Longitudinal changes in neurometabolite concentrations in the dorsal anterior cingulate cortex after concentrated exposure therapy for obsessive-compulsive disorder

Background The dorsal anterior cingulate cortex (dACC) plays an important role in the pathophysiology of obsessive-compulsive disorder (OCD) due to its role in error processing, cognitive control and emotion regulation. OCD patients have shown altered concentrations in neurometabolites in the dACC, particularly Glx (glutamate+glutamine) and tNAA (N-acetylaspartate+N-acetyl-aspartyl-glutamate). We investigated the immediate and prolonged effects of exposure and response prevention (ERP) on these neurometabolites. Methods Glx and tNAA concentrations were measured using magnetic resonance spectroscopy (1H-MRS) in 24 OCD patients and 23 healthy controls at baseline. Patients received concentrated ERP over four days. A subset was re-scanned after one week and three months. Results No Glx and tNAA abnormalities were observed in OCD patients compared to healthy controls before treatment or over time. Patients with childhood or adult onset differed in the change over time in tNAA (F(2,40) = 7.24, ɳ2p= 0.27, p = 0.004): concentrations increased between one week after treatment and follow-up in the childhood onset group (t(39) = -2.43, d = -0.86, p = 0.020), whereas tNAA concentrations decreased between baseline and follow-up in patients with an adult onset (t(42) = 2.78, d = 1.07, p = 0.008). In OCD patients with versus without comorbid mood disorders, lower Glx concentrations were detected at baseline (t(38) = -2.28, d = -1.00, p = 0.028). Glx increased after one week of treatment within OCD patients with comorbid mood disorders (t(30) = -3.09, d = -1.21, p = 0.004). Limitations Our OCD sample size allowed the detection of moderate to large effect sizes only. Conclusion ERP induced changes in neurometabolites in OCD seem to be dependent on mood disorder comorbidity and disease stage rather than OCD itself.publishedVersio

Dopamine Increases a Value-Independent Gambling Propensity

Although the impact of dopamine on reward learning is well documented, its influence on other aspects of behavior remains the subject of much ongoing work. Dopaminergic drugs are known to increase risk-taking behavior, but the underlying mechanisms for this effect are not clear. We probed dopamine’s role by examining the effect of its precursor L-DOPA on the choices of healthy human participants in an experimental paradigm that allowed particular components of risk to be distinguished. We show that choice behavior depended on a baseline (ie, value-independent) gambling propensity, a gambling preference scaling with the amount/variance, and a value normalization factor. Boosting dopamine levels specifically increased just the value-independent baseline gambling propensity, leaving the other components unaffected. Our results indicate that the influence of dopamine on choice behavior involves a specific modulation of the attractiveness of risky options—a finding with implications for understanding a range of reward-related psychopathologies including addiction

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

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

BOLD fMRI responses in amygdala and visual cortex for the contrast “1^st presentation” > “2^nd presentation”.

<p>Data are small volume corrected using anatomically defined bilateral amygdala, inferior occipital gyrus and fusiform gyrus (WFU Pickatlas <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096146#pone.0096146-Maldjian1" target="_blank">[41]</a>).</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

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

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

Prefrontal glutamate levels predict altered amygdala-prefrontal connectivity in traumatized youths

Background Neurobiological models of stress and stress-related mental illness, including post-traumatic stress disorder, converge on the amygdala and the prefrontal cortex (PFC). While a surge of research has reported altered structural and functional connectivity between amygdala and the medial PFC following severe stress, few have addressed the underlying neurochemistry. Methods We combined resting-state functional magnetic resonance imaging measures of amygdala connectivity with in vivo MR-spectroscopy (1H-MRS) measurements of glutamate in 26 survivors from the 2011 Norwegian terror attack and 34 control subjects. Results Traumatized youths showed altered amygdala–anterior midcingulate cortex (aMCC) and amygdala–ventromedial prefrontal cortex (vmPFC) connectivity. Moreover, the trauma survivors exhibited reduced levels of glutamate in the vmPFC which fits with the previous findings of reduced levels of Glx (glutamate + glutamine) in the aMCC (Ousdal et al., 2017) and together suggest long-term impact of a traumatic experience on glutamatergic pathways. Importantly, local glutamatergic metabolite levels predicted the individual amygdala–aMCC and amygdala–vmPFC functional connectivity, and also mediated the observed group difference in amygdala–aMCC connectivity. Conclusions Our findings suggest that traumatic stress may influence amygdala–prefrontal neuronal connectivity through an effect on prefrontal glutamate and its compounds. Understanding the neurochemical underpinning of altered amygdala connectivity after trauma may ultimately lead to the discovery of new pharmacological agents which can prevent or treat stress-related mental illness