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Diminished appetitive startle modulation following targeted inhibition of prefrontal cortex.

ABSTRACT: From an evolutionary perspective the startle eye-blink response forms an integral part of the human avoidance behavioral repertoire and is typically diminished by pleasant emotional states. In major depressive disorder (MDD) appetitive motivation is impaired, evident in a reduced interference of positive emotion with the startle response. Given the pivotal role of frontostriatal neurocircuitry in orchestrating appetitive motivation, we hypothesized that inhibitory transcranial magnetic stimulation (TMS) would reduce appetitive neuromodulation in a manner similar to MDD. Based on a pre-TMS functional MRI (fMRI) experiment we selected the left dorsolateral and dorsomedial prefrontal cortices as target regions for subsequent sham-controlled inhibitory theta-burst TMS (TBS) in 40 healthy male volunteers. Consistent with our hypothesis, between-group comparisons revealed a TBS-induced inhibition of appetitive neuromodulation, manifest in a diminished startle response suppression by hedonic stimuli. Collectively, our results suggest that functional integrity of left dorsolateral and dorsomedial prefrontal cortex is critical for mediating a pleasure-induced down-regulation of avoidance responses which may protect the brain from a depressogenic preponderance of defensive stress.

SUBMITTER: Hurlemann R

PROVIDER: S-EPMC4354029 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Diminished appetitive startle modulation following targeted inhibition of prefrontal cortex.

Hurlemann René R Arndt Stephan S Schlaepfer Thomas E TE Reul Juergen J Maier Wolfgang W Scheele Dirk D

Scientific reports 20150310

From an evolutionary perspective the startle eye-blink response forms an integral part of the human avoidance behavioral repertoire and is typically diminished by pleasant emotional states. In major depressive disorder (MDD) appetitive motivation is impaired, evident in a reduced interference of positive emotion with the startle response. Given the pivotal role of frontostriatal neurocircuitry in orchestrating appetitive motivation, we hypothesized that inhibitory transcranial magnetic stimulati ...[more]

PMID: 25752944

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Project description:RATIONALE:Drug-related cues evoke craving and stimulate motivational systems in the brain. The acoustic startle reflex captures activation of these motivational processes and affords a unique measure of reactivity to drug cues. OBJECTIVES:This study examined the effects of cannabis-related cues on subjective and eye blink startle reactivity in the human laboratory and tested whether these effects predicted youth's cue-elicited cannabis craving in the natural environment. METHODS:Participants were 55 frequent cannabis users, ages 16 to 24 years (M?=?19.9, SD?=?1.9; 55% male; 56% met criteria for cannabis dependence), who were recruited from a clinical trial to reduce cannabis use. Eye blink electromyographic activity was recorded in response to acoustic probes that elicited startle reactivity while participants viewed pleasant, unpleasant, neutral, and cannabis picture cues. Following the startle assessment, participants completed an ecological momentary assessment protocol that involved repeated assessments of cue-elicited craving in real time in their real-world environments. RESULTS:Multilevel models included the presence or absence of visible cannabis cues in the natural environment, startle magnitude, and the cross-level interaction of cues by startle to test whether cue-modulated startle reactivity in the laboratory was associated with cue-elicited craving in the natural environment. Analyses showed that cannabis-related stimuli evoked an appetitive startle response pattern in the laboratory, and this effect was associated with increased cue-elicited craving in the natural environment, b?=?- 0.15, p?=?.022, 95% CI [- 0.28, - 0.02]. Pleasant stimuli also evoked an appetitive response pattern, but in this case, blunted response was associated with increased cue-elicited craving in the natural environment, b?=?0.27, p?<?.001, 95% CI [0.12, 0.43]. CONCLUSIONS:Our findings support cue-modulated startle reactivity as an index of the phenotypic expression of cue-elicited cannabis craving.

