobiological mechanisms. Here we examined the degree to which neural activity during inhibition was associated with subjective reports of stimulation following alcohol. To assess neural changes during inhibition, moderate alcohol drinkers performed a stop signal task during fMRI without drug. To assess subjective responses to alcohol they ingested alcohol (0.8 g/kg) or placebo beverages under double-blind conditions and provided subjective reports of stimulation and sedation. Feelings of stimulation following alcohol were inversely associated with activity in the supplementary motor area, insula, and middle frontal gyrus during inhibition (successful stop trials compared to go trials). Feelings of sedation did not correlate with brain activation. These results extend previous findings suggesting that poor inhibitory control is associated with more positive subjective responses to alcohol. These interrelated risk factors may contribute to susceptibility to future excessive alcohol use, and ultimately lead to neurobiological targets to prevent or treat AUD.
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Alcoholismo , Estimulantes del Sistema Nervioso Central , Consumo de Bebidas Alcohólicas , Mapeo Encefálico , Etanol/farmacología , Humanos , Inhibición Psicológica , Imagen por Resonancia MagnéticaRESUMEN
Preclinical models of alcohol use disorder (AUD) have advanced theoretical, mechanistic, and pharmacological study of the human condition. "Liking" and "wanting" behaviors reflect core processes underlying several models of AUD. However, the development and application of translational models of these preclinical approaches are at an incipient stage. The goal of this study was to examine how intravenous free-access and progressive-ratio, operant-response human alcohol self-administration paradigms can be used as translational human model parallels of preclinical "liking" and "wanting." Participants were 40 adults (mean age = 23.7, SD = 2.0; 45% female) of European descent who reported 12.6 drinking days (SD = 5.2) out of the previous 30 (average = 4.1 drinks per drinking day [SD = 1.7]). Individuals diverged in their alcohol self-administration behavior, such that free-access and progressive-ratio paradigm outcomes were not significantly correlated (p = 0.44). Free-access alcohol seeking was related to enjoying alcohol (p < 0.001), but not craving (p = 0.48), whereas progressive-ratio seeking at similar levels of alcohol exposure was related to craving (p = 0.02), but not enjoying (p = 0.30). Family history of alcoholism, venturesomeness traits, and disinhibition traits were unrelated (ps > 0.70) to preferred level of breath alcohol concentration (BrAC) in the free-access session, a measure of liking alcohol. Family history of alcoholism, disinhibition traits, and recent drinking history were significantly related (ps < 0.05) to alcohol seeking in the progressive-ratio paradigm, a measure of wanting alcohol. We conclude that intravenous alcohol self-administration paradigms show promise in modeling behaviors that characterize and parallel alcohol "liking" and "wanting" in preclinical models. These paradigms provide a translational link between preclinical methods and clinical trials.
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Consumo de Bebidas Alcohólicas/psicología , Alcoholismo/psicología , Comportamiento de Búsqueda de Drogas , Adulto , Nivel de Alcohol en Sangre , Ansia , Femenino , Humanos , Masculino , Anamnesis , Motivación , Autoadministración , Factores Sexuales , Adulto JovenRESUMEN
BACKGROUND: The preference for immediate rewards and high sensation seeking are both potent risk factors for alcohol use disorder (AUD), but how they interact during intoxication is poorly understood. To model decision making linked to AUD risk, we tested heavy drinkers for impulsive choice (delay discounting with alcohol:money or money:money) and behavioral sensation seeking using a novel odor choice task. Laboratory tasks measured actual behavior with real contingencies. Our goals were to determine, in heavy drinkers, (i) alcohol's effects on delay discounting, and (ii) how AUD risk factors relate to delay discounting, and (iii) how delay discounting with alcohol choices compares with strictly monetary choices. METHODS: Thirty-five heavy drinkers (≥2 binges per month; age = 22.8 ± 2.2; 20 male; 5.8 ± 2.3 drinks/drinking day) performed cross-commodity discounting (CCD) of immediate alcohol vs. delayed money, a monetary delay discounting (DD), and behavioral sensation-seeking tasks. CCD and DD were performed while sober and during controlled alcohol infusion targeting 0.08 g/dl. The behavioral sensation-seeking task presented binary choices of odorants varying in intensity and novelty, and the risk of exposure to a malodorant. RESULTS: CCD and DD behaviors were highly correlated across conditions, mean r = 0.64. Alcohol increased delayed reward preference in DD, p = 0.001, but did not alter mean CCD, p > 0.16. However, alcohol-induced changes in CCD correlated with behavioral sensation seeking, such that higher sensation seekers' immediate alcohol preference increased when intoxicated, p = 0.042; self-reported sensation seeking was uncorrelated, ps > 0.08. Behavioral sensation seeking also correlated with "want" alcohol following a priming dose targeting 0.035 g/dl, p = 0.021. CCD and DD did not correlate with self-reported drinking problems or other personality risk traits. CONCLUSIONS: Alcohol increased impulsive alcohol choice in high sensation seekers, suggesting an interaction that may underlie impaired control of drinking, at least in a subset of heavy drinkers-consistent with models highlighting high novelty/sensation-seeking AUD subtypes. Discounting behavior overall appears to be a generalized process, and relatively stable across methods, repeated testing, and intoxication. These findings further support the utility of behavioral tasks in uncovering key behavioral phenotypes in AUD.
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Consumo de Bebidas Alcohólicas/psicología , Intoxicación Alcohólica/psicología , Descuento por Demora , Conducta Impulsiva , Olfato , Adulto , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
Human functional brain connectivity is usually measured either at "rest" or during cognitive tasks, ignoring life's moments of mental transition. We propose a different approach to understanding brain network transitions. We applied a novel independent component analysis of functional connectivity during motor inhibition (stop signal task) and during the continuous transition to an immediately ensuing rest. A functional network reconfiguration process emerged that: (i) was most prominent in those without familial alcoholism risk, (ii) encompassed brain areas engaged by the task, yet (iii) appeared only transiently after task cessation. The pattern was not present in a pre-task rest scan or in the remaining minutes of post-task rest. Finally, this transient network reconfiguration related to a key behavioral trait of addiction risk: reward delay discounting. These novel findings illustrate how dynamic brain functional reconfiguration during normally unstudied periods of cognitive transition might reflect addiction vulnerability, and potentially other forms of brain dysfunction.
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Alcoholismo/fisiopatología , Corteza Cerebral/fisiopatología , Conectoma , Descuento por Demora/fisiología , Predisposición Genética a la Enfermedad , Inhibición Psicológica , Actividad Motora/fisiología , Red Nerviosa/fisiología , Recompensa , Adulto , Alcoholismo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Factores de Tiempo , Adulto JovenRESUMEN
Alcohol use disorder is a destructive compulsion characterized by chronic relapse and poor recovery outcomes. Heightened reactivity to alcohol-associated stimuli and compromised executive function are hallmarks of alcohol use disorder. Interventions targeting these two interacting domains are thought to ameliorate these altered states, but the mutual brain sites of action are yet unknown. Although interventions on alcohol cue reactivity affect reward area responses, how treatments alter brain responses when subjects exert executive effort to delay gratification is not as well-characterized. Focusing on interventions that could be developed into effective clinical treatments, we review and identify brain sites of action for these two categories of potential therapies. Using activation likelihood estimation (ALE) meta-analysis, we find that interventions on alcohol cue reactivity localize to ventral prefrontal cortex, dorsal anterior cingulate, and temporal, striatal, and thalamic regions. Interventions for increasing delayed reward preference elicit changes mostly in midline default mode network regions, including posterior cingulate, precuneus, and ventromedial prefrontal cortex-in addition to temporal and parietal regions. Anatomical co-localization of effects appears in the ventromedial prefrontal cortex, whereas effects specific to delay-of-gratification appear in the posterior cingulate and precuneus. Thus, the current available literature suggests that interventions in the domains of cue reactivity and delay discounting alter brain activity along midline default mode regions, specifically in the ventromedial prefrontal cortex for both domains, and the posterior cingulate/precuneus for delay-of-gratification. We believe that these findings could facilitate targeting and development of new interventions, and ultimately treatments of this challenging disorder.
