Consciousness of subjective time in the brain.

"Mental time travel" refers to conscious experience of remembering the personal past and imagining the personal future. Little is known about its neural correlates. Here, using functional magnetic resonance imaging, we explored the hypothesis that mental time travel into "nonpresent" times (past and future) is enabled by a special conscious state (chronesthesia). Well-trained subjects repeatedly imagined taking one and the same short walk in a familiar environment, doing so either in the imagined past, present, or future. In an additional condition, they recollected an instance in which they actually performed the same short walk in the same familiar setting. This design allowed us to measure brain activity correlated with "pure" conscious states of different moments of subjective time. The results showed that the left lateral parietal cortex was differentially activated by nonpresent subjective times compared with the present (past and future > present). A similar pattern was observed in the left frontal cortex, cerebellum, and thalamus. There was no evidence that the hippocampal region is involved in subjective time travel. These findings provide support for theoretical ideas concerning chronesthesia and mental time travel.

Cognitive association formation in episodic memory: evidence from event-related potentials.

The present study focused on the processes underlying cognitive association formation by investigating subsequent memory effects. Event-related potentials were recorded as participants studied pairs of words, presented one word at a time, for later recall. The findings showed that a frontal-positive late wave (LW), which occurred 1-1.6s after the presentation of the second word of a pair during study, was associated with later paired associate recall. The observed LW likely reflected cognitive association formation processing. Paired associate recall was also associated with a larger P555 to each word of a pair, likely reflecting the encoding of each individual word of a pair, which necessarily precedes association formation between the two words. Moreover a larger N425 was elicited by pairs that were encoded in a low context-similarity condition compared to that of a high context-similarity condition, likely reflecting semantic integration. Minimum norm source analyses showed that the likely sources of these ERP effects changed dynamically in time: a widespread fronto-temporo-parietal activation during the N425 was followed by a fronto-temporal activation during the P555, and finally by a left prefrontal activation during the LW.

Seeing sounds and hearing sights: the influence of prior learning on current perception.

It is well known that previous perceptual experiences alter subsequent perception, but the details of the neural underpinnings of this general phenomenon are still sketchy. Here, we ask whether previous experiences with an item (such as seeing a person's face) leads to the alteration of the neural correlates related to processing of the item as such, or whether it creates additional associative connections between such substrates and those activated during prior experience. To address this question, we used magnetoencephalography (MEG) to identify neural changes accompanying subjects' viewing of unfamiliar versus famous faces and hearing the names of unfamiliar versus famous names. We were interested in the nature of the involvement of auditory brain regions in the viewing of faces, and in the involvement of visual regions in the hearing of names. Evoked responses from MEG recordings for the names and faces conditions were localized to auditory and visual cortices, respectively. Unsurprisingly, peak activation strength of evoked responses was larger for famous versus nonfamous names within the superior temporal gyrus (STG), and was similar for famous and nonfamous faces in the occipital cortex. More relevant to the issue of experience on perception, peak activation strength in the STG was larger for viewed famous versus nonfamous faces, and peak activation within the occipital cortex was larger for heard famous versus nonfamous names. Critically, these experience-related responses were present within 150-250 msec of stimulus onset. These findings support the hypothesis that prior experiences may influence processing of faces and names such that perception encompasses more than what is imparted on the senses.

Theory of mind is independent of episodic memory.

Theory of mind (ToM) to infer other people's current mental states and episodic memory of personal happenings have been assumed to be closely related. We report two participants with severely impaired episodic memory who perform indistinguishably from healthy controls on objective ToM tests. These results suggest that ToM can function independently of episodic memory.

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.

Memory encoding and retrieval on the ascending and descending limbs of the blood alcohol concentration curve.