Project description:Altered excitatory and inhibitory neurotransmission has been implicated in autism spectrum disorder (ASD). Interventions using repetitive transcranial magnetic stimulation (rTMS) to enhance or inhibit cortical excitability are under study for various targets, though the mechanistic effects of rTMS have yet to be examined in ASD. Here, we examined whether an excitatory rTMS treatment course modulates glutamatergic (Glx) or γ-aminobutyric acid (GABA) metabolite levels in emerging adults with ASD. Twenty-eight participants with ASD and executive function impairment [23.3 ± 4.69 years; seven-female] underwent two magnetic resonance spectroscopy (MRS) scans of the left dorsolateral prefrontal cortex (DLPFC). MRS scans were acquired before and after participants with ASD were randomized to receive a 20-session course of active or sham rTMS to the DLPFC. Baseline MRS data was available for 19 typically developing controls [23.8 ± 4.47 years; six-female]. Metabolite levels for Glx and GABA+ were compared between ASD and control groups, at baseline, and metabolite level change, pre-to-post-rTMS treatment, was compared in ASD participants that underwent active vs. sham rTMS. Absolute change in Glx was greater in the active vs. sham-rTMS group [F (1, 19) = 6.54, p = 0.02], though the absolute change in GABA+ did not differ between groups. We also examined how baseline metabolite levels related to pre/post-rTMS metabolite level change, in the active vs. sham groups. rTMS group moderated the relation between baseline Glx and pre-to-post-rTMS Glx change, such that baseline Glx predicted Glx change in the active-rTMS group only [b = 1.52, SE = 0.32, t (18) = 4.74, p < 0.001]; Glx levels increased when baseline levels were lower, and decreased when baseline levels were higher. Our results indicate that an interventional course of excitatory rTMS to the DLPFC may modulate local Glx levels in emerging adults with ASD, and align with prior reports of glutamatergic alterations following rTMS. Interventional studies that track glutamatergic markers may provide mechanistic insights into the therapeutic potential of rTMS in ASD. Clinical Trial Registration: Clinicaltrials.gov (ID: NCT02311751), https://clinicaltrials.gov/ct2/show/NCT02311751?term=ameis&rank=1; NCT02311751.

Project description:Transcranial direct current stimulation over the dorsolateral prefrontal cortex has been shown to be clinically useful in the treatment of drug addiction.We conducted a double-blind randomized clinical trial aiming to assess the effects of bilateral dorsolateral prefrontal cortex transcranial direct current stimulation (left cathodal/right anodal) on crack-cocaine addiction. We defined craving as the primary outcome, and other clinical measurements, including depressive and anxiety symptoms, and quality of life, as secondary outcomes. Seventeen male crack-cocaine users (mean age 30.4 ± 9.8 SD) were randomized to receive 5 sessions of active transcranial direct current stimulation (2 mA, 35 cm(2), for 20 minutes), every other day, and 19 males (mean age 30.3 ± 8.4 SD) to receive sham-transcranial direct current stimulation (placebo) as control group.Craving scores were significantly reduced in the transcranial direct current stimulation group after treatment when compared with sham-transcranial direct current stimulation (P = .028) and baseline values (P = .003), and decreased linearly over 4 weeks (before, during, and after treatment) in the transcranial direct current stimulation group only (P = .047). Changes of anxiety scores towards increase in the sham-transcranial direct current stimulation and decrease in the transcranial direct current stimulation group (P = .03), and of the overall perception of quality of life (P = .031) and of health (P = .048) towards decrease in the sham-transcranial direct current stimulation group and increase in the transcranial direct current stimulation group differed significantly between groups.Repetitive bilateral transcranial direct current stimulation over the dorsolateral prefrontal cortex reduced craving for crack-cocaine use, decreased anxiety, and improved quality of life. We hypothesize that transcranial direct current stimulation effects may be associated with increased prefrontal processing and regulation of craving behavior.

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Diminished appetitive startle modulation following targeted inhibition of prefrontal cortex.

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Diminished appetitive startle modulation following targeted inhibition of prefrontal cortex.

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