Biomedical subjects

Mieke Verfaellie

Publications and source records attributed to Mieke Verfaellie.

At least 19 recordsLinked to original sources

PubMed2024

Blood-based DNA methylation and exposure risk scores predict PTSD with high accuracy in military and civilian cohorts.

BACKGROUND: Incorporating genomic data into risk prediction has become an increasingly useful approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not. METHODS: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip. The first risk score, exposure and methylation risk score (eMRS) used cumulative and childhood trauma exposure and DNAm variables; the second, methylation-only risk score (MoRS) was based solely on DNAm data; the third, methylation-only risk scores with adjusted exposure variables (MoRSAE) utilized DNAm data adjusted for the two exposure variables. The potential of these risk scores to predict future PTSD based on pre-deployment data was also assessed. External validation of risk scores was conducted in four independent cohorts. RESULTS: The eMRS model showed the highest accuracy (92%), precision (91%), recall (87%), and f1-score (89%) in classifying PTSD using 3730 features. While still highly accurate, the MoRS (accuracy = 89%) using 3728 features and MoRSAE (accuracy = 84%) using 4150 features showed a decline in classification power. eMRS significantly predicted PTSD in one of the four independent cohorts, the BEAR cohort (beta = 0.6839, p-0.003), but not in the remaining three cohorts. Pre-deployment risk scores from all models (eMRS, beta = 1.92; MoRS, beta = 1.99 and MoRSAE, beta = 1.77) displayed a significant (p < 0.001) predictive power for post-deployment PTSD. CONCLUSION: Results, especially those from the eMRS, reinforce earlier findings that methylation and trauma are interconnected and can be leveraged to increase the correct classification of those with vs. without PTSD. Moreover, our models can potentially be a valuable tool in predicting the future risk of developing PTSD. As more data become available, including additional molecular, environmental, and psychosocial factors in these scores may enhance their accuracy in predicting the condition and, relatedly, improve their performance in independent cohorts.

DNA methylation↗

PubMed2006

The contribution of familiarity to associative memory in amnesia.

In Experiment 1, using the remember/know paradigm with control participants, we compared the contribution of recollection and familiarity to associative recognition for compound stimuli and for unrelated word pairs. It was demonstrated that familiarity makes a greater contribution to associative recognition of compound stimuli than to associative recognition of unrelated word pairs. In Experiment 2, we examined associative recognition memory in medial temporal lobe amnesics, diencephalic amnesics, and control participants for the stimuli employed in Experiment 1. Whereas associative recognition for compounds and unrelated words was nearly identical in control participants, associative recognition was higher for compounds than for unrelated word pairs in amnesic patients. This pattern was observed in the medial temporal amnesic group as well as in the diencephalic amnesic group. These results suggest that associative recognition in amnesia is enhanced to the extent that performance can be supported by study-induced familiarity for the studied pair.

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PubMed2006

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.

Aged↗

PubMed2006

Working memory and long-term memory for faces: Evidence from fMRI and global amnesia for involvement of the medial temporal lobes.

Behavioral studies with amnesic patients and imaging studies with healthy adults have suggested that medial temporal lobe (MTL) structures known to be essential for long-term declarative memory (LTM) may also be involved in the maintenance of information in working memory (WM). To examine whether MTL structures are involved in WM maintenance for faces, and the nature of that involvement, WM and LTM for faces were examined in normal participants via functional magnetic resonance imaging (fMRI) and in amnesic patients behaviorally. In Experiment 1, participants were scanned while performing a WM task in which they determined if two novel faces, presented 7 s apart, were the same or different. Later, participants' LTM for the faces they saw during the WM task was measured in an unexpected recognition test. During WM maintenance, the hippocampus was activated bilaterally, and there was greater activation during maintenance for faces that were later remembered than faces later forgotten. A conjunction analysis revealed overlap in hippocampal activations across WM maintenance and LTM contrasts, which suggested that the same regions were recruited for WM maintenance and LTM encoding. In Experiment 2, amnesic and control participants were tested on similar WM and LTM tasks. Amnesic patients, as a group, had intact performance with a 1-s maintenance period, but were impaired after a 7-s WM maintenance period and on the LTM task. Thus, parallel neuroimaging and lesion designs suggest that the same hippocampal processes support WM maintenance, for intervals as short as 7 s, and LTM for faces.

