Heterogeneity of amygdala response in major depressive disorder: the impact of lifetime subthreshold mania.

BACKGROUND: Patients with major depressive disorder (MDD) present with highly heterogeneous symptom profiles. We aimed to examine whether individual differences in amygdala activity to emotionally salient stimuli were related to heterogeneity in lifetime levels of depressive and subthreshold manic symptoms among adults with MDD. METHOD: We compared age- and gender-matched adults with MDD (n = 26) with healthy controls (HC, n = 28). While undergoing functional magnetic resonance imaging, participants performed an implicit emotional faces task: they labeled a color flash superimposed upon initially neutral faces that dynamically morphed into one of four emotions (angry, fearful, sad, happy). Region of interest analyses examined group differences in amygdala activity. For conditions in which adults with MDD displayed abnormal amygdala activity versus HC, within-group analyses examined amygdala activity as a function of scores on a continuous measure of lifetime depression-related and mania-related pathology. RESULTS: Adults with MDD showed significantly greater right-sided amygdala activity to angry and happy conditions than HC (p < 0.05, corrected). Multiple regression analyses revealed that greater right-amygdala activity to the happy condition in adults with MDD was associated with higher levels of subthreshold manic symptoms experienced across the lifespan (p = 0.002). CONCLUSIONS: Among depressed adults with MDD, lifetime features of subthreshold mania were associated with abnormally elevated amygdala activity to emerging happy faces. These findings are a first step toward identifying biomarkers that reflect individual differences in neural mechanisms in MDD, and challenge conventional mood disorder diagnostic boundaries by suggesting that some adults with MDD are characterized by pathophysiological processes that overlap with bipolar disorder.

Positional firing properties of postrhinal cortex neurons.

Hippocampal cell firing in awake, behaving rats is often spatially selective, and such cells have been called place cells. Similar spatial correlates have also been described for neurons in the medial entorhinal and perirhinal cortices. All three regions receive sensory associational input from postrhinal cortex, which, in turn, is heavily interconnected with visuospatial neocortical regions. The spatial selectivity of postrhinal cells, however, has never been examined. Here, we report the activity of neurons in postrhinal cortex of freely moving rats performing a spatial task on a four-arm radial maze. Data are also reported for visual association cortex neurons. The four-arm radial maze was defined by multisensory cues on the surfaces of the maze arms (proximal) and complex visual cues at the surround (distal). On each recording day, rats were run in three conditions: baseline, double cue rotation (proximal +90 degrees; distal -90 degrees ), and baseline. In this task, hippocampal place field activity is robust and can be controlled by proximal or distal cues. The majority of postrhinal neurons (64%) exhibited positional correlates during performance on the task; however, characteristics of these postrhinal cells were substantially different from those previously described for hippocampal place cells. Most postrhinal cells with firing fields exhibited split or multiple subfields (93%). Unlike hippocampal place fields, the large majority of postrhinal firing fields (84%) adopted new spatial correlates when experimental cues were rotated, but did so neither predictably nor concordantly. This is the first report of positional firing correlates in the postrhinal cortex. The data are consistent with the idea that postrhinal cortex participates in visuospatial functions by monitoring changes in environmental stimuli rather than encoding stable spatial cues. Thus, postrhinal neurons appear to participate in higher-level perceptual functions rather than mnemonic functions. We propose that the response properties of postrhinal neurons represent an early step in a spatial pathway that culminates in the specific and stable place fields of the hippocampus.