Medial temporal lobe activity associated with the successful retrieval of destination memory.

Destination memory is the process of remembering to whom we tell particular things. Although recent behavioral studies have clarified the cognitive nature of destination memory, the neural mechanisms underlying destination memory retrieval remain unclear. We used functional magnetic resonance imaging (fMRI) to determine whether the medial temporal lobe (MTL), a structure that has been implicated in recollection-based memory, is activated during the successful retrieval of destination information. During a study phase before fMRI scanning, the subjects told a series of facts to either a woman or a man. During fMRI scanning, the subjects were asked to judge whether each fact presented was old or new, and if they judged it as old, to indicate, including a confidence rating (high or low), whether the subjects had told that fact to either a man or a woman. We found that successful destination retrieval, when compared to failed destination retrieval, was associated with increased activity in the parahippocampal gyrus. We also found that the confidence level (high vs. low) for destination memory retrieval was associated with increased activity in another (posterior) region of the parahippocampal gyrus. The present study suggests that the successful retrieval of destination information depends highly on MTL-mediated recollection processes.

Distinct neural correlates of the preference-related valuation of supraliminally and subliminally presented faces.

Recent neuroimaging studies have investigated the neural substrates involved in the valuation of supraliminally presented targets and the subsequent preference decisions. However, the neural mechanisms of the valuation of subliminally presented targets, which can guide subsequent preference decisions, remain to be explored. In the present study, we determined whether the neural systems associated with the valuation of supraliminally presented faces are involved in the valuation of subliminally presented faces. The subjects were supraliminally and subliminally presented with faces during functional magnetic resonance imaging (fMRI). Following fMRI, the subjects were presented with pairs of faces and were asked to choose which face they preferred. We analyzed brain activation by back-sorting the fMRI data according to the subjects' choices. The present study yielded two main findings. First, the ventral striatum and the ventromedial prefrontal cortex predict preferences only for supraliminally presented faces. Second, the dorsomedial prefrontal cortex may predict preferences for subliminally presented faces. These findings indicate that neural correlates of the preference-related valuation of faces are dissociable, contingent upon whether the subjects consciously perceive the faces.

The neural basis of dishonest decisions that serve to harm or help the target.

We conducted a functional magnetic resonance imaging (fMRI) study to elucidate the neurocognitive mechanisms of harmful and helpful dishonest decisions. During scanning, the subjects read scenarios concerning events that could occur in real-life situations and were asked to decide whether to tell a lie as though they were experiencing those events. Half of the scenarios consisted of harmful stories in which the dishonest decisions could be regarded as bad lies, and the other half consisted of helpful stories in which the dishonest decisions could be regarded as good lies. In contrast to the control decision-making task, we found that the decision-making tasks that involved honesty or dishonesty recruited a network of brain regions that included the left dorsolateral prefrontal cortex. In the harmful stories, the right temporoparietal junction and the right medial frontal cortex were activated when the subjects made dishonest decisions compared with honest decisions. No region discriminated between the honest and dishonest decisions made in the helpful stories. These preliminary findings suggest that the neural basis of dishonest decisions is modulated by whether the lying serves to harm or help the target.

Changing the criteria for old/new recognition judgments can modulate activity in the anterior hippocampus.

Numerous functional magnetic resonance imaging (fMRI) studies have reported that the medial temporal lobe (MTL) is activated to a greater extent when subjects encounter novel items as compared with familiar ones. However, it remains unclear whether the novelty signals in the MTL are modulated by the criteria for old/new recognition judgments. In this study, we used fMRI to test our hypothesis that when subjects encounter items similar to previously encountered ones, the novelty signals in the MTL will differ depending on whether the subjects focus on the perceptual features or the semantic aspects of the items. The subjects studied a series of photographs and were later asked to make a recognition judgment of (a) Same items (items identical to those seen during encoding), (b) Similar items (items similar to but not identical to those seen during encoding), and (c) New items (unstudied items) in two types of tasks: Perceptual and Semantic. The subjects judged whether the items were perceptually identical to those seen during encoding in the Perceptual task and whether the items were semantically identical to those seen during encoding in the Semantic task. The left anterior hippocampus was activated when subjects were presented with New items relative to Same items in both tasks. In addition, the hippocampal activity in response to the Similar items was increased only in the Perceptual, but not the Semantic task. Our results indicate that the novelty signals in the hippocampus can be modulated by criteria for old/new recognition judgments.