Adolescent↗

PubMed2006

Rapid response learning in amnesia: delineating associative learning components in repetition priming.

Functional brain imaging studies of priming assume that the behavioral facilitation and activity reductions resulting from multiple repetitions reflect the continued tuning of processes engaged during the initial processing of items. Utilizing an object priming paradigm in which participants were asked to make relative size judgments about visually presented common objects, we tested an alternate hypothesis that states that with multiple repetitions participants come to rely on a more efficient response learning mechanism. In experiment 1, the decision cue was inverted such that previous judgments made either once or three times were rendered invalid. Decision inversion resulted in a reduction of all priming, but most critically, led to a reduction of multiple-repetition priming to the level of single-repetition priming. In experiment 2, patients with amnesia failed to show a priming advantage for multiple repetitions, indicating that response learning is dependent on the medial temporal lobes. Taken together, these results suggest that a different process increasingly mediates priming behavior as repetitions increase. With repeated exposure, behavioral facilitation rapidly comes to reflect a more efficient response learning mechanism rather than facilitated access to object knowledge.

Adult↗

PubMed2006

Transverse patterning and human amnesia.

The transverse patterning (TP) task (A+ B-, B+ C-, C+ A-) has played a central role in testing the hypothesis that medial-temporal (and, in particular, hippocampal) brain damage selectively impairs learning on at least some classes of configural (i.e., nonlinear) learning tasks. Results in the animal and human literature generally support that hypothesis. Reed and Squire [Impaired transverse patterning in human amnesia is a special case of impaired memory for two-choice discrimination tasks. Behavioral Neuroscience, 113, 3-9, 1999], however, advanced an alternative account in which impaired TP performance in amnesia reflects a generic scaling artifact arising from the greater difficulty of the TP task compared to the elemental (i.e., linear) control task that is typically used. We begin with a critique of Reed and Squire, countering their conceptual arguments and showing that their results, when analyzed appropriately, support the configural deficit hypothesis. We then report results from eight new amnesic patients and controls on an improved version of the TP task. Despite substantial practice, accuracy of patients with bilateral hippocampal damage due to anoxia reached and maintained an asymptote of only 54% correct, well below the maximum accuracy obtainable (67%) in the absence of configural learning. A patient with selective bilateral damage to the anterior thalamic nuclei exhibited a TP accuracy asymptote that was near 67%, a pattern of two out of three correct consecutive trials, and a pattern of nearly always answering correctly for two of the three TP item pairs. These results are consistent with a set of unique and parameter-free predictions of the configural deficit hypothesis.

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PubMed2006

Implicit memory for novel conceptual associations in amnesia.

In two experiments, we evaluated the status of implicit memory for novel associations in amnesia. Experiment 1 assessed priming in a category exemplar generation task in which contextual information associated with a target could increase the likelihood of target generation. Control participants, but not amnesic patients, showed associative priming. Amnesics' impairment was not due to the use of explicit memory by control subjects but reflected a genuine impairment in implicit memory for novel conceptual associations. Experiment 2 assessed priming in a relatednessjudgment task, in which associative priming was manifest as longer latencies for old than for recombined pairs of unrelated words. Amnesic patients showed intact associative priming in this task. We discuss differences in the status of implicit memory for novel conceptual associations in amnesia, with reference to the nature of the representation that supports priming in the two tasks and the type of processing that is required at test.

Adult↗

PubMed2005

Increasing the salience of fluency cues reduces the recognition memory impairment in amnesia.

