Sensory hypo- and hypersensitivity in patients with brain tumors.

OBJECTIVES: Hyper- and hyposensitivity in multiple modalities have been well-documented in subjects with autistic spectrum disorder (ASD) but not in subjects with acquired brain injury (ABI). The purpose of this study was to determine whether subjects with ABI experience altered sensory processing in multiple sensory modalities, and to examine the relationships between impaired sensory processing and the emotional state. METHODS AND PROCEDURES: Sixty-eight patients with brain or spinal cord tumors participated in the study. Cognitive ability and emotional function were tested, and subjective changes were evaluated in two directions (hyper- and hyposensitivity) and five modalities (visual, auditory, tactile, olfactory, and gustatory) at two time points (after disease onset and after surgery). RESULTS: One-fifth of the participants complained of hypersensitivity in the visual domain, and a similar proportion complained of hyposensitivity in the auditory and tactile domains. Additionally, one-third of participants complained of two or more sensory abnormalities after disease onset. A hierarchical regression analysis indicated that auditory and tactile sensory changes predicted a depressive state. CONCLUSION: In conclusion, multimodal sensory changes occurred in patients with brain tumors, manifesting as hyper- or hyposensitivity. Sensory changes might be related to depressive state, but the results were inconclusive.

Decreased sensitivity to loss of options in patients with Parkinson's disease.

Humans prefer to have many options when making decisions. When there is a threat of options disappearing, humans invest more to keep these options available, indicating that they are sensitive to the loss of options. This study examined whether patients with Parkinson's disease (PD), a disease characterized by dopamine depletion, try to keep options available when options are disappearing. Twenty-seven PD patients without dementia and 27 healthy controls (HCs) performed the door game, in which participants were presented with multiple alternatives in the form of three doors, each associated with a different point distribution. The participants were asked to maximize their point earnings by finding the best door. The task included two conditions. In the shutter condition, shutters gradually closed on doors that were not chosen; once the shutters completely closed, the door was no longer available. There were no shutters in the control condition. The results revealed that the HCs switched doors more often in the shutter condition than in the control condition, indicating a tendency to keep options available. However, the PD patients did not show such differences between the two conditions. The difference in the number of switches between the shutter and control conditions in the PD patients was significantly positively correlated with the distribution of dopamine transporters in the left striatum, as measured by 123I-ioflupane-SPECT (DaTSCAN) images. These results suggest that PD patients are less sensitive to the loss of options, and this decreased sensitivity may be caused by a decline in dopaminergic neurotransmission.

Neural Representations of Death in the Cortical Midline Structures Promote Temporal Discounting.

Death is an important reminder that our lives are finite. Although some studies have shown that thinking about one's own death increases temporal discounting (i.e., the devaluing of future rewards), the underlying neural mechanisms are still unknown. In a functional magnetic resonance imaging experiment, we compared the neural and behavioral processes of temporal discounting across four conditions involving distinct types of future thinking (death related, negative, neutral, and positive). Replicating prior research, the behavioral evidence showed that temporal discounting increased when thinking about one's own future death. Multivoxel pattern analysis showed that death-related future thinking was decoded in default mode regions, including the inferior parietal lobule, precuneus, and medial prefrontal cortex (MPFC). When future thinking was death related (vs. negative), increased temporal discounting was associated with a higher decoding accuracy in the precuneus and MPFC. The present findings suggest that death-related neural representations are distributed across default mode regions, and neural populations in the cortical midline structures play a crucial role in the integration of one's own death into economic decision-making.

Intrinsic motivation in patients with Parkinson's disease: a neuropsychological investigation of curiosity using dopamine transporter imaging.

