Social reward processing in depressed and healthy individuals across the lifespan: A systematic review and a preliminary coordinate-based meta-analysis of fMRI studies.

BACKGROUND: Social rewards (e.g., social feedback, praise, and social interactions) are fundamental to social learning and relationships across the life span. Exposure to social rewards is linked to activation in key brain regions, that are impaired in major depression. This is the first summary of neuroimaging literature on social reward processing in depressed and healthy individuals. METHOD: We screened 409 studies and identified 25 investigating task-based fMRI activation during exposure to social stimuli in depressed and healthy populations across the lifespan. We conducted a systematic review followed by an Activation Likelihood Estimation (ALE) analysis of three main contrasts: a) positive social feedback vs. neutral stimuli; b) negative social feedback vs. neutral stimuli; c) positive vs. negative social feedback. We also compared activation patterns in depressed versus healthy controls. RESULTS: Systematic review revealed that social rewards elicit increased activation in subcortical reward regions (NAcc, amygdala, ventral striatum, thalamus) in healthy and depressed individuals; and decreased activation in prefrontal reward regions (medial prefrontal cortex, orbitofrontal cortex) among depressed persons. Our meta-analysis showed, in both depressed and healthy individuals, increased cluster activation of the putamen and caudate in response to negative social stimuli vs. positive stimuli. We also found increased cluster activation in the inferior frontal gyrus (IFG) and the medial frontal gyrus (MFG) in healthy controls vs. depressed individuals, in response to negative social stimuli. CONCLUSIONS: Processing of social stimuli elicits activation of key brain regions involved in affective and social information processing. Interventions for depression can increase social reward responsivity to improve outcomes.

Expansion of a frontostriatal salience network in individuals with depression.

Hundreds of neuroimaging studies spanning two decades have revealed differences in brain structure and functional connectivity in depression, but with modest effect sizes, complicating efforts to derive mechanistic pathophysiologic insights or develop biomarkers. 1 Furthermore, although depression is a fundamentally episodic condition, few neuroimaging studies have taken a longitudinal approach, which is critical for understanding cause and effect and delineating mechanisms that drive mood state transitions over time. The emerging field of precision functional mapping using densely-sampled longitudinal neuroimaging data has revealed unexpected, functionally meaningful individual differences in brain network topology in healthy individuals, 2-5 but these approaches have never been applied to individuals with depression. Here, using precision functional mapping techniques and 11 datasets comprising n=187 repeatedly sampled individuals and >21,000 minutes of fMRI data, we show that the frontostriatal salience network is expanded two-fold in most individuals with depression. This effect was replicable in multiple samples, including large-scale, group-average data (N=1,231 subjects), and caused primarily by network border shifts affecting specific functional systems, with three distinct modes of encroachment occurring in different individuals. Salience network expansion was unexpectedly stable over time, unaffected by changes in mood state, and detectable in children before the subsequent onset of depressive symptoms in adolescence. Longitudinal analyses of individuals scanned up to 62 times over 1.5 years identified connectivity changes in specific frontostriatal circuits that tracked fluctuations in specific symptom domains and predicted future anhedonia symptoms before they emerged. Together, these findings identify a stable trait-like brain network topology that may confer risk for depression and mood-state dependent connectivity changes in frontostriatal circuits that predict the emergence and remission of depressive symptoms over time.

Comparison of Functional and Structural Neural Network Features in Older Adults With Depression With vs Without Apathy and Association With Response to Escitalopram: Secondary Analysis of a Nonrandomized Clinical Trial.

