Mieke Verfaellie

Working Memory for Conjunctions Relies on the Medial Temporal Lobe

A prominent theory of hippocampal function proposes that the hippocampus is importantly involved in relating or binding together separate pieces of information to form an episodic representation. This hypothesis has only been applied to studies of long-term memory because the paradigmatic view of the hippocampus is that it is not critical for short-term forms of memory. However, relational processing is important in many working memory tasks, especially tasks using visual stimuli. Here, we test the hypothesis that the medial temporal lobes are important for relational memory even over short delays. The task required patients with medial temporal lobe amnesia and controls to remember three objects, locations, or object-location conjunctions over 1 or 8 s delays. The results show that working memory for objects and locations was at normal levels, but that memory for conjunctions was severely impaired at 8 s delays. Additional analyses suggest that the hippocampus per se is critical for accurate conjunction working memory. We propose that the hippocampus is critically involved in memory for conjunctions at both short and long delays.

Cortical activity reductions during repetition priming can result from rapid response learning

Recent observation of objects speeds up their subsequent identification and classification. This common form of learning, known as repetition priming, can operate in the absence of explicit memory for earlier experiences, and functional neuroimaging has shown that object classification improved in this way is accompanied by ‘neural priming’ (reduced neural activity) in prefrontal, fusiform and other cortical regions. These observations have led to suggestions that cortical representations of items undergo ‘tuning’, whereby neurons encoding irrelevant information respond less as a given object is observed repeatedly, thereby facilitating future availability of pertinent object knowledge. Here we provide experimental support for an alternative hypothesis, in which reduced cortical activity occurs because subjects rapidly learn their previous responses. After a primed object classification (such as ‘bigger than a shoebox’), cue reversal (‘smaller than a shoebox’) greatly slowed performance and completely eliminated neural priming in fusiform cortex, which suggests that these cortical item representations were no more available for primed objects than they were for new objects. In contrast, prefrontal cortex activity tracked behavioural priming and predicted the degree to which cue reversal would slow down object classification—highlighting the role of the prefrontal cortex in executive control.

Medial temporal lobe damage causes deficits in episodic memory and episodic future thinking not attributable to deficits in narrative construction.

The medial temporal lobe (MTL) makes critical contributions to episodic memory, but its contributions to episodic future thinking remain a matter of debate. By one view, imagining future events relies on MTL mechanisms that also support memory for past events. Alternatively, it has recently been suggested that future thinking is independent of MTL-mediated processes and can be supported by regions outside the MTL. The current study investigated the nature and necessity of MTL involvement in imagining the future and tested the novel hypothesis that the MTL contributes to future thinking by supporting online binding processes related to narrative construction. Human amnesic patients with well characterized MTL damage and healthy controls constructed narratives about (1) future events, (2) past events, and (3) visually presented pictures. While all three tasks place similar demands on narrative construction, only the past and future conditions require memory/future thinking to mentally generate relevant narrative information. Patients produced impoverished descriptions of both past and future events but were unimpaired at producing detailed picture narratives. In addition, future-thinking performance positively correlated with episodic memory performance but did not correlate with picture narrative performance. Finally, future-thinking impairments were present when MTL lesions were restricted to the hippocampus and did not depend on the presence of neural damage outside the MTL. These results indicate that the ability to generate and maintain a detailed narrative is preserved in amnesia and suggest that a common MTL mechanism supports both episodic memory and episodic future thinking.

Mild traumatic brain injury and posttraumatic stress disorder in returning veterans: Perspectives from cognitive neuroscience

A significant proportion of military personnel deployed in support of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) has been exposed to war-zone events potentially associated with traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). There has been significant controversy regarding healthcare policy for those service members and military veterans who returned from OEF/OIF deployments with both mild TBI and PTSD. There is currently little empirical evidence available to address these controversies. This review uses a cognitive neuroscience framework to address the potential impact of mild TBI on the development, course, and clinical management of PTSD. The field would benefit from research efforts that take into consideration the potential differential impact of mild TBI with versus without persistent cognitive deficits, longitudinal work examining the trajectory of PTSD symptoms when index trauma events involve TBI, randomized clinical trials designed to examine the impact of mild TBI on response to existing PTSD treatment interventions, and development and examination of potential treatment augmentation strategies.

The neurological and cognitive sequelae of cardiac arrest

Background: Although cardiac arrest (CA) is commonly cited as a cause of amnesia, patients referred to the authors’ center with a diagnosis of “amnesia” after CA rarely have isolated memory deficits. Objective: To determine whether CA is a cause of pure amnesia and to assess patterns of cognitive deficits after CA. Methods: The authors used cognitive assessment of 11 consecutive patients referred for memory deficits after CA, targeted at deficit domains identified in the literature reviews, and analysis of specific case reports and prospective studies of cognition after CA. Results: The most common pattern of impairment in their patients was a combination of memory and motor deficits with variable executive impairment. No patient had isolated memory impairment. The case reports do not support the claim that isolated amnesia is a residual of CA; most cases of isolated amnesia are caused by subacute episodes of anoxia or excitotoxic injury. The prospective reports identify highly variable patterns of impairment, but isolated amnesia remains rare. Conclusions: Diffuse, sudden ischemic-hypoxic injury caused by cardiac arrest (CA) does not preferentially damage memory systems. Subacute or stepwise hypoxic or excitotoxic injury may cause isolated hippocampal injury and amnesia. The common pattern of impairment in the postacute phase after CA is a combination of memory, subtle motor, and variable executive deficits.