The present study examined whether the recognition memory deficit in amnesia would be attenuated under conditions that increased the salience of study-induced fluency. Studied and unstudied items were drawn either from separate pools of letters (no-overlap condition) or from the same pool of letters (overlap condition). Study-induced fluency was more salient in the no-overlap than in the overlap condition, because in the no-overlap condition, such fluency occurred at the letter level as well as at the word level. The recognition memory impairment in amnesia was smaller in the no-overlap than in the overlap condition. These findings are consistent with the idea that enhancing the salience of fluency cues promotes reliance on a fluency heuristic that ordinarily is not fully engaged in amnesia, and reduces the recognition memory impairment in amnesia.

Amnesia↗

PubMed2005

Failing to get the gist: reduced false recognition of semantic associates in semantic dementia.

In 2 experiments involving patients with semantic dementia, the authors investigated the impact of semantic memory loss on both true and false recognition. Experiment 1 involved recognition memory for categories of everyday objects that shared a predominantly semantic relationship. The patients showed preserved item-specific recollection for the pictorial stimuli but, compared with control participants, exhibited significantly reduced utilization of gist information regarding the categories of objects. The latter result is consistent with the patients' degraded semantic knowledge. Experiment 2 involved categories of abstract objects that were related to one another perceptually rather than semantically. Patients with semantic dementia obtained item-specific recollection and gist memory scores that were indistinguishable from those of control participants. These results suggest that the reduction in gist memory in semantic dementia is largely specific to semantic representations and cannot be attributed to general difficulty with abstracting and/or utilizing gistlike commonalities between stimuli.

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PubMed2005

Impaired implicit memory for gist information in amnesia.

In 2 experiments using a converging associates paradigm, the authors evaluated implicit memory for gist information in amnesic patients. In Experiment 1, participants saw multiple sets of associates, each converging on a nonpresented theme word, and were then tested using an implicit word stem completion test and an explicit cued recall test. Amnesic patients showed intact implicit and impaired explicit memory for studied words, but memory for nonpresented lures was impaired, regardless of retrieval instructions. To evaluate whether impaired implicit memory for lures was due to accelerated forgetting of gist information, short study lists were used in Experiment 2, each consisting of a single set of associates. Amnesics' implicit memory for lures was again impaired. These results point to an inability to encode robust gist representations as the cause of impaired gist memory in amnesia.

Aged↗

PubMed2005

Source memory in the real world: a neuropsychological study of flashbulb memory.

A flashbulb memory (FM) is a vivid, enduring memory for how one learned about a surprising, shocking event. It thus involves memory for the source of event information, as opposed to memory for the event itself. Which brain regions are involved in FM, however, is uncertain. Although medial temporal lobe/diencephalic (MTL/D) damage impairs content or item memory, frontal lobe (FL) damage has been associated with impaired source memory. One would therefore expect that FM should depend on the FLs, although two recent reports do not support this idea. In the current study, we examined memory for the events of September 11th, and memory for the source of that information, in MTL/D patients, FL patients, and healthy subjects. Only the MTL/D patients were impaired in long-term memory for the event itself, measured after a 6 month retention interval. The FL patients, on the other hand, showed a selective deficit in source memory, although their memory for the target event was unimpaired. MTL/D and FL structures appear to play different roles in memory for flashbulb events.

Adult↗

PubMed2005

The role of VMPC in metamemorial judgments of content retrievability.

