Activation In Fronto-striatal Regions Research Articles

Effects of baclofen on insular gain anticipation in alcohol-dependent patients — a randomized, placebo-controlled, pharmaco-fMRI pilot trial

RationaleOne hallmark of addiction is an altered neuronal reward processing. In healthy individuals (HC), reduced activity in fronto-striatal regions including the insula has been observed when a reward anticipation task was performed repeatedly. This effect could indicate a desensitization of the neural reward system due to repetition. Here, we investigated this hypothesis in a cohort of patients with alcohol use disorder (AUD), who have been treated with baclofen or a placebo. The efficacy of baclofen in AUD patients has been shown to have positive clinical effects, possibly via indirectly affecting structures within the neuronal reward system.ObjectivesTwenty-eight recently detoxified patients (13 receiving baclofen (BAC), 15 receiving placebo (PLA)) were investigated within a longitudinal, double-blind, and randomized pharmaco-fMRI design with an individually adjusted daily dosage of 30–270 mg.MethodsBrain responses were captured by functional magnetic resonance imaging (fMRI) during reward anticipation while participating in a slot machine paradigm before (t1) and after 2 weeks of individual high-dose medication (t2).ResultsAbstinence rates were significantly higher in the BAC compared to the PLA group during the 12-week high-dose medication phase. At t1, all patients showed significant bilateral striatal activation. At t2, the BAC group showed a significant decrease in insular activation compared to the PLA group.ConclusionsBy affecting insular information processing, baclofen might enable a more flexible neuronal adaptation during recurrent reward anticipation, which could resemble a desensitization as previously observed in HC. This result strengthens the modulation of the reward system as a potential mechanism of action of baclofen.Trial registrationIdentifier of the main trial (the BACLAD study) at clinical.gov: NCT0126665.

Belief Updating in Subclinical and Clinical Delusions

Abstract Background and Hypothesis Current frameworks propose that delusions result from aberrant belief updating due to altered prediction error (PE) signaling and misestimation of environmental volatility. We aimed to investigate whether behavioral and neural signatures of belief updating are specifically related to the presence of delusions or generally associated with manifest schizophrenia. Methods Our cross-sectional design includes human participants (n[female/male] = 66[25/41]), stratified into four groups: healthy participants with minimal (n = 22) or strong delusional-like ideation (n = 18), and participants with diagnosed schizophrenia with minimal (n = 13) or strong delusions (n = 13), resulting in a 2 × 2 design, which allows to test for the effects of delusion and diagnosis. Participants performed a reversal learning task with stable and volatile task contingencies during fMRI scanning. We formalized learning with a hierarchical Gaussian filter model and conducted model-based fMRI analysis regarding beliefs of outcome uncertainty and volatility, precision-weighted PEs of the outcome- and the volatility-belief. Results Patients with schizophrenia as compared to healthy controls showed lower accuracy and heightened choice switching, while delusional ideation did not affect these measures. Participants with delusions showed increased precision-weighted PE-related neural activation in fronto-striatal regions. People with diagnosed schizophrenia overestimated environmental volatility and showed an attenuated neural representation of volatility in the anterior insula, medial frontal and angular gyrus. Conclusions Delusional beliefs are associated with altered striatal PE-signals. Juxtaposing, the potentially unsettling belief that the environment is constantly changing and weaker neural encoding of this subjective volatility seems to be associated with manifest schizophrenia, but not with the presence of delusional ideation.

Prefrontal Responses during Proactive and Reactive Inhibition Are Differentially Impacted by Stress in Anorexia and Bulimia Nervosa

Binge eating is a distressing, transdiagnostic eating disorder symptom associated with impulsivity, particularly in negative mood states. Neuroimaging studies of bulimia nervosa (BN) report reduced activity in frontostriatal regions implicated in self-regulatory control, and an influential theory posits that binge eating results from self-regulation failures under stress. However, there is no direct evidence that psychological stress impairs self-regulation in binge-eating disorders, or that any such self-regulatory deficits generalize to binge eating in underweight individuals (i.e., anorexia nervosa bingeing/purging subtype; AN-BP). We therefore determined the effect of acute stress on inhibitory control in 85 women (BN, 33 women; AN-BP, 22 women; 30 control participants). Participants underwent repeated functional MRI scanning during performance of the Stop-signal anticipation task, a validated measure of proactive (i.e., anticipation of stopping) and reactive (outright stopping) inhibition. Neural and behavioral responses to induced stress and a control task were evaluated on 2 consecutive days. Women with BN had reduced proactive inhibition, while prefrontal responses were increased in both AN-BP and BN. Reactive inhibition was neurally and behaviorally intact in both diagnostic groups. Both AN-BP and BN groups showed distinct stress-induced changes in inferior and superior frontal activity during both proactive and reactive inhibition. However, task performance was unaffected by stress. These results offer novel evidence of reduced proactive inhibition in BN, yet inhibitory control deficits did not generalize to AN-BP. Our findings identify intriguing alterations of stress responses and inhibitory function associated with binge eating, but they counsel against stress-induced failures of inhibitory control as a comprehensive explanation for loss-of-control eating.SIGNIFICANCE STATEMENT Binge eating is a common psychiatric syndrome that feels uncontrollable to the sufferer. Theoretically, it has been related to reduced self-regulation under stress, but there remains no direct evidence for this link in binge-eating disorders. Here, we examined how experimentally induced stress affected response inhibition in control participants and women with anorexia nervosa and bulimia nervosa. Participants underwent repeated brain scanning under stressful and neutral conditions. Although patient groups had intact action cancellation, the slowing of motor responses was impaired in bulimia nervosa, even when the likelihood of having to stop increased. Stress altered brain responses for both forms of inhibition in both groups, yet performance remained unimpaired. These findings counsel against a simple model of stress-induced disinhibition as an adequate explanation for binge eating.