RATIONALE: Little is known about acute effects of alcohol on memory encoding and retrieval on different limbs (ascending and descending) of the blood alcohol concentration (BAC) curve. OBJECTIVES: This extensive experiment was designed to examine alcohol's effects on memory encoding and retrieval throughout a protracted drinking episode. METHODS: In a 9-h session, male participants consumed either alcohol (1 ml/kg) or placebo (n = 32/32) over a period of 90 min and learned various materials in different memory tasks before, during, and after consuming the drinks, while their BAC levels were monitored. A week later, in a similar session, they were tested on learned materials before, during, and after drinking. Mood was assessed throughout both sessions. RESULTS: Alcohol impaired recall of words more than recognition, and cued recall most severely. Perceptual priming and picture recognition were not affected by alcohol. Alcohol impaired encoding in cued recall, recognition of completed word fragments, and free recall regardless of limb, but impaired retrieval in word recognition only during the ascending BAC. Alcohol increased negative mood on the descending limb during the first session, and on the ascending limb during the second session. CONCLUSIONS: Under naturalistic drinking conditions, alcohol's effects on memory depend on task, memory process, and limb of the BAC curve. The differential effects of alcohol on retrieval during the ascending and descending limbs demonstrate the importance of examining the differential effects on the two limbs.

The case of K.C.: contributions of a memory-impaired person to memory theory.

K.C. has been investigated extensively over some 20 years since a motorcycle accident left him with widespread brain damage that includes large bilateral hippocampal lesions, which caused a remarkable case of memory impairment. On standard testing, K.C.'s anterograde amnesia is as severe as that of any other case reported in the literature, including H.M. However, his ability to make use of knowledge and experiences from the time before his accident shows a sharp dissociation between semantic and episodic memory. A good deal of his general knowledge of the world, including knowledge about himself, is preserved, but he is incapable of recollecting any personally experienced events. In displaying such "episodic amnesia," which encompasses an entire lifetime of personal experiences, K.C. differs from many other amnesic cases. Here, we document for the first time the full extent of K.C.'s brain damage using MRI-based quantitative measurements. We then review the many investigations with K.C. that have contributed to our understanding not only of episodic and semantic memory but also to the development of other aspects of memory theory. These include the distinction between implicit and explicit memory, the prospect of new learning in amnesia, and the fate of recent and remote memory for autobiographical and public events, people, and spatial locations.

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.

Hemispheric asymmetries of memory: the HERA model revisited.

The hemispheric encoding/retrieval asymmetry (HERA) model is a process-specific description of experimental data provided by a large set of functional neuroimaging studies. According to HERA, left prefrontal cortex (PFC) is more involved than right PFC in episodic memory encoding, whereas right PFC is more involved than left PFC in episodic memory retrieval. Recently it has been claimed that this description does not hold for non-verbal materials. Here we propose a more precise formulation of HERA than previously, and argue that there is sufficient evidence to conclude that HERA, as reformulated, is true for both verbal and non-verbal materials.

Memory encoding and hippocampally-based novelty/familiarity discrimination networks.

Novelty discrimination refers to the ability to decide whether information is new or has been previously encountered. Recent functional neuroimaging work has demonstrated that the hippocampus plays an important function in novelty discrimination. In the study described here, we explored the idea that novelty discrimination does not depend on the hippocampus alone but involves large-scale functional neural networks consisting of spatially remote brain regions. We measured blood flow with positron emission tomography (PET) while subjects semantically encoded visually and auditorily presented situationally novel and familiar words. Following each PET scan, subjects' memory was tested with a standard yes/no recognition test. Blood flow data were analyzed with the covariance-based seed partial least squares (PLS) method. Behaviorally, subjects' recognition performance was higher for novel than familiar words. Neurally, two large-scale functional networks involving the same region of the hippocampus were identified which showed coherent activity either during the encoding of situationally novel (but not familiar) items or situationally familiar (but not novel) items. These findings indicate that different neural networks are active in the processing of situationally novel and familiar information. The observation that the hippocampus participates in both networks supports the principle of neural context.

Episodic memory: from mind to brain.

Episodic memory is a neurocognitive (brain/mind) system, uniquely different from other memory systems, that enables human beings to remember past experiences. The notion of episodic memory was first proposed some 30 years ago. At that time it was defined in terms of materials and tasks. It was subsequently refined and elaborated in terms of ideas such as self, subjective time, and autonoetic consciousness. This chapter provides a brief history of the concept of episodic memory, describes how it has changed (indeed greatly changed) since its inception, considers criticisms of it, and then discusses supporting evidence provided by (a) neuropsychological studies of patterns of memory impairment caused by brain damage, and (b) functional neuroimaging studies of patterns of brain activity of normal subjects engaged in various memory tasks. I also suggest that episodic memory is a true, even if as yet generally unappreciated, marvel of nature.