Institute Affiliations


  • Member, Maternal & Child Health Research Institute (MCHRI)

Stanford Advisors


All Publications


  • Finding the neural correlates of collaboration using a three-person fMRI hyperscanning paradigm. Proceedings of the National Academy of Sciences of the United States of America Xie, H., Karipidis, I. I., Howell, A., Schreier, M., Sheau, K. E., Manchanda, M. K., Ayub, R., Glover, G. H., Jung, M., Reiss, A. L., Saggar, M. 2020

    Abstract

    Humans have an extraordinary ability to interact and cooperate with others. Despite the social and evolutionary significance of collaboration, research on finding its neural correlates has been limited partly due to restrictions on the simultaneous neuroimaging of more than one participant (also known as hyperscanning). Several studies have used dyadic fMRI hyperscanning to examine the interaction between two participants. However, to our knowledge, no study to date has aimed at revealing the neural correlates of social interactions using a three-person (or triadic) fMRI hyperscanning paradigm. Here, we simultaneously measured the blood-oxygenation level-dependent signal from 12 triads (n = 36 participants), while they engaged in a collaborative drawing task based on the social game of Pictionary General linear model analysis revealed increased activation in the brain regions previously linked with the theory of mind during the collaborative phase compared to the independent phase of the task. Furthermore, using intersubject correlation analysis, we revealed increased synchronization of the right temporo-parietal junction (R TPJ) during the collaborative phase. The increased synchrony in the R TPJ was observed to be positively associated with the overall team performance on the task. In sum, our paradigm revealed a vital role of the R TPJ among other theory-of-mind regions during a triadic collaborative drawing task.

    View details for DOI 10.1073/pnas.1917407117

    View details for PubMedID 32843342

  • Specific learning disorders in sex chromosome aneuploidies: Neural circuits of literacy and mathematics. American journal of medical genetics. Part C, Seminars in medical genetics Karipidis, I. I., Hong, D. S. 2020

    Abstract

    Sex chromosome aneuploidies (SCA) are associated with an increased risk for specific learning disorders (SLD). Individuals with Klinefelter Syndrome (KS) show an increased incidence of developmental dyslexia and individuals with Turner Syndrome (TS) are often affected by developmental dyscalculia. Accordingly, KS frequently coincides with verbal deficits, and TS with visual-spatial impairments. Though neurocognitive profiles of KS and TS are well-established, little is known about the neurobiology underling learning in SCA. This review summarizes current structural and functional magnetic resonance imaging (MRI) studies in KS and TS related to literacy and mathematical skills. It includes studies that focus on correlates between brain anatomy and cognition in SCA and on functional brain responses during learning-related tasks and at rest. We highlight important neural circuits that are related to domain-specific skills of literacy and mathematics. We discuss how identifying neuroendophenotypes of learning in SCA might contribute to developing a novel framework for SLD that accounts for potential genetic effects on learning, and from the X and Y chromosomes specifically. Future research directions are considered to establish clear brain-behavior relationships that might ultimately improve the treatment of SLD in SCA across development.

    View details for DOI 10.1002/ajmg.c.31801

    View details for PubMedID 32463563

  • Dyslexia in Pediatrics: Simple Practices to Tackle a Complex Issue. Pediatrics Karipidis, I. I., Hong, D. S. 2020

    View details for DOI 10.1542/peds.2020-1470

    View details for PubMedID 32576594

  • Editorial: The Role of Letter-Speech Sound Integration in Normal and Abnormal Reading Development. Frontiers in psychology Tijms, J., Fraga-González, G., Karipidis, I. I., Brem, S. 2020; 11: 1441

    View details for DOI 10.3389/fpsyg.2020.01441

    View details for PubMedID 32733324

    View details for PubMedCentralID PMC7358608

  • (Swiss) GraphoLearn: an app-based tool to support beginning readers. Research and practice in technology enhanced learning Mehringer, H., Fraga-Gonzalez, G., Pleisch, G., Rothlisberger, M., Aepli, F., Keller, V., Karipidis, I. I., Brem, S. 2020; 15 (1): 5

    Abstract

    We assessed the Swiss-German version of GraphoLearn, a computer game designed to support reading by training grapheme-phoneme correspondences. A group of 34 children at risk for dyslexia trained three times a week during 14weeks, on top of their standard school instruction. The sample was divided into two groups of 18 and 16 children, who started training at either the middle or the end of first grade. We found beneficial training effects in pseudoword reading in both training groups and for rapid automatized naming skills in the group that trained earlier. Our results suggest that both the efficiency in phonological decoding and rapid access to verbal representations are susceptible to facilitation by GraphoLearn. These findings confirm the utility of the training software as a tool to support school instruction and reading-related abilities in beginning readers. We discuss ideas to improve the content and outcomes of future versions of the training software.

