Ventromedial prefrontal cortex activation and neurofeedback modulation during episodic future thinking for individuals with suicidal thoughts and behaviors.

Individuals experiencing suicidal thoughts and behaviors (STBs) show less specificity and positivity during episodic future thinking (EFT). Here, we present findings from two studies aiming to (1) further our understanding of how STBs may relate to neural responsivity during EFT and (2) examine the feasibility of modulating EFT-related activation using real-time fMRI neurofeedback (rtfMRI-nf). Study 1 involved 30 individuals with major depressive disorder (MDD; half with STBs) who performed an EFT task during fMRI, for which they imagined personally-relevant future positive, negative, or neutral events. Positive EFT elicited greater ventromedial prefrontal cortex (vmPFC) activation compared to negative EFT. Importantly, the MDD + STB group exhibited reduced vmPFC activation across all EFT conditions compared to MDD-STB; although EFT fluency and subjective experience remained consistent across groups. Study 2 included rtfMRI-nf focused on vmPFC modulation during positive EFT for six participants with MDD + STBs. Results support the feasibility and acceptability of the rtfMRI-nf protocol and quantitative and qualitative observations are provided to help inform future, larger studies aiming to examine similar neurofeedback protocols. Results implicate vmPFC blunting as a promising treatment target for MDD + STBs and suggest rtfMRI-nf as one potential technique to explore for enhancing vmPFC engagement.

Priming and human memory systems.

Priming is a nonconscious form of human memory, which is concerned with perceptual identification of words and objects and which has only recently been recognized as separate from other forms of memory or memory systems. It is currently under intense experimental scrutiny. Evidence is converging for the proposition that priming is an expression of a perceptual representation system that operates at a pre-semantic level; it emerges early in development, and access to it lacks the kind of flexibility characteristic of other cognitive memory systems. Conceptual priming, however, seems to be based on the operations of semantic memory.

Building memories: remembering and forgetting of verbal experiences as predicted by brain activity.

A fundamental question about human memory is why some experiences are remembered whereas others are forgotten. Brain activation during word encoding was measured using blocked and event-related functional magnetic resonance imaging to examine how neural activation differs for subsequently remembered and subsequently forgotten experiences. Results revealed that the ability to later remember a verbal experience is predicted by the magnitude of activation in left prefrontal and temporal cortices during that experience. These findings provide direct evidence that left prefrontal and temporal regions jointly promote memory formation for verbalizable events.

On the tip of the tongue: an event-related fMRI study of semantic retrieval failure and cognitive conflict.

The tip of the tongue (TOT) state refers to a temporary inaccessibility of information that one is sure exists in long-term memory and is on the verge of recovering. Using event-related fMRI, we assessed the neural correlates of this semantic retrieval failure to determine whether the anterior cingulate-lateral prefrontal neural circuit posited to mediate conflict resolution is engaged during metacognitive conflicts that arise during the TOT. Results revealed that, relative to successful retrieval or unsuccessful retrieval not accompanied by a TOT, retrieval failures accompanied by TOTs elicited a selective response in anterior cingulate-prefrontal cortices. During a TOT, cognitive control mechanisms may be recruited in attempts to resolve the conflict and retrieval failure that characterize this state.

Neuroanatomical correlates of veridical and illusory recognition memory: evidence from positron emission tomography.

Memory distortions and illusions have been thoroughly documented in psychological studies, but little is known about the neuroanatomical correlates of true and false memories. Vivid but illusory memories can be induced by asking people whether they recall or recognize words that were not previously presented, but are semantically related to other previously presented words. We used positron emission tomography to compare brain regions involved in veridical recognition of printed words that were heard several minutes earlier and illusory recognition of printed words that had not been heard earlier. Veridical and illusory recognition were each associated with blood flow increases in a left medial temporal region previously implicated in episodic memory; veridical recognition was distinguished by additional blood flow increases in a left temporoparietal region previously implicated in the retention of auditory/phonological information. This study reveals similarities and differences in the way the brain processes accurate and illusory memories.

