Asymmetric neural dynamics characterize loss and recovery of consciousness.

Anesthetics are known to disrupt neural interactions in cortical and subcortical brain circuits. While the effect of anesthetic drugs on consciousness is reversible, the neural mechanism mediating induction and recovery may be different. Insight into these distinct mechanisms can be gained from a systematic comparison of neural dynamics during slow induction of and emergence from anesthesia. To this end, we used functional magnetic resonance imaging (fMRI) data obtained in healthy volunteers before, during, and after the administration of propofol at incrementally adjusted target concentrations. We analyzed functional connectivity of corticocortical and subcorticocortical networks and the temporal autocorrelation of fMRI signal as an index of neural processing timescales. We found that en route to unconsciousness, temporal autocorrelation across the entire brain gradually increased, whereas functional connectivity gradually decreased. In contrast, regaining consciousness was associated with an abrupt restoration of cortical but not subcortical temporal autocorrelation and an abrupt boost of subcorticocortical functional connectivity. Pharmacokinetic effects could not account for the difference in neural dynamics between induction and emergence. We conclude that the induction and recovery phases of anesthesia follow asymmetric neural dynamics. A rapid increase in the speed of cortical neural processing and subcorticocortical neural interactions may be a mechanism that reboots consciousness.

PPARγ activation by pioglitazone does not suppress cravings for alcohol, and is associated with a risk of myopathy in treatment seeking alcohol dependent patients: a randomized controlled proof of principle study.

RATIONALE: Proinflammatory processes have been implicated in alcohol addiction, craving, and relapse, while studies in experimental animals have suggested that activation of peroxisome proliferator-activated receptor gamma (PPARγ) inhibits proinflammatory signaling. Accordingly, it is hypothesized that medications with PPARγ activity may have therapeutic potential in alcohol dependence. OBJECTIVES: We conducted a double-blind, placebo-controlled mechanistic proof of principle study in alcohol-dependent inpatients to investigate the effect of pioglitazone on alcohol craving. METHODS: Participants were treated for withdrawal, if needed, and then randomized to pioglitazone (target dose 45 mg/day) or placebo. Once at target dose, they completed two experimental manipulations: guided imagery, which used personalized auditory scripts to induce alcohol cravings, and a low-dose challenge with i.v. lipopolysaccharide (LPS; 0.8 ng/kg) or placebo, on two separate sessions, in counterbalanced order. Behavioral and endocrine responses as well as CSF levels of proinflammatory cytokines were evaluated. RESULTS: The study was prematurely terminated after randomization of 16 subjects, following an independent review that established a high risk of myopathy in the active treatment group. Analysis of those who completed the study indicated that pioglitazone was associated with elevated, rather than suppressed alcohol cravings in response to alcohol-associated stimuli. LPS did not induce cravings for alcohol and thus did not lend itself to evaluating pioglitazone effects; however, pioglitazone increased the neuroendocrine stress response to LPS. CSF levels of IL-6, TNF-α, or MCP-1 were unaffected by pioglitazone treatment. CONCLUSIONS: Both safety and efficacy biomarker data suggest that pioglitazone lacks potential as a medication for the treatment of alcohol dependence. CLINICAL TRIAL REGISTRATION: NCT01631630.

The Affective and Neural Correlates of Heroin versus Cocaine Use in Addiction Are Influenced by Environmental Setting But in Opposite Directions.