    View details for DOI 10.1186/s41039-020-0125-0

    View details for PubMedID 32175013

  • Development of print-speech integration in the brain of beginning readers with varying reading skills Frontiers in Human Neuroscience Wang, F., Karipidis, I. I., Pleisch, G., Fraga-González, G., Brem, S. 2020; 14: 289

    Abstract

    Learning print-speech sound correspondences is a crucial step at the beginning of reading acquisition and often impaired in children with developmental dyslexia. Despite increasing insight into audiovisual language processing, it remains largely unclear how integration of print and speech develops at the neural level during initial learning in the first years of schooling. To investigate this development, 32 healthy, German-speaking children at varying risk for developmental dyslexia (17 typical readers and 15 poor readers) participated in a longitudinal study including behavioral and fMRI measurements in first (T1) and second (T2) grade. We used an implicit audiovisual (AV) non-word target detection task aimed at characterizing differential activation to congruent (AVc) and incongruent (AVi) audiovisual non-word pairs. While children's brain activation did not differ between AVc and AVi pairs in first grade, an incongruency effect (AVi > AVc) emerged in bilateral inferior temporal and superior frontal gyri in second grade. Of note, pseudoword reading performance improvements with time were associated with the development of the congruency effect (AVc > AVi) in the left posterior superior temporal gyrus (STG) from first to second grade. Finally, functional connectivity analyses indicated divergent development and reading expertise dependent coupling from the left occipito-temporal and superior temporal cortex to regions of the default mode (precuneus) and fronto-temporal language networks. Our results suggest that audiovisual integration areas as well as their functional coupling to other language areas and areas of the default mode network show a different development in poor vs. typical readers at varying familial risk for dyslexia.

    View details for DOI 10.3389/fnhum.2020.00289

    View details for PubMedCentralID PMC7457077

  • Simultaneous EEG and fMRI reveals stronger sensitivity to orthographic strings in the left occipito-temporal cortex of typical versus poor beginning readers. Developmental cognitive neuroscience Pleisch, G., Karipidis, I. I., Brem, A., Rothlisberger, M., Roth, A., Brandeis, D., Walitza, S., Brem, S. 2019; 40: 100717

    Abstract

    The level of reading skills in children and adults is reflected in the strength of preferential neural activation to print. Such preferential activation appears in the N1 event-related potential (ERP) over the occipitotemporal scalp after around 150-250 ms and the corresponding blood oxygen level dependent (BOLD) signal in the ventral occipitotemporal (vOT) cortex. Here, orthography-sensitive (print vs. false font) processing was examined using simultaneous EEG-fMRI in 38 first grade children with poor and typical reading skills, and at varying familial risk for developmental dyslexia. Coarse orthographic sensitivity was observed as an increased activation to print in the N1 ERP and in the BOLD signal of individually varying vOT regions in 57% of beginning readers. Finer differentiation in processing orthographic strings (words vs. nonwords) further occurred in specific vOT clusters. Neither method alone showed robust differences in orthography-sensitive processing between typical and poor reading children. Importantly, using single-trial N1 ERP-informed fMRI analysis, we found differential modulation of the orthography-sensitive BOLD response in the left vOT for typical readers only. This result, thus, confirms subtle functional alterations in a brain structure known to be critical for fluent reading at the very beginning of reading instruction.