Both intrinsic and extrinsic motivation are believed to involve brain regions that are innervated by the dopaminergic pathway. Although dopaminergic neurons in the midbrain deteriorate in Parkinson's disease (PD), it remains unclear whether intrinsic motivation is impaired in PD patients. To address this issue, we investigated intrinsic motivation in PD patients using a task designed to assess the "Pandora effect," which constitutes a curiosity for resolving uncertainty, even if this curiosity is likely to result in negative consequences. Twenty-seven PD patients and 27 age-matched healthy controls (HCs) completed a curiosity task in which they were required to decide either to view or skip negative pictures (e.g., snakes, spiders) and an examination battery that included the Mini-Mental State Examination, a verbal fluency test, the Trail Making Test, 10-word recall tests, and questionnaires for behavioral inhibition/activation and depression. DaTSCAN images to assess the distribution of dopamine transporters in the striatum were acquired only from PD patients. The results revealed that PD patients, relative to the HCs, viewed the pictures less frequently under both the certain and uncertain conditions. However, both the PD patients and HCs viewed the pictures at a higher frequency under the uncertain condition than under the certain condition. In the PD patients, the proportion of pictures viewed under the certain condition was positively correlated with the distribution of dopamine transporters in the striatum. These results suggest that despite the overall decreasing level of interest in viewing negative pictures, the motivation to resolve uncertainty is relatively intact in PD patients.

Measuring the sense of self in brain-damaged patients: A STROBE-compliant article.

Recently, researchers have focused on the embodied sense of self (ESS), which consists of the minimal and narrative selves. Although a study demonstrated that the ESS is related to brain dysfunction empirically, the subjective aspects of the ESS, and a systematic approach to it, have not yet been examined in brain-damaged patients. To examine this, we measured the ESS of patients with brain tumors before and after awake craniotomy.A self-reported questionnaire called the Embodied Sense of Self Scale (ESSS) was used to measure the ESS in patients with brain tumors before and after surgery. For comparison, age-matched controls also completed the ESSS.The ESSS scores of the patients with brain tumors before surgery were higher than those of the controls and improved after surgery. Before surgery, patients with left hemispheric lesions had a poorer ESSS than those with right hemispheric lesions. Episodic memory disturbance was highly correlated with malfunction of narrative self and ownership.Brain lesions were associated with anomalous ESSS, associated with hemispheric laterality and cognitive dysfunction.

[Neuropsychology of the Psychological Present].

The psychological present is a diverse psychological phenomenon, including the perception and evaluation of time, which has been studied from different perspectives. The experience of the psychological present is known to differ according to psychological state and cognitive processes, such as attention. Neuropsychological studies focused on brain-damaged patients have explored several aspects of the present, but few studies have examined the subjective aspect of the phenomenon. In this article, we focus on the subjective aspect of the present in brain-damaged patients and propose that the psychological present is maintained by several brain regions through the integration of multiple information sources.

Remembering my friends: Medial prefrontal and hippocampal contributions to the self-reference effect on face memories in a social context.

Memories associated with the self are remembered more accurately than those associated with others. The memory enhancement related to the self is known as the self-reference effect (SRE). However, little is known regarding the neural mechanisms underlying the SRE in a social context modulated by social relationships. In the present fMRI study, we investigated encoding-related activation of face memories encoded with the self-referential process in a social context that was manipulated by imagining a person-to-person relationship. Healthy young adults participated in the present study. During encoding, participants encoded unfamiliar target faces by imagining a future friendship with themselves (Self), their friends (Friend), or strangers (Other). During retrieval, participants were presented with target and distracter faces one by one, and they judged whether each face had been previously learned. In the behavioral results, target faces encoded in the Self condition were remembered more accurately than those encoded in the Other condition. fMRI results demonstrated that encoding-related activation in the medial prefrontal cortex (mPFC) was significantly greater in the Self condition than in the Friend or Other conditions. In addition, the generalized psycho-physiological interaction (gPPI) analysis showed that functional connectivity between activation in the hippocampus and the cortical midline structures (CMSs), including the mPFC and precuneus, was significant in the Self but not in the Other condition. These findings suggest that the SRE in a social context could be involved in the interaction between the CMS regions, which are related to the self-referential process, and the hippocampus related to the memory process. Hum Brain Mapp 38:4256-4269, 2017. © 2017 Wiley Periodicals, Inc.