Importance: Apathy is prevalent among individuals with late-life depression and is associated with poor response to pharmacotherapy, including chronicity and disability. Elucidating brain networks associated with apathy and poor treatment outcomes can inform intervention development. Objectives: To assess the brain network features of apathy among individuals with late-life depression and identify brain network abnormalities associated with poor antidepressant response. Design, Setting, and Participants: This secondary analysis of a single-group, open-label nonrandomized clinical trial of escitalopram conducted at an outpatient geriatric psychiatry clinic enrolled 40 adults aged 59 to 85 years with major depressive disorder from July 1, 2012, to July 31, 2019. Interventions: After a 2-week washout period, participants received escitalopram titrated to a target of 20 mg/d for 12 weeks. Main Outcomes and Measures: Baseline and posttreatment magnetic resonance imaging (MRI), clinical, and cognitive assessments were conducted. Functional MRI was used to map group differences in resting state functional connectivity (rsFC) of the salience network, and diffusion MRI connectometry was performed to evaluate pathway-level disruptions in structural connectivity. The Apathy Evaluation Scale was used to quantify apathy, and the Hamilton Depression Rating Scale (HAM-D) was used to quantify the primary outcome of depression severity. Results: Forty participants (26 women [65%]; mean [SD] age, 70.0 [6.6] years [range, 59-85 years]) with depression were included; 20 participants (50%) also had apathy. Relative to nonapathetic participants with depression, those with depression and apathy had lower rsFC of salience network seeds with the dorsolateral prefrontal cortex (DLPFC), premotor cortex, midcingulate cortex, and paracentral lobule and greater rsFC with the lateral temporal cortex and temporal pole (z score >2.7; Bonferroni-corrected threshold of P < .0125). Compared with participants without apathy, those with apathy had lower structural connectivity in the splenium, cingulum, and fronto-occipital fasciculus (t score >2.5; false discovery rate-corrected P = .02). Twenty-seven participants completed escitalopram treatment; 16 (59%) achieved remission (HAM-D score <10). Lower insula-DLPFC/midcingulate cortex rsFC was associated with less symptomatic improvement (HAM-D % change) (ß [df] = 0.588 [26]; P = .001) and a higher likelihood of nonremission (odds ratio, 1.041 [95% CI, 1.003-1.081]; P = .04) after treatment and, in regression models, was a mediator of the association between baseline apathy and persistence of depression. Lower dorsal anterior cingulate-DLPFC/paracentral rsFC was associated with residual cognitive difficulties on measures of attention (ß [df] = 0.445 [26]; P = .04) and executive function (ß [df] = 0.384 [26]; P = .04). Conclusions and Relevance: This study suggests that disturbances in connectivity between the salience network and other large-scale networks that support goal-directed behavior may give rise to apathy and may be associated with poor response of late-life depression to antidepressant pharmacotherapy. These network disturbances may serve as targets for novel interventions. Trial Registration: ClinicalTrials.gov Identifier: NCT01728194.

Estimated Regional White Matter Hyperintensity Burden, Resting State Functional Connectivity, and Cognitive Functions in Older Adults.

OBJECTIVE: White matter hyperintensities (WMH) are linked to deficits in cognitive functioning, including cognitive control and memory; however, the structural, and functional mechanisms are largely unknown. We investigated the relationship between estimated regional disruptions to white matter fiber tracts from WMH, resting state functional connectivity (RSFC), and cognitive functions in older adults. DESIGN: Cross-sectional study. SETTING: Community. PARTICIPANTS: Fifty-eight cognitively-healthy older adults. MEASUREMENTS: Tasks of cognitive control and memory, structural MRI, and resting state fMRI. We estimated the disruption to white matter fiber tracts from WMH and its impact on gray matter regions in the cortical and subcortical frontoparietal network, default mode network, and ventral attention network by overlaying each subject's WMH mask on a normative tractogram dataset. We calculated RSFC between nodes in those same networks. We evaluated the interaction of regional WMH burden and RSFC in predicting cognitive control and memory. RESULTS: The interaction of estimated regional WMH burden and RSFC in cortico-striatal regions of the default mode network and frontoparietal network was associated with delayed recall. Models predicting working memory, cognitive inhibition, and set-shifting were not significant. CONCLUSION: Findings highlight the role of network-level structural and functional alterations in resting state networks that are related to WMH and impact memory in older adults.

A digital intervention targeting cognitive control network dysfunction in middle age and older adults with major depression.