    View details for DOI 10.1016/j.dcn.2019.100717

    View details for PubMedID 31704655

  • Valence-dependent coupling of prefrontal-amygdala effective connectivity during facial affect processing. eNeuro Willinger, D., Karipidis, I. I., Beltrani, S., Pietro, S. V., Sladky, R., Walitza, S., Stampfli, P., Brem, S. 2019

    Abstract

    Despite the importance of the prefrontal-amygdala network for emotion processing, valence-dependent coupling within this network remains elusive. In this study, we assessed the effect of emotional valence on brain activity and effective connectivity. We tested which functional pathways within the prefrontal-amygdala network are specifically engaged during the processing of emotional valence. Thirty-three healthy adults were examined with functional magnetic resonance imaging while performing a dynamic faces and dynamic shapes matching task. The valence of the facial expressions varied systematically between positive, negative, and neutral across the task. Functional contrasts determined core areas of the emotion processing circuitry, comprising the medial prefrontal cortex (MPFC), the right lateral prefrontal cortex, the amygdala and the right fusiform face area. Dynamic causal modelling demonstrated that the bidirectional coupling within the prefrontal-amygdala circuitry is modulated by emotional valence. Additionally, Bayesian model averaging showed significant bottom-up connectivity from the amygdala to the MPFC during negative and neutral, but not positive, valence. Thus, our study provides strong evidence for alterations of bottom-up coupling within the prefrontal-amygdala network as a function of emotional valence. Thereby our results not only advance the understanding of the human prefrontal-amygdala circuitry in varying valence context, but, moreover, provide a model to examine mechanisms of valence-sensitive emotional dysregulation in neuropsychiatric disorders.Significance statement Recent neuroimaging studies have emphasized the importance of valence-sensitivity within the prefrontal-amygdala network during emotion processing. Yet, it remains elusive which specific pathways are involved in processing affective information, and how this information is integrated in the brain's network. In particular, the amygdala's role in signaling valence information to the cortex is subject to ongoing discussions. Moreover, as aberrant brain function has been found in the amygdala and the prefrontal cortex in various debilitating psychiatric disorders, understanding the mechanisms of processing emotional stimuli with different valence (positive, negative, neutral) is particularly relevant for the field. Our findings indicate changes in coupling strength as a function of emotional valence within the prefrontal-amygdala network.

    View details for DOI 10.1523/ENEURO.0079-19.2019

    View details for PubMedID 31289107

  • Emerging neural specialization of the ventral occipitotemporal cortex to characters through phonological association learning in preschool children NEUROIMAGE Pleisch, G., Karipidis, I. I., Brauchli, C., Rothlisberger, M., Hofstetter, C., Stampfli, P., Walitza, S., Brem, S. 2019; 189: 813–31

    Abstract

    The ventral occipitotemporal (vOT) cortex serves as a core region for visual processing, and specific areas of this region show preferential activation for various visual categories such as faces and print. The emergence of such functional specialization in the human cortex represents a pivotal developmental process, which provides a basis for targeted and efficient information processing. For example, functional specialization to print in the left vOT is an important prerequisite for fluent reading. However, it remains unclear, which processes initiate the preferential cortical activations to characters arising in the vOT during child development. Using a multimodal neuroimaging approach with preschool children at familial risk for developmental dyslexia, we demonstrate how varying levels of expertise modulate the neural response to single characters, which represent the building blocks of print units. The level of expertise to characters was manipulated firstly through brief training of false-font speech-sound associations and secondly by comparing characters for which children differed in their level of familiarity and expertise accumulated through abundant exposure in their everyday environment. Neural correlates of character processing were tracked with simultaneous high-density electroencephalography and functional magnetic resonance imaging in a target detection task. We found training performance and expertise-dependent modulation of the visual event-related potential around 220 ms (N1) and the corresponding vOT activation. Additionally, trained false-font characters revealed stronger functional connectivity between the left fusiform gyrus (FFG) seed and left superior parietal/lateral occipital cortex regions with higher training performance. In sum, our results demonstrate that learning artificial-character speech-sound associations enhances activation to trained characters in the vOT and that the magnitude of this activation and the functional connectivity of the left FFG to the parieto-occipital cortex depends on learning performance. This pattern of results suggests emerging development of the reading network after brief training that parallels network specialization during reading acquisition.

    View details for DOI 10.1016/j.neuroimage.2019.01.046

    View details for Web of Science ID 000461166900070

    View details for PubMedID 30677503

  • Reply to "Dyslexia: Still Not a Neurodevelopmental Disorder" BRAIN SCIENCES Gonzalez, G., Karipidis, I. I., Tijms, J. 2019; 9 (3)

    Abstract

    In a recent opinion article, we explained why we think that defining developmental dyslexia as a neurodevelopmental disorder and neuroimaging studies on dyslexia are useful. A recent response has made some claims of generalized misinterpretation and misconception in the field. Since that was a direct reply to our article, we would like to clarify our opinion on some of those claims.

