Biomedical subjects

Sabine Grimm

Publications and source records attributed to Sabine Grimm.

7 recordsLinked to original sources

PubMed2026

An Application of Iterative Health Economic Evaluation: An Update on the Early Cost Effectiveness of Whole-Genome Sequencing in Advanced Non-small-Cell Lung Cancer.

OBJECTIVE: Whole genome sequencing (WGS) can identify more druggable targets than the standard of care (SoC) panels, however, its health effects and costs are highly uncertain. Given the rapidly evolving treatment landscape and pricing, an iterative approach is crucial to continuously reassess evidence and adapt economic models. Our objective was to update a previously developed economic model for WGS. METHODS: We used a structured approach to identify and report model elements requiring updates, based on established tools and methodological guidance, and applied it to the probabilistic decision model by Simons et al.(2021), which compared SoC, WGS, and SoC followed by WGS in patients with inoperable stage IIIB, C/IV NSCLC in the Dutch setting. RESULTS: Updates included a new treatment (sotorasib), revised drug and diagnostic costs, and adherence to the latest guidelines. Drug and WGS diagnostics costs fell by 8% and 26%, respectively. SoC diagnostic prices increased by 17%. We explored the impact of the prevalence of druggable targets, effectiveness of off-label treatments, (academic-specific) diagnostic costs, and price negotiations. The ICER of WGS versus SoC decreased from €737,197 to €419,053/QALY. WGS would become cost-effective if diagnostic costs descended from €2,180 to €1,246 or if additional druggable targets were identified in ≥3.3% of patients. CONCLUSION: Our structured approach effectively identified items in the original analysis requiring updates and provides a foundation for further developing a checklist to guide iterative HTA. Continued monitoring and assessment of new treatment options, the dynamic diagnostics and costs throughout the life-cycle remain necessary to determine when WGS can be considered cost-effective.

NSCLC↗

PubMed2006

Mismatch negativity on the cone of confusion.

Localization of sounds by the auditory system is based on the analysis of three sources of information: interaural level differences (ILD, caused by an attenuation of the sound as it travels to the more distant ear), interaural time differences (ITD, caused by the additional amount of time it takes for the sound to arrive at the more distant ear), and spectral cues (caused by direction-specific spectral filter properties of the pinnae). Although in a number of psychophysiological studies cortical processes of ITD and ILD analysis were investigated, there is hitherto no evidence on the cortical processing of spectral cues for sound localization. The objective of the present experiment was to test whether it is possible to observe electrophysiological correlates of sound localization based on spectral cues. In an auditory oddball experiment, 80 ms of broadband noise from varying free field locations were presented to inattentive participants. Mismatch negativities (MMNs) were observed for pairs of standards and location deviants located symmetrically with respect to the interaural axis. As interaural time and level differences are identical for such pairs of sounds, the observed MMNs most likely reflect cognitive processes of sound localization utilizing the spectral filter properties of the pinnae. MMN latencies suggest that sound localization based on spectral cues is slower than ITD- or ILD-based localization.

Acoustic Stimulation↗

PubMed2006

Mechanisms for detecting auditory temporal and spectral deviations operate over similar time windows but are divided differently between the two hemispheres.

In order to keep track of potentially relevant information in the acoustic environment, the human brain processes sounds to a high extent even when they are not attended: it extracts basic features, encodes regularities, and detects deviances. Here, we deliver evidence that the initial 300 ms of a sound contribute more to this preattentive processing than the sound's later parts. We directly compared the influence of the temporal distance relative to sound onset on the processing of the sound's duration and frequency information. The mismatch negativity (MMN), an event-related potential indicator for preattentive feature encoding and deviance detection, was measured for infrequent duration deviants and frequency modulation deviants. The onset of either deviancy was at 100, 200, 300, or 400 ms relative to sound onset. MMN was only elicited for deviations occurring within the first 300 ms after sound onset for both types of deviants. Its neural sources were localized in supra-temporal cortices with source current density analyses (SCD) and variable resolution electromagnetic tomography (VARETA), revealing a right-hemispheric preponderance for frequency modulations but not for duration shortenings. This suggests that preattentive deviance detection is based upon partly diverging functional memory registers for temporal and dynamic spectral information. The influence of temporal distance on MMN in both conditions supports the view that temporal and spectral sound properties are integrated into an auditory object representation prior to preattentive deviance detection. Importantly, the decline of MMN to unattended sounds with larger temporal distance suggests that parts beyond 300 ms are less important for preattentive auditory object representation.