Nonpharmacological interventions targeting putative network mechanisms of major depressive disorder (MDD) may represent novel treatments. This mechanistic study investigates how a video game-like intervention, designed to improve cognitive control network (CCN) functioning by targeting multitasking, influences the CCN of middle-aged and older adults with MDD. The sample consisted of 34 adults aged 45-75 with SCID-defined diagnosis of MDD, Hamilton depression rating scale scores ≥20, and a deficit in cognitive control. Participants were instructed to play at home for 20-25 min per day, at least 5 times per week, for 4 weeks. Evidence of target engagement was defined a priori as >2/3 of participants showing CCN improvement. CCN engagement was defined as a change in a Z score of ≥0.5 on functional magnetic resonance imaging (fMRI) in activation and functional connectivity of the CCN during task-based and resting-state fMRI, respectively. 74% of participants showed a change in activation of the CCN, and 72% showed an increase in resting-state functional connectivity. Sixty-eight percent demonstrated improved cognitive control function, measured as either improvement on sustained attention or working memory performance or reduced self-reported symptoms of apathy on the frontal systems behavioral scale (FrsBe). Participants also reported a significant reduction in mood symptoms measured by PHQ-9. A remotely deployed neuroscience-informed video game-like intervention improves both CCN functions and mood in middle-aged and older adults with MDD. This easily-disseminated intervention may rescue CCN dysfunction present in a substantial subset of middle-aged and older adults with MDD.

Brain-based mechanisms of late-life depression: Implications for novel interventions.

Late-life depression (LLD) is a particularly debilitating illness. Older adults suffering from depression commonly experience poor outcomes in response to antidepressant treatments, medical comorbidities, and declines in daily functioning. This review aims to further our understanding of the brain network dysfunctions underlying LLD that contribute to disrupted cognitive and affective processes and corresponding clinical manifestations. We provide an overview of a network model of LLD that integrates the salience network, the default mode network (DMN) and the executive control network (ECN). We discuss the brain-based structural and functional mechanisms of LLD with an emphasis on their link to clinical subtypes that often fail to respond to available treatments. Understanding the brain networks that underlie these disrupted processes can inform the development of targeted interventions for LLD. We propose behavioral, cognitive, or computational approaches to identifying novel, personalized interventions that may more effectively target the key cognitive and affective symptoms of LLD.

Accelerated brain aging predicts impulsivity and symptom severity in depression.

Multiple structural and functional neuroimaging measures vary over the course of the lifespan and can be used to predict chronological age. Accelerated brain aging, as quantified by deviations in the MRI-based predicted age with respect to chronological age, is associated with risk for neurodegenerative conditions, bipolar disorder, and mortality. Whether age-related changes in resting-state functional connectivity are accelerated in major depressive disorder (MDD) is unknown, and, if so, it is unclear if these changes contribute to specific cognitive weaknesses that often occur in MDD. Here, we delineated age-related functional connectivity changes in a large sample of normal control subjects and tested whether brain aging is accelerated in MDD. Furthermore, we tested whether accelerated brain aging predicts individual differences in cognitive function. We trained a support vector regression model predicting age using resting-state functional connectivity in 710 healthy adults aged 18-89. We applied this model trained on normal aging subjects to a sample of actively depressed MDD participants (n = 109). The difference between predicted brain age and chronological age was 2.11 years greater (p = 0.015) in MDD patients compared to control participants. An older MDD brain age was significantly associated with increased impulsivity and, in males, increased depressive severity. Unexpectedly, accelerated brain aging was also associated with increased placebo response in a sham-controlled trial of high-frequency repetitive transcranial magnetic stimulation targeting the dorsomedial prefrontal cortex. Our results indicate that MDD is associated with accelerated brain aging, and that accelerated aging is selectively associated with greater impulsivity and depression severity.

Resting State Functional Connectivity and Outcomes of Psychotherapies for Late-Life Depression.