    View details for DOI 10.3390/brainsci9030061

    View details for Web of Science ID 000464372800001

    View details for PubMedID 30875810

    View details for PubMedCentralID PMC6468896

  • Dyslexia as a Neurodevelopmental Disorder and What Makes It Different from a Chess Disorder BRAIN SCIENCES Gonzalez, G., Karipidis, I. I., Tijms, J. 2018; 8 (10)

    Abstract

    The convenience of referring to dyslexia as a neurodevelopmental disorder has been repeatedly brought into question. In this opinion article, we argue in favor of the current diagnosis of dyslexia based on the criteria of harm and dysfunction. We discuss the favorable clinical and educational outcomes of a neuroscience-informed approach of dyslexia as a disorder. Furthermore, we discuss insights derived from neuroimaging studies and their importance to address problems related to developmental dyslexia.

    View details for DOI 10.3390/brainsci8100189

    View details for Web of Science ID 000448655700012

    View details for PubMedID 30347764

    View details for PubMedCentralID PMC6209961

  • Simulating reading acquisition: The link between reading outcome and multimodal brain signatures of letter-speech sound learning in prereaders SCIENTIFIC REPORTS Karipidis, I. I., Pleisch, G., Brandeis, D., Roth, A., Rothlisberger, M., Schneebeli, M., Walitza, S., Brem, S. 2018; 8: 7121

    Abstract

    During reading acquisition, neural reorganization of the human brain facilitates the integration of letters and speech sounds, which enables successful reading. Neuroimaging and behavioural studies have established that impaired audiovisual integration of letters and speech sounds is a core deficit in individuals with developmental dyslexia. This longitudinal study aimed to identify neural and behavioural markers of audiovisual integration that are related to future reading fluency. We simulated the first step of reading acquisition by performing artificial-letter training with prereading children at risk for dyslexia. Multiple logistic regressions revealed that our training provides new precursors of reading fluency at the beginning of reading acquisition. In addition, an event-related potential around 400 ms and functional magnetic resonance imaging activation patterns in the left planum temporale to audiovisual correspondences improved cross-validated prediction of future poor readers. Finally, an exploratory analysis combining simultaneously acquired electroencephalography and hemodynamic data suggested that modulation of temporoparietal brain regions depended on future reading skills. The multimodal approach demonstrates neural adaptations to audiovisual integration in the developing brain that are related to reading outcome. Despite potential limitations arising from the restricted sample size, our results may have promising implications both for identifying poor-reading children and for monitoring early interventions.

    View details for DOI 10.1038/s41598-018-24909-8

    View details for Web of Science ID 000431622700001

    View details for PubMedID 29740067

    View details for PubMedCentralID PMC5940897

  • Increasing expertise to a novel script modulates the visual N1 ERP in healthy adults INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT Brem, S., Hunkeler, E., Machler, M., Kronschnabel, J., Karipidis, I., Pleisch, G., Brandeis, D. 2018; 42 (3): 333–41
  • The dopaminergic reward system underpins gender differences in social preferences NATURE HUMAN BEHAVIOUR Soutschek, A., Burke, C. J., Beharelle, A., Schreiber, R., Weber, S. C., Karipidis, I. I., ten Velden, J., Weber, B., Haker, H., Kalenscher, T., Tobler, P. N. 2017; 1 (11): 819–27

    Abstract

    Women are known to have stronger prosocial preferences than men, but it remains an open question as to how these behavioural differences arise from differences in brain functioning. Here, we provide a neurobiological account for the hypothesized gender difference. In a pharmacological study and an independent neuroimaging study, we tested the hypothesis that the neural reward system encodes the value of sharing money with others more strongly in women than in men. In the pharmacological study, we reduced receptor type-specific actions of dopamine, a neurotransmitter related to reward processing, which resulted in more selfish decisions in women and more prosocial decisions in men. Converging findings from an independent neuroimaging study revealed gender-related activity in neural reward circuits during prosocial decisions. Thus, the neural reward system appears to be more sensitive to prosocial rewards in women than in men, providing a neurobiological account for why women often behave more prosocially than men.