Neural mechanisms underlying the reward-related enhancement of motivation when remembering episodic memories with high difficulty.

The motivation to receive rewards enhances episodic memories, and the motivation is modulated by task difficulty. In episodic retrieval, however, functional neuroimaging evidence regarding the motivation that mediates interactions between reward and task difficulty is scarce. The present fMRI study investigated this issue. During encoding performed without fMRI, participants encoded Japanese words using either deep or shallow strategies, which led to variation in difficulty level during subsequent retrieval. During retrieval with fMRI, participants recognized the target words in either high or low monetary reward conditions. In the behavioral results, a reward-related enhancement of memory was found only when the memory retrieval was difficult, and the rewarding effect on subjective motivation was greater in the retrieval of memories with high difficulty than those with low difficulty. The fMRI data showed that reward-related increases in the activation of the substantia nigra/ventral tegmental area (SN/VTA), medial temporal lobe (MTL), dorsomedial prefrontal cortex (dmPFC), and dorsolateral prefrontal cortex (dlPFC) were greater during the retrieval of memories with high difficulty than those with low difficulty. Furthermore, reward-related enhancement of functional connectivity between the SN/VTA and MTL and between the SN/VTA and dmPFC during the retrieval of memories with high difficulty was significantly correlated with reward-related increases of retrieval accuracy and subjective motivation. The reward-related enhancement of episodic retrieval and retrieval-related motivation could be most effective when the level of retrieval difficulty is optimized. Such reward-related enhancement of memory and motivation could be modulated by a network including the reward-related SN/VTA, motivation-related dmPFC, and memory-related MTL. Hum Brain Mapp 38:3428-3443, 2017. © 2017 Wiley Periodicals, Inc.

Lateral and medial prefrontal contributions to emotion generation by semantic elaboration during episodic encoding.

Memories for emotion-laden stimuli are remembered more accurately than those for neutral stimuli. Although this enhancement reflects stimulus-driven modulation of memory by emotions, functional neuroimaging evidence of the interacting mechanisms between emotions generated by intentional processes, such as semantic elaboration, and memory is scarce. The present fMRI study investigated how encoding-related activation is modulated by emotions generated during the process of semantic elaboration. During encoding with fMRI, healthy young adults viewed neutral (target) pictures either passively or with semantic elaboration. In semantic elaboration, participants imagined background stories related to the pictures. Encoding trials with semantic elaboration were subdivided into conditions in which participants imagined negative, positive, or neutral stories. One week later, memories for target pictures were tested. In behavioral results, memories for target pictures were significantly enhanced by semantic elaboration, compared to passive viewing, and the memory enhancement was more remarkable when negative or positive stories were imagined. fMRI results demonstrated that activations in the left inferior frontal gyrus and dorsal medial prefrontal cortex (dmPFC) were greater during the encoding of target pictures with semantic elaboration than those with passive viewing, and that these activations further increased during encoding with semantic elaboration of emotional stories than of neutral stories. Functional connectivity between the left inferior frontal gyrus and dmPFC/hippocampus during encoding significantly predicted retrieval accuracies of memories encoded with self-generated emotional stories. These findings suggest that networks including the left inferior frontal region, dmPFC, and hippocampus could contribute to the modulation of memories encoded with the emotion generation.

Competing against a familiar friend: Interactive mechanism of the temporo-parietal junction with the reward-related regions during episodic encoding.

Competition enhances learning under certain circumstances. However, little is known about how the neural mechanisms involved in a competition during the episodic encoding are modulated by the social distance of personal relationships with opponents. To investigate this issue, using functional magnetic resonance imaging (fMRI), we scanned healthy young adults during a competition with their familiar friends and unfamiliar others in the episodic encoding. Three major findings emerged from this study. First, activations in the right temporo-parietal junction (rTPJ) were significantly greater in the competition with familiar friends than with unfamiliar others, and the activations in this region were significantly correlated with the subjective ratings of motivation. Second, striatum and amygdala activations increased by the competition with familiar friends were significantly correlated with the increased ratings of pleasantness, which reflected emotionally positive feelings in victory for the competition with familiar opponents. Third, the functional connectivity between the rTPJ and reward-related regions, including the striatum and substantia nigra, was higher in the competition with familiar friends than with unfamiliar others. Taken together with our behavioral findings, in which memories encoded by competing with familiar friends were remembered more accurately than those with unfamiliar others, the interacting mechanisms between the rTPJ that is involved in social motivation and the reward-related regions that are involved in social reward could contribute to the enhancement of memories encoded in the competition with familiar others.