Cholinergic deficit and response to donepezil therapy in Parkinson's disease with dementia.

BACKGROUND: Although donepezil, an acetylcholinesterase inhibitor, has been proved to be effective in ameliorating cognitive impairment in Parkinson's disease with dementia (PDD), the responsiveness of patients to donepezil therapy varies. [5-(11)C-methoxy]donepezil, the radiolabeled form of donepezil, is a ligand for positron emission tomography (PET), which can be exploited for the quantitative analysis of donepezil binding to acetylcholinesterase and for cholinergic imaging. OBJECTIVES: To investigate the deficits of the cholinergic system in the brain in PDD and its association with response to donepezil therapy. METHODS: Twelve patients with PDD and 13 normal control subjects underwent [5-(11)C-methoxy]donepezil-PET imaging. For patients with PDD, daily administration of donepezil was started after [5-(11)C-methoxy]donepezil-PET imaging and continued for 3 months. RESULTS: In the PDD group, the mean total distribution volume of the cerebral cortices was 22.7% lower than that of the normal control group. The mean total distribution volume of the patients with PDD was significantly correlated with improvement of visuoperceptual function after 3 months of donepezil therapy. CONCLUSION: The results suggest that donepezil therapy is more effective in patients with less decrease in acetylcholinesterase, a binding site of donepezil, at least in the specific cognitive domain.

The Role of the Ventromedial Prefrontal Cortex in Preferential Decisions for Own- and Other-Age Faces.

Own-age bias is a well-known bias reflecting the effects of age, and its role has been demonstrated, particularly, in face recognition. However, it remains unclear whether an own-age bias exists in facial impression formation. In the present study, we used three datasets from two published and one unpublished functional magnetic resonance imaging (fMRI) study that employed the same pleasantness rating task with fMRI scanning and preferential choice task after the fMRI to investigate whether healthy young and older participants showed own-age effects in face preference. Specifically, we employed a drift-diffusion model to elaborate the existence of own-age bias in the processes of preferential choice. The behavioral results showed higher rating scores and higher drift rate for young faces than for older faces, regardless of the ages of participants. We identified a young-age effect, but not an own-age effect. Neuroimaging results from aggregation analysis of the three datasets suggest a possibility that the ventromedial prefrontal cortex (vmPFC) was associated with evidence accumulation of own-age faces; however, no clear evidence was provided. Importantly, we found no age-related decline in the responsiveness of the vmPFC to subjective pleasantness of faces, and both young and older participants showed a contribution of the vmPFC to the parametric representation of the subjective value of face and functional coupling between the vmPFC and ventral visual area, which reflects face preference. These results suggest that the preferential choice of face is less susceptible to the own-age bias across the lifespan of individuals.

Small gray matter volume in orbitofrontal cortex in Prader-Willi syndrome: a voxel-based MRI study.

Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder presenting with behavioral symptoms including hyperphagia, disinhibition, and compulsive behavior. The behavioral problems in individuals with PWS are strikingly similar to those in patients with frontal pathologies, particularly those affecting the orbitofrontal cortex (OFC). However, neuroanatomical abnormalities in the frontal lobe have not been established in PWS. The aim of this study was to look, using volumetric analysis, for morphological changes in the frontal lobe, especially the OFC, of the brains of individuals with PWS. Twelve adults with PWS and 13 age- and gender-matched control subjects participated in structural magnetic resonance imaging (MRI) scans. The whole-brain images were segmented and normalized to a standard stereotactic space. Regional gray matter volumes were compared between the PWS group and the control group using voxel-based morphometry. The PWS subjects showed small gray-matter volume in several regions, including the OFC, caudate nucleus, inferior temporal gyrus, precentral gyrus, supplementary motor area, postcentral gyrus, and cerebellum. The small gray-matter volume in the OFC remained significant in a separate analysis that included total gray matter volume as a covariate. These preliminary findings suggest that the neurobehavioral symptoms in individuals with PWS are related to structural brain abnormalities in these areas.

The effects of aging and Alzheimer's disease on associative recognition memory.

We investigated the effects of aging and Alzheimer's disease (AD) on item and associative recognition memory. Three groups of participants (younger adults, elderly adults, and AD patients) studied photographs of common objects that were located on either the left or the right side of a black computer screen inside either a red or a blue square. In a subsequent old/new recognition memory test, the participants were presented with four kinds of stimuli: "intact" stimuli, which were presented as they were during the study phase; "location-altered" stimuli, which were presented in a different location; "color-altered" stimuli, which were presented with a different surrounding color; and "new" stimuli, which consisted of photographs that had not been presented during the study phase. Compared with younger adults, the older adults showed equivalent performance in simple item recognition but worse performance in discriminating location-altered and color-altered stimuli. Compared with older adults, the AD patients showed equivalent performance in discriminating color-altered stimuli but worse performance in simple item recognition and the discrimination of location-altered stimuli. We speculate that distinct structural and functional changes in specific brain regions that are caused by aging and AD are responsible for the different patterns of memory impairment.

Memory repression: brain mechanisms underlying dissociative amnesia.

Dissociative amnesia usually follows a stressful event and cannot be attributable to explicit brain damage. It is thought to reflect a reversible deficit in memory retrieval probably due to memory repression. However, the neural mechanisms underlying this condition are not clear. We used fMRI to investigate neural activity associated with memory retrieval in two patients with dissociative amnesia. For each patient, three categories of face photographs and three categories of people's names corresponding to the photographs were prepared: those of "recognizable" high school friends who were acquainted with and recognizable to the patients, those of "unrecognizable" colleagues who were actually acquainted with but unrecognizable to the patients due to their memory impairments, and "control" distracters who were unacquainted with the patients. During fMRI, the patients were visually presented with these stimuli and asked to indicate whether they were personally acquainted with them. In the comparison of the unrecognizable condition with the recognizable condition, we found increased activity in the pFC and decreased activity in the hippocampus in both patients. After treatment for retrograde amnesia, the altered pattern of brain activation disappeared in one patient whose retrograde memories were recovered, whereas it remained unchanged in the other patient whose retrograde memories were not recovered. Our findings provide direct evidence that memory repression in dissociative amnesia is associated with an altered pattern of neural activity, and they suggest the possibility that the pFC has an important role in inhibiting the activity of the hippocampus in memory repression.

Do parkinsonian patients have trouble telling lies? The neurobiological basis of deceptive behaviour.

Parkinson's disease is a common neurodegenerative disorder with both motor symptoms and cognitive deficits such as executive dysfunction. Over the past 100 years, a growing body of literature has suggested that patients with Parkinson's disease have characteristic personality traits such as industriousness, seriousness and inflexibility. They have also been described as 'honest', indicating that they have a tendency not to deceive others. However, these personality traits may actually be associated with dysfunction of specific brain regions affected by the disease. In the present study, we show that patients with Parkinson's disease are indeed 'honest', and that this personality trait might be derived from dysfunction of the prefrontal cortex. Using a novel cognitive task, we confirmed that patients with Parkinson's disease (n = 32) had difficulty making deceptive responses relative to healthy controls (n = 20). Also, using resting-state (18)F-fluorodeoxyglucose PET, we showed that this difficulty was significantly correlated with prefrontal hypometabolism. Our results are the first to demonstrate that the ostensible honesty found in patients with Parkinson's disease has a neurobiological basis, and they provide direct neuropsychological evidence of the brain mechanisms crucial for human deceptive behaviour.

Quantitative analysis of donepezil binding to acetylcholinesterase using positron emission tomography and [5-(11)C-methoxy]donepezil.

The aim of this study was to establish kinetic analysis of [5-(11)C-methoxy]donepezil ([(11)C]donepezil), which was developed for the in-vivo visualization of donepezil binding to acetylcholinesterase (AChE) using positron emission tomography (PET). Donepezil is an AChE inhibitor that is widely prescribed to ameliorate the cognitive impairment of patients with dementia. Six healthy subjects took part in a dynamic study involving a 60-min PET scan after intravenous injection of [(11)C]donepezil. The total distribution volume (tDV) of [(11)C]donepezil was quantified by compartmental kinetic analysis and Logan graphical analysis. A one-tissue compartment model (1TCM) and a two-tissue compartment model (2TCM) were applied in the kinetic analysis. Goodness of fit was assessed with chi(2) criterion and Akaike's Information Criterion (AIC). Compared with a 1TCM, goodness of fit was significantly improved by a 2TCM. The tDVs provided by Logan graphical analysis were slightly lower than those provided by a 2TCM. The rank order of the mean tDVs in 10 regions was in line with the AChE activity reported in a previous post-mortem study. Logan graphical analysis generated voxel-wise images of tDV, revealing the overall distribution pattern of AChE in individual brains. Significant correlation was observed between tDVs calculated with and without metabolite correction for plasma time-activity curves, indicating that metabolite correction could be omitted. In conclusion, this method enables quantitative analysis of AChE and direct investigation of the pharmacokinetics of donepezil in the human brain.