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Alcoholismo/fisiopatología , Alcoholismo/psicología , Encéfalo/fisiopatología , Descuento por Demora/fisiología , Recompensa , Mapeo Encefálico , Condicionamiento Psicológico/fisiología , Función Ejecutiva/fisiología , Humanos , Imagen por Resonancia MagnéticaRESUMEN
Our goal was to develop a behavioral measure of sensation seeking (SS). The Aroma Choice Task (ACT) assesses preference for an intense, novel, varied, and risky (exciting) option versus a mild, safe (boring) option using real-time odorant delivery. A total of 147 healthy young adults completed 40 binary choice trials. We examined (1) intensity and pleasantness of odorants, (2) stability of responding, (3) association with SS self-report, and (4) association with self-reported illicit drug use. Participants' preference for the "exciting" option versus the safe option was significantly associated with self-reported SS (p < .001) and illicit drug use (p = .041). Odorant ratings comported with their intended intensity. The ACT showed good internal, convergent, and criterion validity. We propose that the ACT might permit more objective SS assessment for investigating the biological bases of psychiatric conditions marked by high SS, particularly addiction. The ACT measures SS behaviorally, mitigating some self-report challenges and enabling real-time assessment, for example, for functional magnetic resonance imaging (fMRI).
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Odorantes , Trastornos Relacionados con Sustancias , Humanos , Motivación , Asunción de Riesgos , Sensación , Adulto JovenRESUMEN
Dynamic functional connectivity (dFC) estimates time-dependent associations between pairs of brain region time series as typically acquired during functional MRI. dFC changes are most commonly quantified by pairwise correlation coefficients between the time series within a sliding window. Here, we applied a recently developed bootstrap-based technique (Kudela et al., 2017) to robustly estimate subject-level dFC and its confidence intervals in a task-based fMRI study (24 subjects who tasted their most frequently consumed beer and Gatorade as an appetitive control). We then combined information across subjects and scans utilizing semiparametric mixed models to obtain a group-level dFC estimate for each pair of brain regions, flavor, and the difference between flavors. The proposed approach relies on the estimated group-level dFC accounting for complex correlation structures of the fMRI data, multiple repeated observations per subject, experimental design, and subject-specific variability. It also provides condition-specific dFC and confidence intervals for the whole brain at the group level. As a summary dFC metric, we used the proportion of time when the estimated associations were either significantly positive or negative. For both flavors, our fully-data driven approach yielded regional associations that reflected known, biologically meaningful brain organization as shown in prior work, as well as closely resembled resting state networks (RSNs). Specifically, beer flavor-potentiated associations were detected between several reward-related regions, including the right ventral striatum (VST), lateral orbitofrontal cortex, and ventral anterior insular cortex (vAIC). The enhancement of right VST-vAIC association by a taste of beer independently validated the main activation-based finding (Oberlin et al., 2016). Most notably, our novel dFC methodology uncovered numerous associations undetected by the traditional static FC analysis. The data-driven, novel dFC methodology presented here can be used for a wide range of task-based fMRI designs to estimate the dFC at multiple levels-group-, individual-, and task-specific, utilizing a combination of well-established statistical methods.
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One of the challenging problems in brain imaging research is a principled incorporation of information from different imaging modalities. Frequently, each modality is analyzed separately using, for instance, dimensionality reduction techniques, which result in a loss of mutual information. We propose a novel regularization-method to estimate the association between the brain structure features and a scalar outcome within the linear regression framework. Our regularization technique provides a principled approach to use external information from the structural brain connectivity and inform the estimation of the regression coefficients. Our proposal extends the classical Tikhonov regularization framework by defining a penalty term based on the structural connectivity-derived Laplacian matrix. Here, we address both theoretical and computational issues. The approach is first illustrated using simulated data and compared with other penalized regression methods. We then apply our regularization method to study the associations between the alcoholism phenotypes and brain cortical thickness using a diffusion imaging derived measure of structural connectivity. Using the proposed methodology in 148 young male subjects with a risk for alcoholism, we found a negative associations between cortical thickness and drinks per drinking day in bilateral caudal anterior cingulate cortex, left lateral OFC and left precentral gyrus.