Previous studies have shown that individuals with heroin and cocaine addiction prefer to use these drugs in distinct settings: mostly at home in the case of heroin and mostly outside the home in the case of cocaine. Here we investigated whether the context would modulate the affective and neural responses to these drugs in a similar way. First, we used a novel emotional task to assess the affective state produced by heroin or cocaine in different settings, based on the recollections of male and female drug users. Then we used fMRI to monitor neural activity during drug imagery (re-creating the setting of drug use) in male drug users. Consistent with our working hypothesis, the majority of participants reported a shift in the affective valence of heroin from mostly pleasant at home to mostly unpleasant outside the home (p < 0.0001). The opposite shift was observed for cocaine; that is, most participants who found cocaine pleasant outside the home found it unpleasant when taken at home (p < 0.0014). Furthermore, we found a double dissociation, as a function of drug and setting imagery, in BOLD signal changes in the left PFC and caudate, and bilaterally in the cerebellum (all p values <0.01), suggesting that the fronto-striatal-cerebellar network is implicated in the contextualization of drug-induced affect. In summary, we report that the same setting can influence in opposite directions the affective and neural response to psychostimulants versus opiates in humans, adding to growing evidence of distinct substrates for the rewarding effects of these two drug classes.SIGNIFICANCE STATEMENT The rewarding effects of addictive drugs are often thought to depend on shared substrates. Yet, environmental influences can unmask striking differences between psychostimulants and opiates. Here we used emotional tasks and fMRI to explore the influence of setting on the response to heroin versus cocaine in individuals with addiction. Simply moving from one setting to another significantly decreased heroin pleasure but increased cocaine pleasure, and vice versa. Similar double dissociation was observed in the activity of the fronto-striatal-cerebellar network. These findings suggest that the effects of opiates and psychostimulants depend on dissociable psychological and neural substrates and that therapeutic approaches to addiction should take into account the peculiarities of different drug classes and the settings of drug use.

Peripheral Immune System Adaptations and Motivation for Alcohol in Non-Dependent Problem Drinkers.

BACKGROUND: Increasing evidence suggests that levels of pro-inflammatory and anti-inflammatory cytokines are dysfunctional in alcohol dependence. Moreover, some initial findings demonstrate that these adaptations in peripheral inflammation may contribute to motivation for alcohol and problem drinking via possible direct effects or the indirect effects of stress responsivity. Importantly, the role of pro-inflammatory and anti-inflammatory cytokines in the progression from healthy to problem drinking is not well understood. The aim of this study was to assess whether alcohol-related peripheral immune system changes affect stress and alcohol cue-induced craving and anxiety and behavioral alcohol motivation and intake in the laboratory among problem drinkers compared with socially drinking controls. METHODS: Twenty-six problem drinkers and 38 moderate, social drinkers participated in a laboratory challenge procedure during which they were exposed to 3 personalized 5-minute imagery conditions (stress [S], relaxing [R], and alcohol cue [C]), followed by the "alcohol taste test" (ATT) as a measure of implicit alcohol motivation and intake, presented across 3 consecutive days, 1 per day in a randomized and counterbalanced order. Measures of tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), alcohol craving, and anxiety were assessed at baseline, immediately following imagery exposure and at discreet beer cue presentation in the ATT. RESULTS: Compared with moderate drinkers, problem drinkers demonstrated tonic attenuation of IL-6 and IL-1ra. In problem drinkers, these changes also accompanied elevated levels of stress- and cue-induced alcohol craving and anxiety and were predictive of provoked alcohol craving, behavioral alcohol motivation and intake, and severity of problem drinking. CONCLUSIONS: Current findings indicate that selective immunosuppression in problem drinkers may play a key role in motivation for alcohol intake.

Oxytocin enhances cognitive control of food craving in women.

In developed countries, obesity has become an epidemic resulting in enormous health care costs for society and serious medical complications for individuals. The homeostatic regulation of food intake is critically dependent on top-down control of reward-driven food craving. There is accumulating evidence from animal studies that the neuropeptide oxytocin (OXT) is involved in regulating hunger states and eating behavior, but whether OXT also contributes to cognitive control of food craving in humans is still unclear. We conducted a counter-balanced, double-blind, within-subject, pharmacological magnetic resonance imaging experiment involving 31 healthy women who received 24 IU of intranasal OXT or placebo and were scanned twice while they were exposed to pictures of palatable food. The participants were instructed either to imagine the immediate consumption or to cognitively control the urge to eat the food. Our results show a trend that OXT specifically reduced food craving in the cognitive control condition. On the neural level, these findings were paralleled by an increase of activity in the middle and superior frontal gyrus, precuneus, and cingulate cortex under OXT. Interestingly, the behavioral OXT effect correlated with the OXT-induced changes in the prefrontal cortex and precuneus. Collectively, the present study provides first evidence that OXT plays a key role in the cognitive regulation of food craving in women by strengthening activity in a broad neurocircuitry implicated in top-down control and self-referential processing. Hum Brain Mapp 37:4276-4285, 2016. © 2016 Wiley Periodicals, Inc.