Cortical mechanisms specific to explicit visual object recognition.

The cortical mechanisms associated with conscious object recognition were studied using functional magnetic resonance imaging (fMRI). Participants were required to recognize pictures of masked objects that were presented very briefly, randomly and repeatedly. This design yielded a gradual accomplishment of successful recognition. Cortical activity in a ventrotemporal visual region was linearly correlated with perception of object identity. Therefore, although object recognition is rapid, awareness of an object's identity is not a discrete phenomenon but rather associated with gradually increasing cortical activity. Furthermore, the focus of the activity in the temporal cortex shifted anteriorly as subjects reported an increased knowledge regarding identity. The results presented here provide new insights into the processes underlying explicit object recognition, as well as the analysis that takes place immediately before and after recognition is possible.

Impaired recruitment of the hippocampus during conscious recollection in schizophrenia.

Poor attention and impaired memory are enduring and core features of schizophrenia. These impairments have been attributed either to global cortical dysfunction or to perturbations of specific components associated with the dorsolateral prefrontal cortex (DLPFC), hippocampus and cerebellum. Here, we used positron emission tomography (PET) to dissociate activations in DLPFC and hippocampus during verbal episodic memory retrieval. We found reduced hippocampal activation during conscious recollection of studied words, but robust activation of the DLPFC during the effort to retrieve poorly encoded material in schizophrenic patients. This finding provides the first evidence of hippocampal dysfunction during episodic memory retrieval in schizophrenia.

An fMRI investigation of the relationship between future imagination and cognitive flexibility.

While future imagination is largely considered to be a cognitive process grounded in default mode network activity, studies have shown that future imagination recruits regions in both default mode and frontoparietal control networks. In addition, it has recently been shown that the ability to imagine the future is associated with cognitive flexibility, and that tasks requiring cognitive flexibility result in increased coupling of the default mode network with frontoparietal control and salience networks. In the current study, we investigated the neural correlates underlying the association between cognitive flexibility and future imagination in two ways. First, we experimentally varied the degree of cognitive flexibility required during future imagination by manipulating the disparateness of episodic details contributing to imagined events. To this end, participants generated episodic details (persons, locations, objects) within three social spheres; during fMRI scanning they were presented with sets of three episodic details all taken from the same social sphere (Congruent condition) or different social spheres (Incongruent condition) and required to imagine a future event involving the three details. We predicted that, relative to the Congruent condition, future simulation in the Incongruent condition would be associated with increased activity in regions of the default mode, frontoparietal and salience networks. Second, we hypothesized that individual differences in cognitive flexibility, as measured by performance on the Alternate Uses Task, would correspond to individual differences in the brain regions recruited during future imagination. A task partial least squares (PLS) analysis showed that the Incongruent condition resulted in an increase in activity in regions in salience networks (e.g. the insula) but, contrary to our prediction, reduced activity in many regions of the default mode network (including the hippocampus). A subsequent functional connectivity (within-subject seed PLS) analysis showed that the insula exhibited increased coupling with default mode regions during the Incongruent condition. Finally, a behavioral PLS analysis showed that individual differences in cognitive flexibility were associated with differences in activity in a number of regions from frontoparietal, salience and default-mode networks during both future imagination conditions, further highlighting that the cognitive flexibility underlying future imagination is grounded in the complex interaction of regions in these networks.

Varieties of priming.

Recent data from brain-damaged and normal subjects converge to suggest several characteristics of repetition priming: firstly, it is sensitive to the physical and structural properties of input; secondly, it is unaffected by semantic processing at encoding; thirdly, it is frequently preserved in amnesic patients with impaired explicit memory; fourthly, it depends upon perceptual representations processed and stored by modality-specific cortical memory systems; and, finally, it is subject to constraints particular to the task employed and the type of information that is primed.

Can cognitive neuroscience illuminate the nature of traumatic childhood memories?