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Human neuroimaging studies of natural rewards and drugs of abuse frequently assay the brain's response to stimuli that, through Pavlovian learning, have come to be associated with a drug's rewarding properties. This might be characterized as a 'sensorial' view of the brain's reward system, insofar as the paradigms are designed to elicit responses to a reward's (drug's) sight, aroma, or flavor. A different field of research nevertheless suggests that the mesolimbic dopamine system may also be critically involved in the motor behaviors provoked by such stimuli. This brief review and commentary surveys some of the preclinical data supporting this more "efferent" (motoric) view of the brain's reward system, and discusses what such findings might mean for how human brain imaging studies of natural rewards and drugs of abuse are designed.
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Condicionamiento Psicológico , Dopamina/metabolismo , Recompensa , Estriado Ventral/diagnóstico por imagen , Encéfalo/fisiología , Vías Eferentes/anatomía & histología , Vías Eferentes/fisiología , Humanos , Aprendizaje/fisiología , Imagen por Resonancia Magnética , Núcleo Accumbens , Tomografía de Emisión de Positrones , Trastornos Relacionados con Sustancias , Estriado Ventral/fisiologíaRESUMEN
RATIONALE: Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication. OBJECTIVES: Extending our prior work to examine the influence of alcoholism risk factors, we paired abstract visual stimuli with intravenous alcohol delivered covertly and examined brain responses to these Pavlovian-conditioned stimuli in fMRI when subjects were not intoxicated. METHODS: Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli. Shapes were paired with a rapidly rising alcohol limb (conditioned stimulus; CS+) using intravenous alcohol infusion targeting a final peak breath alcohol concentration of 0.045 g/dL or saline (CS-) infusion at matched rates. On day 2, subjects performed monetary delay discounting outside the scanner to assess delay tolerance and then underwent event-related fMRI while performing the same task with CS+, CS-, and an irrelevant symbol. RESULTS: CS+ elicited stronger activation than CS- in frontoparietal executive/attention and orbitofrontal reward-associated networks. Risk factors including family history, recent drinking, sex, and age of drinking onset did not relate to the [CS+ > CS-] activation. Delay-tolerant choice and [CS+ > CS-] activation in right inferior parietal cortex were positively related. CONCLUSIONS: Networks governing executive attention and reward showed enhanced responses to stimuli experimentally paired with intoxication, with the right parietal cortex implicated in both alcohol cue pairing and intertemporal choice. While different from our previous study results in 14 men, we believe this paradigm in a large sample of male and female drinkers offers novel insights into Pavlovian processes less affected by idiosyncratic drug associations.