Association between impulsivity and neural activation to alcohol cues in heavy drinkers

This study examines associations between two measures of impulsivity and brain response to alcohol taste cues. Impulsivity is both a risk factor for and a consequence of alcohol use and misuse. Frontostriatal circuits are linked to both impulsivity and addiction-related behaviors, including response to alcohol cues. Non-treatment-seeking heavy drinkers (n = 55) completed (i) an fMRI alcohol taste cue-reactivity paradigm; (ii) the monetary choice questionnaire (MCQ), a measure of choice impulsivity where participants choose between smaller, sooner rewards and larger, delayed rewards; (iii) and the UPPS-P Impulsive Behavior Scale, a self-report measure assessing five impulsivity factors. General linear models identified associations between neural alcohol taste cue-reactivity and impulsivity, adjusting for age, gender, and smoking status. Self-reported sensation seeking was positively associated with alcohol taste cue-elicited activation in frontostriatal regions, such that individuals who reported higher sensation seeking displayed greater neural response to alcohol taste cues. Conversely, delay discounting was negatively associated with activation in frontoparietal regions, such that individuals who reported greater discounting showed less cue-elicited activation. There were no significant associations between other self-reported impulsivity subscales and alcohol taste cue-reactivity. These results indicate that sensation seeking is associated with reward responsivity, while delay discounting is associated with recruitment of self-control circuitry.

Neural activations associated with feedback and retrieval success

There is substantial behavioral evidence for a phenomenon commonly called “the testing effect”, i.e. superior memory performance after repeated testing compared to re-study of to-be-learned materials. However, considerably less is known about the underlying neuro-cognitive processes that are involved in the initial testing phase, and thus underlies the actual testing effect. Here, we investigated functional brain activity related to test-enhanced learning with feedback. Subjects learned foreign vocabulary across three consecutive tests with correct-answer feedback. Functional brain-activity responses were analyzed in relation to retrieval and feedback events, respectively. Results revealed up-regulated activity in fronto-striatal regions during the first successful retrieval, followed by a marked reduction in activity as a function of improved learning. Whereas feedback improved behavioral performance across consecutive tests, feedback had a negligable role after the first successful retrieval for functional brain-activity modulations. It is suggested that the beneficial effects of test-enhanced learning is regulated by feedback-induced updating of memory representations, mediated via the striatum, that might underlie the stabilization of memory commonly seen in behavioral studies of the testing effect.

Reward sensitivity modulates brain activity in the prefrontal cortex, ACC and striatum during task switching.

Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS) sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies.

From Circuit Activity to Network Connectivity and Back: The Case of Obsessive-Compulsive Disorder

From Circuit Activity to Network Connectivity and Back: The Case of Obsessive-Compulsive Disorder

Behavioral Activation System modulation of brain activity during task switching

The aim of this work was to study the relationship between individual differences in Behavioral Activation System (BAS) sensitivity and brain activity during task switching. BAS sensitivity was hypothesized to modulate activity in brain regions involved in cognitive flexibility, including anterior cingulate, dorsolateral prefrontal cortex, inferior frontal gyrus and striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task devised by Barcelo et al. (2008). BAS sensitivity was measured with the Sensitivity to Reward (SR) scale from the SPSRQ (Torrubia et al., 2001). The task yielded the expected behavioral switch costs and brain activity in fronto-striatal regions associated with the switching cue. SR scores were negatively associated with brain activity during task switching in dorsolateral prefrontal cortex, anterior cingulate and right anterior insula. These results indicate that BAS sensitivity may modulate cognitive processes occurring in brain areas commonly involved in attention, working memory and cognitive flexibility.

