Neural responses to acute cocaine administration in the human brain detected by fMRI

Kufahl, Peter R.; Li, Zhu; Risinger, Robert; Rainey, Charles; Wu, Guo‐Rong; Bloom, Alan S.; Li, Shi‐Jiang

doi:10.1016/j.neuroimage.2005.06.039

Cited by 138 publications

(130 citation statements)

References 61 publications

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“…A number of recent studies propose fMRI as a promising tool for investigating system level actions of various pharmacological agents (23)(24)(25)(26)(27). These studies generally support the hypothesis of tight coupling between neuronal activity, energy metabolism and CBF.…”

Section: Discussionmentioning

confidence: 70%

“…Extensive studies during the past several decades demonstrate that the mesocorticolimbic (MCL) dopamine (DA) system, which originates from the midbrain ventral tegmental area and projects predominantly to the nucleus accumbens (NAc) and prefrontal cortex, is the central neuronal circuitry underlying cocaine's reinforcing actions (19)(20)(21)(22). Previous fMRI studies have demonstrated regionally restricted activations in humans and experimental animals after acute cocaine administration (23)(24)(25)(26)(27)). Nevertheless, a major outstanding issue in these studies is the inability to separate cocaine's specific neuronal actions from its potential direct effects on the cerebrovasular system (10).…”

mentioning

confidence: 99%

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Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI)

Gitajn

et al. 2007

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

103

108

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Dynamic manganese-enhanced magnetic resonance imaging (MEMRI) detects neuronal activity based on the passage of Mn 2؉ into active neurons. Because this mechanism is independent of any hemodynamic response, it is potentially ideal for pharmacological studies and was applied to investigate the acute CNS effects of cocaine in the rat. Dose-dependent, region-specific MEMRI signals were seen mostly in cortical and subcortical mesocorticolimbic structures. To verify the spatial accuracy and physiological mechanisms of MEMRI, neuronal activation following electrical forepaw stimulation revealed somatotopic signal enhancement in the primary and secondary somatosensory cortices, which was blocked by diltiazem, a Ca 2؉ channel antagonist. These data suggest that MEMRI may serve as a tool for investigating the effects of pharmacological agents and opens an application of MRI to study CNS drug effects at a systems level.Ca 2ϩ channel ͉ dopamine ͉ drug abuse

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Section: Discussionmentioning

confidence: 70%

mentioning

confidence: 99%

Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI)

Gitajn

et al. 2007

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

103

108

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“…Since the mesocortical DA system facilitates executive function and attention via its projections to the PFC and ACG (Gaspar P, 1992;Goldman-Rakic P et al, 2000), and to the thalamus (Pinto A et al, 2003;Sanchez-Gonzalez M et al, 2005) and DA is necessary for the proper performance of cognitive functions that are modulated by frontal cortical regions (Nieoullon A, 2002), we hypothesized that cocaine abusers tested during abstinence would have significant disruptions in the pattern of corticolimbic activation underlying the performance of these cognitive tasks. It has been previously hypothesized that frontal abnormalities may underlie the disruption in cognitive functioning in cocaine abusers during abstinence and detoxification (Bolla K et al, 2000;Kufahl P et al, 2005); however, this association has not been widely documented using functional magnetic resonance imaging (fMRI). To our knowledge there is only one published fMRI study that used inhibitory GO-NO/GO WM tasks; here the authors reported lower PFC activation in abstinent cocaine abusers than in control subjects (Hester R and H Garavan, 2004).…”

Section: Introductionmentioning

confidence: 99%

Widespread disruption in brain activation patterns to a working memory task during cocaine abstinence