Neural correlates of true memory, false memory, and deception.

We used functional magnetic resonance imaging (fMRI) to determine whether neural activity can differentiate between true memory, false memory, and deception. Subjects heard a series of semantically related words and were later asked to make a recognition judgment of old words, semantically related nonstudied words (lures for false recognition), and unrelated new words. They were also asked to make a deceptive response to half of the old and unrelated new words. There were 3 main findings. First, consistent with the notion that executive function supports deception, 2 types of deception (pretending to know and pretending not to know) recruited prefrontal activity. Second, consistent with the sensory reactivation hypothesis, the difference between true recognition and false recognition was found in the left temporoparietal regions probably engaged in the encoding of auditorily presented words. Third, the left prefrontal cortex was activated during pretending to know relative to correct rejection and false recognition, whereas the right anterior hippocampus was activated during false recognition relative to correct rejection and pretending to know. These findings indicate that fMRI can detect the difference in brain activity between deception and false memory despite the fact that subjects respond with "I know" to novel events in both processes.

[Neuroimaging studies on higher brain functions].

For the research on human higher brain functions, both neuropsychological and neuroimaging studies are useful, but each of these two methodologies has merits and demerits. In neuropsychological studies, damaged regions are necessary for the normal execution of cognitive functions underlying the symptoms that patients show. However, it is usually difficult to determine to what extent the lesion has affected a specific psychological subprocess amongst several subprocesses related to the symptoms. On the other hand, in neuroimaging studies, activated regions may not be necessary for but simply participate in a targeted higher brain function. However, if we can set up an adequate experimental design, it provides an opportunity to identify brain regions related to a specific psychological subprocess necessary for the targeted higher brain function. In this symposium, I talked about several neuroimaging studies using positron emission tomography and functional magnetic resonance imaging. We can take advantage of neuroimaging techniques for the research on human brain functions, but it should be kept in mind that neuroimaging techniques are not the purpose of the research but simply one of the useful means.

Effect of aging on choice-induced cognitive conflict.

When individuals are forced to choose between similarly preferable alternatives, a negatively arousing cognitive conflict occurs, and the preference attitudes toward the chosen and rejected alternatives diverge. This phenomenon, often referred to as "cognitive dissonance", is of interest in psychological and decision neuroscience research. The dorsal anterior cingulate cortex (dACC) is involved in representing the cognitive conflict induced by difficult-choice tasks. Previous studies have shown age-related decline of the dACC function. However, whether the heightened activity of the dACC regarding cognitive conflict, and choice-induced preference change that behaviorally occur in young subjects also occur in the elderly is unclear. Furthermore, recent studies have noted substantial methodological flaw with the free-choice paradigm that often used in studies focusing on cognitive dissonance. Here, we used functional magnetic resonance imaging (fMRI) and a modified free-choice paradigm to formally test the effect of aging on choice-induced cognitive conflict. In the young participants, behavioral data confirmed the existence of cognitive conflict and preference change for the alternatives that they rejected in the difficult-choice trials. The imaging data revealed that the right dACC displayed an interaction effect associated with cognitive conflict. In contrast, we did not observe such effects in the elderly participants. These suggest a possibility that elderly people likely feel less cognitive dissonance.

[Medial Temporal Lobe Amnesia].

The medial temporal lobe was identified as an important neural structure in human memory by the advent of patient H.M., who suffered from severe amnesia caused by bilateral medial temporal lobectomy. Dozens of neuropsychological study of H.M. led to the classification of human memory into declarative and non-declarative memory, as well as short-term and long-term memory. The medial temporal lobe subserves declarative memory and long-term memory. It also plays an important role especially in the process of memory consolidation. The psychological and neurological mechanisms of the consolidation process can be investigated through the study of retrograde amnesia and epileptic amnesia.

Activity changes in the left superior temporal sulcus reflect the effects of childcare training on young female students' perceptions of infants' negative facial expressions.

