Biomedical subjects

Emrah Düzel

Publications and source records attributed to Emrah Düzel.

17 recordsLinked to original sources

PubMed2006

Absolute coding of stimulus novelty in the human substantia nigra/VTA.

Novelty exploration can enhance hippocampal plasticity in animals through dopaminergic neuromodulation arising in the substantia nigra/ventral tegmental area (SN/VTA). This enhancement can outlast the exploration phase by several minutes. Currently, little is known about dopaminergic novelty processing and its relationship to hippocampal function in humans. In two functional magnetic resonance imaging (fMRI) studies, SN/VTA activations in humans were indeed driven by stimulus novelty rather than other forms of stimulus salience such as rareness, negative emotional valence, or targetness of familiar stimuli, whereas hippocampal responses were less selective. SN/VTA novelty responses were scaled according to absolute rather than relative novelty in a given context, unlike adaptive SN/VTA responses recently reported for reward outcome in animal studies. Finally, novelty enhanced learning and perirhinal/parahippocampal processing of familiar items presented in the same context. Thus, the human SN/VTA can code absolute stimulus novelty and might contribute to enhancing learning in the context of novelty.

Adolescent↗

PubMed2006

Category-specific organization of prefrontal response-facilitation during priming.

Perceptual priming is a fundamental long-term memory capability that allows more efficient and faster responding to a stimulus as a result of prior exposure to that stimulus. The two major components of priming are facilitated response expression and improved stimulus identification. Recent fMRI studies have identified a potential neural correlate for response-facilitation, namely the repetition-related activity decrements in prefrontal cortex that are linearly correlated with improvements in reaction times. However, the neural processes underlying such response-facilitation are still unclear. They could be stimulus-selective stimulus-response mapping processes or general response-learning mechanisms. In human imaging studies, behavioral priming has been associated with decreased hemodynamic responses in prefrontal cortex and in category-specific brain regions of the ventral visual stream. Currently, it is unclear whether priming-related response decreases in prefrontal cortex are also category-specific. In this fMRI study, 16 subjects performed a repetition priming task employing category-specific identification judgments on pictures of faces (male/female judgment), scenes (indoor/outdoor judgment) and scrambled 'noise' pictures (simple button press). The repeated faces and scenes were identified faster than first presentations indicating priming. Hemodynamic decreases for repetitions were observed in a left inferior (near Brodman Area, BA, 44) and middle frontal (BA8) region of the prefrontal cortex, in category-specific areas of the ventral stream (bilateral fusiform face area, FFA, parahippocampal place area, PPA), and two category-specific right lateral occipital (LOC) regions. Hemodynamic increases for repetitions appeared in the caudate and cerebellum. However, the prefrontal areas were the only regions that showed a correlation between repetition-related reaction time improvement and hemodynamic decrease. Importantly, the correlations were category-specific in their relationship to reaction time improvement: in the left inferior frontal cortex the correlations were specific for scenes whereas and in left middle frontal gyrus they were specific for faces. There were no correlations between behavior and repetition suppression for both LOC regions, FFA and PPA. These data reveal that response-facilitation in prefrontal cortex is organized according to stimulus-properties, compatible with learning of stimulus-response mapping rather than response learning in general.

Adult↗

PubMed2006

The dopaminergic midbrain participates in human episodic memory formation: evidence from genetic imaging.

Recent data from animal studies raise the possibility that dopaminergic neuromodulation promotes the encoding of novel stimuli. We investigated a possible role for the dopaminergic midbrain in human episodic memory by measuring how polymorphisms in dopamine clearance pathways affect encoding-related brain activity (functional magnetic resonance imaging) in an episodic memory task. In 51 young, healthy adults, successful episodic encoding was associated with activation of the substantia nigra. This midbrain activation was modulated by a functional variable number of tandem repeat (VNTR) polymorphism in the dopamine transporter (DAT1) gene. Despite no differences in memory performance between genotype groups, carriers of the (low expressing) 9-repeat allele of the DAT1 VNTR showed relatively higher midbrain activation when compared with subjects homozygous for the 10-repeat allele, who express DAT1 at higher levels. The catechol-O-methyl transferase (COMT) Val108/158Met polymorphism, which is known to modulate enzyme activity, affected encoding-related activity in the right prefrontal cortex (PFC) and in occipital brain regions but not in the midbrain. Moreover, subjects homozygous for the (low activity) Met allele showed stronger functional coupling between the PFC and the hippocampus during encoding. Our finding that genetic variations in the dopamine clearance pathways affect encoding-related activation patterns in midbrain and PFC provides strong support for a role of dopaminergic neuromodulation in human episodic memory formation. It also supports the hypothesis of anatomically and functionally distinct roles for DAT1 and COMT in dopamine metabolism, with DAT1 modulating rapid, phasic midbrain activity and COMT being particularly involved in prefrontal dopamine clearance.

