Where is the link between Synesthesia and Autism? A twin study on shared neural mechanisms and their causes
For people with synesthesia, certain sensory stimuli like sounds, written letters or tastes lead to additional inner sensations such as color, texture or shape. The mechanisms underlying synesthesia are unknown but the brains of synesthetes are atypically connected. While synesthesia is regarded as non-pathological, it is more common for people with Autism Spectrum Disorder (ASD). ASD is characterized by impairments in social functioning, but is also commonly associated with altered sensory sensitivity and enhanced attention to details. People with synesthesia show a similarly altered profile in sensory processing but no deficits in social functioning. The co-occurrence of the two conditions might further be associated with special talents (savant skills) observed in a proportion of people with ASD.
Using a twin design, we will investigate the impact of genes vs environment on the link between synesthesia and ASD and the role of altered sensory processing therein. Using brain imaging, we will further investigate patterns of altered brain connectivity - generally and in association with enhanced detail focus - overlapping between the two conditions.
The results will inform us about the developmental and neural mechanisms of both synesthesia and ASD and their potentially common genetic and neuronal origins. They will also provide insights into the mechanism underlying enhanced detail focus and the role of synesthesia and sensory processing in the development of savant skills.
Final report
Overarching aim and development of the project
Synesthesia is a phenomenon where certain sensory inputs (e.g. sounds or written letters) lead to additional internally generated sensations (e.g. color). Synesthesia is much more common in people with autism and the conditions share common profiles of altered sensory processing, altered brain connectivity, and a genetic background involving multiple genes. Given their shared characteristics and high co-occurrence, autism and synesthesia are likely to share aspects of their developmental pathways. However, the mechanisms and etiology underlying both synesthesia and autism and their co-occurrence are not well understood.
The overarching goal of this project was to generate new insights regarding the mechanisms underlying both synesthesia and autism and their potentially shared developmental routes. To achieve this goal, we applied a twin design. Comparing monozygotic vs dizygotic twins in a large population twin cohort enabled us to investigate the contributions of both genetic and environmental factors to synesthesia per se and its association with autism. We also investigated to what extent alterations in perception, which were previously reported to be similar in both conditions, and their underlying brain mechanisms were truly the same. Comparing individuals to their twins thereby allowed us to investigate these effects with maximum control over confounding factors.
Being the first synesthesia twin study, the project produced several new insights regarding the heritability of synesthesia, the genetic and environmental contributions to the link between synesthesia and autism, and the similarities and differences regarding the altered perceptual profiles associated with synesthesia and autism.
Procedure
This project was conducted in four data collection stages.
In stage 1, a brief synesthesia screening was implemented into a comprehensive survey administered to eighteen-year-old twins within the Child and Adolescent Twin Study in Sweden (CATSS). Using classical twin modelling, we assessed the heritability of synesthesia and the genetic and environmental architecture of its link to autism in 4262 twins.
In stage 2, twins with and without autism from the Roots of Autism and ADHD Twin Study in Sweden completed an objective synesthesia test, assessing synesthesia status and the degree of synesthesia (a score indicating the consistency of color choices for letters and digits). We then assessed the associations between the degree of synesthesia and autistic traits, sensory sensitivity and attention to detail (self-reported and tested) within twin pairs.
In stage 3, twin pairs from CATSS where at least one twin indicated experiencing synesthesia were objectively tested for synesthesia in order to identify twin pairs where only one twin was a synesthete (synesthesia discordant pairs).
Twin pairs discordant for synesthesia or autism, respectively, and neurotypical twins recruited from RATSS were then invited to an investigation on site (stage 4) that included several experiments. These comprised a functional magnetic resonance imaging experiment on detail-oriented attention (Embedded Figures Task), a behavioral test battery with different tasks on detail-oriented or globally oriented sensory processing, and assessments memory, intellectual ability, extraordinary talents and potential influences of synesthesia on daily living (advantages and disadvantages).
The three most important results and conclusions
1. Results from stage 1 indicated that self-reported synesthesia was heritable (~46%) but also influenced by environmental factors that were not shared by twins (54%). The association between synesthesia and autistic traits was estimated to be strongly (>70%) genetic. Further, it appeared to be primarily driven by non-social aspects of autistic traits, namely repetitive behaviors, restricted interests and attention to detail, while the association with social and communication difficulties was negligible (Taylor et al., submitted to Nature Human Behaviour).
