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

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↗

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.

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↗

PubMed2003

Differential impairment of person-specific knowledge in a patient with semantic dementia.

We report the case of ST, a 61-year-old gentleman of superior intelligence, who presented with a five-year history of slowly progressive word finding difficulty for proper names. MRI (magnetic resonance imaging) showed marked atrophy in the left anterior temporal lobe and SPECT (single photon emission computed tomography) demonstrated hypoperfusion in the left anterior and inferior temporal region. A detailed behavioral analysis of the integrity of his semantic system revealed naming deficits for both proper and common names. ST also showed severe impairments in person-specific semantic knowledge, but preservation of knowledge for famous places and common objects. ST's semantic knowledge deficit for people emerged whether he was tested with the faces or the names of famous individuals. Variables that affect name retrieval, such as familiarity, age of acquisition, and frequency of concept encounter, do not account for the selective impairment of person-specific knowledge evidenced by ST. Qualitative differences between the nature of knowledge representations for people and for common objects may underlie this effect. Disruptions in left temporal regions associated with semantic processing may be sufficient to produce a selective deficit in person-specific knowledge.

Attention↗

PubMed2003

Disproportionate deficit in associative recognition relative to item recognition in global amnesia.

In two experiments, we tested the hypothesis that medial temporal lobe (MTL) amnesic patients and, likewise, diencephalic (DNC) amnesic patients evidence a disproportionate deficit in memory for associations in comparison with memory for single items. In Experiment 1, we equated item recognition in amnesic and control participants and found that, under these conditions, associative recognition remained impaired both for MTL patients and for DNC patients. To rule out an alternative interpretation of the results of Experiment 1, in Experiment 2 we compared the performance of amnesic and control participants on a one-item recognition task and a two-item recognition task that required no memory for the association between members of word pairs. In the MTL group, when single-item recognition was equated to that of the controls, two-item nonassociative pair memory was equivalent as well. In the DNC group, nonassociative pair memory was impaired, but this impairment did not fully account for the impairment in associative memory. These findings indicate that memory for novel associations between items is disproportionately impaired in comparison with memory for single items in amnesia.

Adult↗

PubMed2003

Absence of size congruency effects in amnesic patients' recognition: a failure of perceptually based recollection.

This study examined the status of recollection in amnesia when recollection is supported by perceptual rather than conceptual processes. Two experiments investigated the size congruency effect-the advantage in recognition of patterns presented in the same size, rather than in different sizes-at study and test. In Experiment 1, the authors used a remember-know paradigm in nonamnesic individuals and demonstrated that the size congruency effect was due to enhanced recollection. In Experiment 2, the authors examined whether amnesic patients would show a size congruency effect when their overall level of performance was matched to that of controls. Amnesic patients failed to show a size congruency effect. These findings provide evidence for a disproportionate disruption in recollection compared with familiarity in amnesia, even when recollection is supported by perceptual processes.

Aged↗

PubMed2002

Reading direction and spatial neglect.

Many American and European investigators have reported that hemispatial neglect is more frequent and more severe after right than left hemisphere lesions. This hemispheric asymmetry may be due to biological asymmetries, learned behavior, or both. Readers of European languages, unlike readers of Semitic languages, scan from left to right. Learned rightward scanning may increase the unilateral neglect associated with right hemisphere lesions and reduce the severity of neglect associated with left hemisphere lesions. To learn if hemispheric asymmetries of neglect are influenced by learned scanning behavior, we used line bisection and cancellation tasks to study patients with unilateral stroke who read only a Semitic or European language before the age of fifteen. We found that independent of reading direction, unilateral neglect was more commonly associated with right than left hemisphere lesions. After right hemisphere damage right to left readers bisected lines closer to center than left to right readers, but on the cancellation test readers of European languages did not perform differently than readers of Semitic languages. These findings suggest that whereas learned scan direction may influence the severity of neglect when measured by line bisection, these learned directional scans cannot fully account for the observed hemisphere asymmetries of neglect. They also suggest that the line bisection test is more influenced by the direction of scanning than is the cancellation test.

Aged↗

PubMed2002

Aware and unaware perception in hemispatial neglect: evidence from a stem completion priming task.

The current study used the process dissociation procedure in conjunction with a stem-completion priming task to disentangle the influences of aware and unaware perception in patients with hemispatial neglect. One lateralized picture prime was presented simultaneously with a filler picture followed by a centrally presented word stem. In the inclusion condition participants were asked to complete the word stem with the previously presented picture name; in the exclusion task they were asked to complete the stem with the name of a picture other than the one previously presented. Findings indicated that neglect patients had reduced unaware perception of pictures presented in the left visual field and an absence of awareness for those same pictures. In addition, patients had reduced awareness for right visual field pictures, but unaware perception remained intact. These findings suggest that observations of preserved information processing in neglect are due to residual unaware perception and not due to residual awareness of information in the neglected hemispace.

Aged↗

PubMed2002

The effect of retrieval instructions on false recognition: exploring the nature of the gist memory impairment in amnesia.

In previous studies, we found that amnesic patients show reduced levels of false recognition in a converging semantic associates paradigm. This finding was interpreted as reflecting an impairment in amnesia in the ability to form, retain and/or retrieve a well-organized representation of the semantic 'gist' of studied items. To further explore the nature of amnesics' impairment in gist memory, the current study compared performance in two retrieval conditions. In a standard retrieval condition, participants were asked to endorse on a recognition test only items that had appeared on the study list. In a meaning retrieval condition, participants were asked to endorse any item that shared the meaning of studied items. Meaning retrieval instructions failed to eliminate the reduction in false recognition in amnesia. These results suggest that amnesics' impairment in gist memory is not attributable to a failure to access well-formed gist representations when given item-specific retrieval cues. Rather, it suggests that amnesic patients are impaired in their ability to encode, store, or maintain strong gist information.

Adult↗