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Pregabalin effects on neural response to emotional faces.

Aupperle RL, Tankersley D, Ravindran LN, Flagan T, Stein NR, Stein MB, Paulus MP - Front Hum Neurosci (2012)

Bottom Line: The 50 mg dose exhibited more robust effects than the 200 mg dose in the right anterior insula and ventral ACC.However, there is evidence that a subclinical 50 mg dose of pregabalin produced more robust and widespread effects on neural responses in this paradigm than the more clinically relevant 200 mg dose.Taken together, pregabalin has a slightly different effect on brain activation as it relates to anticipation and emotional face processing, which may account for its unique characteristic as an agent for the treatment of anxiety disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of California, San Diego, La Jolla CA, USA.

ABSTRACT
Pregabalin has shown promise in the treatment of anxiety disorders. Previous functional magnetic resonance imaging (fMRI) studies indicate agents used to treat anxiety, e.g., SSRIs and benzodiazepines, attenuate amygdala, insula, and medial prefrontal cortex (mPFC) activation during emotional processing. Our prior study has shown that during anticipation of an emotional stimulus, pregabalin attenuates amygdala and insula activation but increases medial PFC activation. In this study, we examined whether, similar to SSRIs and benzodiazepines, pregabalin attenuates amygdala, insula, and medial PFC during emotional face processing. Sixteen healthy volunteers underwent a double-blind within-subjects fMRI study investigating effects of placebo, 50 mg, and 200 mg pregabalin on neural activation during an emotional face-matching task. Linear mixed model analysis revealed that pregabalin dose-dependently attenuated left amygdala activation during fearful face-matching and left anterior insula activation during angry face-matching. The 50 mg dose exhibited more robust effects than the 200 mg dose in the right anterior insula and ventral ACC. Thus, pregabalin shares some similarity to SSRIs and benzodiazepines in attenuating anger and fear-related insula and amygdala activation during emotional face processing. However, there is evidence that a subclinical 50 mg dose of pregabalin produced more robust and widespread effects on neural responses in this paradigm than the more clinically relevant 200 mg dose. Taken together, pregabalin has a slightly different effect on brain activation as it relates to anticipation and emotional face processing, which may account for its unique characteristic as an agent for the treatment of anxiety disorders.

No MeSH data available.


Related in: MedlinePlus

Regions of interest masks used for fMRI analyses, shown from axial views.(A) bilateral amygdala (green) and fusiform gyrus (yellow) (shown at z = −20), (B) bilateral anterior (green) and posterior (yellow) insula (shown at z = 2), (C) ventral medial prefrontal cortex (PFC; shown at z = −6), and (D) dorsal medial PFC (shown at z = 4). These anatomical regions were defined using Talairach Atlas [Lancaster et al. (2000)].
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Figure 2: Regions of interest masks used for fMRI analyses, shown from axial views.(A) bilateral amygdala (green) and fusiform gyrus (yellow) (shown at z = −20), (B) bilateral anterior (green) and posterior (yellow) insula (shown at z = 2), (C) ventral medial prefrontal cortex (PFC; shown at z = −6), and (D) dorsal medial PFC (shown at z = 4). These anatomical regions were defined using Talairach Atlas [Lancaster et al. (2000)].