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Intoxicación Alcohólica/diagnóstico por imagen , Atención/fisiología , Encéfalo/diagnóstico por imagen , Señales (Psicología) , Etanol/administración & dosificación , Red Nerviosa/diagnóstico por imagen , Adulto , Consumo de Bebidas Alcohólicas/psicología , Intoxicación Alcohólica/psicología , Atención/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Conducta de Elección/efectos de los fármacos , Conducta de Elección/fisiología , Condicionamiento Clásico/efectos de los fármacos , Condicionamiento Clásico/fisiología , Descuento por Demora/efectos de los fármacos , Descuento por Demora/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Red Nerviosa/efectos de los fármacos , Red Nerviosa/fisiología , Adulto JovenRESUMEN
BACKGROUND: The P3 component of the event-related potential (ERP) has been particularly useful in alcohol research for identifying endophenotypes of alcohol-use disorder (AUD) risk in sober subjects. However, practice and/or fatigue reduce P3 amplitude, limiting the ability to ascertain acute and adaptive effects of alcohol exposure. Here, we report acute alcohol effects on P3 amplitude and latency using an adaptive stop signal task (aSST). METHODS: One hundred forty-eight non-dependent moderate to heavy social drinkers, ages 21 to 27, participated in two single-blind, alcohol or placebo, counterbalanced sessions approximately 1 week apart. During each session, subjects performed an adaptive stop signal task (aSST) at 1) baseline, 2) upon reaching the target 60 mg/dL breath alcohol concentration or at the equivalent time during the placebo session, and 3) approximately 135 min later while the breath alcohol concentration was clamped. Here, we report on differences between baseline and first subsequent measurements across the experimental sessions. During each aSST run, the stop signal delay (SSD, the time between stop and go signals) adjusted trial-by-trial, based on the subject's performance. RESULTS: The aSST reliably generated a STOP P3 component that did not change significantly with repeated task performance. The pre-infusion SSD distribution was bimodal, with mean values several hundred msec apart (FAST: 153 msec and SLOW: 390 msec). This suggested different response strategies: FAST SSD favoring "going" over "stopping", and SLOW SSD favoring "stopping" over "going". Exposure to alcohol at 60 mg/dL differentially affected the amplitude and latency of the STOP P3 according to SSD group. Alcohol significantly reduced P3 amplitude in the SLOW SSD compared to the FAST SSD group, but significantly increased P3 latency in the FAST SSD compared to the SLOW SSD group. CONCLUSIONS: The aSST is a robust and sensitive task for detecting alcohol-induced changes in inhibition behavior as measured by the P3 component in a within-subject design. Alcohol was associated with P3 component changes, which varied by SSD group, suggesting a differential effect as a function of task strategy. Overall, the data support the potential utility of the aSST in the detection of alcohol response-related AUD risk.
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Etanol/farmacología , Potenciales Relacionados con Evento P300/efectos de los fármacos , Inhibición Psicológica , Adulto , Potenciales Relacionados con Evento P300/fisiología , Femenino , Humanos , Masculino , Desempeño Psicomotor/efectos de los fármacos , Desempeño Psicomotor/fisiología , Método Simple Ciego , Adulto JovenRESUMEN
A heightened hedonic response to sweet tastes has been associated with increased alcohol preference and alcohol consumption in both humans and animals. The principal goal of this study was to examine blood oxygenation level dependent (BOLD) activation to high- and low-concentration sweet solutions in subjects who are either positive (FHP) or negative (FHN) for a family history of alcoholism. Seventy-four non-treatment seeking, community-recruited, healthy volunteers (22.8 ± 1.6 SD years; 43% men) rated a range of sucrose concentrations in a taste test and underwent functional magnetic resonance imaging (fMRI) during oral delivery of water, 0.83 M, and 0.10 M sucrose. Sucrose compared to water produced robust activation in primary gustatory cortex, ventral insula, amygdala, and ventral striatum. FHP subjects displayed greater bilateral amygdala activation than FHN subjects in the low sucrose concentration (0.10 M). In secondary analyses, the right amygdala response to the 0.10 M sucrose was greatest in FHP women. When accounting for group differences in drinks per week, the family history groups remained significantly different in their right amygdala response to 0.10 M sucrose. Our findings suggest that the brain response to oral sucrose differs with a family history of alcoholism, and that this response to a mildly reinforcing primary reward might be an endophenotypic marker of alcoholism risk.