Dissociations between familiarity processes in explicit recognition and implicit perceptual memory.

Dual-process theories of recognition posit that a perceptual familiarity process contributes to both explicit recognition and implicit perceptual memory. This putative single familiarity process has been indexed by inclusion-exclusion, remember-know, and repetition priming measures. The present studies examined whether these measures identify a common familiarity process. Familiarity-based explicit recognition (as indexed by the inclusion-exclusion and the independence remember-know procedures) increased with conceptual processing. In contrast, implicit word-identification priming and familiarity-based word-stem completion (as indexed by inclusion-exclusion) increased with study-test perceptual similarity. These dissociations indicate that familiarity-based explicit recognition may be more sensitive to conceptual than to perceptual processing and is functionally distinct from the perceptual familiarity process mediating implicit perceptual memory.

A role for right medial prefrontal cortex in accurate feeling-of-knowing judgments: evidence from patients with lesions to frontal cortex

The hypothesis that prefrontal cortex plays a critical role in accurate predictions of episodic memory performance was tested using the feeling-of-knowing (FOK) paradigm. Fourteen patients with a broad spectrum of damage to the frontal cortex and matched controls read sentences and later were tested for recall memory, confidence judgments, and FOK accuracy using as cues the sentences with the final word missing. While frontal patients were impaired at recall and recognition memory, they were able to make accurate confidence judgments about their recall attempts. By contrast, as a group, the patients were markedly impaired in the accuracy of their prospective FOK judgments. Lesion analysis of frontal patients with clear FOK impairment revealed an overlapping region of damage in right medial prefrontal cortex. These findings provide functional and anatomical evidence for a dissociation between recall confidence and prospective memory monitoring and are discussed in terms of familiarity and access theories of FOK predictions.

Patterns of Autobiographical Memory Loss in Medial-Temporal Lobe Amnesic Patients

The issue of whether the hippocampus and related structures in the medial-temporal lobe (MTL) play a temporary or permanent role in autobiographical episodic memory remains unresolved. One long-standing belief is that autobiographical memory (AM), like semantic memory, is initially dependent on the MTL but ultimately can be retained and recovered independently of it. However, evidence that hippocampal amnesia results in severe loss of episodic memory for a lifetime of personally experienced events suggests otherwise. To test the opposing views, we conducted detailed investigations of autobiographical episodic memory in people with amnesia resulting from MTL lesions of varying extent. By combining precise quantification of MTL and neocortical volumes with sensitive measures of recollection of ones personal past, we show that the severity of episodic, but not semantic, AM loss is best accounted for by the degree of hippocampal damage and less likely related to additional neocortical compromise.

When True Recognition Suppresses False Recognition: Evidence from Amnesic Patients

False recognition occurs when people mistakenly claim that a novel item is familiar. After studying lists of semantically related words, healthy controls show extraordinarily high levels of false recognition to nonstudied lures that are semantic associates of study list words. In previous experiments, we found that both Korsakoff and non-Korsakoff amnesic patients show reduced levels of false recognition to semantic associates, implying that the medial temporal/diencephalic structures that are damaged in amnesic patients are involved in the encoding and/or retrieval of information that underlies false recognition. These data contrast with earlier results indicating greater false recognition in Korsakoff amnesics than in control subjects. The present experiment tests the hypothesis that greater or lesser false recognition of semantic associates in amnesic patients, relative to normal controls, can be demonstrated by creating conditions that are more or less conducive to allowing true recognition to suppress false recognition. With repeated presentation and testing of lists of semantic associates, control subjects and both Korsakoff and non-Korsakoff amnesics showed increasing levels of true recognition across trials. However, control subjects exhibited decreasing levels of false recognition across trials, whereas Korsakoff amnesic patients showed increases across trials and non-Korsakoff amnesics showed a fluctuating pattern. Consideration of signal detection analyses and differences between the two types of amnesic patients provides insight into how mechanisms of veridical episodic memory can be used to suppress false recognition.

Acquisition of novel semantic information in amnesia : effects of lesion location

Two patients with severe global amnesia are described who differ in the extent to which they have acquired new semantic information. Patient SS, who has extensive medial temporal lobe damage including the hippocampus as well as surrounding cortical areas, has failed to acquire virtually any new information regarding vocabulary or famous faces that entered the public domain since the onset of his amnesia. In contrast, patient PS, who has a selective lesion of the hippocampus proper, has gained a sense of familiarity of novel vocabulary and famous people, even though her effortful retrieval of this new semantic knowledge remains impaired. These findings extend to amnesia of adult onset, the proposal of Vargha-Khadem and colleagues that in patients with selective hippocampal injury, cortical areas surrounding the hippocampus may play an important role in new semantic learning [Vargha-Khadem, F., Gadian, D.G., Watkins, K. E., Connelly, A., Van Paesschen, W. and Mishkin, M., regarding the importance of the subhippocampal cortices in the mediation of new semantic learning in children with hippocampal lesions, Science, 1997, 277, 376-380].