Remembering with gains and losses: effects of monetary reward and punishment on successful encoding activation of source memories.

The motivation of getting rewards or avoiding punishments reinforces learning behaviors. Although the neural mechanisms underlying the effect of rewards on episodic memory have been demonstrated, there is little evidence of the effect of punishments on this memory. Our functional magnetic resonance imaging (fMRI) study investigated the effects of monetary rewards and punishments on activation during the encoding of source memories. During encoding, participants memorized words (item) and locations of presented words (source) under 3 conditions (Reward, Punishment, and Control). During retrieval, participants retrieved item and source memories of the words and were rewarded or penalized according to their performance. Source memories encoded with rewards or punishments were remembered better than those without such encoding. fMRI data demonstrated that the ventral tegmental area and substantia nigra and nucleus accumbens activations reflected both the processes of reward and punishment, whereas insular activation increased as a linear function of punishment. Activation in the hippocampus and parahippocampal cortex predicted subsequent retrieval success of source memories. Additionally, correlations between these reward/punishment-related regions and the hippocampus were significant. The successful encoding of source memories could be enhanced by punishments and rewards, and interactions between reward/punishment-related regions and memory-related regions could contribute to memory enhancement by reward and/or punishment.

Encoding- and retrieval-related brain activity underlying false recognition.

We examined the neural activity associated with true and false recognition during both encoding and retrieval using the Remember/Know procedure to separate recollection (i.e., mental reinstatement of experienced events during which unique details of a memory are recalled) and familiarity (i.e., mental awareness that an event has been experienced previously without the unique details of the event) in recognition memory. Neuroimaging data at retrieval revealed that the right parahippocampal gyrus was activated during recollection-based true recognition compared with familiarity-based true recognition, indicating the item-specific retrieval of visual details. This effect in the right parahippocampal gyrus was not observed for false recognition. Contrary to our expectation, the reactivation effect in early visual cortex was not observed during true recognition, as opposed to false recognition. Neuroimaging data at encoding revealed that the right visual cortex (the right occipitotemporal sulcus) was activated during the encoding of items that yielded recollection-based true recognition compared with familiarity-based true recognition, indicating item-specific visual processing. This effect in the right visual cortex was not observed for false recognition. These results suggest that the subjective feeling of Remember/Know with respect to both veridical and false memories varies with the neural activity during both encoding and retrieval.

Insular and hippocampal contributions to remembering people with an impression of bad personality.

Our impressions of other people are formed mainly from the two possible factors of facial attractiveness and trustworthiness. Previous studies have shown the importance of orbitofrontal-hippocampal interactions in the better remembering of attractive faces, and psychological data have indicated that faces giving an impression of untrustworthiness are remembered more accurately than those giving an impression of trustworthiness. However, the neural mechanisms of the latter effect are largely unknown. To investigate this issue, we investigated neural activities with event-related fMRI while the female participants rated their impressions of the personalities of men in terms of trustworthiness. After the rating, memory for faces was tested to identify successful encoding activity. As expected, faces that gave bad impressions were remembered better than those that gave neutral or good impressions. In fMRI data, right insular activity reflected an increasing function of bad impressions, and bilateral hippocampal activities predicted subsequent memory success. Additionally, correlation between these insular and hippocampal regions was significant only in the encoding of faces associated with a bad impression. Better memory for faces associated with an impression of bad personality could reflect greater interaction between the avoidance-related insular region and the encoding-related hippocampal region.

Brain training game improves executive functions and processing speed in the elderly: a randomized controlled trial.

