Neurite density of the hippocampus is associated with trace eyeblink conditioning latency in 4- to 6-year-olds.

Limited options exist to evaluate the development of hippocampal function in young children. Research has established that trace eyeblink conditioning (EBC) relies on a functional hippocampus. Hence, we set out to investigate whether trace EBC is linked to hippocampal structure, potentially serving as a valuable indicator of hippocampal development. Our study explored potential associations between individual differences in hippocampal volume and neurite density with trace EBC performance in young children. We used onset latency of conditioned responses (CR) and percentage of conditioned responses (% CR) as measures of hippocampal-dependent associative learning. Using a sample of typically developing children aged 4 to 6 years (N = 30; 14 girls; M = 5.70 years), participants underwent T1- and diffusion-weighted MRI scans and completed a 15-min trace eyeblink conditioning task conducted outside the MRI. % CR and CR onset latency were calculated based on all trials involving tone-puff presentations and tone-alone trials. Findings revealed a connection between greater left hippocampal neurite density and delayed CR onset latency. Children with higher neurite density in the left hippocampus tended to blink closer to the onset of the unconditioned stimulus, indicating that structural variations in the hippocampus were associated with more precise timing of conditioned responses. No other relationships were observed between hippocampal volume, cerebellum volume or neurite density, hippocampal white matter connectivity and any EBC measures. Preliminary results suggest that trace EBC may serve as a straightforward yet innovative approach for studying hippocampal development in young children and populations with atypical development.

Nucleus Reuniens: Modulating Negative Overgeneralization in Periadolescents with Anxiety.

Background: Anxiety affects 4.4-million children in the United States with an onset between childhood and adolescence, a period marked by neural changes that impact emotions and memory. Negative overgeneralization - or responding similarly to innocuous events that share features with past aversive experiences - is common in anxiety but remains mechanistically underspecified. The nucleus reuniens (RE) has been considered a crucial candidate in the modulation of memory specificity. Our study investigated its activation and functional connectivity with the medial prefrontal cortex (mPFC) and hippocampus (HPC) as neurobiological mechanisms of negative overgeneralization in anxious youth. Methods: As part of a secondary data analysis, we examined data from 34 participants between 9-14 years (mean age ± SD, 11.4 ± 2.0 years, 16 females) with varying degrees of anxiety severity. During the Study session participants rated images as negative, neutral, and positive. After 12-hours, participants returned for a Test session, where they performed a memory recognition test with repeated (targets) and similar (lures) images. Labeling negative relative to neutral lures as "old" (false alarms) was our operational definition of negative overgeneralization. Results: Negative relative to neutral false alarmed stimuli displayed elevated RE activation (at Study and Test) and increased functional connectivity with the CA1 (at Test only). Elevated anxiety severity was associated with reductions in the RE-mPFC functional coupling for neutral relative to negative stimuli. Exploratory analyses revealed similar patterns in activation and functional connectivity with positive stimuli. Conclusions: Our findings demonstrate the importance of the RE in the overgeneralization of memories in anxious youth.

Towards a mechanistic understanding of the role of error monitoring and memory in social anxiety.

Cognitive models state social anxiety (SA) involves biased cognitive processing that impacts what is learned and remembered within social situations, leading to the maintenance of SA. Neuroscience work links SA to enhanced error monitoring, reflected in error-related neural responses arising from mediofrontal cortex (MFC). Yet, the role of error monitoring in SA remains unclear, as it is unknown whether error monitoring can drive changes in memory, biasing what is learned or remembered about social situations. Thus, we developed a novel paradigm to investigate the role of error-related MFC theta oscillations (associated with error monitoring) and memory biases in SA. EEG was collected while participants completed a novel Face-Flanker task, involving presentation of task-unrelated, trial-unique faces behind target/flanker arrows on each trial. A subsequent incidental memory assessment evaluated memory biases for error events. Severity of SA symptoms were associated with greater error-related theta synchrony over MFC, as well as between MFC and sensory cortex. SA was positively associated with memory biases for error events. Consistent with a mechanistic role in biased cognitive processing, greater error-related MFC-sensory theta synchrony during the Face-Flanker predicted subsequent memory biases for error events. Our findings suggest high SA individuals exhibit memory biases for error events, and that this behavioral phenomenon may be driven by error-related MFC-sensory theta synchrony associated with error monitoring. Moreover, results demonstrate the potential of a novel paradigm to elucidate mechanisms underlying relations between error monitoring and SA.

Differential effects of emotional valence on mnemonic performance with greater hippocampal maturity.