Acoustic Stimulation↗

PubMed2005

Pre-attentive and attentive processing of temporal and frequency characteristics within long sounds.

Attention effects on the processing of deviations in the duration and the frequency dimension of a long sound were investigated in three conditions: (1) when auditory stimuli were ignored, (2) when they were attended and frequency dimension was task-relevant, and (3) when they were attended and duration dimension was task-relevant. The mismatch negativity (MMN) of the event-related potential (ERP) to infrequent shortenings of a sound (600 ms vs. 1000 ms) and to infrequent frequency modulations at one of nine possible intervals within the sound (change from 440 Hz to 480 Hz and back to 440 Hz, e.g. in the 600-650 ms interval) was measured. Duration MMN was slightly enhanced when directing attention towards the frequency dimension but notably enhanced when attention was focused on duration. The early phase of frequency-modulated MMN was of equal amplitude in all three conditions, and the late phase was equally enlarged in both attend conditions. Interestingly, MMN to frequency-modulated deviants decreased the later the deviation occurred within the sound; there was no indication for an MMN being present in Ignore condition when frequency modulations occurred 400 ms after sound onset or later. Thus, with increasing temporal distance between the onset of a sound and the onset of a deviation within the sound (e.g. frequency modulation or sound offset), MMN for frequency modulations and duration shortenings decreases. This suggests that the initial part of a sound ( approximately 300 ms) contributes more to the unitary sound representation underlying MMN than the later parts.

Acoustic Stimulation↗

PubMed2005

Human auditory event-related potentials predict duration judgments.

Internal clock models postulate a pulse accumulation process underlying timing activities, with more accumulated pulses resulting in longer perceived durations. We investigated whether this accumulation is reflected in the amplitude of event-related brain potentials (ERPs) elicited by auditory stimuli with durations of 400-600 ms. In a duration discrimination paradigm, we found more negative amplitudes to physically identical stimuli when they were judged as longer than the memorized standard duration (500 ms) as compared to being classified as shorter. This sustained negativity was already developing during the first 100 ms after stimulus onset. It could not be explained as a bias to respond with a particular hand (lateralized readiness potential), but rather reflects a processing difference between the tones to be judged as shorter or longer. Our results are in line with models of time processing which assume that higher numbers of accumulated pulses of a temporal processor result in an increase in perceived duration.

Acoustic Stimulation↗

PubMed2004

Kanizsa subjective figures capture visual spatial attention: evidence from electrophysiological and behavioral data.

Figural binding and attention are two important processes that help to perceive the outside world. Binding is necessary to link together the different features of single objects which are represented in a distributed fashion in the brain. Attention serves to focus onto a small subset of incoming information. It is still not clear how exactly these two mechanisms operate and interact. We performed two experiments employing illusory Kanizsa figures (KFs) to investigate the temporal order of figural binding and spatial attention. In a visual search task, subjects had to detect the presence of a KF among distractor stimuli. We found only a slight increase of reaction times when increasing the number of distractors, indicating that KFs popped out and drew the perceiver's attention. In a further event-related potential (ERP) study, we used displays of the search task as non-informative cue for a subsequent target choice-reaction task. Enhanced contralateral negative amplitudes (starting at about 230 ms) over ventral occipital areas were found for cue displays which included a KF. For target stimuli, faster reaction times and enhanced ipsilateral N1 amplitudes over occipito-parietal areas were observed for validly (target presentation inside a KF) as compared to invalidly cued targets (target presentation outside a KF). Furthermore, enhanced contralateral N1 amplitudes were found for invalidly cued targets. It might be that interactions between perceptual closure processing of the ventral pathway and spatial target processing of the dorsal pathway contributed to the present result. We conclude that KFs automatically capture spatial attention when used as visual cues.

Adult↗

PubMed2004

Differential processing of duration changes within short and long sounds in humans.

It has been postulated that there exist two different mechanisms of duration processing. Brief durations, shorter than 500 ms, are processed sensorially, whereas longer durations are processed via a cognitive mechanism. We investigated whether electrophysiological evidence for this distinction can be found. In particular, we measured the mismatch negativity (MMN) to auditory duration deviants (40% decrements) in blocks of short (200 ms) and long sounds (1000 ms) in Ignore and in Attend conditions. Our results show a typical MMN for long and short durations in the Attend condition, whereas no MMN was obtained for long durations in the Ignore condition. This interaction between duration and attention seems to reflect a breakdown of the sensorial mechanism of temporal processing at some critical duration of about 1 s when sounds are ignored.

Acoustic Stimulation↗