Male-typical visuospatial functioning in gynephilic girls with gender dysphoria - organizational and activational effects of testosterone.

BACKGROUND: Sex differences in performance and regional brain activity during mental rotation have been reported repeatedly and reflect organizational and activational effects of sex hormones. We investigated whether adolescent girls with gender dysphoria (GD), before and after 10 months of testosterone treatment, showed male-typical brain activity during a mental rotation task (MRT). METHODS: Girls with GD underwent fMRI while performing the MRT twice: when receiving medication to suppress their endogenous sex hormones before onset of testosterone treatment, and 10 months later during testosterone treatment. Two age-matched control groups participated twice as well. RESULTS: We included 21 girls with GD, 20 male controls and 21 female controls in our study. In the absence of any group differences in performance, control girls showed significantly increased activation in frontal brain areas compared with control boys (pFWE = 0.012). Girls with GD before testosterone treatment differed significantly in frontal brain activation from the control girls (pFWE = 0.034), suggesting a masculinization of brain structures associated with visuospatial cognitive functions. After 10 months of testosterone treatment, girls with GD, similar to the control boys, showed increases in brain activation in areas implicated in mental rotation. LIMITATIONS: Since all girls with GD identified as gynephilic, their resemblance in spatial cognition with the control boys, who were also gynephilic, may have been related to their shared sexual orientation rather than their shared gender identity. We did not account for menstrual cycle phase or contraceptive use in our analyses. CONCLUSION: Our findings suggest atypical sexual differentiation of the brain in natal girls with GD and provide new evidence for organizational and activational effects of testosterone on visuospatial cognitive functioning.

LSD modulates music-induced imagery via changes in parahippocampal connectivity.

Psychedelic drugs such as lysergic acid diethylamide (LSD) were used extensively in psychiatry in the past and their therapeutic potential is beginning to be re-examined today. Psychedelic psychotherapy typically involves a patient lying with their eyes-closed during peak drug effects, while listening to music and being supervised by trained psychotherapists. In this context, music is considered to be a key element in the therapeutic model; working in synergy with the drug to evoke therapeutically meaningful thoughts, emotions and imagery. The underlying mechanisms involved in this process have, however, never been formally investigated. Here we studied the interaction between LSD and music-listening on eyes-closed imagery by means of a placebo-controlled, functional magnetic resonance imaging (fMRI) study. Twelve healthy volunteers received intravenously administered LSD (75µg) and, on a separate occasion, placebo, before being scanned under eyes-closed resting conditions with and without music-listening. The parahippocampal cortex (PHC) has previously been linked with (1) music-evoked emotion, (2) the action of psychedelics, and (3) mental imagery. Imaging analyses therefore focused on changes in the connectivity profile of this particular structure. Results revealed increased PHC-visual cortex (VC) functional connectivity and PHC to VC information flow in the interaction between music and LSD. This latter result correlated positively with ratings of enhanced eyes-closed visual imagery, including imagery of an autobiographical nature. These findings suggest a plausible mechanism by which LSD works in combination with music listening to enhance certain subjective experiences that may be useful in a therapeutic context.

Noradrenergic signaling in the medial prefrontal cortex and amygdala differentially regulates vicarious trial-and-error in a spatial decision-making task.