The hippocampal formation (HF) facilitates declarative memory, with subfields providing unique contributions to memory performance. Maturational differences across subfields facilitate a shift toward increased memory specificity, with peripuberty sitting at the inflection point. Peripuberty is also a sensitive period in the development of anxiety disorders. We believe HF development during puberty is critical to negative overgeneralization, a common feature of anxiety disorders. To investigate this claim, we examined the relationship between mnemonic generalization and a cross-sectional pubertal maturity index (PMI) derived from partial least squares correlation (PLSC) analyses of subfield volumes and structural connectivity from T1-weighted and diffusion-weighted scans, respectively. Participants aged 9-14 yr, from clinical and community sources, performed a recognition task with emotionally valent (positive, negative, and neutral) images. HF volumetric PMI was positively associated with generalization for negative images. Hippocampal-medial prefrontal cortex connectivity PMI evidenced a behavioral relationship similar to that of the HF volumetric approach. These findings reflect a novel developmentally related balance between generalization behavior supported by the hippocampus and its connections with other regions, with maturational differences in this balance potentially contributing to negative overgeneralization during peripuberty.

The impact of ADHD symptom severity on reinforcement and punishment learning among adults.

Introduction: Aberrations in feedback learning are hypothesised to contribute to the behavioural disruptions and impairment of attention-deficit/hyperactivity disorder (ADHD). However, few studies have evaluated the relation of reward/punishment feedback and ADHD symptom severity on learning. The current study evaluates the differential effects of reward and punishment feedback on learning among adults with elevated ADHD. Methods: One hundred five participants self-reported their level of current ADHD symptoms and completed an innovative instrumental learning task. Results: Consistent with predictions, participants with low self-reported ADHD symptom severity benefitted equally from reward and punishment feedback during the learning task, whereas participants with high self-reported symptom severity performed better (indexed by accuracy on learning task) from reward than punishment feedback trials. Conclusions: Overall, adults with high self-reported symptom severity of ADHD learned more from reward-based feedback, which provides critical implications for motivational theories about ADHD, as well as for treatment protocols. Future work should examine the translatability of results within a treatment setting.

Sleep fails to depotentiate amygdala-reactivity to negative emotional stimuli in youth with elevated symptoms of anxiety.

Sleep-related problems often precede escalating anxiety in early adolescence. Pushing beyond broad sleep-mental health associations and toward mechanistic theories of their interplay can inform etiological models of psychopathology. Recent studies suggest that sleep depotentiates neural (e.g., amygdala) reactivity during reexposure to negative emotional stimuli in adults. Persistent amygdala reactivity to negative experiences and poor sleep characterize anxiety, particularly at the transition to adolescence. We propose that sleep depotentiates amygdala reactivity in youth but fails to do so among youth with anxiety. Participants (n = 34; 18 males; age, mean [M] = 11.35, standard deviation [SD] = 2.00) recruited from the community and specialty anxiety clinics viewed valenced images (positive, negative, and neutral) across two fMRI sessions (Study, Test), separated by a 10-12-hour retention period of sleep or wake (randomized). Mixed linear models regressed basolateral amygdala (BLA) activation and BLA-medial prefrontal cortex (mPFC) functional connectivity to negative images on Time, Condition, and Anxiety Severity. There were greater reductions in BLA activations to negative target images from Study to Test in the Sleep Condition, which was blunted with higher anxiety (b = -0.065, z = -2.355, p = 0.019). No such sleep- or anxiety-related effects were observed for BLA-mPFC functional connectivity (ps > 0.05). Sleep supports depotentiation of amygdala reactivity to negative stimuli in youth, but this effect is blunted at higher levels of anxiety. Disruptions in sleep-related affective habituation may be a critical, modifiable driver of anxiety.

Identifying the midline thalamus in humans in vivo.