Recent findings from cognitive neuroscience and cognitive psychology may help explain why recovered memories of trauma are sometimes illusory. In particular, the notion of defective source monitoring has been used to explain a wide range of recently established memory distortions and illusions. Conversely, the results of a number of studies may potentially be relevant to forgetting and recovery of accurate memories, including studies demonstrating reduced hippocampal volume in survivors of sexual abuse, and recovery from functional and organic retrograde amnesia. Other recent findings of interest include the possibility that state-dependent memory could be induced by stress-related hormones, new pharmacological models of dissociative states, and evidence for 'repression' in patients with right parietal brain damage.

False memories and aging.

Although memory processes and systems usually operate reliably, they are sometimes prone to distortions and illusions. Here we review evidence indicating that cognitive aging is often associated with increased susceptibility to various kinds of false recollections. Accumulating data indicate that older adults frequently have special difficulties recollecting the source of information, which in turn renders them vulnerable to confusing perceived and imagined experiences, and to related kinds of memory distortions. Evidence from studies of false recall and recognition indicate that older adults are sometimes more likely than younger adults to remember events that never happened, reflecting the influence of indistinct encoding of events and the use of lenient criteria during retrieval. Neuroimaging studies suggest that age-related changes in medial temporal and frontal regions may play a role in the altered functioning of specific encoding and retrieval processes that give rise to memory distortions. Future studies of aging and false memories are likely to provide a promising avenue for illuminating basic mechanisms of memory distortion.

Functional imaging of memory retrieval in deficit vs nondeficit schizophrenia.

BACKGROUND: Neuroimaging studies have provided evidence of abnormal frontal and temporal lobe function in schizophrenia. Frontal cortex abnormalities have been associated with negative symptoms and temporal lobe abnormalities with positive symptoms. The deficit and nondeficit forms of schizophrenia were predicted to differ in prefrontal cortical activity, but not in medial temporal lobe activity. METHODS: Regional cerebral blood flow was studied using oxygen 15 positron emission tomography during 3 different memory retrieval conditions in 8 control subjects, 8 patients with the deficit syndrome, and 8 patients without the deficit syndrome. Behavioral and positron emission tomography data were analyzed using a mixed-effects model to test for population differences. RESULTS: In all memory conditions, frontal cortex activity was higher in patients without the deficit syndrome than in patients with the deficit syndrome. During the attempt to retrieve poorly encoded words, patients without the deficit syndrome recruited the left frontal cortex to a significantly greater degree than did patients with the deficit syndrome. The 2 schizophrenia subtypes did not differ in the activity or recruitment of the hippocampus during memory retrieval. CONCLUSION: Frontal cortex function during memory retrieval is differentially impaired in deficit and nondeficit schizophrenia, whereas hippocampal recruitment deficits are not significantly different between the 2 schizophrenia groups.

Abnormalities in the thalamus and prefrontal cortex during episodic object recognition in schizophrenia.

BACKGROUND: Many patients with schizophrenia demonstrate memory deficits. We studied patterns of brain activity during episodic recognition of new and previously seen three-dimensional objects. METHODS: We used (15)O positron emission tomography to study regional cerebral blood flow in eight normal subjects and nine patients with schizophrenia during a visual object recognition task. RESULTS: In comparison with control subjects, patients with schizophrenia showed less regional cerebral blood flow increases in the pulvinar region of the right thalamus and the right prefrontal cortex during the recognition of new objects and significantly greater left prefrontal cortex regional cerebral blood flow increases during the recognition of previously seen objects. Patients with schizophrenia exhibited alarm rates to new objects similar to those of control subjects, but significantly lower recognition rates for previously seen objects. CONCLUSIONS: Schizophrenia is associated with attenuated right thalamic and right prefrontal activation during the recognition of novel visual stimuli and with increased left prefrontal cortical activation during impaired episodic recognition of previously seen visual stimuli. This study provides further evidence for abnormal thalamic and prefrontal cortex function in schizophrenia.

Neurochemical dissociation of memory systems.