In uncertain choice situations, we deliberately search and evaluate possible options before taking an action. Once we form a preference regarding the current situation, we take an action more automatically and with less deliberation. In rats, the deliberation process can be seen in vicarious trial-and-error behavior (VTE), which is a head-orienting behavior toward options at a choice point. Recent neurophysiological findings suggest that VTE reflects the rat's thinking about future options as deliberation, expectation, and planning when rats feel conflict. VTE occurs depending on the demand: an increase occurs during initial learning, and a decrease occurs with progression in learning. However, the brain circuit underlying the regulation of VTE has not been thoroughly examined. In situations in which VTE often appears, the medial prefrontal cortex (mPFC) and the amygdala (AMY) are crucial for learning and decision making. Our previous study reported that noradrenaline regulates VTE. Here, to investigate whether the mPFC and AMY are involved in regulation of VTE, we examined the effects of local injection of clonidine, an alpha2 adrenergic autoreceptor agonist, into either region in rats during VTE and choice behavior during a T-maze choice task. Injection of clonidine into either region impaired selection of the advantageous choice in the task. Furthermore, clonidine injection into the mPFC suppressed occurrence of VTE in the early phase of the task, whereas injection into the AMY inhibited the decrease in VTE in the later phase and thus maintained a high level of VTE throughout the task. These results suggest that the mPFC and AMY play a role in the increase and decrease in VTE, respectively, and that noradrenergic mechanisms mediate the dynamic regulation of VTE over experiences.

Pharmacological blockade of memory reconsolidation in posttraumatic stress disorder: three negative psychophysiological studies.

Posttraumatic stress disorder (PTSD) may involve over-consolidated emotional memories of the traumatic event. Reactivation (RP) can return a memory to an unstable state, from which it must be restabilized (reconsolidated) if it is to persist. Pharmacological agents administered while the memory is unstable have been shown to impair reconsolidation. The N-methyl-d-aspartate (NMDA) partial agonist d-cycloserine (DCS) may promote memory destabilization. In the three studies reported here, we investigated whether the ß-adrenergic blocker propranolol or the glucocorticoid (GR) antagonist mifepristone, given at the time of traumatic memory reactivation, could reduce PTSD symptoms and physiological responding during subsequent traumatic imagery. Individuals with PTSD were randomized as follows: Study One: propranolol with memory reactivation (n=10) or without reactivation (n=8); Study Two: reactivation mifepristone (n=13), non-reactivation (NRP) mifepristone (n=15), or double placebo (PL) (n=15); Study Three: reactivation mifepristone plus d-cycloserine (n=16), or two placebos (n=15). Subjects underwent memory retrieval by describing their traumatic event. A week later they engaged in script-driven traumatic mental imagery, while heart rate (HR), skin conductance (SC), and facial electromyogram (EMG) responses were measured. There were no significant group differences in physiological responsivity or change in PTSD symptoms in any of the studies. These results do not support successful blockade of reconsolidation of traumatic memories in PTSD.

Transdermal nicotine during cue reactivity in adult smokers with and without anxiety disorders.

Transdermal nicotine almost doubles tobacco cessation rates; however, little is known about what happens to smokers during the quit process when they are wearing the nicotine patch and are confronted with high-risk smoking triggers. This is particularly important for smokers with psychological disorders who disproportionately represent today's smokers and have more trouble quitting. Using a mixed between- and within-subjects design, smokers with anxiety disorders (n=61) and smokers without any current Axis I disorders (n=38) received transdermal nicotine (21 mg) or a placebo patch over two assessment days separated by 48 hr. Urge to smoke was evaluated during a 5-hr patch absorption period (reflecting general smoking deprivation) and during imaginal exposure to theoretically high-risk triggers containing smoking cues, anxiety cues, both, or neutral cues. No differences were observed between smokers with and without anxiety disorders. Significant Patch×Time and Patch×Cue Content interactions were found. Both patch conditions experienced an increase in urge during the deprivation period, but postabsorption urge was significantly higher in the placebo condition, suggesting that transdermal nicotine attenuated the degree to which urge to smoke increased over time. During the cue reactivity trials, when participants received the nicotine patch, they experienced significantly lower urge in response to both smoking-only and neutral cues, but not when anxiety cues were present (alone or in combination with smoking cues). These data suggest that transdermal nicotine alleviates urge only under certain circumstances and that adjunctive interventions are likely necessary to address smoking urges in response to spikes in distress among smokers trying to quit.

Erasing fear for an imagined threat event.

Although memory for emotionally arousing and stressful experiences is strong and resistant to change, recent years have witnessed rapidly emerging evidence for the plasticity of fear memories. Upon retrieval a memory may be rendered labile and vulnerable to the disruptive effects of amnestic agents. This process is referred to as "disrupting reconsolidation" and may point to a novel therapeutic strategy for the permanent reduction of fear in patients suffering from anxiety disorders. However, the fear-reducing effects are thus far only demonstrated for freezing reactions in rodents and autonomic fear responding in humans. If disrupting reconsolidation will be of value for clinical practice, it should also target the subjective feelings of anxiety. Using an instructed fear-learning paradigm in humans, we here tested whether disrupting reconsolidation would diminish the subjective feelings of anxiety for a noxious event that was anticipated but never actually experienced. Beta-adrenergic receptor blockade during reconsolidation strongly diminished the behavioral expression of the instructed fear memory (i.e., startle responding) as well as the subjective feelings of anxiety 24h later, yet without affecting both the physiological and cognitive component of the anticipation of threat (i.e., skin conductance responding, expectancy ratings). Together, the present findings suggest that the various memory traces of a learned fear association do not necessarily undergo reconsolidation in harmony. Considering that patients with anxiety disorders (1) often fear objects and situations that they have never actually experienced, and (2) primarily suffer from the subjective feelings of anxiety, the present findings may have important ramifications for psychotherapy.

Effects of levodopa on vividness of motor imagery in Parkinson disease.

INTRODUCTION: Motor imagery during functional magnetic resonance imaging is commonly used to understand the neural underpinnings of complex movements. This approach has recently been applied to individuals with Parkinson disease (PD) to better understand how brain function may relate to movement dysfunction. However, the ability of individuals with PD to imagine movements when "Off" dopamine replacement medication is poorly understood. Therefore, the primary purpose of the current study is to test the ability of people with PD to imagine movements while "On" and "Off" anti-Parkinson medication. METHODS: Vividness of imagery was assessed in 28 individuals with mild to moderate PD (Hoehn and Yahr stages 1-3) via the Kinesthetic Visual Imagery Questionnaire (KVIQ-20) both "On" and "Off" anti-Parkinson medication. Vividness of imagery of 32 age-matched older adults was also assessed. RESULTS: No differences in vividness of imagery were observed between "Off" and "On" medication states (p = 0.15). Imagery was similar between controls and PD both "Off" (p = 0.25) and "On" (p = 0.46) anti-Parkinson medication. A significant correlation was observed between imagery and disease severity while "On" anti-Parkinson medication (r = -0.49; p = 0.008). DISCUSSION AND CONCLUSIONS: Vividness of movement imagery was not different between "Off" and "On" anti-Parkinson medications or between PD and controls. These results suggest that people with PD are able to imagine similarly to older adults both when "On" and "Off" anti-Parkinson medication, and supports the use of motor imagery in the "Off" medication state.

Effects of intranasal oxytocin on 'compassion focused imagery'.

This study explored the effects of oxytocin on Compassion Focused Imagery (CFI), that is, imagining another "mind" being deeply compassionate to oneself, and the interaction of these effects with self-criticism and feeling socially safe with others. Forty-four healthy participants (29 men and 15 women) completed self-report measures of self-criticism, attachment style, and social safeness before taking part in a double-blind randomized placebo controlled study. They attended two imagery sessions, receiving oxytocin in one and a placebo in the other. Positive affect was measured before and after each imagery session, and "imagery experience" was assessed after each session. Overall, oxytocin increased the ease of imagining compassionate qualities but there were important individual differences in how CFI was experienced. Participants higher in self-criticism, lower in self-reassurance, social safeness, and attachment security had less positive experiences of CFI under oxytocin than placebo, indicating that the effects of oxytocin on affiliation may depend on attachment and self-evaluative styles.

Dopamine enhances expectation of pleasure in humans.