The midline thalamus is critical for flexible cognition, memory, and stress regulation in humans and its dysfunction is associated with several neurological and psychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. Despite the pervasive role of the midline thalamus in cognition and disease, there is a limited understanding of its function in humans, likely due to the absence of a rigorous noninvasive neuroimaging methodology to identify its location. Here, we introduce a new method for identifying the midline thalamus in vivo using probabilistic tractography and k-means clustering with diffusion weighted imaging data. This approach clusters thalamic voxels based on data-driven cortical and subcortical connectivity profiles and then segments the midline thalamus according to anatomical connectivity tracer studies in rodents and macaques. Results from two different diffusion weighted imaging sets, including adult data (22-35 years) from the Human Connectome Project (n = 127) and adolescent data (9-14 years) collected at Florida International University (n = 34) showed that this approach reliably classifies midline thalamic clusters. As expected, these clusters were most evident along the dorsal/ventral extent of the third ventricle and were primarily connected to the agranular medial prefrontal cortex (e.g., anterior cingulate cortex), nucleus accumbens, and medial temporal lobe regions. The midline thalamus was then bisected based on a human brain atlas into a dorsal midline thalamic cluster (paraventricular and paratenial nuclei) and a ventral midline thalamic cluster (rhomboid and reuniens nuclei). This anatomical connectivity-based identification of the midline thalamus offers the opportunity for necessary investigation of this region in vivo in the human brain and how it relates to cognitive functions in humans, and to psychiatric and neurological disorders.

More time awake after sleep onset is linked to reduced ventral striatum response to rewards in youth with anxiety.

BACKGROUND: Poor sleep and anxiety disorders are highly comorbid in youth, and each predicts altered ventral striatum (VS) response to rewards, which may impact mental health risk. Contrasting evidence suggests previously reported negative associations between sleep health and VS response may be stronger or weaker in youth with anxiety, indicating sensitivity to win/loss information or blunted reward processing, respectively. We cross-sectionally examined the role of sleep in VS response to rewards among youth with anxiety versus a no-psychiatric-diagnosis comparison (ND) group. We expected a group*sleep interaction on VS response to rewards but did not hypothesize directionality. METHODS: As part of the pretreatment battery for a randomized clinical trial, 74 youth with anxiety and 31 ND youth (ages 9-14 years; n = 55 female) completed a monetary reward task during fMRI. During the same pretreatment window, actigraphy and diary-estimated sleep were collected over 5 days, and participants and their parents each reported participants' total sleep problems. We examined group*sleep interactions on VS response to monetary rewards versus losses via three mixed linear models corresponding to actigraphy, diary, and questionnaires, respectively. RESULTS: Each model indicated group*sleep interactions on VS response to rewards. Actigraphy and diary-estimated time awake after sleep onset predicted reduced VS response in youth with anxiety but not ND youth. Parent-reported sleep problems similarly interacted with group, but simple slopes were nonsignificant. CONCLUSIONS: Wake after sleep onset was associated with blunted reward response in youth with anxiety. These data suggest a potential pathway through which sleep could contribute to perturbed reward function and reward-related psychopathology (e.g., depression) in youth with anxiety.

Volumetric development of hippocampal subfields and hippocampal white matter connectivity: Relationship with episodic memory.

The hippocampus is a complex structure composed of distinct subfields. It has been central to understanding neural foundations of episodic memory. In the current cross-sectional study, using a large sample of 830, 3- to 21-year-olds from a unique, publicly available dataset we examined the following questions: (1) Is there elevated grey matter volume of the hippocampus and subfields in late compared to early development? (2) How does hippocampal volume compare with the rest of the cerebral cortex at different developmental stages? and (3) What is the relation between hippocampal volume and connectivity with episodic memory performance? We found hippocampal subfield volumes exhibited a nonlinear relation with age and showed a lag in volumetric change with age when compared to adjacent cortical regions (e.g., entorhinal cortex). We also observed a significant reduction in cortical volume across older cohorts, while hippocampal volume showed the opposite pattern. In addition to age-related differences in gray matter volume, dentate gyrus/cornu ammonis 3 volume was significantly related to episodic memory. We did not, however, find any associations with episodic memory performance and connectivity through the uncinate fasciculus, fornix, or cingulum. The results are discussed in the context of current research and theories of hippocampal development and its relation to episodic memory.

Sleep to Internalizing Pathway in Young Adolescents (SIPYA): A proposed neurodevelopmental model.

The prevalence of internalizing disorders, i.e., anxiety and depressive disorders, spikes in adolescence and has been increasing amongst adolescents despite the existence of evidence-based treatments, highlighting the need for advancing theories on how internalizing disorders emerge. The current review presents a theoretical model, called the Sleep to Internalizing Pathway in Young Adolescents (SIPYA) Model, to explain how risk factors, namely sleep-related problems (SRPs), are prospectively associated with internalizing disorders in adolescence. Specifically, SRPs during late childhood and early adolescence, around the initiation of pubertal development, contribute to the interruption of intrinsic brain networks dynamics, both within the default mode network and between the default mode network and other networks in the brain. This interruption leaves adolescents vulnerable to repetitive negative thought, such as worry or rumination, which then increases vulnerability to internalizing symptoms and disorders later in adolescence. Sleep-related behaviors are observable, modifiable, low-stigma, and beneficial beyond treating internalizing psychopathology, highlighting the intervention potential associated with understanding the neurodevelopmental impact of SRPs around the transition to adolescence. This review details support for the SIPYA Model, as well as gaps in the literature and future directions.