Adolescent↗

PubMed2006

Neuroanatomical dissociation of encoding processes related to priming and explicit memory.

Priming is a facilitation of cognitive processing with stimulus repetition that can occur without explicit memory. Whereas the functional neuroanatomy of perceptual priming at retrieval is established, encoding processes that initiate priming and explicit memory have not yet been anatomically separated, and we investigated them using event-related functional magnetic resonance imaging. Activations predicting later explicit memory occurred in the bilateral medial temporal lobe (MTL) and left prefrontal cortex (PFC). Activity predicting later priming did not occur in these areas, but rather in the bilateral extrastriate cortex, left fusiform gyrus, and bilateral inferior PFC, areas linked with stimulus identification. Surprisingly, these regions showed response reductions. Our results demonstrate that priming and explicit memory have distinct functional neuroanatomies at encoding, with MTL activations being specific for explicit memory, and suggest that priming is initiated by sharpness of neural responding in stimulus identification areas, consistent with recent electrophysiological evidence regarding priming-related neural oscillations at encoding. We tentatively suggest that this sharpened responding at encoding may set the stage for increased neural processing efficiency at retrieval, with these different neural mechanisms both leading to observed priming-related hemodynamic decreases, and argue that neural measurements at encoding, and not just at retrieval, will be critical in resolving the debate about the neural mechanisms of learning that underlie priming.

Adolescent↗

PubMed2005

Hippocampal atrophy in temporal lobe epilepsy is correlated with limbic systems atrophy.

Hippocampal sclerosis in temporal lobe epilepsy (TLE) is often associated with hippocampal atrophy. This study assessed whether such atrophy is correlated with loss of gray matter volume in other brain regions. In 16 patients with TLE and clear magnetic resonance imaging-based evidence of hippocampal sclerosis, hippocampal volumes were determined manually and the local gray matter (LGM) amount was estimated throughout the entire brain using voxel-based morphometry. Voxelwise correlations between the volume of the sclerotic hippocampus and LGM were computed. The pattern of voxels whose LGM correlated with hippocampal volume outlined remarkably well the anatomy of the extended limbic system and included the parahippocampal region, cingulate gyrus throughout its extent, basal forebrain, thalamic nuclei, medial orbitofrontal areas and the insula. These correlations emerged mainly on the side ipsilateral to the affected hippocampus but were also found contralaterally. No such correlations were found in a group of 16 healthy controls. The present data show that hippocampal volume loss in TLE is associated with a widespread limbic systems atrophy. These findings are helpful to better understand the functional deficit and reorganization often found in temporal lobe epilepsy and will also provide a basis to assess neural plasticity in the limbic system for those patients who will undergo curative temporal lobe surgery.

Adult↗

PubMed2005

The control of memory retrieval: insights from event-related potentials.

Effective performance on episodic retrieval tasks requires the ability to flexibly adapt to changing retrieval demands ('retrieval orientations'; [M.D. Rugg, E.L. Wilding, Retrieval processing and episodic memory, Trends Cogn. Sci. 4 (2000) 108-115]). We used event-related potentials (ERP) to examine whether maintaining a specific retrieval orientation and changing flexibly between different retrieval demands are mediated by the same brain systems or whether dissociable aspects of cognitive control are involved. Sixteen participants performed two recognition memory tasks. One required mere old/new decisions for words (general task), whereas the other task required the additional retrieval of each word's study font typeface (specific task). Furthermore, the participants either were asked to perform the same task continuously or to switch between the two tasks after every second test word. ERPs elicited by correctly rejected new (unstudied) words were analyzed. This enabled us to examine the ERP correlates of having adapted and maintained a task instruction as required during continuous blocks and of flexibly changing between retrieval demands during alternating blocks. The ERP analysis revealed more positive-going ERP slow waves for alternating blocks than for continuous blocks over bilateral frontal recording sites. This effect started around 250 ms after the test word and extended for several hundred milliseconds. As it was present for trials requiring a switch to the other task or to stay on the same task between 500 and 750 ms and no differences between the latter two trial types were obtained, it can be assumed that it is more related to general coordination requirements in alternating blocks, rather than to the actual control required to switch the retrieval task set. In addition, contrasting ERPs for the two task types revealed more positive-going ERP slow waves in the specific task than in the general task in the continuous blocks at lateral frontal recording sites between 250 and 700 ms. Together, these findings suggest that there are electrophysiologically dissociable aspects of cognitive control, namely for adapting and maintaining a retrieval orientation and for flexibly changing between varying retrieval demands.