BACKGROUND: The beneficial effects of brain training games are expected to transfer to other cognitive functions, but these beneficial effects are poorly understood. Here we investigate the impact of the brain training game (Brain Age) on cognitive functions in the elderly. METHODS AND RESULTS: Thirty-two elderly volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). This study was completed by 14 of the 16 members in the Brain Age group and 14 of the 16 members in the Tetris group. To maximize the benefit of the interventions, all participants were non-gamers who reported playing less than one hour of video games per week over the past 2 years. Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Each group played for a total of about 20 days. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into four categories (global cognitive status, executive functions, attention, and processing speed). Results showed that the effects of the brain training game were transferred to executive functions and to processing speed. However, the brain training game showed no transfer effect on any global cognitive status nor attention. CONCLUSIONS: Our results showed that playing Brain Age for 4 weeks could lead to improve cognitive functions (executive functions and processing speed) in the elderly. This result indicated that there is a possibility which the elderly could improve executive functions and processing speed in short term training. The results need replication in large samples. Long-term effects and relevance for every-day functioning remain uncertain as yet. TRIAL REGISTRATION: UMIN Clinical Trial Registry 000002825.

Effects of aging on hippocampal and anterior temporal activations during successful retrieval of memory for face-name associations.

Memory for face-name associations is an important type of memory in our daily lives, and often deteriorates in older adults. Although difficulty retrieving face-name associations is often apparent in the elderly, there is little neuroscientific evidence of age-related decline in this memory. The current fMRI study investigated differences in brain activations between healthy young and older adults during the successful retrieval of people's names (N) and job titles (J) associated with faces. During encoding, participants viewed unfamiliar faces, each paired with a job title and name. During retrieval, each learned face was presented with two job titles or two names, and participants were required to choose the correct job title or name. Retrieval success activity (RSA) was identified by comparing retrieval-phase activity for hits versus misses in N and J, and the RSAs in each task were compared between young and older adults. The study yielded three main findings. First, the hippocampus showed significant RSA in both tasks of N and J, and the activity was greater for young compared to older subjects. Second, the left anterior temporal lobe (ATL) showed greater RSA in N than in J, but there was no age difference in the activity in this region. Third, functional connectivity between hippocampal and ATL activities in both retrieval tasks was higher for young than for older adults. Taken together, age-related differences in hippocampal activities and hippocampus-ATL connectivity could contribute to age-related decline in relational memory and to complaints of poor retrieval of people's names by older adults.

Right temporal-lobe contribution to the retrieval of family relationships in person identification.

We previously reported a patient who exhibited a peculiar form of delusional misidentification. She had a selective deficit in retrieving family relationships between herself and her daughters and husband (i.e., she misidentified her daughters as her sisters and her husband as her father) despite being able to retrieve their names and faces and some person-specific semantic information (e.g., occupation). Based on this finding, the present positron emission tomography study was designed to elucidate the brain mechanisms underlying the retrieval of family relationships in healthy individuals. We found that the right inferior temporal gyrus, in which hypoperfusion was detected in the patient we had reported, was significantly activated during the retrieval of family relationships compared with names and occupations. These findings indicate that the retrieval of the relationships between oneself and one's family members may require a specific cognitive process dissociated from the retrieval of names and other person-specific semantic information.

Neural correlates of forgiveness for moral transgressions involving deception.

We used positron emission tomography (PET) to investigate the neural mechanisms underlying the willingness to forgive another person's moral transgression involving deception. During scanning, 12 subjects were asked to judge the forgivability of a perpetrator's moral transgression. These transgressions were described by four kinds of scenarios composed of a combination of two factors: the attitude of the perpetrator (dishonest or honest) and the severity of the moral transgression (serious or minor). Behavioral data showed that both the perpetrator's dishonesty and the seriousness of the scenario decreased the subjects' willingness to forgive the moral transgression. Neuroimaging data revealed that, relative to honest responses, a perpetrator's dishonest responses were associated with right ventromedial prefrontal activity, which possibly reflects the subjects' identification of the perpetrator's deception. The opposite comparison did not show significant activation. Moreover, a comparison of serious scenarios with minor scenarios did not reveal significant activation. Instead, minor scenarios, relative to serious scenarios, evoked activity in the right middle frontal gyrus and the right caudate nucleus, possibly reflecting increased demand on frontal control system function. Further analysis revealed that the left ventromedial prefrontal cortex showed a significant interaction between the two factors, indicating that this region functions as a mediator of the two factors, modulating judgments regarding the forgivability of moral transgressions. Taken together, these findings suggest that the ventromedial prefrontal cortex plays a key role in the forgiveness of moral transgressions involving deception.

