Effects of haloperidol and aripiprazole on the human mesolimbic motivational system: A pharmacological fMRI study

The atypical antipsychotic drug aripiprazole is a partial dopamine (DA) D2 receptor agonist, which differentiates it from most other antipsychotics. This study compares the brain activation characteristic produced by aripiprazole with that of haloperidol, a typical D2 receptor antagonist. Healthy participants received an acute oral dose of haloperidol, aripiprazole or placebo, and then performed an active aversive conditioning task with aversive and neutral events presented as sounds, while blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was carried out. The fMRI task, targeting the mesolimbic motivational system that is thought to be disturbed in psychosis, was based on the conditioned avoidance response (CAR) animal model – a widely used test of therapeutic potential of antipsychotic drugs. In line with the CAR animal model, the present results show that subjects given haloperidol were not able to avoid more aversive than neutral task trials, even though the response times were shorter during aversive events. In the aripiprazole and placebo groups more aversive than neutral events were avoided. Accordingly, the task-related BOLD-fMRI response in the mesolimbic motivational system was diminished in the haloperidol group compared to the placebo group, particularly in the ventral striatum, whereas the aripiprazole group showed task-related activations intermediate of the placebo and haloperidol groups. The current results show differential effects on brain function by aripiprazole and haloperidol, probably related to altered DA transmission. This supports the use of pharmacological fMRI to study antipsychotic properties in humans

The left inferior frontal gyrus is involved in adjusting response bias during a perceptual decision-making task

Introduction Changing the way we make decisions from one environment to another allows us to maintain optimal decision-making. One way decision-making may change is how biased one is toward one option or another. Identifying the regions of the brain that underlie the change in bias will allow for a better understanding of flexible decision-making. Methods An event-related, perceptual decision-making task where participants had to detect a picture of an animal amongst distractors was used during functional magnetic resonance imaging. Positive and negative financial motivation were used to affect a change in response bias, and changes in decision-making behavior were quantified using signal detection theory. Results Response bias became relatively more liberal during both positive and negative motivated trials compared to neutral trials. For both motivational conditions, the larger the liberal shift in bias, the greater the left inferior frontal gyrus (IFG) activity. There was no relationship between individuals' belief that they used a different strategy and their actual change in response bias. Conclusions The present findings suggest that the left IFG plays a role in adjusting response bias across different decision environments. This suggests a potential role for the left IFG in flexible decision-making

The human amygdala encodes value and space during decision making

Valuable stimuli are invariably localized in space. While our knowledge regarding the neural networks supporting value assignment and comparisons is considerable, we lack a basic understanding of how the human brain integrates motivational and spatial information. The amygdala is a key structure for learning and maintaining the value of sensory stimuli and a recent non-human primate study provided initial evidence that it also acts to integrate value with spatial location, a question we address here in a human setting. We measured haemodynamic responses (fMRI) in amygdala while manipulating the value and spatial configuration of stimuli in a simple stimulus-reward task. Subjects responded significantly faster and showed greater amygdala activation when a reward was dependent on a spatial specific response, compared to when a reward required less spatial specificity. Supplemental analysis supported this spatial specificity by demonstrating that the pattern of amygdala activity varied based on whether subjects responded to a motivational target presented in the ipsilateral or contralateral visual space. Our data show that the human amygdala integrates information about space and value, an integration of likely importance for assigning cognitive resources towards highly valuable stimuli in our environment

Correlation between state anxiety scores and individual amygdala activation.

<p>Negative correlation between the individual state anxiety scores and the activity in right amygdala. Subjects with a high score on state anxiety had less amygdala signal change between the 1^st time and the 2^nd time presentation of the emotional faces. (A) Statistical parametric map (SPM) showing the right amygdala cluster. The image is thresholded at p<0.005, 25 voxels extent threshold, for illustrative reasons. The colors refer to t-values as coded in the bar to the right of the image (B) Scatter-plot demonstrating the negative correlation.</p

Amygdala and visual cortex BOLD activation to stimulus novelty.

<p>BOLD fMRI responses in the amygdala and visual cortex obtained for the contrast ”1^st presentation” >”2^nd presentation”. (A) Statistical parametric maps (SPM) demonstrating the responses in visual cortex for the given contrast. The image is thresholded at p = 0.005, k = 25 voxels for illustrative reasons. The colors refer to t-values as coded in the bar to the left of the image (B) Statistical parametric maps (SPM) demonstrating the responses in amygdala for the same contrast. The image is thresholded at p = 0.005, k = 25 voxels for illustrative reasons. (C) Beta values for the peak voxel in right amygdala (x = 24, y = −6, z = −14) and right inferior occipital gyrus (x = 34, y = −78, z = −12) for the conditions 1^st presentation and 2^nd presentation of the emotional faces.</p

BOLD activation by condition in right inferior occipital gyrus.

<p>Beta values for the peak voxel in right inferior occipital gyrus (x = 34, y = −78, z = −12) for the conditions 1^st presentation, 2^nd presentation and other presentations of the emotional faces. The figure illustrates that the right inferior occipital gyrus BOLD fMRI response was significantly reduced in the 2^nd compared to the 1^st presentation. However, the BOLD response during the 2^nd presentation was significantly greater than the mean response from the remaining presentations of the faces.</p

Psychophysiological interaction analysis.

<p>The results of the psychophysiological interaction analysis. (A) Statistical parametric map (SPM) showing regions in the visual cortex that showed condition-specific BOLD signal changes with right amygdala activity. The image is thresholded at p<0.005, 25 voxels extent threshold, for illustrative reasons. The colors refer to t-values as coded in the bar to the right of the image (B) Scatter plot with regression lines demonstrating the pattern of functional connectivity. The x-axis represents activity in the right amygdala (beta values) peak voxel and the y-axis represents activity in the right inferior occipital gyrus peak voxel (beta values).</p

Accuracy and response time by conditions in the emotional faces task.

<p>Accuracy and response time by conditions in the emotional faces task.</p