Adult↗

PubMed2005

Early, partly anticipatory, neural oscillations during identification set the stage for priming.

Perceptual priming is a fundamental long-term memory capability by which exposure to a stimulus improves later perceptual processing of that stimulus. A widespread hypothesis is that priming is the later result of perceptual learning during stimulus identification. Testing this hypothesis involves isolating priming without explicit memory, and appropriately measuring brain activity during initial experimental exposure to assess whether brain activity related to identification differs as a function of later priming. Here, we show, using magnetoencephalography (MEG), that words primed in a later test are distinguished from unprimed words at initial exposure by (a) more specific responses in perceptual brain areas, indicated by an early (within 240 ms after word onset) decrease in amplitude but increase in phase alignment of beta and gamma oscillations, and (b) improved coordination of responses across perceptual and higher brain areas in the same time window, indicated by an increase in interareal phase synchrony of alpha oscillations. The increase in interareal phase synchrony partly started already in the pre-stimulus period, approximately 60-80 ms prior to word onset, showing that the improved coordination of responses across areas was partly anticipatory. The anatomy and early timing of these patterns reveal a neural link between identification and long-term memory. The pre-stimulus findings additionally show that priming is related to the stimulus-specific anticipatory state of visual identification areas at initial exposure.

Adult↗

PubMed2005

The oscillatory dynamics of recognition memory and its relationship to event-related responses.

The large-scale neural dynamics underlying higher cognitive processes are characterized by at least three types of stimulus-response: (i) the resetting of ongoing oscillatory brain activity without concomitant changes in response amplitude (phase alignment response); (ii) the addition of response amplitude to the ongoing brain activity in a time-locked manner (evoked response); and (iii) the addition of response amplitude that is not time-locked (induced response). Recent animal studies identified evoked responses as a characteristic neural response during stimulus perception but leave open the possibility that higher cognition, such as memory, is characterized more predominantly by phase alignment and/or induced responses. Using whole-head single-trial magnetoencephalography data from eight healthy adults, we show that all three types of response are related to the discrimination of old and new stimuli in a visual word recognition memory paradigm. In four subjects, single-trial evoked responses were the single constituents of event-related field old/new differences that have been previously related to familiarity-based and recollection-based recognition memory. While these data show that the oscillatory brain dynamics underlying recognition memory are characterized by a complex mix of three types of stimulus-response, they also clearly implicate evoked responses in higher cognitive processes such as recognition memory.

Adult↗

PubMed2005

Reward-related FMRI activation of dopaminergic midbrain is associated with enhanced hippocampus-dependent long-term memory formation.

Long-term potentiation in the hippocampus can be enhanced and prolonged by dopaminergic inputs from midbrain structures such as the substantia nigra. This improved synaptic plasticity is hypothesized to be associated with better memory consolidation in the hippocampus. We used a condition that reliably elicits a dopaminergic response, reward anticipation, to study the relationship between activity of dopaminergic midbrain areas and hippocampal long-term memory in healthy adults. Pictures of object drawings that predicted monetary reward were associated with stronger fMRI activity in reward-related brain areas, including the substantia nigra, compared with non-reward-predicting pictures. Three weeks later, recollection and source memory were better for reward-predicting than for non-reward-predicting pictures. FMRI activity in the hippocampus and the midbrain was higher for reward-predicting pictures that were later recognized compared with later forgotten pictures. These data are consistent with the hypothesis that activation of dopaminergic midbrain regions enhances hippocampus-dependent memory formation, possibly by enhancing consolidation.

Adult↗

PubMed2005

Redefining implicit and explicit memory: the functional neuroanatomy of priming, remembering, and control of retrieval.

We used event-related functional MRI to study awareness of prior episodes during memory retrieval and its relationship to the intention to retrieve memories. Participants completed cues with words from a prior list (intentional test) or with the first words that came to mind (incidental test). During both tests, explicit memory was separated from priming in the absence of explicit memory. Priming was associated with hemodynamic decreases in left fusiform gyrus and bilateral frontal and occipital brain regions; explicit memory was associated with bilateral parietal and temporal and left frontal increases. Retrieval intention did not change these patterns but was associated with activity in right prefrontal cortex. Our results provide firm evidence that implicit and explicit memory have distinct functional neuroanatomies, and that strategic control of retrieval engages brain structures distinct from those involved in both implicit and explicit memory. They have critical implications for theories of memory and consciousness, which often equate consciousness with control.