Disentangling common and specific neural subprocesses of response inhibition

Response inhibition is disturbed in several disorders sharing impulse control deficits as a core symptom. Since response inhibition is a cognitively and neurally multifaceted function which has been shown to rely on differing neural subprocesses and neurotransmitter systems, further differentiation to define neurophysiological endophenotypes is essential. Response inhibition may involve at least three separable cognitive subcomponents, i.e. interference inhibition, action withholding, and action cancelation. Here, we introduce a novel paradigm - the Hybrid Response Inhibition task - to disentangle interference inhibition, action withholding and action cancelation and their neural subprocesses within one task setting during functional magnetic resonance imaging (fMRI). To validate the novel task, results were compared to a battery of separate, standard response inhibition tasks independently capturing these subcomponents and subprocesses. Across all subcomponents, mutual activation was present in the right inferior frontal cortex (rIFC), pre-supplementary motor area (pre-SMA) and parietal regions. Interference inhibition revealed stronger activation in pre-motor and parietal regions. Action cancelation resulted in stronger activation in fronto-striatal regions. Our results show that all subcomponents share a common neural network and thus all constitute different subprocesses of response inhibition. Subprocesses, however, differ to the degree of regional involvement: interference inhibition relies more pronouncedly on a fronto-parietal-pre-motor network suggesting its close relation to response selection processes. Action cancelation, in turn, is more strongly associated with the fronto-striatal pathway implicating it as a late subcomponent of response inhibition. The new paradigm reliably captures three putatively subsequent subprocesses of response inhibition and might be a promising tool to differentially assess disturbed neural networks in disorders showing impulse control deficits.

Reversal Learning as a Neuropsychological Indicator for the Neuropathology of Obsessive Compulsive Disorder? A Behavioral Study

Reversal Learning as a Neuropsychological Indicator for the Neuropathology of Obsessive Compulsive Disorder? A Behavioral Study

Reversal Learning as a Neuropsychological Indicator for the Neuropathology of Obsessive Compulsive Disorder? A Behavioral Study

A dysfunction of the fronto-striatal loop has been associated with obsessive-compulsive disorder (OCD). Functional imaging studies suggest that reversal learning is affected by deficits in fronto-striatal brain areas and thus should be impaired in patients with OCD. The authors compared patients with OCD and healthy comparison subjects on a reversal learning task. Correlation analyses and group comparisons showing prolonged reaction times of different response parameters are associated with increasing severity of compulsions. The reversal learning task has been shown to be associated with ventral fronto-striatal brain activation by functional magnetic resonance imaging (fMRI) in healthy comparison subjects. The purpose of this article is to suggest that the reversal learning task can be used as a neuropsychiatric measurement of the ventral fronto-striatal dysfunction in OCD.

ADHD‐ and medication‐related brain activation effects in concordantly affected parent–child dyads with ADHD

Several studies have documented fronto-striatal dysfunction in children and adolescents with attention deficit/hyperactivity disorder (ADHD) using response inhibition tasks. Our objective was to examine functional brain abnormalities among youths and adults with ADHD and to examine the relations between these neurobiological abnormalities and response to stimulant medication. A group of concordantly diagnosed ADHD parent-child dyads was compared to a matched sample of normal parent-child dyads. In addition, ADHD dyads were administered double-blind methylphenidate and placebo in a counterbalanced fashion over two consecutive days of testing. Frontostriatal function was measured using functional magnetic resonance imaging (fMRI) during performance of a go/no-go task. Youths and adults with ADHD showed attenuated activity in fronto-striatal regions. In addition, adults with ADHD appeared to activate non-fronto-striatal regions more than normals. A stimulant medication trial showed that among youths, stimulant medication increased activation in fronto-striatal and cerebellar regions. In adults with ADHD, increases in activation were observed in the striatum and cerebellum, but not in prefrontal regions. This study extends findings of fronto-striatal dysfunction to adults with ADHD and highlights the importance of frontostriatal and frontocerebellar circuitry in this disorder, providing evidence of an endophenotype for examining the genetics of ADHD.

Larger deficits in brain networks for response inhibition than for visual selective attention in attention deficit hyperactivity disorder (ADHD)

Brain activation differences between 12 control and 12 attention deficit hyperactivity disorder (ADHD) children (9- to 12-year-olds) were examined on two cognitive tasks during functional magnetic resonance imaging (fMRI). Visual selective attention was measured with the visual search of a conjunction target (red triangle) in a field of distracters and response inhibition was measured with a go/no-go task. There were limited group differences in the selective attention task, with control children showing significantly greater intensity of activation in a small area of the superior parietal lobule region of interest. There were large group differences in the response inhibition task, with control children showing significantly greater intensity of activation in fronto-striatal regions of interest including the inferior, middle, superior and medial frontal gyri as well as the caudate nucleus and globus pallidus. The widespread hypoactivity for the ADHD children on the go/no-go task is consistent with the hypothesis that response inhibition is a specific deficit in attention deficit hyperactivity disorder.