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Alcoholismo/tratamiento farmacológico , Alcoholismo/patología , Encéfalo/efectos de los fármacos , Salud de la Familia , Sacarosa/administración & dosificación , Edulcorantes/administración & dosificación , Administración Oral , Adulto , Consumo de Bebidas Alcohólicas , Alcoholismo/diagnóstico por imagen , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Motivación , Oxígeno/sangre , Factores Sexuales , Gusto , Adulto JovenRESUMEN
Mild cognitive impairment (MCI) is characterised by subjective and objective memory impairment in the absence of dementia. MCI is a strong predictor for the development of Alzheimer's disease, and may represent an early stage in the disease course in many cases. A standard task used in the diagnosis of MCI is verbal fluency, where participants produce as many items from a specific category (e.g., animals) as possible. Verbal fluency performance is typically analysed by counting the number of items produced. However, analysis of the semantic path of the items produced can provide valuable additional information. We introduce a cognitive model that uses multiple types of lexical information in conjunction with a standard memory search process. The model used a semantic representation derived from a standard semantic space model in conjunction with a memory searching mechanism derived from the Luce choice rule (Luce, 1977). The model was able to detect differences in the memory searching process of patients who were developing MCI, suggesting that the formal analysis of verbal fluency data is a promising avenue to examine the underlying changes occurring in the development of cognitive impairment. (PsycINFO Database Record
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Encéfalo/fisiopatología , Cognición/fisiología , Disfunción Cognitiva/complicaciones , Trastornos del Lenguaje , Modelos Psicológicos , Semántica , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Trastornos del Lenguaje/diagnóstico , Trastornos del Lenguaje/etiología , Trastornos del Lenguaje/patología , Masculino , Pruebas NeuropsicológicasRESUMEN
INTRODUCTION: We investigated the association between olfactory identification and Alzheimer's disease biomarkers, including amyloid, tau, and neurodegeneration. METHODS: Thirty-four older adults, including 19 cognitively normal (CN), 10 subjective cognitive decline (SCD), and 5 mild cognitive impairment, underwent amyloid positron emission tomography, magnetic resonance imaging, and the University of Pennsylvania Smell Identification Test (UPSIT). Twenty-six also underwent tau positron emission tomography. Associations between the UPSIT and regionally sampled amyloid, tau, and temporal atrophy were evaluated. Voxel-wise regression models were also utilized. Analyses were conducted with the full sample and only CN/SCD. RESULTS: Lower UPSIT scores were associated with increased temporal and parietal tau burden in regional and voxel-wise analyses in the full sample and in CN and SCD only. Temporal lobe atrophy was associated with lower UPSIT score. Amyloid was not associated with the UPSIT. DISCUSSION: Impairment on the UPSIT may be a good marker for tau and neurodegeneration in preclinical or prodromal Alzheimer's disease.
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Poor inhibitory control and sensitivity to drug reward are two significant risk factors for drug abuse. Although the two have been largely viewed as separate and independent risk factors, there is new evidence to suggest that they may be related at both the behavioral and neural level. This study examined associations between behavioral and neural correlates of inhibitory control and sensitivity to the subjective rewarding effects of amphetamine in humans. Healthy volunteers (n=63) first completed the stop signal task, a behavioral measure of inhibitory control. Then they participated in four sessions in which they received amphetamine (20 mg) and placebo in alternating order, providing self-report measures of euphoria and arousal at regular intervals. Finally, a subset of participants (n=38) underwent an fMRI scan to assess neural correlates of inhibitory control. In the first phase of the study, participants with longer stop signal reaction time (SSRT) reported greater amphetamine-induced euphoria and stimulation than those with shorter SSRT. In the second phase, fMRI of response inhibition showed the expected activation in right prefrontal regions. Further, individuals who exhibited less activation in the right middle frontal gyrus during the inhibition task reported more euphoria during the amphetamine sessions. This study is the first to show associations between poor inhibitory control and amphetamine reward sensitivity at both behavioral and neural levels in humans. These findings extend our understanding of risk for drug abuse in individuals with poor inhibitory control and suggest novel targets for prevention efforts.
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Anfetamina/farmacología , Encéfalo/fisiología , Estimulantes del Sistema Nervioso Central/farmacología , Inhibición Psicológica , Actividad Motora/efectos de los fármacos , Recompensa , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Mapeo Encefálico , Circulación Cerebrovascular , Euforia/efectos de los fármacos , Femenino , Humanos , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Oxígeno/sangre , Autoinforme , Adulto JovenRESUMEN
OBJECTIVE: The brain's reward system influences ingestive behavior and subsequently obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. This study sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. METHODS: A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n = 16) and men (n = 12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the two testing days. RESULTS: Mean fasting-state brain responses on day 2 were reduced compared with day 1 in the left insula and right amygdala, but mean day 1 and day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. CONCLUSIONS: fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies.