Acute tryptophan depletion improves performance and modulates the BOLD response during a Stroop task in healthy females

To gain more insight into the effect of low brain serotonin (5-HT) on brain activation related to conflict, the present study examined the effect of acute tryptophan depletion (ATD) on performance and the blood oxygen level dependent (BOLD) response during a combined cognitive and emotional Stroop task. Fifteen healthy female volunteers were tested during a placebo and tryptophan depletion session in an event-related fMRI design. ATD improved performance during Stroop interference. Two effects of ATD on the BOLD response were found. Firstly, ATD increased the BOLD response in the anterior cingulate cortex (ACC) (BA 32) when incongruent color words were compared with congruent color words in the first Stroop block the participants performed. Secondly, ATD increased the BOLD response in the left precuneus (BA 31) and cuneus (BA 18) during congruent color words. ATD did not affect the BOLD response accompanying emotional stimuli. However, we showed that ATD increased the interference of negative words on color naming. This finding was explained in terms of an emotional processing bias in favor of negative words, which leads to stronger interference of these words. In line with previous studies, the present study showed that a temporary reduction of 5-HT improved Stroop performance and changed the underlying brain activation pattern in healthy female participants. Moreover, we replicated our previous finding that ATD modulated the BOLD response in the dorsomedial prefrontal cortex during tasks that require cognitive control.     

Acute effects of alcohol on neural correlates of episodic memory encoding

Although it is well established that alcohol impairs episodic memory encoding, it is unknown how this occurs on a cerebral level. We scanned intoxicated and sober individuals with functional magnetic resonance imaging (fMRI) while they encoded various materials that were recalled the following day. Alcohol impaired memory for object pairs and face-name pairs, but not for words and phrase-word pairs. Impaired performance was associated with reduced bilateral prefrontal activation and non-specific activation of the parahippocampal gyrus. These results suggest that alcohol impairs episodic memory by interfering with activity of regions involved in encoding, and further indicate which regions are critical for human memory.     

Emotion suppression reduces hippocampal activity during successful memory encoding

People suppressing their emotions while facing an emotional event typically remember it less well. However, the neural mechanisms underlying the impairing effect of emotion suppression on successful memory encoding are not well understood. Because successful memory encoding relies on the hippocampus and the amygdala, we hypothesized that memory impairments due to emotion suppression are associated with down-regulated activity in these brain areas. 59 healthy females were instructed either to simply watch the pictures or to down-regulate their emotions by using a response-focused emotion suppression strategy. Brain activity was recorded using functional magnetic resonance imaging (fMRI), and free recall of pictures was tested afterwards. As expected, suppressing one's emotions resulted in impaired recall of the pictures. On the neural level, the memory impairments were associated with reduced activity in the right hippocampus during successful encoding. No significant effects were observed in the amygdala. In addition, functional connectivity between the hippocampus and the right dorsolateral prefrontal cortex was strongly reduced during emotion suppression, and these reductions predicted free-recall performance. Our results indicate that emotion suppression interferes with memory encoding on the hippocampal level, possibly by decoupling hippocampal and prefrontal encoding processes, suggesting that response-focused emotion suppression might be an adaptive strategy for impairing hippocampal memory formation in highly arousing situations.     

Performance on an episodic encoding task yields further insight into functional brain development

To further characterize changes in functional brain development that are associated with the emergence of cognitive control, participants 14 to 28 years of age were scanned while performing an episodic encoding task with a levels-of-processing manipulation. Using data from the 12 youngest and oldest participants (endpoint groups), 18 regions were identified that showed group differences in task-related activity as a function of processing depth. One region, located in left inferior frontal gyrus, showed enhanced activity in deep relative to shallow encoding that was larger in magnitude for the older group. Seventeen regions showed enhanced activity in shallow relative to deep encoding that was larger in magnitude for the youngest group. These regions were distributed across a broad network that included both cortical and subcortical areas. Regression analyses using the entire sample showed that age made a significant contribution to the difference in beta weights between deep and shallow encoding for 17 of the 18 identified regions in the direction predicted by the endpoint analysis. We conclude that the patterns of brain activation associated with deep and shallow encoding differ between adolescents and young adults in a manner that is consistent with the interactive specialization account of functional brain development.     

Human cortical EEG rhythms during long-term episodic memory task. A high-resolution EEG study of the HERA model

Many recent neuroimaging studies of episodic memory have indicated an asymmetry in prefrontal involvement, with the left prefrontal cortex more involved than the right in encoding, the right more than the left in retrieval (hemispheric encoding and retrieval asymmetry, or HERA model). In this electroencephalographic (EEG) high-resolution study, we studied brain rhythmicity during a visual episodic memory (recognition) task. The theta (4-6 Hz), alpha (6-12 Hz) and gamma (28-48 Hz) oscillations were investigated during a visuospatial long-term episodic memory task including an encoding (ENC) and retrieval (RET) phases. During the ENC phase, 25 figures representing interiors of buildings ("indoor") were randomly intermingled with 25 figures representing landscapes ("landscapes"). Subject's response was given at left ("indoor") or right ("landscapes") mouse button. During the RET phase (1 h later), 25 figures representing previously presented "indoor" pictures ("tests") were randomly intermingled with 25 figures representing novel "indoor" ("distractors"). Again, a mouse response was required. Theta and alpha EEG results showed no change of frontal rhythmicity. In contrast, the HERA prediction of asymmetry was fitted only by EEG gamma responses, but only in the posterior parietal areas. The ENC phase was associated with gamma EEG oscillations over left parietal cortex. Afterward, the RET phase was associated with gamma EEG oscillations predominantly over right parietal cortex. The predicted HERA asymmetry was thus observed in an unexpected location. This discrepancy may be due to the differential sensitivity of neuroimaging methods to selected components of cognitive processing. The strict relation between gamma response and perception suggests that retrieval processes of long-term memory deeply impinged upon sensory representation of the stored material.     

Functional network in the prefrontal cortex during episodic memory retrieval

A recent consistent finding in neuroimaging studies of human memory is that the prefrontal cortex (PFC) is activated during episodic memory retrieval. To date, however, there has been no direct evidence to explain how activity in the right and left PFC and in the anterior and posterior PFC are functionally interconnected. The goal of the present study was to obtain such evidence by event-related functional magnetic resonance imaging (MRI) and the functional connectivity method. Subjects were first asked to try to remember a series of associate-word lists outside the MRI scanner in preparation for a later recognition test. In the MRI scanning phase, they were asked to make recognition judgments in regard to old words, semantically related lure words, and unrelated new words. The analysis of functional connectivity revealed that the posterior PFC in each hemisphere had strong functional interconnections with the contralateral posterior PFC, whereas the anterior PFC in each hemisphere had only weak functional interconnections with the contralateral anterior PFC. No strong functional interconnections were found between the anterior and posterior PFC in either hemisphere. These findings support the hypothesis of an associative contribution of the bilateral posterior PFC to episodic memory retrieval and a dissociative contribution of the bilateral anterior PFC.     

The reliability of fMRI activations in the medial temporal lobes in a verbal episodic memory task

The test-retest reliability of activation patterns elicited by encoding and recognition of word-pair associates within the whole brain and a predefined medial temporal region of interest (ROI) was investigated. Twenty healthy right-handed subjects were studied within two sessions, either on the same day or 210-308 days later. Three quantitative measures of reliability were calculated for the contrasts encoding and recognition versus a control condition within the ROI and also for the whole brain: A group correlational analysis between the lateralization indices of the first and second session, correlations of the individual SPM(t) maps of the first and the second run, and overlap ratios between both sessions. For the ROI, correlational analysis of lateralization indices during both encoding trials was significant. Eighty percent of the individual positive correlation coefficients of SPM(t) maps during encoding, and 75% during recognition reached significance. The mean percentage of overlapping voxels was 18% during encoding and 19% during recognition. The reproducibility measures evaluated for the whole brain demonstrated significantly higher values compared to the ROI. For the group that stayed inside the scanner, better whole brain test-retest reliability was observed, and no influence of the memory process (encoding or recognition) on reproducibility was found.     

Feeling-of-knowing in episodic memory: an event-related fMRI study

An individual may fail to recall an item from memory but still feel that it would be recognized on a later test, a retrieval state termed the "feeling-of-knowing" (FOK). In this study we used event-related fMRI and the FOK to examine both encoding- and retrieval-related factors that are associated with different levels of recall performance: successful retrieval of a previously studied item, retrieval failure accompanied by the FOK, and retrieval failure without any FOK. The results revealed one predominant pattern of retrieval-related activation: an intermediate level of activation for FOK-less than that associated with successful recall and greater than that associated with unsuccessful recall (frontal and left parietal cortices). Two further patterns were also observed: greater activation for both successful recall and FOK than for unsuccessful recall (left midlateral prefrontal cortex) and greater activation for successful recall than for both FOK and unsuccessful recall (left MTL). Analysis of encoding trials conditional upon subsequent retrieval success revealed a pattern of activation that appeared to predict subsequent recall, but which further analysis indicated to be a better predictor of subsequent recognition. These results provide evidence that the phenomenology of graded recall is represented neurally in frontal and parietal cortices, but that activation at encoding may not precipitate the different levels of recall experience.     

Being right is its own reward: load and performance related ventral striatum activation to correct responses during a working memory task in youth

The ventral striatum (VS) is a critical brain region for reinforcement learning and motivation. Intrinsically motivated subjects performing challenging cognitive tasks engage reinforcement circuitry including VS even in the absence of external feedback or incentives. However, little is known about how such VS responses develop with age, relate to task performance, and are influenced by task difficulty. Here we used fMRI to examine VS activation to correct and incorrect responses during a standard n-back working memory task in a large sample (n=304) of healthy children, adolescents and young adults aged 8-22. We found that bilateral VS activates more strongly to correct than incorrect responses, and that the VS response scales with the difficulty of the working memory task. Furthermore, VS response was correlated with discrimination performance during the task, and the magnitude of VS response peaked in mid-adolescence. These findings provide evidence for scalable intrinsic reinforcement signals during standard cognitive tasks, and suggest a novel link between motivation and cognition during adolescent development.     

Isolating the retrieval of imagined pictures during episodic memory: activation of the left precuneus and left prefrontal cortex

The posterior medial parietal cortex and the left prefrontal cortex have both been implicated in the recollection of past episodes. In order to clarify their functional significance, we performed this functional magnetic resonance imaging study, which employed event-related source memory and item recognition retrieval of words paired with corresponding imagined or viewed pictures. Our results suggest that episodic source memory is related to a functional network including the posterior precuneus and the left lateral prefrontal cortex. This network is activated during explicit retrieval of imagined pictures and results from the retrieval of item-context associations. This suggests that previously imagined pictures provide a context with which encoded words can be more strongly associated.     

The right hippocampus participates in short-term memory maintenance of object-location associations

Doubts have been cast on the strict dissociation between short- and long-term memory systems. Specifically, several neuroimaging studies have shown that the medial temporal lobe, a region almost invariably associated with long-term memory, is involved in active short-term memory maintenance. Furthermore, a recent study in hippocampally lesioned patients has shown that the hippocampus is critically involved in associating objects and their locations, even when the delay period lasts only 8 s. However, the critical feature that causes the medial temporal lobe, and in particular the hippocampus, to participate in active maintenance is still unknown. This study was designed in order to explore hippocampal involvement in active maintenance of spatial and non-spatial associations. Eighteen participants performed a delayed-match-to-sample task in which they had to maintain either object-location associations, color-number association, single colors, or single locations. Whole-brain activity was measured using event-related functional magnetic resonance imaging and analyzed using a random effects model. Right lateralized hippocampal activity was evident when participants had to maintain object-location associations, but not when they had to maintain object-color associations or single items. The present results suggest a hippocampal involvement in active maintenance when feature combinations that include spatial information have to be maintained online.     

An examination of the effects of stimulus type, encoding task, and functional connectivity on the role of right prefrontal cortex in recognition memory

Right anterior prefrontal cortex and other brain areas are active during memory retrieval but the role of prefrontal cortex and how it interacts with these other regions to mediate memory function remain unclear. To explore these issues we used positron emission tomography to examine the effects of stimulus material and encoding task on brain activity during visual recognition, assessing both task-related changes and functional connectivity. Words and pictures of objects were encoded using perceptual and semantic strategies, resulting in better memory for semantically encoded items. There was no significant effect of prior encoding strategy on brain activity during recognition. Right anterior prefrontal cortex was equally active during recognition of both types of stimuli irrespective of initial encoding strategy. Regions whose activity was positively correlated with activity in right anterior prefrontal cortex included widespread areas of prefrontal and inferior temporal cortices bilaterally. Activity in this entire network of regions was negatively correlated with recognition accuracy of semantically encoded items. These results suggest that initial encoding task has little impact on the set of brain regions that is active during subsequent recognition. Right anterior prefrontal cortex appears to be involved in retrieval mode, reflected in its equivalent activity across conditions differing in both stimulus type and encoding task, and also in retrieval effort, shown by the negative correlation between its functional connectivity and individual differences in recognition accuracy.     

Decoding different working memory states during an operation span task from prefrontal fNIRS signals

We propose an effective and practical decoding method of different mental states for potential applications for the design of brain-computer interfaces, prediction of cognitive behaviour, and investigation of cognitive mechanism. Functional near infrared spectroscopy (fNIRS) signals that interrogated the prefrontal and parietal cortices and were evaluated by generalized linear model were recorded when nineteen healthy adults performed the operation span (OSPAN) task. The oxygenated hemoglobin changes during OSPAN, response, and rest periods were classified with a support vector machine (SVM). The relevance vector regression algorithm was utilized for prediction of cognitive performance based on multidomain features of fNIRS signals from the OSPAN task. We acquired decent classification accuracies for OSPAN vs. response (above 91.2%) and for OSPAN vs. rest (above 94.7%). Eight of the ten cognitive testing scores could be predicted from the combination of OSPAN and response features, which indicated the brain hemodynamic responses contain meaningful information suitable for predicting cognitive performance.     

Increased frontocerebellar activation in alcoholics during verbal working memory: an fMRI study

Although there is clear evidence of alcoholism-related damage to the frontal lobes and cerebellum from neuroimaging, neuropathological, and neuropsychological studies, the functional role of the cerebellum and cerebrocerebellar circuits related to verbal working memory deficits of alcoholics have not been well studied. Alcoholic and nonalcoholic subjects performed a Sternberg verbal working memory task while receiving an fMRI scan in a 3T magnet. This task has been found in previous studies to reliably activate the articulatory control and phonological storage components of the phonological loop (left frontal, left temporal/parietal structures, right superior cerebellar regions) in young healthy controls. We hypothesized that the alcoholics would show a different pattern of activation from the controls, based on the regions of interest (ROIs) identified from a previous study of healthy subjects. Behavioral results showed the alcoholics to be performing at a comparable level to the matched controls in terms of accuracy and median reaction time, with no statistically significant differences. However, analysis of the functional data revealed that the alcoholics exhibited greater activation in the left frontal (BA44/45) and right superior cerebellum (HVI) regions relative to the matched controls. These findings suggest that brain activation in left frontal and right cerebellar regions that support the articulatory control system of verbal working memory may require a compensatory increase in alcoholics in order to maintain the same level of performance as controls.     

Recognition memory for studied words is determined by cortical activation differences at encoding but not during retrieval

Prior work has shown that when responses to incidentally encoded words are sorted, subsequently remembered words elicit greater left prefrontal BOLD signal change relative to forgotten words. Similarly, low-frequency words elicit greater activation than high-frequency words in the same left prefrontal regions, contributing to their better subsequent memorability. This study examined the relative contribution of encoding and retrieval processes to the correct recognition of target words. A mixture of high- and low-frequency words was incidentally encoded. Scanning was performed at encoding as well as during retrieval. During encoding, greater activation in the left prefrontal and anterior cingulate regions predicted a higher proportion of hits for low-frequency words. However, data acquired during recognition showed that word frequency did not modulate activation in any of the areas tracking successful recognition. This result demonstrates that under some circumstances, the recognition of studied words is determined purely by processes that are active during encoding. In contrast to the finding for hits, activation associated with correctly rejected foils was modulated by word frequency, being higher for high-frequency words in the left lateral parietal and anterior prefrontal regions. These findings were replicated in two further experiments, one in which the number of test items at recognition was doubled and another where encoding strength for high-frequency words was varied (once vs. 10 times). These results indicate that word frequency modulates activity in the left lateral parietal and anterior prefrontal regions contingent on whether the item involved is correctly recognized as a target or a foil. This observation is consistent with a dual process account of episodic memory.     

On the effects of spatial filtering--a comparative fMRI study of episodic memory encoding at high and low resolution

The effects of spatial filtering in functional magnetic resonance imaging were investigated by reevaluating the data of a previous study of episodic memory encoding at 2 x 2 x 4-mm(3) resolution with use of a SPM99 analysis involving a Gaussian kernel of 8-mm full width at half maximum. In addition, a multisubject analysis of activated regions was performed by normalizing the functional images to an approximate Talairach brain atlas. In individual subjects, spatial filtering merged activations in anatomically separated brain regions. Moreover, small foci of activated pixels which originated from veins became blurred and hence indistinguishable from parenchymal responses. The multisubject analysis resulted in activation of the hippocampus proper, a finding which could not be confirmed by the activation maps obtained at high resolution. It is concluded that the validity of multisubject fMRI analyses can be considerably improved by first analyzing individual data sets at optimum resolution to assess the effects of spatial filtering and minimize the risk of signal contamination by macroscopically visible vessels.     

Oscillatory correlates of the primacy effect in episodic memory

Both intracranial and scalp EEG studies have demonstrated that oscillatory activity, especially in the gamma band (28 to 100 Hz), can differentiate successful and unsuccessful episodic encoding [Sederberg, P.B., Kahana, M.J., Howard, M.W., Donner, E.J., Madsen, J.R., 2003. Theta and gamma oscillations during encoding predict subsequent recall. Journal of Neuroscience, 23(34), 10809-10814; Fell, J., Klaver, P., Lehnertz, K., Grunwald, T., Schaller, C., Elger, C.E., Fernandez, G., 2001. Human memory formation is accompanied by rhinal-hippocampal coupling and decoupling. Nature Neuroscience, 4 (12), 1259-1264; Gruber, T., Tsivilis, D., Montaldi, D., and Müller, M. (2004). Induced gamma band responses: An early marker of memory encoding and retrieval. Neuroreport, 15, 1837-1841; Summerfield, C., Mangels, J.A., in press. Dissociable neural mechanisms for encoding predictable and unpredictable events. Journal of Cognitive Neuroscience]. Although the probability of recalling an item varies as a function of where it appeared in the list, the relation between the oscillatory dynamics of successful encoding and serial position remains unexplored. We recorded scalp EEG as participants studied lists of common nouns in a delayed free-recall task. Because early list items were recalled better than items from later serial positions (the primacy effect), we analyzed encoding-related changes in 2 to 100 Hz oscillatory power as a function of serial position. Increases in gamma power in posterior regions predicted successful encoding at early serial positions; widespread low-frequency (4-14 Hz) power decreases predicted successful memory formation for later serial positions. These results suggest that items in early serial positions receive an encoding boost due to focused encoding without having to divide resources among numerous list items. Later in the list, as memory load increases, encoding is divided between multiple items.     

Functional connectivity in an fMRI working memory task in high-functioning autism

An fMRI study was used to measure the brain activation of a group of adults with high-functioning autism compared to a Full Scale and Verbal IQ and age-matched control group during an n-back working memory task with letters. The behavioral results showed comparable performance, but the fMRI results suggested that the normal controls might use verbal codes to perform the task, while the adults with autism might use visual codes. The control group demonstrated more activation in the left than the right parietal regions, whereas the autism group showed more right lateralized activation in the prefrontal and parietal regions. The autism group also had more activation than the control group in the posterior regions including inferior temporal and occipital regions. The analysis of functional connectivity yielded similar patterns for the two groups with different hemispheric correlations. The temporal profile of the activity in the prefrontal regions was more correlated with the left parietal regions for the control group, whereas it was more correlated with the right parietal regions for the autism group.     

Interindividual differences of medial temporal lobe activation during encoding in an elderly population studied by fMRI

Functional MRI (fMRI) is used to study medial temporal lobe (MTL) activation during encoding of new information into memory. In most studies, fMRI data of different subjects are averaged in standard coordinate space. However, interindividual differences in activation can be extensive, reflecting functional heterogeneity. Further, anatomical differences in brain structure cause additional variance and loss of registration accuracy. Such differences in structural and functional MTL characteristics may interfere with the efficiency of averaging data across subjects, and may become more significant with aging and dementia. The current study concerns the analysis of individual differences in MTL activation associated with episodic encoding.Twenty-nine healthy elderly men between 60 and 70 years old performed a simple face encoding task during fMRI scanning. Individual data were analyzed in native space, and compared to the group average in standard space (Talairach and Tournoux).MTL volumes between subjects varied between 6.34 and 11.27 cm(3), and had considerable variation when mapped to standard space. Eighteen of the 29 subjects showed MTL activity and activation patterns varied both in location and size (ranging from 0.11 to 1.78 cm(3)), with the strongest activation in the left posterior part of the MTL. In standard space, no region was significantly activated on a group level at a comparable alpha level. We conclude that while the majority of elderly subjects show MTL activation during episodic encoding of faces, there is considerable structural and functional variability between subjects. Group analysis in standard space may not be appropriate for studies of a complex structure such as the MTL, particularly not in aging and dementia.