BACKGROUND: Problem solving therapy (PST) and "Engage," a reward-exposure" based therapy, are important treatment options for late-life depression, given modest efficacy of antidepressants in this disorder. Abnormal function of the reward and default mode networks has been observed during depressive episodes. This study examined whether resting state functional connectivity (rsFC) of reward and DMN circuitries is associated with treatment outcomes. METHODS: Thirty-two older adults with major depression (mean age = 72.7) were randomized to 9-weeks of either PST or "Engage." We assessed rsFC at baseline and week 6. We placed seeds in three a priori regions of interest: subgenual anterior cingulate cortex (sgACC), dorsal anterior cingulate cortex (dACC), and nucleus accumbens (NAcc). Outcome measures included the Hamilton Depression Rating Scale (HAMD) and the Behavioral Activation for Depression Scale (BADS). RESULTS: In both PST and "Engage," higher rsFC between the sgACC and middle temporal gyrus at baseline was associated with greater improvement in depression severity (HAMD). Preliminary findings suggested that in "Engage" treated participants, lower rsFC between the dACC and dorsomedial prefrontal cortex at baseline was associated with HAMD improvement. Finally, in Engage only, increased rsFC from baseline to week 6 between NAcc and Superior Parietal Cortex was associated with increased BADS scores. CONCLUSION: The results suggest that patients who present with higher rsFC between the sgACC and a structure within the DMN may benefit from behavioral psychotherapies for late life depression. "Engage" may lead to increased rsFC within the reward system reflecting a reconditioning of the reward systems by reward exposure.

Cognitive Control Network Homogeneity and Executive Functions in Late-Life Depression.

BACKGROUND: Late-life depression is characterized by network abnormalities, especially within the cognitive control network. We used alternative functional connectivity approaches, regional homogeneity (ReHo) and network homogeneity, to investigate late-life depression functional homogeneity. We examined the association between cognitive control network homogeneity and executive functions. METHODS: Resting-state functional magnetic resonance imaging data were analyzed for 33 older adults with depression and 43 healthy control subjects. ReHo was performed as the correlation between each voxel and the 27 neighbor voxels. Network homogeneity was calculated as global brain connectivity restricted to 7 networks. T-maps were generated for group comparisons. We measured cognitive performance and executive functions with the Dementia Rating Scale, Trail-Making Test (A and B), Stroop Color Word Test, and Digit Span Test. RESULTS: Older adults with depression showed increased ReHo in the bilateral dorsal anterior cingulate cortex (dACC) and the right middle temporal gyrus, with no significant findings for network homogeneity. Hierarchical linear regression models showed that higher ReHo in the dACC predicted better performance on Trail-Making Test B (p < .001; R2 = .49), Digit Span Backward (p < .05; R2 = .23), and Digit Span Total (p < .05; R2 = .23). Used as a seed, the dACC cluster of higher ReHo showed lower functional connectivity with bilateral precuneus. CONCLUSIONS: Higher ReHo within the dACC and right middle temporal gyrus distinguish older adults with depression from control subjects. The correlations with executive function performance support increased ReHo in the dACC as a meaningful measure of the organization of the cognitive control network and a potential compensatory mechanism. Lower functional connectivity between the dACC and the precuneus in late-life depression suggests that clusters of increased ReHo may be functionally segregated.

The relative contributions of visual and semantic information in the neural representation of object categories.

INTRODUCTION: How do multiple sources of information interact to form mental representations of object categories? It is commonly held that object categories reflect the integration of perceptual features and semantic/knowledge-based features. To explore the relative contributions of these two sources of information, we used functional magnetic resonance imaging (fMRI) to identify regions involved in the representation object categories with shared visual and/or semantic features. METHODS: Participants (N = 20) viewed a series of objects that varied in their degree of visual and semantic overlap in the MRI scanner. We used a blocked adaptation design to identify sensitivity to visual and semantic features in a priori visual processing regions and in a distributed network of object processing regions with an exploratory whole-brain analysis. RESULTS: Somewhat surprisingly, within higher-order visual processing regions-specifically lateral occipital cortex (LOC)-we did not obtain any difference in neural adaptation for shared visual versus semantic category membership. More broadly, both visual and semantic information affected a distributed network of independently identified category-selective regions. Adaptation was seen a whole-brain network of processing regions in response to visual similarity and semantic similarity; specifically, the angular gyrus (AnG) adapted to visual similarity and the dorsomedial prefrontal cortex (DMPFC) adapted to both visual and semantic similarity. CONCLUSIONS: Our findings suggest that perceptual features help organize mental categories throughout the object processing hierarchy. Most notably, visual similarity also influenced adaptation in nonvisual brain regions (i.e., AnG and DMPFC). We conclude that category-relevant visual features are maintained in higher-order conceptual representations and visual information plays an important role in both the acquisition and neural representation of conceptual object categories.

