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Peter Falkai

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12 papers
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12

YNICL Journal 2025 Journal Article

Brain age gap reduction following exercise mirrors clinical improvements in schizophrenia spectrum disorders

  • Deniz Yilmaz
  • Sergi Papiol
  • Daniel Keeser
  • James H. Cole
  • Berend Malchow
  • Henrik Walter
  • Andreas Meyer-Lindenberg
  • Dusan Hirjak

Schizophrenia spectrum disorders (SSD) are associated with accelerated brain aging, reflected in an increased brain age gap. This gap serves as a biomarker, indicating poorer brain health, cognitive deficits, and greater severity in specific symptom domains. Exercise holds promise as an adjunct therapy to mitigate these deficits by potentially promoting brain recovery. However, the extent of overall improvements in brain health following exercise, along with their predictors and relationships to symptom clusters, are yet to be determined. This study examined the brain age gap metric as a quantitative indicator of brain recovery in response to exercise. To achieve this, we aggregated data from two randomized controlled trials, analyzing baseline (n = 134) and 3- or 6-month post-exercise (n = 46) data from individuals with SSD. Our findings revealed that patients with a higher baseline body mass index (BMI) demonstrated greater brain recovery, as evidenced by a reduced brain age gap post-exercise. Furthermore, changes in the brain age gap were associated with improvements in negative symptoms and cognition, suggesting that reductions in brain-predicted age may reflect symptom relief, particularly in domains beyond positive symptoms. These results underscore the importance of BMI in brain health, support using the brain age gap as a surrogate marker for tracking clinically relevant brain recovery, and highlight the need for stratified interventions and combined lifestyle modifications to enhance outcomes in SSD.

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YNIMG Journal 2025 Journal Article

How to measure functional connectivity using resting-state fMRI? A comprehensive empirical exploration of different connectivity metrics

  • Lukas Roell
  • Stephan Wunderlich
  • David Roell
  • Florian Raabe
  • Elias Wagner
  • Zhuanghua Shi
  • Andrea Schmitt
  • Peter Falkai

BACKGROUND: Functional connectivity in the context of functional magnetic resonance imaging is typically quantified by Pearson´s or partial correlation between regional time series of the blood oxygenation level dependent signal. However, a recent interdisciplinary methodological work proposes >230 different metrics to measure similarity between different types of time series. OBJECTIVE: Hence, we systematically evaluated how the results of typical research approaches in functional neuroimaging vary depending on the functional connectivity metric of choice. We further explored which metrics most accurately detect presumed reductions in connectivity related to age and malignant brain tumors, aiming to initiate a debate on the best approaches for assessing brain connectivity in functional neuroimaging research. METHODS: We addressed both research questions using four independent neuroimaging datasets, comprising multimodal data from a total of 1187 individuals. We analyzed resting-state functional sequences to calculate functional connectivity using 20 representative metrics from four distinct mathematical domains. We further used T1- and T2-weighted images to compute regional brain volumes, diffusion-weighted imaging data to build structural connectomes, and pseudo-continuous arterial spin labeling to measure regional brain perfusion. RESULTS: First, our findings demonstrate that the results of typical functional neuroimaging approaches differ fundamentally depending on the functional connectivity metric of choice. Second, we show that correlational and distance metrics are most appropriate to cover reductions in connectivity linked to aging. In this context, partial correlation performs worse than other correlational metrics. Third, our findings suggest that the FC metric of choice depends on the utilized scanning parameters, the regions of interest, and the individual investigated. Lastly, beyond the major objective of this study, we provide evidence in favor of brain perfusion measured via pseudo-continuous arterial spin labeling as a robust neural entity mirroring age-related neural and cognitive decline. CONCLUSION: Our empirical evaluation supports a recent theoretical functional connectivity framework. Future functional imaging studies need to comprehensively define the study-specific theoretical property of interest, the methodological property to assess the theoretical property, and the confounding property that may bias the conclusions.