2. Findings from stage 2 indicated that twins who scored more like synesthetes in an objective synesthesia test compared to their co-twins, also scored higher on self-reported sensory sensitivity and attention to detail and performed better on a task requiring the integration of fragmented visual information into a global whole (van Leeuwen et al., 2021, Cortex).
3. Results from stage 4 pointed towards differences between the perceptual alterations linked to synesthesia and autism. For instance, individuals with higher autistic traits were better in detecting small changes in naturalistic scenes compared to their twins and other individuals with lower autistic traits (p<.05). in contrast, synesthetic twins (but not twins with autism or higher autistic traits) were deceived less by certain visual illusions, indicating a less automatic integration of task-irrelevant visual information (p><.05). using brain imaging, we observed task-related activation in an expected network of parietal, frontal and visual areas (p><.05, fwe corrected) across all participant groups. similar brain regions have previously been reported to be activated during a less controlled version of the same task (e.g. see walter et al, 2011, plos one). group differences showed increased activity for controls in parietal regions (p=".001)," while for autistic participants, more activity was observed in middle frontal gyrus and the precuneus (both p><.001). for synesthetic twins vs their cotwin, we found more activation in right putamen, lateral occipital complex, and precuneus and hyper-connectivity within the parietal cortex (all p><.001). we are planning to publish these results in peer-reviewed journals until the end of 2023.>
Conclusions
We conclude that synesthesia is heritable, but also influenced by environmental factors not shared between twins, while genetic factors seem to play a predominant role in the link between synesthesia and autism. Further, evidence from both stage 1 and 2 suggests that synesthesia is specifically linked to the non-social domain of the autism spectrum. Our results indicate further that there are differences in the specific nature of attention to detail in synesthesia and autism, although both show advantages in detail perception, dependent on specific task conditions. That synesthetes show more integrations of visual features when the task at hand demands it, but less in the context of visual illusions might indicate and enhanced flexibility in this process in synesthetes.
Our brain imaging results indicated that higher-order integration regions are differently involved in detail processing in autistics, synesthetes, and controls, potentially indicating differences in how these regions influence perception via top-down processes. The increased visual, parietal and limbic brain activation in synesthetes when compared to their co-twins might indicate differences in perception specific to this group also further down in the processing hierarchy and illustrate the additional experimental power of the discordant twin design.
Taken together, synesthesia and autism appear to be linked via shared genetic factors, which might be more associated with attentional and perceptual processes rather than social skills. While a detail-oriented processing style characterizes both synesthesia and autism, the conditions differ in how and under which circumstances it is expressed.
New research Questions
Next steps include identifying what types of genes influence both, synesthesia and autism, and to identify concrete (non-shared) environmental influences in synesthesia, such as individual experiences at school, trauma, or other kind of events that can affect only one twin. We also would like to further investigate potential modulation effects on sensory task performance based on cognitive load or sensory sensitivity, which could explain the differences between the performance of synesthetic and autistic individuals. Another interesting question is as to whether the mechanisms underlying sensory hyper-sensitivity in synesthesia and autism are the same.
Communication of the project results and collaborations
We presented the results and the concept of the project during several international conferences and are regularly engaging with the community by giving popular science talks and interviews about synesthesia and its link to autism (listed below). We collaborated with the groups of Prof. Lichtenstein (Karolinska Institutet) on classical twin modelling analyses and the group of Prof. Wagemans (Leuven University) on the design of two perceptual tasks, and are involving these groups in the according publications.