Adolescent↗

PubMed2005

Induced theta oscillations mediate large-scale synchrony with mediotemporal areas during recollection in humans.

One functional aspect of theta oscillations that recent studies have begun to explore in humans is their role for the recollection of personal events. A specific role of theta for recollection but not for stimulus-familiarity would support links between cortical theta oscillations and hippocampal functioning, given that the hippocampus seems to be more critical for recollection than for stimulus-familiarity. During recollection, theta oscillations might mediate a dynamic link between hippocampal and neocortical areas, thereby allowing to recruit and bind distributed cortical representations. We recorded theta oscillations using whole-head magnetoencephalography while nine healthy subjects made recognition memory judgments on previously studied and unstudied pictures of faces. For each recognized face, subjects indicated whether they also recollected the background image in front of which that face was studied. Theta oscillations were higher in amplitude during recollection than during recognition in the absence of accurate memory for the background. These theta oscillations were induced in nature, meaning that they showed considerable phase variability from trial to trial. To nevertheless extract the field distribution of coherent theta oscillations from single trials, we calculated phase differences between sensor pairs at each time point of each single trial. This field information was used to localize the brain sources of synchronized theta-generators. The results suggest that recollection is associated with induced activity increase in a distributed synchronous theta network, including prefrontal, mediotemporal, and visual areas. These findings are compatible with the notion that theta oscillations are related to the binding of distributed cortical representations during recollection.

Biological Clocks↗

PubMed2005

Recapitulating emotional context: activity of amygdala, hippocampus and fusiform cortex during recollection and familiarity.

The amygdala is thought to enhance long-term memory for emotionally arousing events by modulating memory formation and storage in the hippocampus and in neocortical areas. Recent animal studies have raised the possibility that cooperativity between amygdala and hippocampus contributes to the retrieval of fear memories. The functional contributions of the amygdala to the retrieval of emotional memories in humans are less well known. Here, in a functional magnetic resonance imaging experiment, 20 healthy subjects studied neutral words in the context of a fearful or a neutral human face. In a subsequent test, they made 'remember' (conscious recollection of the study context), 'know' (familiarity in the absence of conscious recollection) and 'new' judgements on the studied and newly presented neutral words, in the absence of face stimuli. At test, bilateral amygdala, hippocampus and fusiform face area (FFA) were more strongly activated during recollection than during familiarity. Higher activity for fearful than for neutral study context was found in bilateral FFA during recollection but not during familiarity. This difference recapitulated higher activity for fearful than for neutral context in the FFA during study. These data suggest that the amygdalae and hippocampi contribute to the retrieval of emotion-laden context memories by coordinating the reactivation of stored representations in neocortical areas, such as the FFA. However, there also was a recapitulation of emotional study context in the right amygdala during familiarity only, which might therefore be related to affective implicit memory.

Adult↗

PubMed2004

Activation of midbrain structures by associative novelty and the formation of explicit memory in humans.

Recent evidence suggests a close functional relationship between memory formation in the hippocampus and dopaminergic neuromodulation originating in the ventral tegmental area and medial substantia nigra of the midbrain. Here we report midbrain activation in two functional MRI studies of visual memory in healthy young adults. In the first study, participants distinguished between familiar and novel configurations of pairs of items which had been studied together by either learning the location or the identity of the items. In the second study, participants studied words by either rating the words' pleasantness or counting syllables. The ventral tegmental area and medial substantia nigra showed increased activation by associative novelty (first study) and subsequent free recall performance (second study). In both studies, this activation accompanied hippocampal activation, but was unaffected by the study task. Thus midbrain regions seem to participate selectively in hippocampus-dependent processes of associative novelty and explicit memory formation, but appear to be unaffected by other task-relevant aspects.

Adolescent↗

PubMed2004

Quantitative MR analyses of the hippocampus: unspecific metabolic changes in aging.

The age-related structural changes of the human hippocampus are not entirely understood. The goal of the present investigation was to understand better the nature of age-related hippocampal changes by a comparative MR-analysis of four complementary aspects of hippocampal integrity: total volume, metabolite concentration, neuron to glial cell ratio and amount of extracellular diffusion space for water. To that end, we applied MR-based methods of manual and computerized (voxel-based morphometry) volumetry, diffusion-weighted imaging and 1H MR spectroscopy to characterize specific age-related hippocampal effects in a group of 22 healthy old adults in comparison with a group of 13 healthy younger adults. Age-related reductions of the hippocampal N-acetyl aspartate to creatine/choline ratio together with only marginal age-related reductions in hippocampal volumes and increases in diffusion parameters suggest that the process of aging affects mainly the metabolic status of the hippocampus with little equivalent age-related changes in hippocampal cell density. The metabolic changes are unspecific as they are not restricted to the hippocampus but equally occur in measures obtained from extrahippocampal temporal lobe regions.