Mentions: Analyses were conducted voxel-wise across the whole-brain as well as for specific a priori ROIs using small volume correction. Bilateral amygdala, mPFC, and anterior insula were selected as a priori ROIs based on previous literature implicating them in emotional processing, anticipation, and anxiety disorders. The fusiform gyrus was included as an a priori region based on previous literature implicating it to play a primary role in face processing. These anatomical regions were defined in AFNI using the ROI plugin and Talairach Atlas (Lancaster et al., 2000) and are displayed in Figure 2. The mPFC included primarily the ventral and dorsal ACC; including BA 32, 24, spreading into ventromedial PFC regions (BA 10). This mPFC region was partitioned into dorsal and ventral extents at z = 0, and the anterior insula was partitioned from the insula as a whole using a linear interpolation for the location of the middle insular gyrus. Thus, in total there were eight a priori ROIs (bilateral amygdala, dorsal and ventral medial PFC, bilateral anterior insula, and bilateral fusiform gyrus). A threshold adjustment method based on Monte–Carlo simulations (conducted via AFNI's program Alpha Sim) was used to guard against identifying false positive areas of activation. This resulted in the following minimum volumes for a cluster to be considered significant: 192 μL (3 voxels) for the amygdala ROIs, 256 μL (4 voxels) for anterior insula ROIs, 320 μL (5 voxels) for medial PFC ROIs, and 832 μL (13 voxels) for whole-brain analyses. While the cluster significance of p < 0.05 (two-tailed) was used for all analyses, the corrected voxel-wise probabilities (determined via AFNI's program Alpha Sim) are as follows: amygdala p < 0.0021, anterior insular p < 0.0015, posterior insula p < 0.0016, ventromedial PFC and dorsomedial PFC p < 0.0008, whole-brain p < 0.00001. All reported coordinates are center of mass Talairach coordinates (x, y, z) and labeled based on visual observation and Talairach Daemon software (Lancaster et al., 2000). For identified activation clusters, mean F-values were extracted and reported. To enable further characterization of the effects, PSC was extracted for each activation cluster and post-hoc linear mixed models were conducted with specific contrasts (e.g., PLB vs. 50 mg, PLB vs. 200 mg, 50 mg vs. 200 mg), which were considered significant at p < 0.05. Spearman's non-parametric correlations were used to investigate potential relationships between extracted PSC for significant clusters and variables that may have influenced BOLD response including (1) fMRI behavioral data and self-report survey data significantly influenced by pregabalin (e.g., fMRI paradigm reaction time, KSS, and VAS ratings of dizziness, tired, trembling, and high) and (2) CBF data collected through ASL (extracted for each ROI activation cluster identified as significant in fMRI analysis). These correlations were considered significant at p < 0.05.


Pregabalin effects on neural response to emotional faces.

Aupperle RL, Tankersley D, Ravindran LN, Flagan T, Stein NR, Stein MB, Paulus MP - Front Hum Neurosci (2012)

Regions of interest masks used for fMRI analyses, shown from axial views.(A) bilateral amygdala (green) and fusiform gyrus (yellow) (shown at z = −20), (B) bilateral anterior (green) and posterior (yellow) insula (shown at z = 2), (C) ventral medial prefrontal cortex (PFC; shown at z = −6), and (D) dorsal medial PFC (shown at z = 4). These anatomical regions were defined using Talairach Atlas [Lancaster et al. (2000)].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3313548&req=5

