Left Prefrontal Regions Research Articles

High neuromagnetic activation in the left prefrontal and frontal cortices correlates with better memory performance for abstract words

The present study aimed to clarify the spatiotemporal characteristics of memory processing for abstract and concrete words. Neuromagnetic responses to memory encoding and recognition tasks of abstract and concrete nouns were obtained in 18 healthy adults using a whole-head neuromagnetometer. During memory encoding, abstract words elicited larger responses in the left temporal area 300–500ms after the stimulus onset. The average peak latency of the right inferior frontal and left prefrontal responses to abstract words was about 70–85ms longer than that to concrete words. Furthermore, greater activation in the left inferior frontal and anterior prefrontal regions was correlated with better recognition memory for abstract words. These findings are consistent with the proposition that both word types are processed with differential integration of semantic information. The present results suggest that the left prefrontal and frontal regions play an important role in both semantic and memory processing for abstract words.

Accommodative response and cortical activity during sustained attention

Greater accommodative lag and vergence deficits have been linked to attentional deficits similar to those observed in Attention Deficit Hyperactivity Disorder (ADHD). The purpose of the present study was to assess the effect of accommodative–vergence stress on a measure of sustained attention (Conners CPT) used in the diagnosis of ADHD. Twenty-seven normal non-ADHD adults completed the Conners CPT twice: wearing −2.00 D lenses and normally (without the −2.00 D lenses) in a counterbalanced order with at least 24h between the sessions. Simultaneous recording of participants’ dynamic accommodative responses was performed from the right eye using the Grand Seiko WAM-5500 auto-refractor and electroencephalographic activity (EEG) in the left prefrontal region using the Neurosky Mindset headset. The results demonstrated a significantly greater accommodative lag in the −2.00 D stress condition and a significantly poorer performance on the Conners CPT as indexed by slower reaction time, greater standard error of hit reaction time, grater response variability, poorer stimulus detectability and a greater number of perseverations. No differences were observed on measures of EEG in the theta (4–7Hz), alpha (8–12Hz), and beta (12–20Hz) bands. Moreover, when directly juxtaposed with each EEG band in multiple linear regression analyses, greater accommodative lag in the stress condition was significantly associated with a greater probability of clinical classification on the Conners CPT, and was also marginally predictive of the number of omissions recorded in the stress condition. The results demonstrated that sustained attention can be influenced by such factors as accommodative–vergence stress and suggest that bottom-up processes can contribute to and potentially exacerbate attentional problems in individuals with ADHD. The study also showed that cortical dysfunction (while sufficient) may not be a necessary condition for attentional deficits.

Antipsychotic drug effects on left prefrontal phospholipid metabolism: A follow-up 31P-2D-CSI study of haloperidol and risperidone in acutely ill chronic schizophrenia patients

Introduction31Phosphorous magnetic resonance spectroscopy (2D chemical shift imaging, CSI) allows multiregional study of membrane phospholipids and high-energy phosphates in vivo. Increased membrane lipid turnover and impaired energy supply have repeatedly been shown in first-episode schizophrenia patients, and might be a target of drug actions other than dopamine receptors. Here, we explored differential metabolic effects of a typical vs. an atypical antipsychotic on brain phospholipids. MethodsWe applied 2D-CSI MR spectroscopy in 17 recurrent-episode schizophrenia patients off antipsychotics at baseline and at follow-up after 6weeks, during which 7 patients were treated with haloperidol (10–16mg/d) and 10 with risperidone (4–6mg/d). Psychopathology changes were assessed using PANSS, BPRS and CGI scores. ResultsFollow-up analysis using repeated measure ANOVA revealed different effects of both antipsychotic agents: while risperidone generally increased metabolite levels, haloperidol showed a tendency to decrease them. This diverging effect was significant for ATP levels in the left lateral frontal cortex. Furthermore, risperidone increased ATP in the left dorsolateral prefrontal cortex, left anterior temporal cortex and left insular cortex, basal ganglia, and anterior cerebellum, along with left frontal and prefrontal increase of PCr, PDE and PME in these brain regions. ConclusionRisperidone seems to stimulate neuronal and synaptic phospholipid remodeling in left frontal and prefrontal regions, and to a lesser extent also in temporal and insular cortices. We discuss these effects with respect to clinical effects on negative and cognitive symptoms, as well as interaction of phospholipid metabolism with glutamatergic neurotransmission.

Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder.

To date, electroconvulsive therapy (ECT) is the most potent treatment in severe depression. Although ECT has been successfully applied in clinical practice for over 70 years, the underlying mechanisms of action remain unclear. We used functional MRI and a unique data-driven analysis approach to examine functional connectivity in the brain before and after ECT treatment. Our results show that ECT has lasting effects on the functional architecture of the brain. A comparison of pre- and posttreatment functional connectivity data in a group of nine patients revealed a significant cluster of voxels in and around the left dorsolateral prefrontal cortical region (Brodmann areas 44, 45, and 46), where the average global functional connectivity was considerably decreased after ECT treatment (P < 0.05, family-wise error-corrected). This decrease in functional connectivity was accompanied by a significant improvement (P < 0.001) in depressive symptoms; the patients' mean scores on the Montgomery Asberg Depression Rating Scale pre- and posttreatment were 36.4 (SD = 4.9) and 10.7 (SD = 9.6), respectively. The findings reported here add weight to the emerging "hyperconnectivity hypothesis" in depression and support the proposal that increased connectivity may constitute both a biomarker for mood disorder and a potential therapeutic target.

Case report: A prototypical experience of ‘poltergeist’ activity, conspicuous quantitative electroencephalographic patterns, and sLORETA profiles – suggestions for intervention

People who report objects moving in their presence, unusual sounds, glows around other people, and multiple sensed presences but do not meet the criteria for psychiatric disorders have been shown to exhibit electrical anomalies over the right temporal lobes. This article reports the striking quantitative electroencephalography, sLORETA results, and experimental elicitation of similar subjective experiences in a middle-aged woman who has been distressed by these classic phenomena that began after a head injury. She exhibited a chronic electrical anomaly over the right temporoinsular region. The rotation of a small pinwheel near her while she ‘concentrated’ upon it was associated with increased coherence between the left and right temporal lobes and concurrent activation of the left prefrontal region. The occurrence of the unusual phenomena and marked ‘sadness’ was associated with increased geomagnetic activity; she reported a similar mood when these variations were simulated experimentally. Our quantitative measurements suggest people displaying these experiences and possible anomalous energies can be viewed clinically and potentially treated.

Transcranial Alternating Current Stimulation Increases Risk-Taking Behavior in the Balloon Analog Risk Task

The process of evaluating risks and benefits involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC). It has been proposed that in conflict and reward situations, theta-band (4–8 Hz) oscillatory activity in the frontal cortex may reflect an electrophysiological mechanism for coordinating neural networks monitoring behavior, as well as facilitating task-specific adaptive changes. The goal of the present study was to investigate the hypothesis that theta-band oscillatory balance between right and left frontal and prefrontal regions, with a predominance role to the right hemisphere (RH), is crucial for regulatory control during decision-making under risk. In order to explore this hypothesis, we used transcranial alternating current stimulation, a novel technique that provides the opportunity to explore the functional role of neuronal oscillatory activities and to establish a causal link between specific oscillations and functional lateralization in risky decision-making situations. For this aim, healthy participants were randomly allocated to one of three stimulation groups (LH stimulation/RH stimulation/Sham stimulation), with active AC stimulation delivered in a frequency-dependent manner (at 6.5 Hz; 1 mA peak-to-peak). During the AC stimulation, participants performed the Balloon Analog Risk Task. This experiment revealed that participants receiving LH stimulation displayed riskier decision-making style compared to sham and RH stimulation groups. However, there was no difference in decision-making behaviors between sham and RH stimulation groups. The current study extends the notion that DLPFC activity is critical for adaptive decision-making in the context of risk-taking and emphasis the role of theta-band oscillatory activity during risky decision-making situations.

“Tooth and Truth”: Brain Activation During Passive Listening to Concrete and Abstract Nouns

The aim of this functional magnetic resonance imaging (fMRI) study was to investigate brain activation associated with the auditory perception of concrete and abstract German nouns during a passive listening task. This procedure allows us to investigate inherent linguistic properties common to either concrete or abstract concepts rather than cognitive operations due to the performance of a given specific task. In addition, a new baseline condition (pseudo- speech) was used allowing us to monitor language-relevant activation common to both word types besides the pre-lexical analysis of the speech sound. Fixed effects analyses indicated increased activation of left hemispheric ventromedial prefrontal brain regions specifically responsive to the comprehension of concrete nouns by the current participants. This was interpreted in terms of the multisensory representation of concrete nouns comprising not only elicitation of visual images but also of multimodal sensoric and manipulation-related context. In contrast, abstract nouns did not activate any brain region exclusively. Random effects analyses revealed only very slight differences between concrete and abstract nouns in left ventromedial prefrontal brain activation. This suggests that the passive listening task is not suitable to canalize the higher cognitive variability in processing abstract items which seem to result in less coherent brain activation.

Prefrontal Cortex and Executive Function Impairments in Primary Breast Cancer

To examine differences in prefrontal-executive function between breast cancer (BC) survivors with and without a history of chemotherapy treatment compared with healthy control women and to determine the associations between prefrontal cortex deficits and behavioral impairments, as well as certain demographic and disease variables. Observational study. University-based research facility. Twenty-five women with BC who had received chemotherapy, 19 women with BC who had not received chemotherapy, and 18 healthy female controls, all matched for age and other demographic variables. Women with BC demonstrated significantly reduced activation in the left middle dorsolateral prefrontal cortex and premotor cortex compared with healthy controls. The chemotherapy group also demonstrated significantly reduced left caudal lateral prefrontal cortex activation and increased perseverative errors and reduced processing speed compared with the other 2 groups. Reduced left caudal lateral prefrontal cortex activation was significantly correlated with higher disease severity and elevated subjective executive dysfunction in the chemotherapy-treated women. Older age and lower educational level were associated with increased executive function impairment in the chemotherapy group. These findings provide further evidence of neurological impairment associated with primary BC irrespective of treatment history. The left caudal lateral prefrontal region may be particularly vulnerable to the effects of chemotherapy and/or disease severity and may represent a novel biomarker of subjective executive dysfunction in chemotherapy-treated women. Furthermore, negative effects of chemotherapy on brain function may be exacerbated by such factors as increased age and lower educational level.

How does a child solve 7 + 8? Decoding brain activity patterns associated with counting and retrieval strategies

Cognitive development and learning are characterized by diminished reliance on effortful procedures and increased use of memory-based problem solving. Here we identify the neural correlates of this strategy shift in 7-9-year-old children at an important developmental period for arithmetic skill acquisition. Univariate and multivariate approaches were used to contrast brain responses between two groups of children who relied primarily on either retrieval or procedural counting strategies. Children who used retrieval strategies showed greater responses in the left ventrolateral prefrontal cortex; notably, this was the only brain region which showed univariate differences in signal intensity between the two groups. In contrast, multivariate analysis revealed distinct multivoxel activity patterns in bilateral hippocampus, posterior parietal cortex and left ventrolateral prefrontal cortex regions between the two groups. These results demonstrate that retrieval and counting strategies during early learning are characterized by distinct patterns of activity in a distributed network of brain regions involved in arithmetic problem solving and controlled retrieval of arithmetic facts. Our findings suggest that the reorganization and refinement of neural activity patterns in multiple brain regions plays a dominant role in the transition to memory-based arithmetic problem solving. Our findings further demonstrate how multivariate approaches can provide novel insights into fine-scale developmental changes in the brain. More generally, our study illustrates how brain imaging and developmental research can be integrated to investigate fundamental aspects of neurocognitive development.

Dissociable brain states linked to common and creative object use.

Studies of conceptual processing have revealed that the prefrontal cortex is implicated in close-ended, deliberate memory retrieval, especially the left ventrolateral prefrontal regions. However, much of human thought-particularly that which is characterized as creative-requires more open-ended, spontaneous memory retrieval. To explore the neural systems that support conceptual processing under these two distinct circumstances, we obtained functional magnetic resonance images from 24 participants either while retrieving the common use of an everyday object (e.g., "blowing your nose," in response to a picture of a tissue) or while generating a creative (i.e., uncommon but plausible) use for it (e.g., "protective padding in a package"). The patterns of activation during open- and closed-ended tasks were reliably different, with regard to the magnitude of anterior versus posterior activation. Specifically, the close-ended task (i.e., Common Use task) reliably activated regions of lateral prefrontal cortex, whereas the open-ended task (i.e., Uncommon Use task) reliably activated regions of occipito-temporal cortex. Furthermore, there was variability across subjects in the types of responses produced on the open-ended task that was associated with the magnitude of activation in the middle occipital gyrus on this task. The present experiment is the first to demonstrate a dynamic tradeoff between anterior frontal and posterior occipitotemporal regions brought about by the close- or open-ended task demands.

Thinning of the Cerebral Cortex During Development: A Dimension of ADHD

Thinning of the Cerebral Cortex During Development: A Dimension of ADHD

Aberrant Brain Activation During a Working Memory Task in Psychotic Major Depression

The authors sought to better understand the neural circuitry associated with working memory deficits in psychotic major depression by examining brain function during an N-back task. Study subjects were 16 patients with psychotic major depression, 15 patients with nonpsychotic major depression, and 19 healthy comparison subjects. Functional MRI data were collected while participants responded to letter stimuli that were repeated from the previous trial (1-back) or the one before that (2-back). Relative to the healthy comparison group, both the psychotic and nonpsychotic major depression groups had significantly greater activation in the right parahippocampal gyrus during the 2-back task, and the psychotic major depression group showed this overactivation during the 1-back task as well. The nonpsychotic major depression group showed significantly lower activation than other groups in the right dorsolateral prefrontal cortex and greater activation than the healthy comparison group in the superior occipital cortex. The psychotic major depression group was unique in showing greater activation than both other groups in the right temporoparietal junction, a cluster that also demonstrated connectivity with activation in the left prefrontal cortex. The psychotic major depression group showed aberrant parahippocampal activation at a lower demand level than observed in nonpsychotic major depression. While the nonpsychotic major depression group showed abnormalities in frontal executive regions, the psychotic major depression group showed abnormalities in temporoparietal regions associated with orienting to unexpected stimuli. Considering the functional connectivity of this cluster with left dorsolateral prefrontal cortex regions, these findings may reflect neural compensation for sensory gating deficits in psychotic major depression.

Sensitive Period for a Multimodal Response in Human Visual Motion Area MT/MST

The middle temporal complex (MT/MST) is a brain region specialized for the perception of motion in the visual modality. However, this specialization is modified by visual experience: after long-standing blindness, MT/MST responds to sound. Recent evidence also suggests that the auditory response of MT/MST is selective for motion. The developmental time course of this plasticity is not known. To test for a sensitive period in MT/MST development, we used fMRI to compare MT/MST function in congenitally blind, late-blind, and sighted adults. MT/MST responded to sound in congenitally blind adults, but not in late-blind or sighted adults, and not in an individual who lost his vision between ages of 2 and 3 years. All blind adults had reduced functional connectivity between MT/MST and other visual regions. Functional connectivity was increased between MT/MST and lateral prefrontal areas in congenitally blind relative to sighted and late-blind adults. These data suggest that early blindness affects the function of feedback projections from prefrontal cortex to MT/MST. We conclude that there is a sensitive period for visual specialization in MT/MST. During typical development, early visual experience either maintains or creates a vision-dominated response. Once established, this response profile is not altered by long-standing blindness.

FMRI BOLD Response of High-risk College Students (Part 2): During Memory Priming of Alcohol, Marijuana and Polydrug Picture Cues

This study examined brain activity using functional magnetic resonance imaging (fMRI) and reaction time (RT) during an implicit repetition priming memory task involving alcohol, polydrug, marijuana and emotional picture cues. Participants were 5 male and 5 female high-risk college students who had just participated in a cue exposure study (Ray et al., this issue). fMRI and RT data were collected while participants made decisions about previously seen and new picture cues. Both behavioral RT and brain imaging data revealed strong memory priming for drug and alcohol cues. Neurologically, a repetition priming effect (suppression in neural activity for repeated cues) was observed in response to alcohol cues in the left prefrontal, bilateral occipital, and bilateral occipitotemporal regions, as well as right insula and right precuneus (Z ranged from 3.03 to 3.31 P < 0.05). Polydrug cues elicited priming in the occipital and temporal areas, and marijuana cues in the occipital area. Prefrontal and insular cortex involvement both in reactivity to alcohol cues (Ray et al., this issue) and subsequent implicit memory processing of these cues, as found in this study, suggests their potential role in the maintenance of high-risk alcohol use behaviors.

P3a and P3b of event-related potentials in persons with Asperger disorder

Although numerous research studies have explored the functional attributes of the human duration perception, the spatio- temporal information on cortical networks underlying this process is still an open question. Moreover, the issue of possible differences in the nature of timing mechanisms responsible for perception of sub- and supra-second intervals requires the implementation of the functional brain imaging techniques with both high spatial and temporal resolution. Attention is very frequently used as a modulating factor for the perceived duration of a sensory stimulus. The non-attended stimuli appear to last shorter than the attended ones, increasing the perceived duration of a concurrent stimulus (Gorea, 2011). This study challenges the accepted model of early sensory responses, activated during the first 100 ms after stimulus presentation, as preattentive, automatic processes which modulate the neural sensitivity to incoming stimuli (gating phenomena). We utilized Elekta Neuromag 306-channel whole-head system for magnetoencephalography (MEG) measurements and multi-dipole Calibrated Start Spatio Temporal (CSST) localization technique (Ranken et al., 2002) to investigate whether voluntary attention directed at the second tone of a pair in the standard paired-click paradigm could affect cortical networks underlying the gating out phenomenon. MEG recordings were obtained in a magnetically shielded room at the Biomagnetic Center in Jena, Germany. Two consecutive (ISI=500 ms) identical short tonnes (S1 and S2; duration=20ms; f=1200 Hz; ITI=8±1s) were used to evoke standard gating cortical responses in 19 healthy participants (21-38 years). In the second condition, the task was to direct attention toward the second tone and to respond to a rarely presented non-identical second tone of the pair (R=1300 Hz, p(S1R)=0.3). MEG recordings showed transient early and middle latency responses with peak amplitudes over the temporo-parietal sensors followed by a peak of a sustained activity. Less prominent transient activity was recorded over the frontal sensors, accompanied with a more steady- state component from 100 until 400 ms post-stimulus for both conditions. Preliminary results of the CSST spatio-temporal analyses revealed 4-6 brain regions activated during 20-500 ms time interval including bilateral superior temporal gyrus (STG), bilateral and medial prefrontal (PF), bilateral parietal (PA) regions, and central motor cortex area. A cortical source underlying the steady-state component was identified in the left prefrontal region for S1 tone, and in central posterior regions (PA) for the repeated tone S2. During the standard paradigm the M50 gating suppression was observed only for bilateral STG sources while bilateral PF and PA sources did not show any reduction in the response during the first 100 ms post-stimulus. Targeting the attention towards the second tone enhanced the M50 amplitude of the bilateral STG responses in respect to the repeated stimulus S2 and caused a change in the activated network evident by the emergence of a new generator in the medial PF area (orbitofrontal) instead of dorsolateral PF generators evoked in non-attended condition. These results demonstrate that voluntary attention can exert a topological and functional modulatory influence on the neural network even during early stages of auditory processing.

Experimental Elicitation of an Out of Body Experience and Concomitant Cross-Hemispheric Electroencephalographic Coherence

Brief exposure to a counterclockwise global externally applied magnetic field generated from an array of 64 solenoids designed to affect the cerebral fields associated with the left and right hemispheric correlates of evoked a powerful out of body experience (OOBE) in a single naive subject. The energy available from the applied field within the cortical volume was within the same order of magnitude as that associated with the sum of action potentials in all cortical neurons. During the OOBE there was a marked generalized increase in coherence in quantitative electroencephalographic activity between the left temporal lobe and right prefrontal region with specific abnormally high increases within the 4 to 7 Hz and 15 to 21 Hz band. These results are congruent with the experience of consciousness detached from the body and moving through space. The diagonal congruence is more consistent with the existence of two quantized fields or a global field with opposing polarities whose vector determines various emergent states experienced as OOBEs or sensed presences during brief periods of perturbation.

Parietal cortex and episodic memory retrieval in schizophrenia

People with schizophrenia consistently show memory impairment on varying tasks including item recognition memory. Relative to the correct rejection of distracter items, the correct recognition of studied items consistently produces an effect termed the old/new effect that is characterized by increased activity in parietal and frontal cortical regions. This effect has received only scant attention in schizophrenia. We examined the old/new effect in 15 people with schizophrenia and 18 controls during an item recognition test, and neural activity was examined with event-related functional magnetic resonance imaging. Both groups performed equally well during the recognition test and showed increased activity in a left dorsolateral prefrontal region and in the precuneus bilaterally during the successful recognition of old items relative to the correct rejection of new items. The control group also exhibited increased activity in the dorsal left parietal cortex. This region has been implicated in the top-down modulation of memory which involves control processes that support memory-retrieval search, monitoring and verification. Although these processes may not be of paramount importance in item recognition memory performance, the present findings suggest that people with schizophrenia may have difficulty with such top-down modulation, a finding consistent with many other studies in information processing.