Making judgments about the retrievability of information is a critical part of the metamemory processes engaged during remembering. A recent study of patients with frontal lesions suggests that ventral medial prefrontal cortex (VMPC) plays a critical role in such judgments [Schnyer, D. M., Verfaellie, M., Alexander, M. P., Lafleche, G., Nicholls, L., & Kaszniak, A. W. A role for right medial prefrontal cortex in accurate feeling of knowing judgments: Evidence from patients with lesions to frontal cortex. Neuropsychologia, 42, 957-966, 2004]. The observed impairment was thought to reflect an inability to determine the accessibility of memory contents. To further examine the neuroanatomical basis of content accessibility assessment, we used fMRI in an episodic feeling-of-knowing (FOK) paradigm. Participants were asked to make trial-by-trial predictions about the retrievability of the final word that completed studied sentences and then to select the correct completion from among alternatives. Results indicated that the VMPC is engaged during accurate FOK judgments and its activation is modulated by retrieval rating. Structural equations modeling supported the notion that VMPC, as part of a broader left hemisphere network involved in memory retrieval, monitors the output of the retrieval process. More generally, VMPC may participate in metacognitive processes that allow for the comparison of available data against an internal model.

Adult↗

PubMed2004

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.

Adolescent↗

PubMed2004

A critical role for the anterior hippocampus in relational memory: evidence from an fMRI study comparing associative and item recognition.

Neuroscientific research has established that the hippocampal formation, a structure within the medial temporal lobe (MTL), plays a critical role in memory for facts and events (declarative memory) (Milner et al., 1998). However, its precise role remains unclear. According to one view, the hippocampus has a special role in relating or binding together previously unrelated pieces of information, while another view proposes that the hippocampus is equally involved in all forms of declarative memory, regardless of their demands on relational processing. Using functional magnetic resonance imaging (fMRI), we show that hippocampal activation is modulated by the extent to which a retrieval task depends on relational processing.

Adult↗

PubMed2004

A role for right medial prefontal cortex in accurate feeling-of-knowing judgements: 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.

Adult↗

PubMed2004

Elevated false recognition in patients with frontal lobe damage is neither a general nor a unitary phenomenon.

This study examined verbal recognition memory in amnesic patients with frontal lesions (AF), nonamnesic patients with frontal lesions (NAF), and amnesic patients with medial temporal lesions (MT). To examine susceptibility to false alarms, the number of studied words drawn from various categories was varied. The AF and MT groups demonstrated reduced hits and increased false alarms. False alarms were especially elevated when item-specific recollection was strongest in control participants. The NAF group performed indistinguishably from control participants, but several patients showed excessive false alarms in the context of normal hit rates. These patients exhibited impaired monitoring and verification processes. The findings demonstrate that elevated false recognition is not characteristic of all frontal patients and may result from more than 1 underlying mechanism.

Aged↗

PubMed2004

Do priming effects in perceptual identification and word judgment reflect different underlying mechanisms?

We examined priming of orthographically illegal nonwords in a perceptual identification task and a word judgment task in undergraduate participants. In perceptual identification, priming was significant and equivalent after structural or phonological encoding. In word judgment, priming was significant after phonological encoding but not structural encoding. In a follow-up experiment in older control participants and amnesic participants, priming in word judgment was not significant. Older control participants found the stimuli more difficult to pronounce than did undergraduate participants, and word judgment priming in undergaduate participants was significant only for the stimuli that were judged easy to pronounce. These findings demonstrate that priming in perceptual identification and word judgment extends to novel stimuli that are not linked to preexisting lexical or sublexical representations but that priming occurs at different levels in the two tasks: at a featural or orthographic level in perceptual identification and at a phonological level in word judgment.

Aged↗

PubMed2003

Hemispheric asymmetries for selective attention apparent only with increased task demands in healthy participants.

This study examined the possibility that lack of behavioral evidence indicating hemispheric specialization for selective attention in healthy individuals is due to the use of tasks that are not sufficiently demanding to require selective attention. In a group of 43 participants (ages 17-23), we compared selective attention on a cued-response time task when the target was presented alone and when a distractor was simultaneously presented. The costs of invalid cueing were minimal when the right hemisphere (RH) processed the target relative to when the left hemisphere (LH) processed the target, but only for the high load condition. These results are interpreted as RH specialization in light of evidence suggesting that the RH can direct attention to a larger portion of the visual field.

Adolescent↗