The impact of white matter hyperintensities on the structural connectome in late-life depression: Relationship to executive functions.

BACKGROUND: White matter hyperintensities (WMH) represent ischemic white matter damage in late-life depression (LLD) and are associated with cognitive control dysfunction. Understanding the impact of WMH on the structural connectivity of gray matter and the cognitive control correlates of WMH-related structural dysconnectivity can provide insight into the pathophysiology of LLD. METHODS: We compared WMH burden and performance on clinical measures of cognitive control in patients with LLD (N = 44) and a control group of non-depressed older adults (N = 59). We used the Network Modification (NeMo) Tool to investigate the impact of WMH on structural dysconnectivity in specific gray matter regions, and how such connectivity was related to cognitive control functions. RESULTS: Compared to the control group, LLD participants had greater WMH burden, poorer performance on Trail Making Test (TMT) A & B, and greater self-reported dysexecutive behavior on the Frosntal Systems Behavior Scale-Executive Function subscale (FrSBe-EF). Within the LLD group, disrupted connectivity in the left supramarginal gyrus, paracentral lobule, thalamus, and pallidum was associated with psychomotor slowing (TMT-A). Altered connectivity in the left supramarginal gyrus, paracentral lobule, precentral gyrus, postcentral gyrus, thalamus, and pallidum was associated with poor attentional set-shifting (TMT-B). A follow-up analysis that isolated set-shifting ability (TMT-B/A ratio) confirmed the association with dysconnectivity in the bilateral paracentral lobule, right thalamus, left precentral gyrus, postcentral gyrus, and pallidum; additionally, it revealed associations with dysconnectivity in the right posterior cingulate, and left anterior cingulate, middle frontal cortex, and putamen. CONCLUSIONS: In LLD, WMH are associated with region-specific disruptions in cortical and subcortical gray matter areas involved in attentional aspects of cognitive control systems and sensorimotor processing, which in turn are associated with slower processing speed, and reduced attentional set-shifting. CLINICAL TRIALS REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01728194.

White matter abnormalities predict residual negative self-referential thinking following treatment of late-life depression with escitalopram: A preliminary study.

BACKGROUND: Negative self-referential thinking is a common symptom of depression associated with poor treatment response. In late-life depression, white matter abnormalities may contribute to negative self-referential thoughts following antidepressant treatment. We investigated the association of fractional anisotropy (FA) in select regions of the negative valence system (NVS) with residual negative self-referential thoughts following treatment with escitalopram for late-life depression. METHODS: The participants were older adults with major depression and psychiatrically normal controls. Depressed participants received 12 weeks of treatment with escitalopram. To assess self-referential thinking, participants completed a Trait Adjective Task at baseline and at week 12. Baseline MRI scans included a diffusion imaging sequence for FA analyses. RESULTS: Participants with late-life depression differed from controls on all performance measures of the Trait Adjective Task at baseline and at 12 weeks. Depressed participants endorsed fewer negative personality traits and more positive personality traits at week 12 compared to baseline. Lower FA in the dorsal anterior cingulate and in the uncinate fasciculus in depressed participants was correlated with residual negative self-referential thinking (e.g., more endorsed negative adjectives, fewer rejected negative adjectives) at treatment end. LIMITATIONS: The sample size is modest so the findings are preliminary. FA analyses were restricted to predetermined regions. CONCLUSIONS: Negative self-referential thinking improved in depressed older adults following 12 weeks of treatment with escitalopram. Baseline FA in select white matter regions of the NVS was associated with residual negative self-referential thinking. These findings may help identify treatment targets for residual negative self-referential thoughts.

Reward learning impairment and avoidance and rumination responses at the end of Engage therapy of late-life depression.