Adult↗

PubMed2003

Human hippocampal and parahippocampal activity during visual associative recognition memory for spatial and nonspatial stimulus configurations.

Evidence from animal studies points to the importance of the parahippocampal region (PHR) [including entorhinal, perirhinal, and parahippocampal (PHC) cortices] for recognition of visual stimuli. Recent findings in animals suggest that PHR may also be involved in visual associative recognition memory for configurations of stimuli. Thus far, however, such involvement has not been demonstrated in humans. In fact, it has been argued that associative recognition in humans is critically dependent on the hippocampal formation (HF). To better understand the division of function between HF and PHR during recognition memory in humans, we measured the activity of both areas in healthy young adults during an associative recognition memory task using functional magnetic resonance imaging. To more precisely characterize the nature of the associations that might be coded by the HF and PHR during recognition, subjects were required to learn and were later tested for associations based on either the spatial arrangements of two stimuli or the identity of two stimuli (a face and a tool). An area in the PHC was found to be more active for recognized old configurations than new configurations in both the spatial and identity conditions. The HF, on the other hand, was more active for recognition of new configurations than old configurations and also more active in the spatial than the identity condition. These data highlight the involvement of PHR in the long-term coding of associative relationships between stimuli and help to clarify the nature of its functional distinction from the HF.

Adult↗

PubMed2002

Perceptual priming versus explicit memory: dissociable neural correlates at encoding.

We addressed the hypothesis that perceptual priming and explicit memory have distinct neural correlates at encoding. Event-related potentials (ERPs) were recorded while participants studied visually presented words at deep versus shallow levels of processing (LOPs). The ERPs were sorted by whether or not participants later used studied words as completions to three-letter word stems in an intentional memory test, and by whether or not they indicated that these completions were remembered from the study list. Study trials from which words were later used and not remembered (primed trials) and study trials from which words were later used and remembered (remembered trials) were compared to study trials from which words were later not used (forgotten trials), in order to measure the ERP difference associated with later memory (DM effect). Primed trials involved an early (200-450 msec) centroparietal negative-going DM effect. Remembered trials involved a late (900-1200 msec) right frontal, positive-going DM effect regardless of LOP, as well as an earlier (600-800 msec) central, positive-going DM effect during shallow study processing only. All three DM effects differed topographically, and, in terms of their onset or duration, from the extended (600-1200 msec) fronto-central, positive-going shift for deep compared with shallow study processing. The results provide the first clear evidence that perceptual priming and explicit memory have distinct neural correlates at encoding, consistent with Tulving and Schacter's (1990) distinction between brain systems concerned with perceptual representation versus semantic and episodic memory. They also shed additional light on encoding processes associated with later explicit memory, by suggesting that brain processes influenced by LOP set the stage for other, at least partially separable, brain processes that are more directly related to encoding success.

Adult↗

PubMed2002

The effect of item sequence on brain activity during recognition memory.

Two basic types of experimental designs are available to measure the brain indices of successful recognition memory. Both designs have in common that brain activity elicited by correctly recognized studied (old) items is compared to brain activity elicited by correctly rejected new items. In blocked designs, the two item types are presented in separate lists. In random-mixed designs, on the other hand, they are randomly intermixed within the same list. Early studies reported that in random-mixed designs, brain activity can be affected by the sequence in which different types of items are presented. Here, we investigated to what extent such sequence effects also occur in random-mixed designs of recognition memory. Event-related potentials (ERPs) were obtained while subjects made recognition judgments on pseudorandom sequences of visually presented new and old words. Changes in the sequence from one item-type to another (change from old to new and from new to old) were associated with a prominent P300 potential for new words following old words but not vice versa. Subjects with larger P300 potentials made less false alarms to such new words. Successive presentations of the same item-type (sequence 'blocks': three old words in a row and three new words in row) were associated with a left parietal positive slow shift for successive old words but not for successive new words. The data suggest that new words require extensive context-updating if they are presented within the context generated by preceding old words. Due to these sequence effects, the present data question the assumption that random-mixed designs are generally favorable over block designs.

Adult↗