Conference presentations
- 2023 – 14th Scientific Congress on the Autism Spectrum, Freiburg, oral presentation and poster
- 2021 – 29th European Congress of Psychiatry (EPA), poster presentation
- 2020 - Annual meeting of the International Society for Autism Research (INSAR), virtual meeting, poster
- 2019 – 42nd edition of the European Conference on Visual Perception, Leuven, Belgium, oral presentation within symposium on synesthesia and autism
- 2019 - 49th Annual Meeting of the Behavior Genetics Association, Stockholm, Sweden, poster
- 2018 - Annual meeting of The Strategic Research Area Neuroscience at Karolinska Institutet, Sånga Säby, Sweden, oral presentation
Popular science contributions
- Interview on synesthesia and autism in Special nest, 2023
- Community engagement: “synestesicafé” for information and exchange, Stockholm, 2022
- Talk about synesthesia, Färgcentrum Stockholm, 2022
- Episode on synesthesia in the podcast “Allt Du velat veta” 2021
- Talk at the 2021 Aha-festival, Chalmers, Göteborg
- Interview in Medicinsk Vetenskap, 2020
- Article on synesthesia and autism in the journal Speciellt, 2017 & 2019
Planned
- Podcast “Funka olika” episode about sensory processing in autism, April 2023
- Podcast ”Medicinvetarna” episode about synesthesia, April 2023
Synesthesia is a phenomenon where certain sensory inputs (e.g. sounds or written letters) lead to additional internally generated sensations (e.g. color). Synesthesia is much more common in people with autism and the conditions share common profiles of altered sensory processing, altered brain connectivity, and a genetic background involving multiple genes. Given their shared characteristics and high co-occurrence, autism and synesthesia are likely to share aspects of their developmental pathways. However, the mechanisms and etiology underlying both synesthesia and autism and their co-occurrence are not well understood.
The overarching goal of this project was to generate new insights regarding the mechanisms underlying both synesthesia and autism and their potentially shared developmental routes. To achieve this goal, we applied a twin design. Comparing monozygotic vs dizygotic twins in a large population twin cohort enabled us to investigate the contributions of both genetic and environmental factors to synesthesia per se and its association with autism. We also investigated to what extent alterations in perception, which were previously reported to be similar in both conditions, and their underlying brain mechanisms were truly the same. Comparing individuals to their twins thereby allowed us to investigate these effects with maximum control over confounding factors.
Being the first synesthesia twin study, the project produced several new insights regarding the heritability of synesthesia, the genetic and environmental contributions to the link between synesthesia and autism, and the similarities and differences regarding the altered perceptual profiles associated with synesthesia and autism.
Procedure
This project was conducted in four data collection stages.
In stage 1, a brief synesthesia screening was implemented into a comprehensive survey administered to eighteen-year-old twins within the Child and Adolescent Twin Study in Sweden (CATSS). Using classical twin modelling, we assessed the heritability of synesthesia and the genetic and environmental architecture of its link to autism in 4262 twins.
In stage 2, twins with and without autism from the Roots of Autism and ADHD Twin Study in Sweden completed an objective synesthesia test, assessing synesthesia status and the degree of synesthesia (a score indicating the consistency of color choices for letters and digits). We then assessed the associations between the degree of synesthesia and autistic traits, sensory sensitivity and attention to detail (self-reported and tested) within twin pairs.
In stage 3, twin pairs from CATSS where at least one twin indicated experiencing synesthesia were objectively tested for synesthesia in order to identify twin pairs where only one twin was a synesthete (synesthesia discordant pairs).
Twin pairs discordant for synesthesia or autism, respectively, and neurotypical twins recruited from RATSS were then invited to an investigation on site (stage 4) that included several experiments. These comprised a functional magnetic resonance imaging experiment on detail-oriented attention (Embedded Figures Task), a behavioral test battery with different tasks on detail-oriented or globally oriented sensory processing, and assessments memory, intellectual ability, extraordinary talents and potential influences of synesthesia on daily living (advantages and disadvantages).
The three most important results and conclusions
1. Results from stage 1 indicated that self-reported synesthesia was heritable (~46%) but also influenced by environmental factors that were not shared by twins (54%). The association between synesthesia and autistic traits was estimated to be strongly (>70%) genetic. Further, it appeared to be primarily driven by non-social aspects of autistic traits, namely repetitive behaviors, restricted interests and attention to detail, while the association with social and communication difficulties was negligible (Taylor et al., submitted to Nature Human Behaviour).
2. Findings from stage 2 indicated that twins who scored more like synesthetes in an objective synesthesia test compared to their co-twins, also scored higher on self-reported sensory sensitivity and attention to detail and performed better on a task requiring the integration of fragmented visual information into a global whole (van Leeuwen et al., 2021, Cortex).
