The structural integrity of an amygdala-prefrontal pathway predicts trait anxiety

“Descriptive statistics for self-report measures are as follows: STAI-S, 32.85 7.03; STAI-T, 37.15 8.25; BDI, 3.40 3.97.”

“Handedness Inventory (Oldfield, 1971).”

“Diffusionweighted images were preprocessed using the Diffusion Toolbox and FSL software of the Oxford Centre for Functional MRI of the Brain (Smith et al., 2004).”

“mented in AlphaSim within AFNI software (Cox, 1996).”

“To generate spatially normalized individual FA images, each individual image was aligned into Montreal Neurological Institute (MNI)-152 standard space using nonlinear registration (Rueckert et al., 1999).”

“Voxels with FA values 0.2 were removed before statistical analyses, and an additional white matter mask derived from the Wake Forest University Pick Atlas (Maldjian et al., 2003) was applied to the images to ensure the results were attributable to white matter.”

“A popular scale that measures the degree of anisotropy is fractional anisotropy (FA), which is thought to be modulated by the degree of myelination, axonal membrane thickness and diameter, and/or amount of parallel organization of axons (Basser and Pierpaoli, 1996; Beaulieu, 2002).”

“Second, other studies showing an inverse relationship between the amygdala and vmPFC involved clinically pathological groups (Rauch et al., 2000; Shin et al., 2005; Etkin and Wager, 2007).”

“Given previous studies demonstrating lower anxiety levels in subjects showing a greater functional coupling between the amygdala and prefrontal cortex (Pezawas et al., 2005), we planned to regress individual differences in the strength of this pathway against the range of trait anxiety scores in our subject sample to…”

“Evidence from the nonhuman animal literature indicates that the ventromedial prefrontal cortex (vmPFC), including the medial orbitofrontal cortex and ventral anterior cingulate cortex, is reciprocally connected with the amygdala, both functionally and anatomically (Amaral et al., 1992; Milad and Quirk, 2002; Ghashghae…”

“Second, other studies showing an inverse relationship between the amygdala and vmPFC involved clinically pathological groups (Rauch et al., 2000; Shin et al., 2005; Etkin and Wager, 2007).”

“These findings might at first seem counterintuitive since numerous studies have shown an inverse relationship between the amygdala and vmPFC (Kim et al., 2003; Shin et al., 2005; Urry et al., 2006; Hare et al., 2008).”

“For regions about which we had no a priori prediction, a more conservative significance threshold of p 0.00001 (uncorrected, 34 mm 3) was used (Shin et al., 2005).”

“These findings might at first seem counterintuitive since numerous studies have shown an inverse relationship between the amygdala and vmPFC (Kim et al., 2003; Shin et al., 2005; Urry et al., 2006; Hare et al., 2008).”

“Evidence from the nonhuman animal literature indicates that the ventromedial prefrontal cortex (vmPFC), including the medial orbitofrontal cortex and ventral anterior cingulate cortex, is reciprocally connected with the amygdala, both functionally and anatomically (Amaral et al., 1992; Milad and Quirk, 2002; Ghashghae…”

“Descriptive statistics for self-report measures are as follows: STAI-S, 32.85 7.03; STAI-T, 37.15 8.25; BDI, 3.40 3.97.”

“However, they could represent fiber tracts projecting in a lateral direction that serve to connect more medial gray matter structures (e.g., amygdala, nucleus basalis) with the UF [Selden et al. (1998), their Fig.”

“These could potentially represent shorter, multisynaptic tracts between the amygdala and the ventral basal forebrain (Aggleton et al., 1980) and striatum (Fudge et al., 2002) and then connec-”

“That said, it should be noted that some studies have reported a significant positive correlation between amygdala reactivity and measures of anxiety (Bishop et al., 2004; Etkin et al., 2004; Haas et al., 2007; Dickie and Armony, 2008).”

“These data converge with a previous DTI study of both human and macaque brains that identified comparable patterns of anatomical connectivity across both species, including extensive connections between the amygdala and vmPFC (Croxson et al., 2005).”

“For example, although conceptually similar, trait anxiety as measured by the STAI is not identical with neuroticism (Costa and McCrae, 1997) nor harm avoidance (Cloninger, 1986).”

“effects of smoothing (Tuch et al., 2005).”

“These findings might at first seem counterintuitive since numerous studies have shown an inverse relationship between the amygdala and vmPFC (Kim et al., 2003; Shin et al., 2005; Urry et al., 2006; Hare et al., 2008).”

“That said, it should be noted that some studies have reported a significant positive correlation between amygdala reactivity and measures of anxiety (Bishop et al., 2004; Etkin et al., 2004; Haas et al., 2007; Dickie and Armony, 2008).”

“Indeed, a positive correlation between structural and functional connectivity between the amygdala and vmPFC has been demonstrated, such that individuals with stronger anatomical connections between these two brain regions demonstrate stronger functional connectivity (Wang et al., 2009).”

“These could potentially represent shorter, multisynaptic tracts between the amygdala and the ventral basal forebrain (Aggleton et al., 1980) and striatum (Fudge et al., 2002) and then connec-”

“The UF is the major fiber tract connecting the anterior temporal lobe to the inferior frontal cortex (Ebeling and von Cramon, 1992; Highley et al., 2002).”

“…inverse relationship between low-expressing serotonin transporter gene (5- HTTLPR) alleles, which have been known to be associated with anxiety or depression, and FA values of the left frontal uncinate fasciculus, which overlaps with the amygdala–vmPFC pathway in our study (Pacheco et al., 2009).”

“That said, it should be noted that some studies have reported a significant positive correlation between amygdala reactivity and measures of anxiety (Bishop et al., 2004; Etkin et al., 2004; Haas et al., 2007; Dickie and Armony, 2008).”

“Disruptions in its developmental trajectory are likely to alter thresholds to emotional information and contribute to psychopathology, particularly, anxiety (Tottenham and Sheridan 2010; Kim and Whalen 2009).”

“…Copyright © 2011 the authors 0270-6474/11/3110937-11$15.00/0 Frontal lobe white matter connections are commonly implicated as underdeveloped in psychiatric disorders including schizophrenia (Kubicki et al., 2007), mood disorders (Heng et al., 2010), and anxiety (Kim and Whalen, 2009).”