    View details for DOI 10.1038/s41562-017-0226-y

    View details for Web of Science ID 000418854500016

    View details for PubMedID 31024122

  • Neural initialization of audiovisual integration in prereaders at varying risk for developmental dyslexia HUMAN BRAIN MAPPING Karipidis, I. I., Pleisch, G., Rothlisberger, M., Hofstetter, C., Dornbierer, D., Stampfli, P., Brem, S. 2017; 38 (2): 1038–55

    Abstract

    Learning letter-speech sound correspondences is a major step in reading acquisition and is severely impaired in children with dyslexia. Up to now, it remains largely unknown how quickly neural networks adopt specific functions during audiovisual integration of linguistic information when prereading children learn letter-speech sound correspondences. Here, we simulated the process of learning letter-speech sound correspondences in 20 prereading children (6.13-7.17 years) at varying risk for dyslexia by training artificial letter-speech sound correspondences within a single experimental session. Subsequently, we acquired simultaneously event-related potentials (ERP) and functional magnetic resonance imaging (fMRI) scans during implicit audiovisual presentation of trained and untrained pairs. Audiovisual integration of trained pairs correlated with individual learning rates in right superior temporal, left inferior temporal, and bilateral parietal areas and with phonological awareness in left temporal areas. In correspondence, a differential left-lateralized parietooccipitotemporal ERP at 400 ms for trained pairs correlated with learning achievement and familial risk. Finally, a late (650 ms) posterior negativity indicating audiovisual congruency of trained pairs was associated with increased fMRI activation in the left occipital cortex. Taken together, a short (<30 min) letter-speech sound training initializes audiovisual integration in neural systems that are responsible for processing linguistic information in proficient readers. To conclude, the ability to learn grapheme-phoneme correspondences, the familial history of reading disability, and phonological awareness of prereading children account for the degree of audiovisual integration in a distributed brain network. Such findings on emerging linguistic audiovisual integration could allow for distinguishing between children with typical and atypical reading development. Hum Brain Mapp 38:1038-1055, 2017. © 2016 Wiley Periodicals, Inc.

    View details for DOI 10.1002/hbm.23437

    View details for Web of Science ID 000393786500034

    View details for PubMedID 27739608

  • Social discounting involves modulation of neural value signals by temporoparietal junction PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Strombach, T., Weber, B., Hangebrauk, Z., Kenning, P., Karipidis, I. I., Tobler, P. N., Kalenscher, T. 2015; 112 (5): 1619–24

    Abstract

    Most people are generous, but not toward everyone alike: generosity usually declines with social distance between individuals, a phenomenon called social discounting. Despite the pervasiveness of social discounting, social distance between actors has been surprisingly neglected in economic theory and neuroscientific research. We used functional magnetic resonance imaging (fMRI) to study the neural basis of this process to understand the neural underpinnings of social decision making. Participants chose between selfish and generous alternatives, yielding either a large reward for the participant alone, or smaller rewards for the participant and another individual at a particular social distance. We found that generous choices engaged the temporoparietal junction (TPJ). In particular, the TPJ activity was scaled to the social-distance-dependent conflict between selfish and generous motives during prosocial choice, consistent with ideas that the TPJ promotes generosity by facilitating overcoming egoism bias. Based on functional coupling data, we propose and provide evidence for a biologically plausible neural model according to which the TPJ supports social discounting by modulating basic neural value signals in the ventromedial prefrontal cortex to incorporate social-distance-dependent other-regarding preferences into an otherwise exclusively own-reward value representation.

    View details for DOI 10.1073/pnas.1414715112

    View details for Web of Science ID 000349087700087

    View details for PubMedID 25605887

    View details for PubMedCentralID PMC4321268

  • Swiss GraphoGame: Concept and design presentation of a computerised reading intervention for children with high risk for poor reading outcomes Rothlisberger, M., Karipidis, I. I., Pleisch, G., Dellwo, V., Richardson, U., Brem, S., ISCA-INT SPEECH COMMUN ASSOC ISCA-INT SPEECH COMMUNICATION ASSOC. 2015: 1878–79