Striatal Dysfunction Marks Preexisting Risk and Medial Prefrontal Dysfunction Is Related to Problem Drinking in Children of Alcoholics

Parental alcoholism substantially raises risk for offspring alcoholism, an effect thought to be mediated by a dysregulation in impulse control. Adult alcoholics have alterations in the frontostriatal system involved in regulating impulsive responses. However, it remains controversial whether these alterations reflect preexisting traits predisposing to problem alcohol use or are secondary to alcohol involvement. Sixty-one 16 to 22 year olds were tested using a go/no-go task during functional magnetic resonance imaging. Forty-one were family history positive (FH+), having at least one parent with a diagnosis of alcohol use disorder (AUD), and 20 were family history negative (FH-). Two FH+ subgroups were created to disentangle alcohol involvement from preexisting risk: the FH+ control group (n = 20) had low alcohol problems, differing from the FH- group only by family history. The FH+ problem group (n = 21) had high alcohol problems. The ventral caudate deactivated during successful inhibition in the FH- but not the FH+ groups, regardless of problem alcohol involvement. Regression analyses showed that ventral caudate deactivation was related to fewer externalizing problems as well as to family history. Orbital and left medial prefrontal regions were deactivated in both the FH- and FH+ control groups but not the FH+ problem group. Activation in these regions was associated with alcohol and other drug use. These findings suggest a preexisting abnormality in ventral striatal function in youth at risk for AUD, which may lead to inappropriate motivational responding, and suggest that with alcohol use, the prefrontal "control" mechanism loses efficiency, further dysregulating the frontostriatal motivational circuitry.

Neural Processing of Emotional Overinvolvement in Borderline Personality Disorder

Patients with borderline personality disorder (BPD) fare better clinically if their families are rated as being high in emotional overinvolvement, which is characterized by marked emotionality, anxious concern, and protective behavior. This is not true of patients with disorders such as schizophrenia or major depression. We used functional magnetic resonance imaging methods to explore the link between emotional overinvolvement (EOI) and better clinical outcome in BPD. Specifically, we tested the hypothesis that, unlike healthy controls or people with other psychiatric problems, people with BPD process EOI as an approach-related stimulus. Participants with BPD (n = 13) and dysthymia (n = 10) (DSM-IV criteria for both) and healthy controls (n = 11) were imaged using a high field strength (3T) scanner while they listened to a standardized auditory stimulus consisting of either 4 neutral or 4 EOI comments. Participants also rated their mood before and after exposure to the comments. All participants reported increased negative mood after hearing EOI and rated the EOI comments as negative stimuli. However, after subtracting activation to neutral comments, participants with BPD showed higher activation in left prefrontal regions during EOI compared to the other groups. Increased left prefrontal activation during EOI was also correlated with clinical measures indicative of borderline pathology. Participants with dysthymia showed increased amygdala activation during EOI. This was not true for the healthy controls or participants with BPD. For people with BPD, EOI may be activating neural circuitry implicated in the processing of approach-related stimuli. Increased left prefrontal activation to EOI may be a vulnerability marker for BPD. These findings may also help explain why BPD patients do better clinically in high EOI family environments.

Prefrontal cortex and age-related changes in strategic processing

Event Abstract Back to Event Prefrontal cortex and age-related changes in strategic processing Brenda Kirchhoff1* 1 University of Missouri – St. Louis , United States Episodic memory impairments are one of the main cognitive changes associated with healthy and disordered aging. For example, healthy older adults typically remember fewer words following intentional encoding than young adults. Under-and over-recruitment of prefrontal cortex have also been reported during intentional encoding in older adults. There is growing evidence that changes in self-initiated encoding strategy use could play an important role in these age-related memory impairments and alterations in brain activity. Behavioral studies have suggested that older adults are less likely than young adults to spontaneously use effective encoding strategies during intentional encoding. In addition, age-related changes in brain activity during intentional encoding have been reported in prefrontal regions associated with self-initiated use of effective encoding strategies in young adults. To further explore the role that age-related changes in self-initiated encoding strategy use may play in age-related changes in brain activity in prefrontal cortex, we recently conducted a cognitive training study in which older adults were taught to use semantic encoding strategies. Strategy use training substantially improved older adults’ ability to consciously recollect studied words. Older adults reported greater self-initiated use of semantic encoding strategies following cognitive training, and were less likely to report not using any learning strategy. Brain activity in left inferior prefrontal regions increased following cognitive training, and individual differences in training-related changes in brain activity in these regions were associated with individual differences in training-related changes in memory performance.