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YNICL Journal 2019 Journal Article

Neurocognitive and neuroanatomical maturation in the clinical high-risk states for psychosis: A pattern recognition study

  • Lana Kambeitz-Ilankovic
  • Shalaila S. Haas
  • Eva Meisenzahl
  • Dominic B. Dwyer
  • Johanna Weiske
  • Henning Peters
  • Hans-Jürgen Möller
  • Peter Falkai

BACKGROUND: Findings from neurodevelopmental studies indicate that adolescents with psychosis spectrum disorders have delayed neurocognitive performance relative to the maturational state of their healthy peers. Using machine learning, we generated a model of neurocognitive age in healthy adults and investigated whether individuals in clinical high risk (CHR) for psychosis showed systematic neurocognitive age deviations that were accompanied by specific structural brain alterations. METHODS: First, a Support Vector Regression-based age prediction model was trained and cross-validated on the neurocognitive data of 36 healthy controls (HC). This produced Cognitive Age Gap Estimates (CogAGE) that measured each participant's deviation from the normal cognitive maturation as the difference between estimated neurocognitive and chronological age. Second, we employed voxel-based morphometry to explore the neuroanatomical gray and white matter correlates of CogAGE in HC, in CHR individuals with early (CHR-E) and late (CHR-L) high risk states. RESULTS: = 0.33, P < .001). Mean (SD) CogAGE measured +4.3 (8.1) years in CHR individuals compared to HC (-0.1 (5.5) years, P = .006). CHR-L individuals differed significantly from HC subjects while this was not the case for the CHR-E group. CogAGE was associated with a distributed bilateral pattern of increased GM volume in the temporal and frontal areas and diffuse pattern of WM reductions. CONCLUSION: Although the generalizability of our findings might be limited due to the relatively small number of participants, CHR individuals exhibit a disturbed neurocognitive development as compared to healthy peers, which may be independent of conversion to psychosis and paralleled by an altered structural maturation process.

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YNIMG Journal 2011 Journal Article

Fear is only as deep as the mind allows

  • Esther Kristina Diekhof
  • Katharina Geier
  • Peter Falkai
  • Oliver Gruber

Humans have the ability to control negative affect and perceived fear. Nevertheless, it is still unclear whether this affect regulation capacity relies on a common neural mechanism in different experimental domains. Here, we sought to identify commonalities in regulatory brain activation in the domains of fear extinction, placebo, and cognitive emotion regulation. Using coordinate-based activation-likelihood estimation meta-analysis we intended to elucidate concordant hyperactivations and the associated deactivations in the three experimental domains, when human subjects successfully diminished negative affect. Our data show that only one region in the ventromedial prefrontal cortex (VMPFC) controlled negative affective responses and reduced the degree of subjectively perceived unpleasantness independent of the experimental domain. This down-regulation of negative affect was further accompanied by a concordant reduction of activation in the left amygdala. Finally, the soothing effect of placebo treatments and cognitive reappraisal strategies, but not extinction retrieval, was specifically accompanied by a coherent hyperactivation in the anterior cingulate and the insular cortex. Collectively, our data strongly imply that the human VMPFC may represent a domain-general controller of perceived fear and aversiveness that modulates negative affective responses in phylogenetically older structures of the emotion processing system. In addition, higher-level regulation strategies may further engage complementary neural resources to effectively deal with the emotion-eliciting events.

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YNIMG Journal 2011 Journal Article

The power of imagination — How anticipatory mental imagery alters perceptual processing of fearful facial expressions

  • Esther K. Diekhof
  • Hanne E. Kipshagen
  • Peter Falkai
  • Peter Dechent
  • Jürgen Baudewig
  • Oliver Gruber

Expectancies strongly shape our perception of the world and preconceptions about stimulus characteristics can even bias the sensory system for illusory percepts. Here we assessed with functional magnetic resonance imaging how anticipatory mental imagery of a mildly fearful face created a predictive bias that proactively altered perception of highly fearful faces and generated the “illusion” of reduced fearfulness. We found that anticipatory activation of the fusiform gyrus (FG) was modulated by the fearfulness of the imagined face. Further during anticipatory imagery, regulatory influences from the lateral and ventromedial prefrontal cortex on the FG primed the perceptual system for a subsequent misperception. This was achieved by increasing perceptual activation in higher-order brain regions for the evaluation of affective valence and contextual framing, while at the same time restricting bottom-up arousal and attention to fearful expressions. Anticipatory mental imagery may thus represent an effective antecedent strategy through which emotional perception can be significantly altered.

Details DOI
v2026.09.13