Mind-Wandering and Childhood ADHD: Experimental Manipulations across Laboratory and Naturalistic Settings.

The conceptual overlap between mind-wandering and attention-deficit/hyperactivity disorder (ADHD)-related impairments is considerable, yet little experimental research examining this overlap among children is available. The current study aims to experimentally manipulate mind-wandering among children with and without ADHD and examine effects on task performance. Participants were 59 children with ADHD and 55 age-matched controls. Participants completed a novel mind-wandering sustained attention to response task (SART) that included non-self-referential and self-referential stimuli to experimentally increase self-referential mind-wandering, reflected by increases in reaction time variability (RTV) following self-referential stimuli. The ADHD group participated in a classroom study with analogue conditions aimed at encouraging self-referential future-oriented thinking (free play/movie before and after class work) compared to a control condition (newscast) and a cross-over methylphenidate trial. The significant interaction between ADHD status and self-referential stimuli on SART performance indicated that self-referential stimuli led to greater RTV among children with ADHD (within-subject d = 1.29) but not among controls. Methylphenidate significantly reduced RTV among youth with ADHD across self-referential (d = 1.07) and non-self-referential conditions (d = 0.72). In the ADHD classroom study, the significant interaction between mind-wandering condition and methylphenidate indicated that methylphenidate led to higher work completion (ds > 5.00), and the free-play mind-wandering condition had more consistent detrimental effects on productivity (ds ≥ 1.25) than the movie mind-wandering condition. This study is the first to manipulate mind-wandering and assess effects among children with ADHD using a behavioral task. Results provide evidence that children with ADHD are uniquely susceptible to mind-wandering interference.

General additive models address statistical issues in diffusion MRI: An example with clinically anxious adolescents.

Statistical models employed to test for group differences in quantized diffusion-weighted MRI white matter tracts often fail to account for the large number of data points per tract in addition to the distribution, type, and interdependence of the data. To address these issues, we propose the use of Generalized Additive Models (GAMs) and supply code and examples to aid in their implementation. Specifically, using diffusion data from 73 periadolescent clinically anxious and no-psychiatric-diagnosis control participants, we tested for group tract differences and show that a GAM allows for the identification of differences within a tract while accounting for the nature of the data as well as covariates and group factors. Further, we then used these tract differences to investigate their association with performance on a memory test. When comparing our high versus low anxiety groups, we observed a positive association between the left uncinate fasciculus and memory overgeneralization for negatively valenced stimuli. This same association was not evident in the right uncinate or anterior forceps. These findings illustrate that GAMs are well-suited for modeling diffusion data while accounting for various aspects of the data, and suggest that the adoption of GAMs will be a powerful investigatory tool for diffusion-weighted analyses.

Negative overgeneralization is associated with anxiety and mechanisms of pattern completion in peripubertal youth.

This study examines neural mechanisms of negative overgeneralization, the increased likelihood of generalizing negative information, in peri-puberty. Theories suggest that weak pattern separation [overlapping representations are made distinct, indexed by dentate gyrus/ cornu ammonis (CA)3 hippocampal subfield activation] underlies negative overgeneralization. We alternatively propose that neuro-maturational changes that favor pattern completion (cues reinstate stored representations, indexed by CA1 activation) are modulated by circuitry involved in emotional responding [amygdala, medial prefrontal cortices (mPFC)] to drive negative overgeneralization. Youth (n = 34, 9-14 years) recruited from community and clinic settings participated in an emotional mnemonic similarity task while undergoing magnetic resonance imaging. At study, participants indicated the valence of images; at test, participants made recognition memory judgments. Critical lure stimuli, which were similar to images at study, were presented at test, and errors ('false alarms') to negative relative to neutral stimuli reflected negative overgeneralization. Negative overgeneralization was related to greater and more similar patterns of activation in CA1 and both dorsal mPFC (dmPFC)and ventral mPFC (vmPFC) for negative relative to neutral stimuli. At study, amygdala exhibited greater functional coupling with CA1 and dmPFC during negative items that were later generalized. Negative overgeneralization is rooted in amygdala and mPFC modulation at encoding and pattern completion at retrieval.