The administration of scopolamine, an anticholinergic drug, reduced the ability to recall and recognize stimuli presented previously--abilities thought to require declarative memory. In contrast, measures of procedural memory were unaffected by scopolamine: performance on a serial reaction time task incorporating a repeating stimulus and response sequence showed no difference in acquisition and retention of the sequence after scopolamine or saline. These results suggest that the cholinergic system is required for declarative but not procedural memory.

Long-term retention of computer learning by patients with memory disorders.

Previous research has demonstrated that patients with memory disorders resulting from closed-head injury can acquire the complex knowledge and skills necessary for the use of a microcomputer. The present paper extends the generality of those findings by showing that (1) amnesic patients with other etiologies could similarly learn how to operate a computer and (2) the knowledge and skills acquired were retained over intervals of up to 9 months.

Extending the limits of complex learning in organic amnesia: computer training in a vocational domain.

This study explored the limits of learning that could be achieved by an amnesic patient in a complex real-world domain. Using a cuing procedure known as the method of vanishing cues, a severely amnesic encephalitic patient was taught over 250 discrete pieces of new information concerning the rules and procedures for performing a task involving data entry into a computer. Subsequently, she was able to use this acquired knowledge to perform the task accurately and efficiently in the workplace. These results suggest that amnesic patients' preserved learning abilities can be extended well beyond what has been reported previously.

Computer learning by memory-impaired patients: acquisition and retention of complex knowledge.

Several investigators have shown that memory-impaired patients are capable of learning relatively simple information in both the laboratory and everyday life. The present research explored whether patients with memory disorders could also acquire complex knowledge--the domain-specific knowledge needed for operating and interacting with a microcomputer. The results indicated that patients with memory disorders of varying severity could learn to manipulate information on the computer screen, to write, edit and execute simple computer programs, and to perform disk storage and retrieval operations. The learning process, however, was slow relative to controls and the knowledge acquired appeared to be qualitatively different. Theoretical and practical implications of these findings are discussed.

Functional retrograde amnesia: a quantitative case study.

The memory impairment of a patient suffering from functional retrograde amnesia was assessed both during the amnesic episode and after its termination. The patient's performance on a task tapping semantic memory was nearly identical on the two test occasions, but his performance on a task tapping episodic memory substantially changed across test sessions. Cueing procedures revealed that in spite of the patient's restricted access to episodic memory during the amnesic period, a relatively intact "island" of episodic memories could be uncovered. The distinction between episodic and semantic memory, as well as the relation between organic and functional retrograde amnesia, are discussed in light of the case study.

False recognition after a right frontal lobe infarction: memory for general and specific information.

We previously reported a case study of a man with right frontal lobe damage, BG, who showed extraordinarily high false alarm rates on remember-know recognition tests (Schacter, D. L. et al., Neuropsychologia, 1996, Vol. 34, pp. 793-808). Experiment 1 extends his high false alarm rate to yes-no recognition tests. BG typically gives false 'remember' responses on remember-know tests, and this pattern was uninfluenced when he was asked to explain the basis for his 'remember' responses (Experiments 2 and 3). When BG was given a semantic encoding task, he stopped giving 'remember'-based false alarms (Experiment 4). Signal detection analyses revealed that BG had a discrimination deficit and an abnormally liberal response bias (especially for 'remember' responses) in most conditions. Overall, BG's high false alarm rate is interpreted as reflecting an over-reliance on the general similarity between a test item and the study episode.

When priming persists: long-lasting implicit memory for a single episode in amnesic patients.

This experiment investigated the durability of implicit memory for a single episode in normal and amnesic subjects. The target materials consisted of sentence puzzles that were difficult to comprehend in the absence of a key word or phrase. Sentences were re-presented at delays ranging from one minute to one week, and implicit memory was indicated by facilitation in solving previously incomprehensible sentences on subsequent exposures. Patients with severe memory impairments on tests of explicit recall and recognition showed substantial and robust facilitation, or priming, from a single prior presentation and there was no evidence of a systematic decay of facilitation over retention intervals up to one week. The long-lasting implicit memory observed in the sentence puzzle task contrasts with previous findings of rapid decay of priming effects in amnesic patients.