Practice and Difficulty Evoke Anatomically and Pharmacologically Dissociable Brain Activation Dynamics

Bullmore, Edward T.; Suckling, John; Zelaya, Fernando; Long, Chris; Honey, Garry D.; Reed, Laurence; Routledge, Carol; Ng, Virginia; Fletcher, Paul C.; Brown, John R.; Williams, Steven

doi:10.1093/cercor/13.2.144

Cited by 48 publications

(30 citation statements)

References 53 publications

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“…Nonetheless, several observations corroborate the notion that the observed SN activity is indeed linked to enhanced dopaminergic neurotransmission: attentional deficits (especially concerning top-down, endogenous attention) have been reported for PD patients, along with deficits in other executive functions (Brown and Marsden, 1988;Yamaguchi and Kobayashi, 1998;Nieoullon, 2002;Cools, 2006). In accord with these findings, pharmacological and lesion studies in animals reported influences of the dopaminergic system on functions related to the recruitment of attentional resources (for review, see Robbins, 2005), and pharmacological investigations in humans have also yielded corroborating results (Clark et al, 1987;Servan-Schreiber et al, 1998;Bullmore et al, 2003). Moreover, demonstrations of a strong correlation between reward-related mesolimbic fMRI responses and rewardrelated striatal dopamine release in the same human subjects ([ 11 C]raclopride displacement PET) suggests a strong relationship between the two measures (Schott et al, 2008).…”

Section: Discussionmentioning

confidence: 70%

Task-Load-Dependent Activation of Dopaminergic Midbrain Areas in the Absence of Reward

Boehler

Hopf²,

Krebs³

et al. 2011

J. Neurosci.

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Dopamine release in cortical and subcortical structures plays a central role in reward-related neural processes. Within this context, dopaminergic inputs are commonly assumed to play an activating role, facilitating behavioral and cognitive operations necessary to obtain a prospective reward. Here, we provide evidence from human fMRI that this activating role can also be mediated by task-demand-related processes and thus extendsbeyondsituationsthatonlyentailextrinsicmotivatingfactors.Usingavisualdiscriminationtaskinwhichvaryinglevelsoftaskdemands were precued, we found enhanced hemodynamic activity in the substantia nigra (SN) for high task demands in the absence of reward or similar extrinsic motivating factors. This observation thus indicates that the SN can also be activated in an endogenous fashion. In parallel to its role in reward-related processes, reward-independent activation likely serves to recruit the processing resources needed to meet enhanced task demands. Simultaneously, activity in a wide network of cortical and subcortical control regions was enhanced in response to high task demands, whereas areas of the default-mode network were deactivated more strongly. The present observations suggest that the SN represents a core node within a broader neural network that adjusts the amount of available neural and behavioral resources to changing situational opportunities and task requirements, which is often driven by extrinsic factors but can also be controlled endogenously.

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Section: Discussionmentioning

confidence: 70%

Task-Load-Dependent Activation of Dopaminergic Midbrain Areas in the Absence of Reward

Boehler

Hopf²,

Krebs³

et al. 2011

J. Neurosci.

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“…Other pharmacological fMRI studies using oral MPH generally show enhanced cortical and subcortical blood oxygen level-dependent (BOLD) responses in healthy controls or individuals with ADHD (reviewed in ref. 42), which are most consistently shown in the PFC (including the ACC and OFC) and dorsal striatum (43). Nevertheless, disparity in direction of results may also be attributed to other factors [e.g., type of task (it would be important to use a sensorimotor task as an active control task) and severity of impairment (baseline capacity needs to be tested in studies with larger sample sizes)] and remains to be tested.…”

Section: Discussionmentioning

confidence: 99%

Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

Goldstein

Woicik

Maloney

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

107

106

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Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.D rug addiction is a chronically relapsing disorder associated with dysregulated dopaminergic neurotransmission as well as functional impairments in the brain regions innervated by dopamine [e.g., the prefrontal cortex (PFC)] (1, 2). Psychostimulants such as cocaine have high abuse and dependence potential because of their ability to increase dopamine in limbic brain regions. Similarly to cocaine, methylphenidate (MPH; e.g., Ritalin) blocks the dopamine transporter increasing extracellular dopamine. However, although speed of uptake of both drugs is similar, rate of clearance of MPH from the brain is substantially slower than that for cocaine (90-vs. 20-min half-life), and these slower pharmacokinetic properties may contribute to the lower abuse potential for MPH (1). Both these neuropharmacological mechanisms, interference with the binding of the drug to its target and different (i.e., slower) pharmacokinetics, proved valuable in the management of heroin (e.g., with methadone and buprenorphine) and nicotine addiction (e.g., with nicotine patch and nicotine gum) (3). In contrast, adapting a similar pharmacological strategy (use of stimulant medications such as MPH) in individuals with cocaine-use disorders (CUD) did not decrease cocaine use or prevent relapse (1).Nevertheless, oral MPH decreases abnormal risk taking in patients with frontotemporal dementia (4) and children with attention deficit hyperactivity disorder (ADHD) (5). Furthermore, when on stimulant medication (including MPH), youth with ADHD showed a trend to improved inhibitor...

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“…Neuroimaging and basic research implicate the striatum in the learning and execution of motor programs (35). Recent research in adults indicates striatal engagement with increasing neurocognitive load (36), and animal research suggests that striatal dopaminergic neurons produce error signals (37). (this paragraph doesn't flowperhaps rewrite the preceding 3 sentences to soften the jump from deficient motor regulation to striatal function) Data presented here and elsewhere (34) suggest that motor inhibition deficits in pediatric BPD may reflect a failure to engage the striatum appropriately during failed inhibition.…”

Section: Discussionmentioning

confidence: 99%

Neural Circuitry Engaged During Unsuccessful Motor Inhibition in Pediatric Bipolar Disorder

Leibenluft¹

2007

Am J Psychiatry

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Dickstein, Daniel P.; Tone, Erin; and Pine, Daniel S., "Neural circuitry engaged during unsuccessful motor inhibition in pediatric bipolar disorder" (2007 Objective: Deficits in motor inhibition may contribute to impulsivity and irritability in children with bipolar disorder (BPD). Therefore, studies of the neural circuitry engaged during failed motor inhibition in pediatric BPD may contribute to our understanding of the pathophysiology of the illness. We tested the hypothesis that children with BPD and controls would differ in ventral prefrontal cortex (vPFC), striatal, and anterior cingulate activation during unsuccessful motor inhibition. We also compared activation in medicated vs.unmedicated children with BPD, and in children with BPD and ADHD (BPD+ADHD) vs.those with BPD but without ADHD (BPD-ADHD).Method: Event-related fMRI study comparing neural activation in children with BPD and controls while they performed a motor inhibition task. The sample included 26 children with BPD (13 unmedicated, 15 with ADHD) and 17 age, gender, and IQ matched controls. Results:On failed inhibitory trials, controls showed greater bilateral striatal and right vPFC activation than did patients. While our findings were somewhat more prominent in unmedicated than medicated, patients, and in BPD+ADHD than BPD-ADHD, the findings did not differ significantly (?) among these subgroups of children with BPD.

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Practice and Difficulty Evoke Anatomically and Pharmacologically Dissociable Brain Activation Dynamics

Cited by 48 publications

References 53 publications

Task-Load-Dependent Activation of Dopaminergic Midbrain Areas in the Absence of Reward

Task-Load-Dependent Activation of Dopaminergic Midbrain Areas in the Absence of Reward

Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

Neural Circuitry Engaged During Unsuccessful Motor Inhibition in Pediatric Bipolar Disorder

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