Human action is strongly influenced by expectations of pleasure. Making decisions, ranging from which products to buy to which job offer to accept, requires an estimation of how good (or bad) the likely outcomes will make us feel [1]. Yet, little is known about the biological basis of subjective estimations of future hedonic reactions. Here, we show that administration of a drug that enhances dopaminergic function (dihydroxy-L-phenylalanine; L-DOPA) during the imaginative construction of positive future life events subsequently enhances estimates of the hedonic pleasure to be derived from these same events. These findings provide the first direct evidence for the role of dopamine in the modulation of subjective hedonic expectations in humans.

Psychophysiological responding to emotional memories in healthy young men after cortisol and propranolol administration.

RATIONALE: Propranolol is found to reduce physiological hyper-responsiveness in post traumatic stress disorder (PTSD), possibly by affecting reconsolidation after the reactivation of traumatic memories. Cortisol is found to attenuate declarative memory retrieval, but it is unknown whether it also reduces physiological responses to emotional memories. OBJECTIVES: To examine whether the effects of propranolol on physiological responding to emotional memories can also be found in healthy controls and to investigate the immediate and prolonged effects of cortisol on physiological responding to emotional memories, we tested these effects in 79 healthy young men. MATERIALS AND METHODS: After preparing a script of a negative disturbing memory, participants were instructed to imagine this event 1 week later after ingestion of either 35 mg cortisol, 80 mg propranolol, or a placebo. Physiological responding to the script-driven imagery was recorded. Another week later, after washout, the imagery was repeated again. During all three sessions as well as 8 months later, subjective emotional reactions to the memories were assessed. RESULTS: The emotionality of the memories was reduced over time, which was not affected by the treatments, however. The personal emotional script did evoke higher skin conductance responses than a neutral story, which decreased 1 week later, but no effects were found of either propranolol or cortisol on this responsiveness. CONCLUSIONS: Whereas healthy males do show psychophysiological responding to personal emotional scripts, the effects of cortisol and propranolol on physiological responses to emotional memories might be specific to clinical groups characterized by hyper-responsiveness, like PTSD. Future studies using longer-acting doses and more elaborate reactivation procedures in both healthy men and women could shed more light on the effects of cortisol and propranolol on psychophysiological responding to emotional memories.

Enhancement of suggestibility and imaginative ability with nitrous oxide.

RATIONALE: Imaginative suggestibility, a trait closely related to hypnotic suggestibility, is modifiable under some circumstances. Nitrous oxide (laughing gas) is commonly used for sedation in dentistry and is reported to be more effective when combined with appropriate suggestions. OBJECTIVE: The aim of this study was to determine whether nitrous oxide inhalation alters imaginative suggestibility and imagery vividness. METHODS: Thirty participants were tested twice in a within-subjects design, once during inhalation of 25% nitrous oxide and once during inhalation of air plus oxygen. Before the study, participants' expectancies regarding the effects of nitrous oxide were assessed. Participants were blinded to drug administration. During each session, participants were verbally administered detailed measures of imagination and suggestibility: the Sheehan-Betts Quality of Mental Imagery scale and the Stanford Hypnotic Susceptibility Scale Form C, minus the hypnotic induction. RESULTS: Imaginative suggestibility and imaginative ability (imagery vividness) were both elevated in the nitrous oxide condition. This effect was unrelated to participants' expectations regarding the effects of the drug. CONCLUSIONS: Nitrous oxide increased imaginative suggestibility and imaginative ability. Possible explanations of these findings are discussed with respect to the effects of N-methyl-d-aspartate antagonists and to other pharmacological effects upon suggestibility and imagination.

Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder.