3. Results from stage 4 pointed towards differences between the perceptual alterations linked to synesthesia and autism. For instance, individuals with higher autistic traits were better in detecting small changes in naturalistic scenes compared to their twins and other individuals with lower autistic traits (p<.05). in contrast, synesthetic twins (but not twins with autism or higher autistic traits) were deceived less by certain visual illusions, indicating a less automatic integration of task-irrelevant visual information (p><.05). using brain imaging, we observed task-related activation in an expected network of parietal, frontal and visual areas (p><.05, fwe corrected) across all participant groups. similar brain regions have previously been reported to be activated during a less controlled version of the same task (e.g. see walter et al, 2011, plos one). group differences showed increased activity for controls in parietal regions (p=".001)," while for autistic participants, more activity was observed in middle frontal gyrus and the precuneus (both p><.001). for synesthetic twins vs their cotwin, we found more activation in right putamen, lateral occipital complex, and precuneus and hyper-connectivity within the parietal cortex (all p><.001). we are planning to publish these results in peer-reviewed journals until the end of 2023.>
Conclusions
We conclude that synesthesia is heritable, but also influenced by environmental factors not shared between twins, while genetic factors seem to play a predominant role in the link between synesthesia and autism. Further, evidence from both stage 1 and 2 suggests that synesthesia is specifically linked to the non-social domain of the autism spectrum. Our results indicate further that there are differences in the specific nature of attention to detail in synesthesia and autism, although both show advantages in detail perception, dependent on specific task conditions. That synesthetes show more integrations of visual features when the task at hand demands it, but less in the context of visual illusions might indicate and enhanced flexibility in this process in synesthetes.
Our brain imaging results indicated that higher-order integration regions are differently involved in detail processing in autistics, synesthetes, and controls, potentially indicating differences in how these regions influence perception via top-down processes. The increased visual, parietal and limbic brain activation in synesthetes when compared to their co-twins might indicate differences in perception specific to this group also further down in the processing hierarchy and illustrate the additional experimental power of the discordant twin design.
Taken together, synesthesia and autism appear to be linked via shared genetic factors, which might be more associated with attentional and perceptual processes rather than social skills. While a detail-oriented processing style characterizes both synesthesia and autism, the conditions differ in how and under which circumstances it is expressed.
New research Questions
Next steps include identifying what types of genes influence both, synesthesia and autism, and to identify concrete (non-shared) environmental influences in synesthesia, such as individual experiences at school, trauma, or other kind of events that can affect only one twin. We also would like to further investigate potential modulation effects on sensory task performance based on cognitive load or sensory sensitivity, which could explain the differences between the performance of synesthetic and autistic individuals. Another interesting question is as to whether the mechanisms underlying sensory hyper-sensitivity in synesthesia and autism are the same.
Communication of the project results and collaborations
We presented the results and the concept of the project during several international conferences and are regularly engaging with the community by giving popular science talks and interviews about synesthesia and its link to autism (listed below). We collaborated with the groups of Prof. Lichtenstein (Karolinska Institutet) on classical twin modelling analyses and the group of Prof. Wagemans (Leuven University) on the design of two perceptual tasks, and are involving these groups in the according publications.
Conference presentations
- 2023 – 14th Scientific Congress on the Autism Spectrum, Freiburg, oral presentation and poster
- 2021 – 29th European Congress of Psychiatry (EPA), poster presentation
- 2020 - Annual meeting of the International Society for Autism Research (INSAR), virtual meeting, poster
- 2019 – 42nd edition of the European Conference on Visual Perception, Leuven, Belgium, oral presentation within symposium on synesthesia and autism
- 2019 - 49th Annual Meeting of the Behavior Genetics Association, Stockholm, Sweden, poster
- 2018 - Annual meeting of The Strategic Research Area Neuroscience at Karolinska Institutet, Sånga Säby, Sweden, oral presentation
Popular science contributions
- Interview on synesthesia and autism in Special nest, 2023
- Community engagement: “synestesicafé” for information and exchange, Stockholm, 2022
- Talk about synesthesia, Färgcentrum Stockholm, 2022
- Episode on synesthesia in the podcast “Allt Du velat veta” 2021
- Talk at the 2021 Aha-festival, Chalmers, Göteborg
- Interview in Medicinsk Vetenskap, 2020
- Article on synesthesia and autism in the journal Speciellt, 2017 & 2019
Planned
- Podcast “Funka olika” episode about sensory processing in autism, April 2023
- Podcast ”Medicinvetarna” episode about synesthesia, April 2023
Publication list
Publications produced
Open access was ensured by choosing the open access option for publishing all scientific articles produced within the grant period. Since Karolinska Institutet had open access agreements with all chosen journals, no costs were charged for this.
