Magnetic resonance imaging (MRI) in association with Jacobian-modulated voxel-based morphometry (VBM) was used to test for regional variation in gray matter over the menstrual cycle. T1-weighted anatomical images were acquired using a spoiled gradient recalled acquisition sequence in 21 women. Each subject was scanned twice: once during the postmenstrual late-follicular phase (Days 10-12 after onset of menses), and once during the premenstrual late-luteal phase (1-5 days before the onset of menses). Gray matter was relatively increased in the right anterior hippocampus and relatively decreased in the right dorsal basal ganglia (globus pallidus/putamen) in the postmenstrual phase. Verbal declarative memory was increased in the postmenstrual vs. premenstrual phase. This first report of human brain structural plasticity associated with the endogenous menstrual cycle extends well-established animal findings of hormone-mediated hippocampal plasticity to humans, and has implications for understanding alterations in cognition and behavior across the menstrual cycle.

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The orbitofrontal cortex (OFC) has been implicated in the representation of emotional stimuli, assignment of emotional valence͞ salience to stimuli, stimulus-reinforcement association learning, motivation, and socio-emotional control. Using functional magnetic resonance imaging in female subjects without premenstrual mood symptoms, we found that OFC activity to emotional linguistic stimuli varies depending on the menstrual cycle phase. Specifically, anterior-medial OFC activity for negative vs. neutral stimuli was increased premenstrually and decreased postmenstrually. The inverse pattern was seen in the lateral OFC. These findings suggest that specific subregional OFC activity to emotional stimuli is modulated across the menstrual cycle. The data also demonstrate that menstrual cycle phase is an important consideration in further studies attempting to elucidate the neural substrates of affective representation.functional MRI ͉ brain ͉ mood ͉ emotion ͉ women D espite a vast literature describing sex hormone influences on the central nervous system and a growing emotional neuroscience literature, there are few data concerning the effects of menstrual cycle phase on the neurobiology of emotional processing in humans. This neuroimaging study specifically probes emotion and limbic activity across the menstrual cycle in women carefully characterized as having no premenstrual mood symptoms. Our results implicate the orbitofrontal cortex (OFC) as a key limbic region in which activity in response to emotional stimuli and behavioral demands is influenced by menstrual cycle phase.Damage to the OFC has long been associated with socioemotional dyscontrol (1-4). Patients with OFC lesions are prone to disadvantageous decision-making, perhaps because of an inability to evoke appropriate somatic-feeling states that would inform advantageous response selection. The OFC has been implicated in inhibitory control and emotional regulation, and has been hypothesized to have a specific role in emotion-influenced decision making (5-7).There is abundant evidence for OFC involvement in motivational operations (8). Rapid stimulus-reinforcement association learning is implemented in the OFC (8), and the OFC is important for the alteration of stimulus-reward associations (9). The OFC appears to respond to the pleasantness of some stimuli (10, 11) as well as to the unpleasantness of other stimuli (8,(12)(13)(14)(15).Regarding emotional processing, a metaanalysis of functional neuroimaging studies on OFC function supports a medio-lateral gradient for representation of positive and negative stimuli, respectively, and an anterio-posterior gradient for complex (higher-order͞ polymodal) and simple (lower-order͞unimodal) stimuli, respectively (16). However, some studies have found medial OFC activity to negative stimuli or lateral OFC activity to positive stimuli (17)(18)(19). Key issues in understanding these discrepancies include sensory modalities of presented stimuli, stimulus characteristics that may confound valence differences, and individu...