Effects of emotion and reward motivation on neural correlates of episodic memory encoding: a PET study.

It is known that emotion and reward motivation promote long-term memory formation. It remains unclear, however, how and where emotion and reward are integrated during episodic memory encoding. In the present study, subjects were engaged in intentional encoding of photographs under four different conditions that were made by combining two factors (emotional valence, negative or neutral; and monetary reward value, high or low for subsequent successful recognition) during H2 15O positron emission tomography (PET) scanning. As for recognition performance, we found significant main effects of emotional valence (negative>neutral) and reward value (high value>low value), without an interaction between the two factors. Imaging data showed that the left amygdala was activated during the encoding conditions of negative pictures relative to neutral pictures, and the left orbitofrontal cortex was activated during the encoding conditions of high reward pictures relative to low reward pictures. In addition, conjunction analysis of these two main effects detected right hippocampal activation. Although we could not find correlations between recognition performance and activity of these three regions, we speculate that the right hippocampus may integrate the effects of emotion (processed in the amygdala) and monetary reward (processed in the orbitofrontal cortex) on episodic memory encoding.

Reactivation of medial temporal lobe and human V5/MT+ during the retrieval of motion information: a PET study.

Recent neuroimaging evidence suggests that the retrieval of a prior episode reactivates sensory-processing brain regions that were active when the episode was encoded. However, with regard to reactivation of the medial temporal lobe (MTL), the results remain controversial. In the present study, we used positron emission tomography (PET) to identify the brain regions associated with the encoding and retrieval of motion information. Specifically, we assessed whether overlapping activity was found in both the MTL structures and motion-related cortical regions during the encoding and retrieval of motion information attached to meaningless shapes. During the study, subjects were asked to encode moving (rotating to the right or left) and static meaningless shapes. At subsequent testing, subjects were presented with only static shapes, which had been presented with or without motion during encoding, and were engaged in retrieval tasks of shapes and motion. Overlapping activity was found in the right middle temporal gyrus (V5/MT+) and the left MTL (hippocampus) during the encoding and retrieval of shapes with motion compared with those without motion. These results support the view that the retrieval of specific event information is associated with reactivation of both the MTL and the regions involved during the encoding of that information.

Prefrontal and medial temporal contributions to episodic memory-based reasoning.

Episodic memory retrieval and reasoning are fundamental psychological components of our daily lives. Although previous studies have investigated the brain regions associated with these processes separately, the neural mechanisms of reasoning based on episodic memory retrieval are largely unknown. Here, we investigated the neural correlates underlying episodic memory-based reasoning using functional magnetic resonance imaging (fMRI). During fMRI scanning, subjects performed three tasks: reasoning, episodic memory retrieval, and episodic memory-based reasoning. We identified dissociable activations related to reasoning, episodic memory retrieval, and linking processes between the two. Regions related to reasoning were identified in the left ventral prefrontal cortices (PFC), and those related to episodic memory retrieval were found in the right medial temporal lobe (MTL) regions. In addition, activations predominant in the linking process between the two were found in the left dorsal and right ventral PFC. These findings suggest that episodic memory-based reasoning is composed of at least three processes, i.e., reasoning, episodic memory retrieval, and linking processes between the two, and that activation of both the PFC and MTL is crucial in episodic memory-based reasoning. These findings are the first to demonstrate that PFC and MTL regions contribute differentially to each process in episodic memory-based reasoning.