Figure 2: Regions of interest masks used for fMRI analyses, shown from axial views.(A) bilateral amygdala (green) and fusiform gyrus (yellow) (shown at z = −20), (B) bilateral anterior (green) and posterior (yellow) insula (shown at z = 2), (C) ventral medial prefrontal cortex (PFC; shown at z = −6), and (D) dorsal medial PFC (shown at z = 4). These anatomical regions were defined using Talairach Atlas [Lancaster et al. (2000)].
Mentions: Analyses were conducted voxel-wise across the whole-brain as well as for specific a priori ROIs using small volume correction. Bilateral amygdala, mPFC, and anterior insula were selected as a priori ROIs based on previous literature implicating them in emotional processing, anticipation, and anxiety disorders. The fusiform gyrus was included as an a priori region based on previous literature implicating it to play a primary role in face processing. These anatomical regions were defined in AFNI using the ROI plugin and Talairach Atlas (Lancaster et al., 2000) and are displayed in Figure 2. The mPFC included primarily the ventral and dorsal ACC; including BA 32, 24, spreading into ventromedial PFC regions (BA 10). This mPFC region was partitioned into dorsal and ventral extents at z = 0, and the anterior insula was partitioned from the insula as a whole using a linear interpolation for the location of the middle insular gyrus. Thus, in total there were eight a priori ROIs (bilateral amygdala, dorsal and ventral medial PFC, bilateral anterior insula, and bilateral fusiform gyrus). A threshold adjustment method based on Monte–Carlo simulations (conducted via AFNI's program Alpha Sim) was used to guard against identifying false positive areas of activation. This resulted in the following minimum volumes for a cluster to be considered significant: 192 μL (3 voxels) for the amygdala ROIs, 256 μL (4 voxels) for anterior insula ROIs, 320 μL (5 voxels) for medial PFC ROIs, and 832 μL (13 voxels) for whole-brain analyses. While the cluster significance of p < 0.05 (two-tailed) was used for all analyses, the corrected voxel-wise probabilities (determined via AFNI's program Alpha Sim) are as follows: amygdala p < 0.0021, anterior insular p < 0.0015, posterior insula p < 0.0016, ventromedial PFC and dorsomedial PFC p < 0.0008, whole-brain p < 0.00001. All reported coordinates are center of mass Talairach coordinates (x, y, z) and labeled based on visual observation and Talairach Daemon software (Lancaster et al., 2000). For identified activation clusters, mean F-values were extracted and reported. To enable further characterization of the effects, PSC was extracted for each activation cluster and post-hoc linear mixed models were conducted with specific contrasts (e.g., PLB vs. 50 mg, PLB vs. 200 mg, 50 mg vs. 200 mg), which were considered significant at p < 0.05. Spearman's non-parametric correlations were used to investigate potential relationships between extracted PSC for significant clusters and variables that may have influenced BOLD response including (1) fMRI behavioral data and self-report survey data significantly influenced by pregabalin (e.g., fMRI paradigm reaction time, KSS, and VAS ratings of dizziness, tired, trembling, and high) and (2) CBF data collected through ASL (extracted for each ROI activation cluster identified as significant in fMRI analysis). These correlations were considered significant at p < 0.05.

Bottom Line: The 50 mg dose exhibited more robust effects than the 200 mg dose in the right anterior insula and ventral ACC.However, there is evidence that a subclinical 50 mg dose of pregabalin produced more robust and widespread effects on neural responses in this paradigm than the more clinically relevant 200 mg dose.Taken together, pregabalin has a slightly different effect on brain activation as it relates to anticipation and emotional face processing, which may account for its unique characteristic as an agent for the treatment of anxiety disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of California, San Diego, La Jolla CA, USA.

ABSTRACT
Pregabalin has shown promise in the treatment of anxiety disorders. Previous functional magnetic resonance imaging (fMRI) studies indicate agents used to treat anxiety, e.g., SSRIs and benzodiazepines, attenuate amygdala, insula, and medial prefrontal cortex (mPFC) activation during emotional processing. Our prior study has shown that during anticipation of an emotional stimulus, pregabalin attenuates amygdala and insula activation but increases medial PFC activation. In this study, we examined whether, similar to SSRIs and benzodiazepines, pregabalin attenuates amygdala, insula, and medial PFC during emotional face processing. Sixteen healthy volunteers underwent a double-blind within-subjects fMRI study investigating effects of placebo, 50 mg, and 200 mg pregabalin on neural activation during an emotional face-matching task. Linear mixed model analysis revealed that pregabalin dose-dependently attenuated left amygdala activation during fearful face-matching and left anterior insula activation during angry face-matching. The 50 mg dose exhibited more robust effects than the 200 mg dose in the right anterior insula and ventral ACC. Thus, pregabalin shares some similarity to SSRIs and benzodiazepines in attenuating anger and fear-related insula and amygdala activation during emotional face processing. However, there is evidence that a subclinical 50 mg dose of pregabalin produced more robust and widespread effects on neural responses in this paradigm than the more clinically relevant 200 mg dose. Taken together, pregabalin has a slightly different effect on brain activation as it relates to anticipation and emotional face processing, which may account for its unique characteristic as an agent for the treatment of anxiety disorders.

No MeSH data available.


Related in: MedlinePlus