In many developed countries, the number of infants who experience non-parent childcare is increasing, and the role of preschool teachers is becoming more important. However, little attention has been paid to the effects of childcare training on students who are studying to become preschool teachers. We used functional magnetic resonance imaging (fMRI) to investigate whether and how childcare training affects brain responses to infants' facial expressions among young females studying to become preschool teachers. Twenty-seven subjects who attended a childcare training session (i.e., the experimental group) and 28 subjects who did not attend the training (i.e., the control group) participated in this study. The participants went through fMRI scanning twice: before and after the childcare training session. They were presented with happy, neutral, and sad infant faces one by one during fMRI scanning. The present neuroimaging results revealed that the activity patterns of the left superior temporal sulcus (STS) for sad faces were modulated by the interaction between the time point of the data collection and group differences. The present results are the first to highlight the effects of childcare training on the human brain.

Selective impairment in the retrieval of family relationships in person identification: a case study of delusional misidentification.

We describe a 74-year-old, right-handed woman who exhibited a peculiar form of delusional misidentification due to Alzheimer's disease (AD) combined with idiopathic normal pressure hydrocephalus (iNPH). The patient's most distinctive symptom was that she often misidentified her daughters as her sisters. She had severe atrophy of the bilateral medial temporal lobe and right-hemisphere-dominant hypoperfusion in the fronto-temporo-parietal cortices. Detailed tests revealed that she had a selective deficit in retrieving the family relationships between herself and her daughters/husband (i.e., she misidentified her daughters as her sisters and her husband as her father), despite being able to retrieve the names and faces of her family members, and some person-specific semantic information (e.g., occupation) related to them. We speculate that this specific type of misidentification can be elicited by failure to update semantic memory through the encoding of new episodic memory due to right-hemisphere-dominant fronto-temporal dysfunction.

Differential involvement of regions of rostral prefrontal cortex (Brodmann area 10) in time- and event-based prospective memory.

Rostral prefrontal cortex (approximating Brodmann area 10) has been shown repeatedly to have a role in the maintenance and realization of delayed intentions that are triggered by event cues (i.e., event-based prospective memory). The cerebral organization of the processes associated with the use of time cues (time-based prospective memory) has however received less attention. In two positron emission tomography (PET) studies we therefore examined brain activity associated with time- and event-based prospective memory tasks. In the time-based condition of the first study, young healthy volunteers were asked to make a prospective response based on their self-estimation of the passage of time while engaged in an attention-demanding ongoing activity. In the time-based condition of the second study, participants had a clock available in the ongoing task display and did not need to estimate the time for the prospective response. In the event-based condition of both studies, participants were asked to make a prospective response when prospective cues were presented in ongoing trials. Both studies showed activation differences in rostral prefrontal cortex according to whether the task was time- or event-based. In study one, an area of left superior frontal gyrus was more active in the time-based condition. In study two, three rostral prefrontal regions were more active in the time-based condition: right superior frontal gyrus, anterior medial frontal lobe and anterior cingulate gyrus. A region in left superior frontal gyrus, different from the area found in the first study, was more active in the event-based condition. These results indicate involvement of multiple brain regions of rostral prefrontal cortex in time- and event-based prospective memory. The results are interpreted as reflecting the differing processing demands made by event- or time-based prospective memory tasks, and the differing demands of time-based tasks according to whether a clock is present as an aid.

Gender differences in ventromedial prefrontal cortex activity associated with valuation of faces.

Psychological studies have indicated that males exhibit stronger preferences for physical attributes in the opposite gender, such as facial attractiveness, than females. However, whether gender differences in mate preference originate from differential brain activity remains unclear. Using functional magnetic resonance imaging (fMRI), we investigated the patterns of brain activity in the ventromedial prefrontal cortex (vmPFC), a region critical for the valuation of faces, in response to elderly male, elderly female, young male, and young female faces. During fMRI, male and female subjects were presented with a face and asked to rate its pleasantness. Following fMRI, the subjects were presented with pairs of faces and asked to select the face that they preferred. We analyzed the vmPFC activity during the pleasantness-rating task according to the gender of the face stimulus (male and female) and the age of the face stimulus (elderly and young). Consistent with the results of previous studies, the vmPFC activity parametrically coded the subjective value of faces. Importantly, the vmPFC activity was sensitive to physical attributes, such as the youthfulness and gender of the faces, only in the male subjects. These findings provide a possible neural explanation for gender differences in mate preference.