Reduced intra-amygdala activity to positively valenced faces in adolescent schizophrenia offspring

Abstract

Studies suggest that the affective response is impaired in both schizophrenia and adolescent offspring of schizophrenia patients. Adolescent offspring of patients are developmentally vulnerable to impairments in several domains, including affective responding, yet the bases of these impairments and their relation to neuronal responses within the limbic system are poorly understood. The amygdala is the central region devoted to the processing of emotional valence and its sub-nuclei including the baso-lateral and centro-medial are organized in a relative hierarchy of affective processing. Outputs from the centro-medial nucleus converge on regions involved in the autonomous regulation of behavior, and outputs from the baso-lateral nucleus modulate the response of reward processing regions. Here using fMRI we assessed the intra-amygdala response to positive, negative, and neutral valenced faces in a group of controls (with no family history of psychosis) and offspring of schizophrenia parents (n=44 subjects in total). Subjects performed an affective continuous performance task during which they continually appraised whether the affect signaled by a face on a given trial was the same or different from the previous trial (regardless of facial identity). Relative to controls, offspring showed reduced activity in the left centro-medial nucleus to positively (but not negatively or neutral) valenced faces. These results were independent of behavioral/cognitive performance (equal across groups) suggesting that an impaired affective substrate in the intra-amygdala response may lie at the core of deficits of social behavior that have been documented in this population.

Figure 1

The figure depicts a conceptual model of affective information flow from sensory to cortical regions via intra-amygdala interactions. As noted in the text, adaptive filtering within the amygdala pathways results in relative specialization and specific patterns of information flow. The lateral nucleus (not depicted) transmits information to the basal and central nuclei , the outputs from which have specific roles related to positively (presumably rewarding) and negatively (presumably aversive) valenced stimuli. The basolateral nucleus most recently associated with anxiety , extensively projects to ventral regions of the frontal cortex, as well as reward related regions such as the nucleus accumbens . The centromedial nucleus receives information from all other nuclei, serving as a key site for signal projections to the cortex, the brainstem and hypothalamic autonomic centers.

Figure 2

The relationship between quantified spatial probability maps (left) of the centro-medial (top) and baso-lateral (bottom) and corresponding maximum probability maps is depicted in single axial and coronal sections. Note that the maximum probability maps are a subset of the spatial probability maps and reflect maximum spatial probabilities on the accompanying color bars.

Figure 3

The task is schematically depicted. The appropriate responses to the individual stimuli are labeled for the sake of exposition. fMRI activity to events (faces, small arrow) was assessed (see text for details) and contrasted between HC and SCZ-Off.

Figure 4

BOLD differences in left centro-medial amygdala (maximum probability map depicted in (a) are shown for positive (b), neutral (c) and negative (d) valenced faces. A progressive difference in activation is observed between HC and SCZ-Off, with increased positive valence reflecting a potentially anhedonic response (see Discussion) to positive valence in SCZ-Off (*, p<.05). Error bars are ± sem.

Figure 5

Based on the analyses of signal intensity (Fig 4), intra-group analyses using SPM’s random fields approach were conducted to assess bi- or uni-lateral amygdala activity in HC and SCZ-Off. (a) In HC, bilateral peaks in the amygdala response to positively valenced faces were observed: Right: t₄₂=3.11, k_E=46, p_FWE<.05, x=30, y=−2, z=−26; Left: t₄₂=2.56, k_E=20, p<.007, x=−30, y=−4, z=−22. (b) By comparison, in SCZ-Off activation was only observed in the right amygdala, t₄₂=3.71, k_E=60, p_FWE<.01, x=30, y=−2, z=−26. Inter-group differences assessed with this approach were not significant.

Figure 6

LOESS curve fits relating age with activity in the left CM for each valence and region’s response in SCZ-Off and HC. Whereas age-related trends to negative valence (a) are comparable, increasing positive valence results in decreases in the age-related response in SCZ-Off but not HC (b and c respectively). These results suggest that in older SCZ-Off, positive stimuli evoke less of a response in the CM and may provide evidence of increased impairment in the affective response closer to the typical age of onset of most psychiatric disorders.