Medial prefrontal cortex and hippocampal activity differentially contribute to ordinal and temporal context retrieval during sequence memory.

Remembering sequences of events defines episodic memory, but retrieval can be driven by both ordinality and temporal contexts. Whether these modes of retrieval operate at the same time or not remains unclear. Theoretically, medial prefrontal cortex (mPFC) confers ordinality, while the hippocampus (HC) associates events in gradually changing temporal contexts. Here, we looked for evidence of each with BOLD fMRI in a sequence task that taxes both retrieval modes. To test ordinal modes, items were transferred between sequences but retained their position (e.g., AB3). Ordinal modes activated mPFC, but not HC. To test temporal contexts, we examined items that skipped ahead across lag distances (e.g., ABD). HC, but not mPFC, tracked temporal contexts. There was a mPFC and HC by retrieval mode interaction. These current results suggest that the mPFC and HC are concurrently engaged in different retrieval modes in support of remembering when an event occurred.

Neural Correlates of Long-Term Memory Enhancement Following Retrieval Practice.

Retrieval practice, relative to further study, leads to long-term memory enhancement known as the "testing effect." The neurobiological correlates of the testing effect at retrieval, when the learning benefits of testing are expressed, have not been fully characterized. Participants learned Swahili-English word-pairs and were assigned randomly to either the Study-Group or the Test-Group. After a week delay, all participants completed a cued-recall test while undergoing functional magnetic resonance imaging (fMRI). The Test-Group had superior memory for the word-pairs compared to the Study-Group. While both groups exhibited largely overlapping activations for remembered word-pairs, following an interaction analysis the Test-Group exhibited differential performance-related effects in the left putamen and left inferior parietal cortex near the supramarginal gyrus. The same analysis showed the Study-Group exhibited greater activations in the dorsal MPFC/pre-SMA and bilateral frontal operculum for remembered vs. forgotten word-pairs, whereas the Test-Group showed the opposite pattern of activation in the same regions. Thus, retrieval practice during training establishes a unique striatal-supramarginal network at retrieval that promotes enhanced memory performance. In contrast, study alone yields poorer memory but greater activations in frontal regions.

Brief report: Evaluation of working memory deficits in children with ADHD using the NIH list sorting working memory task.

Variability in working memory (WM) task selection likely contributes to heterogeneity in effect size estimates of deficiencies in youth with attention-deficit/hyperactivity disorder (ADHD). This has resulted in the development of brief, easy to administer assessments such as the NIH List Sorting Working Memory (LSWM) task from the NIH Cognitive Toolbox in hopes of standardizing measurement of this construct. Unfortunately, substantial questions persist regarding the specific constructs being evaluated by this task (e.g., visuospatial [VS] or phonological [PH] WM) as well as the ability of this task to detect WM deficits in previously identified impaired groups (e.g., ADHD). The current study examines the extent to which the LSWM task is associated with VS and PHWM performance as well as symptoms of ADHD. Additionally, we examined the magnitude of differences between ADHD and Typically Developing (TD) youth on this task relative to empirically derived WM tasks utilized in the past. Forty-six children (25 ADHD, 21 TD) completed multiple WM tasks. The LSWM task was moderately associated with PHWM and demonstrated relatively weaker associations with VSWM. Symptoms of inattention and hyperactivity/impulsivity were unrelated to the LSWM task; whereas tasks assessing PH and VSWM were moderately associated with inattention and weakly associated with hyperactivity (VSWM only). No significant between-group differences in performance emerged on the LSWM task; however, significant large-magnitude group differences were observed on both the PH and VSWM tasks. These findings suggest that the LSWM task may lack the ability to detect WM difficulties in youth with ADHD.

Distinct Neural Circuits Underlie Prospective and Concurrent Memory-Guided Behavior.

The past is the best predictor of the future. This simple postulate belies the complex neurobiological mechanisms that facilitate an individual's use of memory to guide decisions. Previous research has shown integration of memories bias decision-making. Alternatively, memories can prospectively guide our choices. Here, we elucidate the mechanisms and timing of hippocampal (HPC), medial prefrontal cortex (mPFC), and striatal contributions during prospective memory-guided decision-making. We develop an associative learning task in which the correct choice is conditional on the preceding stimulus. Two distinct networks emerge: (1) a prospective circuit consisting of the HPC, putamen, mPFC, and other cortical regions, which exhibit increased activation preceding successful conditional decisions and (2) a concurrent circuit comprising the caudate, dorsolateral prefrontal cortex (dlPFC), and additional cortical structures that engage during the execution of correct conditional choices. Our findings demonstrate distinct neurobiological circuits through which memory prospectively biases decisions and influences choice execution.