et al. 2007

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Cocaine abstinence is associated with impaired performance in cognitive functions including attention, vigilance and executive function. Here we test the hypothesis that cognitive dysfunction during cocaine abstinence reflects in part impairment of cortical and subcortical regions modulated by dopamine. We used functional magnetic resonance imaging (fMRI) to study brain activation to a verbal working memory task in cocaine abusers (n = 16) and healthy controls (n = 16). Compared to controls, cocaine abusers showed: (1) hypoactivation in the mesencephalon, where dopamine neurons are located, as well as the thalamus, a brain region involved in arousal; (2) larger deactivation in dopamine projection regions (putamen, anterior cingulate, parahippocampal gyrus, and amygdala); and (3) hyperactivation in cortical regions involved with attention (prefrontal and parietal cortices), which probably reflects increased attention and control processes as compensatory mechanisms. Furthermore, the working memory load activation was lower in the prefrontal and parietal cortices in cocaine abusers when compared with controls, which might reflect limited network capacity. These abnormalities were accentuated in the cocaine abusers with positive urines for cocaine at time of study (as compared to cocaine abusers with negative urines) suggesting that the deficits may reflect in part early cocaine abstinence. These findings provide evidence of impaired function of regions involved with executive control, attention and vigilance in cocaine abusers. This widespread neurofunctional disruption is likely to underlie the cognitive deficits during early cocaine abstinence, and to reflect involvement of dopamine as well as other neurotransmitters.

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“…Using a stop signal task, we (and others) have demonstrated that patients with cocaine (and other stimulant) misuse display impaired inhibitory control and prefrontal activation during a stop signal task (5,(23)(24)(25)(26)(27). Whereas prior research has examined stimulants in clinical trials of therapeutic efficacy (28)(29)(30)(31)(32)(33) and neuroimaging studies of regional brain activation and connectivity in cocaine users (34)(35)(36)(37), none to our knowledge have specifically evaluated their association with the behavioral and neural aspects of inhibitory control. In the current study, we sought to address this gap in a pharmacological functional MRI (fMRI) study in which cocaine-dependent individuals received an i.v.…”

mentioning

confidence: 99%

Biological markers of the effects of intravenous methylphenidate on improving inhibitory control in cocaine-dependent patients

Morgan²,

Matuskey³

et al. 2010

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

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Prior research points to the importance of psychostimulants in improving self-control. However, the neural substrates underlying such improvement remain unclear. Here, in a pharmacological functional MRI study of the stop signal task, we show that methylphenidate (as compared with placebo) robustly decreased stop signal reaction time (SSRT), an index of improved control, in cocaine-dependent patients (a population in which inhibitory control is impaired). Methylphenidate-induced decreases in SSRT were positively correlated with inhibition-related activation of left middle frontal cortex (MFC) and negatively with activation of the ventromedial prefrontal cortex (vmPFC) in whole brain linear regressions. Inhibition-related MFC but not vmPFC activation distinguished individuals with short and long SSRT in 36 demographically matched healthy individuals, whereas vmPFC but not MFC activation, along with improvement in SSRT, was correlated with a previously implicated biomarker of methylphenidate response (systolic blood pressure). These results implicate a specific neural (i.e., vmPFC) mechanism whereby stimulants improve inhibitory control. Altered ventromedial prefrontal activation and increased blood pressure may represent useful CNS and peripheral biomarkers in individualized treatment with methylphenidate for patients with cocaine dependence.D eficits in cognitive control have been implicated in the pathophysiology of several neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD) and cocaine dependence (1-5), and a wide literature supports the utility of stimulants, including methylphenidate, in improving cognitive control (6-9, see ref. 10 for review). For example, studies have shown that stimulants alter cerebral activation and influence cognitive functions, including improving inhibitory control, in healthy individuals (11-21). Similarly, Overtoom et al. (22) reported that methylphenidate improved stopping performance and restored the electrophysiological potential of stopping in a stop signal task, whereas it did not affect go trial reaction time, in adult patients with ADHD. Although neuroimaging studies have examined the effects of stimulants on regional brain activation and connectivity, the neural substrates underlying stimulant-mediated improvements in inhibitory control remain unclear. A more complete understanding of the neural mechanisms whereby stimulants improve cognitive control will be critically important, not only for an improved understanding of its biological basis but also for understanding the pathophysiology and treatment of conditions associated with its impairment. Using a stop signal task, we (and others) have demonstrated that patients with cocaine (and other stimulant) misuse display impaired inhibitory control and prefrontal activation during a stop signal task (5, 23-27). Whereas prior research has examined stimulants in clinical trials of therapeutic efficacy (28-33) and neuroimaging studies of regional brain activation and connectivity in cocaine user...

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Neural responses to acute cocaine administration in the human brain detected by fMRI

Cited by 138 publications

References 61 publications

Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI)

Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI)

Widespread disruption in brain activation patterns to a working memory task during cocaine abstinence

Biological markers of the effects of intravenous methylphenidate on improving inhibitory control in cocaine-dependent patients

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