OBJECTIVES: This study examined the association between reward processing, as measured by performance on the probabilistic reversal learning (PRL) task and avoidance/rumination in depressed older adults treated with Engage, a psychotherapy that uses "reward exposure" to increase behavioral activation. METHODS: Thirty older adults with major depression received 9 weeks of Engage treatment. At baseline and treatment end, the 24-item Hamilton Depression Rating Scale (HAM-D) was used to assess depression severity and the Behavioral Activation for Depression Scale (BADS) to assess behavioral activation and avoidance/rumination. Participants completed the PRL task at baseline and at treatment end. The PRL requires participants to learn stimulus-reward contingencies through trial and error, and switch strategies when the contingencies unexpectedly change. RESULTS: At the end of Engage treatment, the severity of depression was lower (HAM-D: t(19) = -7.67, P < .001) and behavioral activation was higher (BADS: t(19) = 2.23, P = .02) compared to baseline. Response time following all switches (r(19) = -0.63, P = .003) and error switches (r(19) = -0.57, P = .01) at baseline was negatively associated with the BADS avoidance/rumination subscale score at the end of Engage treatment. CONCLUSIONS: Impaired reward learning, evidenced by slower response following all switches and error switches, contributes to avoidant, ruminative behavior at the end of Engage therapy even when depression improves. Understanding reward processing abnormalities of avoidance and rumination may improve the timing and targeting of interventions for these symptoms, whose persistence compromises quality of life and increases the risk of depression relapse.

Age-Related Repetitive Transcranial Magnetic Stimulation Effects on Executive Function in Depression: A Systematic Review.

OBJECTIVE: The aims of the current review were to: 1) examine whether the rTMS effects on executive function increase as age advances; 2) to examine the potential of rTMS to remediate executive function in older depressed patients; and 3) to assess the relationship between the executive function and mood benefits from rTMS in depression. METHODS: Randomized or matched-groups, blind, sham-controlled studies (12 studies, 347 participants) on excitatory rTMS applied to left DLPFC in depression were reviewed. RESULTS: A series of meta-regressions found no evidence of greater rTMS effects on executive functions as age advances. Similarly, meta-analyses showed no significant rTMS effects on executive functions in older depressed individuals. However, meta-regression analyses showed that the size of the executive function benefits from rTMS in depression are positively related to the effect size of mood symptom reduction. Despite its correlational nature, this finding is consistent with the idea that improvement in executive function may play a critical role in depression recovery. CONCLUSIONS: The authors consider these findings preliminary because of the modest number of available studies. Based on a qualitative review, the authors describe methodologic modifications that may increase rTMS efficacy for both executive functions and mood in late-life depression.

"Engage" therapy: Prediction of change of late-life major depression.

OBJECTIVE: Engage grew out of the need for streamlined psychotherapies that can be accurately used by community therapists in late-life depression. Engage was based on the view that dysfunction of reward networks is the principal mechanism mediating depressive symptoms. Accordingly, Engage uses "reward exposure" (exposure to meaningful activities) and assumes that repeated activation of reward networks will normalize these systems. This study examined whether change in a behavioral activation scale, an index of reward system function, predicts change in depressive symptomatology. METHODS: The participants (N = 48) were older adults with major depression treated with 9 weekly sessions of Engage and assessed 27 weeks after treatment. Depression was assessed with the 24-item Hamilton Depression Rating Scale (HAM-D) and behavioral activation with the four subscales of Behavioral Activation for Depression Scale (activation, avoidance/rumination, work impairment, social impairment) at baseline, 6 weeks (mid-treatment), 9 weeks (end of treatment), and 36 weeks. RESULTS: Change only in the Activation subscale during successive periods of assessment predicted depression severity (HAM-D) at the end of each period (F1, 47 = 21.05, p<0.0001). An increase of one standard deviation in the Activation score resulted in a 2.04 (95% CI: 1.17-2.92) point decrease in HAM-D. For every one point increase in the Activation score, HAM-D was decreased by 0.22 points (95% CI: 0.12-0.31). LIMITATIONS: No comparison group. Partial overlap of Activation Subscale with HAM-D, lack of detailed neurocognitive assessment and social support. CONCLUSION: Change in behavioral activation predicts improvement of depressive symptoms and signs in depressed older adults treated with Engage.

