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Poster #199 - Infant reactivity predicts changes in amygdala volume

Sat, March 23, 4:15 to 5:30pm, Baltimore Convention Center, Floor: Level 1, Exhibit Hall B

Integrative Statement

In the first few months of life, infants begin to exhibit differences in their reactions to novel stimuli. Some infants are highly aroused and distressed by novelty (i.e., negative reactive), whereas others remain calm (i.e., positive reactive). These differences in infants’ reactivity to novelty are associated with arousal of the sympathetic nervous system (Fox, 1989; Kagan, Reznick, Snidman, 1987) and behavioral responses of fear in toddlerhood (Fox et al, 2001). The amygdala is central to interpreting and responding to perceived threats (LeDoux, 2003) and (along with subcortical reward regions) it is thought to be central to infant reactivity (Kagan, Reznick, & Snidman, 1988). Despite considerable speculation that reactivity arises from amygdala responsivity, to date there is very limited evidence that infant reactivity is linked to differences in amygdala structure or function. The current study is the first to investigate whether infant reactivity is linked to structural differences in amygdala development in middle childhood.

At four months of age, we assessed reactivity in 291 infants (See Calkin, Fox, Marshall, 1996 for details on paradigm). Infants were either identified as positive reactive, negative reactive, or controls based on their behavioral responses (See Calkin, Fox, Marshall, 1996). At 10 and 12 years of age high resolution T1-weighted MRI images were acquired (n=125). Images were processed using FreeSurfer 5.3.0 (http://surfer.nmr.mgh.harvard.edu/)(Fischl and Dale, 1999; Dale, Fischl, & Sereno 1999), producing surfaces delineating the inner (white) and outer (pial) limits of the cortical gray matter, and subcortical volume segmentation. Surfaces were visually inspected for defects and, where necessary, edited and regenerated. Automated segmentation was used to derive sub-cortical volume estimates. To extract reliable volume estimates, images were processed using FreeSurfer’s longitudinal pipeline (Reuter et al., 2012).

Focal analyses examined longitudinal changes in amygdala volume as a function of infant temperament group (between subjects: positive, negative and control) and time (repeated measures: age 10 and age 12) covarying for estimated total intracranial volume, gender, and maternal education using linear mixed effects modeling. Amygdala volume was tested separately for each hemisphere. To correct for laterality, significance criterion was set at =.025 (Bonferroni correction α=.05/2). Results indicate that across middle childhood left amygdala volume increases more slowly in negative reactive infants than in positive reactive infants (2(2)=8.627, p<.0134; See Figure 1). There was a marginally significant reactivity x time interaction on right amygdala volume (2(2)=5.824, p<.054).

We also conducted exploratory analyses examining the link between temperament and the development of three subcortical regions associated with reward (caudate, putamen, NAcc). Exploratory analyses demonstrate that those with positive reactive temperament showed a larger increase in right NAcc volume over middle childhood than those with negative reactive temperament (2(2)=12.214, p<.002; See Figure 2). Supplemental analyses also demonstrate that there were no changes in cortical thickness or surface area as a function of reactivity or time.

In conclusion, the amygdala has long been hypothesized to be the biological basis of infant reactivity. Together, these results suggest that differences in early temperament are related to distinct patterns in sub-cortical brain development in middle childhood.

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