Modulation of associative learning in the hippocampal-striatal circuit based on item-set similarity.

Mounting evidence suggests that the medial temporal lobe (MTL) and striatal learning systems support different forms of learning, which can be competitive or cooperative depending on task demands. We have previously shown how activity in these regions can be modulated in a conditional visuomotor associative learning task based on the consistency of response mappings or reward feedback (Mattfeld & Stark, 2015). Here, we examined the shift in learning towards the MTL and away from the striatum by placing strong demands on pattern separation, a process of orthogonalizing similar inputs into distinct representations. Mnemonically, pattern separation processes have been shown to rely heavily on processing in the hippocampus. Therefore, we predicted modulation of hippocampal activity by pattern separation demands, but no such modulation of striatal activity. Using a variant of the conditional visuomotor associative learning task that we have used previously, we presented participants with two blocked conditions: items with high and low perceptual overlap during functional magnetic resonance imaging (fMRI). As predicted, we observed learning-related activity in the hippocampus, which was greater in the high than the low overlap condition, particularly in the dentate gyrus. In contrast, the associative striatum also showed learning related activity, but it was not modulated by overlap condition. Using functional connectivity analyses, we showed that the correlation between the hippocampus and dentate gyrus with the associative striatum was differentially modulated by high vs. low overlap, suggesting that the coordination between these regions was affected when pattern separation demands were high. These findings contribute to a growing literature that suggests that the hippocampus and striatal network both contribute to the learning of arbitrary associations that are computationally distinct and can be altered by task demands.

Resting-State Functional Connectivity of the Subthalamic Nucleus to Limbic, Associative, and Motor Networks.

The subthalamic nucleus (STN) is a small structure situated deep in the midbrain that exhibits wide-ranging functionality. In addition to its role in motor control, the STN is considered a hub for synchronizing aspects of emotion and cognition including attention, inhibitory control, motivation, and working memory. Evidence from neuroanatomical tracer studies suggests that the medial, ventromedial, and dorsolateral parts of the STN correspond to limbic, associative, and motor subdivisions, respectively. Although the extent of STN functional anatomical overlap remains unclear, blood oxygenation level dependent imaging of the STN may provide complementary information about the diverse functions of this structure. Methodological limitations in spatial and temporal resolutions, however, have prevented a comprehensive exploration of temporal correlations from the STN to the whole brain. In this study, we optimize spatial (2 mm isotropic) and temporal (TR = 1 s) resolutions to take full advantage of the time series signal-to-noise ratio capabilities of multichannel array coils and simultaneous multislice imaging. We interrogated STN seed-to-voxel resting-state functional MRI connectivity in a group of 30 healthy participants that included the whole brain at high-temporal and spatial resolutions. This analysis revealed STN functional connectivity to limbic, associative, and motor networks. Our findings contribute to the understanding of STN functional neuroanatomy in humans and are clinically relevant for ongoing research in deep brain stimulation.

Human aging reduces the neurobehavioral influence of motivation on episodic memory.

The neural circuitry mediating the influence of motivation on long-term declarative or episodic memory formation is delineated in young adults, but its status is unknown in healthy aging. We examined the effect of reward and punishment anticipation on intentional declarative memory formation for words using an event-related functional magnetic resonance imaging (fMRI) monetary incentive encoding task in twenty-one younger and nineteen older adults. At 24-hour memory retrieval testing, younger adults were significantly more likely to remember words associated with motivational cues than neutral cues. Motivational enhancement of memory in younger adults occurred only for recollection ("remember" responses) and not for familiarity ("familiar" responses). Older adults had overall diminished memory and did not show memory gains in association with motivational cues. Memory encoding associated with monetary rewards or punishments activated motivational (substantia nigra/ventral tegmental area) and memory-related (hippocampus) brain regions in younger, but not older, adults during the target word periods. In contrast, older and younger adults showed similar activation of these brain regions during the anticipatory motivational cue interval. In a separate monetary incentive delay task that did not require learning, we found evidence for relatively preserved striatal reward anticipation in older adults. This supports a potential dissociation between incidental and intentional motivational processes in healthy aging. The finding that motivation to obtain rewards and avoid punishments had reduced behavioral and neural influence on intentional episodic memory formation in older compared to younger adults is relevant to life-span theories of cognitive aging including the dopaminergic vulnerability hypothesis.