Improvement in Depression is Associated with Improvement in Cognition in Late-Life Psychotic Depression.

OBJECTIVE: To characterize cognitive function at baseline and investigate the relationship between change in cognition, depression, and psychosis after treatment among older adults with major depressive disorder with psychotic features. METHODS: This was a secondary analysis of a double-blind, randomized, controlled treatment trial at inpatient and outpatient settings at four academic health centers on "Young Old" (aged 60-71 years, N = 71) and "Older" (aged 72-86 years, N = 71) participants diagnosed with psychotic depression. Olanzapine plus sertraline or olanzapine plus placebo were given until week 12 or termination. RESULTS: At baseline, Young Old and Older participants did not differ on measures of depression severity or global cognition, information processing speed, and executive function. Improvement in depressive and psychotic symptoms from baseline to treatment end was similar in both the Young Old and Older groups. However, improvement in depressive symptoms was significantly associated with improvement in global cognitive function in Young Old participants but not in Older participants. CONCLUSION: Cognitive dysfunction was not a detriment to improvement in symptoms of psychotic major depression in our geriatric patients. Young Old and Older patients improved to a similar degree on measures of depression and delusions from baseline to treatment end. However, improvement in cognition over the course of treatment was more prominent in the Young Old group than in the Older group.

The mother as hunter: significant reduction in foraging costs through enhancements of predation in maternal rats.

In previous laboratory investigations, we have identified enhanced cognition and reduced stress in parous rats, which are likely adaptations in mothers needing to efficiently exploit resources to maintain, protect and provision their immature offspring. Here, in a series of seven behavioral tests on rats, we examined a natural interface between cognition and resource gathering: predation. Experiment 1 compared predatory behavior (toward crickets) in age-matched nulliparous mothers (NULLs) and postpartum lactating mothers (LACTs), revealing a highly significant enhancement of predation in LACT females (mean = -65s in LACTs, vs. -270s in NULLs). Experiment 2 examined the possibility that LACTs, given their increased metabolic rate, were hungrier, and thus more motivated to hunt; doubling the length of time of food deprivation in NULLs did not decrease their predatory latencies. Experiments 3-5, which examined sensory regulation of the effect, indicated that olfaction (anosmia), audition (blockade with white noise), and somatosensation (trimming the vibrissae) appear to play little role in the behavioral enhancement observed in the LACTs; Experiment 6 examined the possibility that visual augmentations may facilitate the improvements in predation; testing LACTs in a 0-lux environment eliminated the behavioral advantage (increasing their latencies from -65s to -212s), which suggests that temporary augmentation to the visual system may be important, and with hormone-neural alterations therein a likely candidate for further study. In contrast, testing NULLS in the 0-lux environment had the opposite effect, reducing their latency to catch the cricket (from -270s to -200s). Finally, Experiment 7 examined the development of predatory behavior in Early-pregnant (PREG), Mid-PREG, and Late-PREG females. Here, we observed a significant enhancement of predation in Mid-PREG and Late-PREG females--at a time when maternity-associated bodily changes would be expected to diminish predation ability--relative to NULLs. Therefore, as with the increasing reports of enhancements to the maternal brain, it is apparent that meaningful behavioral adaptations occur that likewise promote the survival of the mother and her infants at a crucial stage of their lives.

Why it's easier to remember seeing a face we already know than one we don't: preexisting memory representations facilitate memory formation.

In two experiments, we provided support for the hypothesis that stimuli with preexisting memory representations (e.g., famous faces) are easier to associate to their encoding context than are stimuli that lack long-term memory representations (e.g., unknown faces). Subjects viewed faces superimposed on different backgrounds (e.g., the Eiffel Tower). Face recognition on a surprise memory test was better when the encoding background was reinstated than when it was swapped with a different background; however, the reinstatement advantage was modulated by how many faces had been seen with a given background, and reinstatement did not improve recognition for unknown faces. The follow-up experiment added a drug intervention that inhibited the ability to form new associations. Context reinstatement did not improve recognition for famous or unknown faces under the influence of the drug. The results suggest that it is easier to associate context to faces that have a preexisting long-term memory representation than to faces that do not.