OBJECTIVE: The strong association between ADHD and cigarette smoking and the known effects of nicotine on cognition has lead to interest in the role of cholinergic function in ADHD cognitive deficits. We have previously demonstrated that acute nicotine improves behavioral inhibition in adolescents with ADHD. This study examined acute nicotine in young adults with ADHD-Combined type on cognitive domains including behavioral inhibition, delay aversion, and recognition memory. METHODS: 15 non-smoking young adults (20+/-1.7 years) diagnosed with ADHD-C received acute nicotine (7 mg patch for 45 min) and placebo on separate days. Cognitive tasks included the Stop Signal Task, Choice Delay task, and the High-Low Imagery Task (a verbal recognition memory task). Three subjects experienced side effects and their data was excluded from analysis of cognitive measures. RESULTS: There was a significant (p<.05) positive effect of nicotine on the Stop Signal Reaction Time measure of the Stop Signal Task. The SSRT was improved without changes in GO reaction time or accuracy. There was a trend (p=.09) for nicotine to increase tolerance for delay and a strong trend (p=.06) for nicotine to improve recognition memory. CONCLUSIONS: Non-smoking young adults with ADHD-C showed improvements in cognitive performance following nicotine administration in several domains that are central to ADHD. The results from this study support the hypothesis that cholinergic system activity may be important in the cognitive deficits of ADHD and may be a useful therapeutic target.

Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder.

The beta-adrenergic blocker propranolol given within hours of a psychologically traumatic event reduces physiologic responses during subsequent mental imagery of the event. Here we tested the effect of propranolol given after the retrieval of memories of past traumatic events. Subjects with chronic post-traumatic stress disorder described their traumatic event during a script preparation session and then received a one-day dose of propranolol (n=9) or placebo (n=10), randomized and double-blind. A week later, they engaged in script-driven mental imagery of their traumatic event while heart rate, skin conductance, and left corrugator electromyogram were measured. Physiologic responses were significantly smaller in the subjects who had received post-reactivation propranolol a week earlier. Propranolol given after reactivation of the memory of a past traumatic event reduces physiologic responding during subsequent mental imagery of the event in a similar manner to propranolol given shortly after the occurrence of a traumatic event.

Paroxetine-induced modulation of cortical activity supporting language representations of action.

INTRODUCTION: Previous studies have shown that paroxetine, a selective serotonin reuptake inhibitor, affects brain motor pathway activity in healthy subjects using simple motor tasks. In this study, we explored the effects of paroxetine on the activity of cortical areas implicated in higher-order representations of goal-directed movements, i.e., action-related language processing. MATERIALS AND METHODS: A double-blind, crossover, randomized paradigm was used to compare two 1-month treatment phases with either paroxetine (20 mg per day) or placebo. A functional magnetic resonance imaging experiment on 12 healthy subjects, conducted at the end of each treatment phase, comprised a single list of verbs and three tasks that consisted in repeating the verbs aloud, generating verbs depicting actions aloud, and mentally simulating the corresponding actions. The effects of the drug, i.e., paroxetine-placebo>0 (hyperactivation) and placebo-paroxetine >0 (hypoactivation) were assessed on the basis of the activation-rest contrast for each task. RESULTS AND DISCUSSION: For both verb generation and mental simulation of action which both engaged higher-order representations of action, we observed hypoactivation in the left-sided prefrontal and right-sided medial premotor cortex. By contrast, we observed hyperactivation in the right-sided Brodmann's area 6 for the less demanding verb repetition task. CONCLUSION: Chronic treatment with paroxetine may modulate the cerebral activities elicited by action-related language tasks depending on the cognitive components involved in such tasks.

Effects of acute antipsychotic treatment on brain activation in first episode psychosis: an fMRI study.

This study aimed to assess the neurophysiological effects of acute atypical antipsychotic treatment on cognitive functioning in subjects presenting with a first episode of psychosis. We used functional MRI to examine the modulatory effects of acute psychopharmacological intervention on brain activation during four different cognitive tasks: overt verbal fluency, random movement generation, n-back and a spatial object memory task. Treatment with atypical antipsychotics was associated with alterations in regional activation during each task and also when task demands were manipulated within paradigms. The initial treatment of psychosis with atypical antipsychotics thus appears to be associated with modifications of the neurofunctional correlates of executive and mnemonic functions. These effects need to be considered when interpreting group differences in activation between medicated patients and controls.