1. Publications in peer-reviewed scientific journals
Wilsson L, van Leeuwen TM & Neufeld J (2022) synr: An R package for handling synesthesia consistency test data. Behavioral Research Methods, https://doi.org/10.3758/s13428-022-02007-y (open access)
van Leeuwen TM, Wilsson L, Nobel Norrman H, Dingemanse M, Bölte S & Neufeld J (2021): Perceptual processing links autism and synesthesia: a co-twin control study. Cortex, 145, 236-249, PMID: 34763130; https://www.sciencedirect.com/science/article/pii/S001094522100321X?via%3Dihub (open access)
van Leeuwen TM, Neufeld J, Hughes J, & Ward J (2020): Synaesthesia and autism: Different developmental outcomes from overlapping mechanisms? Cognitive Neuropsychology, 37(7-8), 433-449, PMID: 32845799; https://www.tandfonline.com/doi/full/10.1080/02643294.2020.1808455 (open access)
Riedel, A, Maier, S, Wenzler, K, Feige, B, Tebartz van Elst, L, Bölte, S, & Neufeld J (2020). A case of co-occuring synesthesia, autism, prodigious talent and strong structural brain connectivity. BMC psychiatry, 20(1), 1-11, PMID: 32605557; https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-020-02722-w#Fun (open access)
2. Submitted articles
Taylor MJ, Leeuwen TM, Kuja-Halkola R, Lundström S, Larsson H, Lichtenstein P, Bölte S & Neufeld J: Genetic and environmental architecture of synesthesia and its association with the autism spectrum - A twin study. Submitted to Nature Human Behaviour.
3. Conference papers & abstracts
- 2023 – 14th Scientific Congress on the Autism Spectrum, Freiburg; https://wgas-autismus.org/wp-content/uploads/2023/03/Tagungsband-WTAS-2023.pdf
- 2021 – 29th European Congress of Psychiatry (EPA); https://info.kenes.com/epa21/index.html
- 2020 - Annual meeting of the International Society for Autism Research (INSAR), virtual meeting; https://insar.confex.com/insar/2020/meetingapp.cgi/Search/0?sort=Relevance&size=10&page=1&searchterm=neufeld
- 2019 – 42nd edition of the European Conference on Visual Perception, Leuven, Belgium; https://journals.sagepub.com/doi/pdf/10.1177/0301006619863862
- 2019 - 49th Annual Meeting of the Behavior Genetics Association, Stockholm, Sweden; https://bga19.exordo.com/programme/presentation/126
4. Popular science contributions
- Interview on synesthesia and autism in Special nest; https://www.specialnest.se/liv-hem/hon-forskar-om-synestesi-de-upplever-varlden-pa-ett-annat-satt
- Talk about synesthesia, Färgcentrum Stockholm, 2022; https://www.facebook.com/svensktfargcentrum/
- Contribution to the podcast “Allt Du velat veta” 2021; https://play.acast.com/s/alltduvelatveta/313omsynestesimedjaninaneufeld
- Talk at the 2021 Aha-festival, Chalmers, Göteborg
- Interview in Medicinsk Vetenskap, 2020: https://ki.se/forskning/en-fargstark-formaga-synestesi
- Article on synesthesia and autism in the journal Speciellt, 2017 & 2019; https://www.autism.se/stockholms-lan/om-oss/medlemstidningen-speciellt/
Own websites
https://medarbetare.ki.se/people/janina-neufeld
https://ki.se/kind/synestesi-och-koppling-till-autism-perception-och-mental-halsa
Open access was ensured by choosing the open access option for publishing all scientific articles produced within the grant period. Since Karolinska Institutet had open access agreements with all chosen journals, no costs were charged for this.
1. Publications in peer-reviewed scientific journals
Wilsson L, van Leeuwen TM & Neufeld J (2022) synr: An R package for handling synesthesia consistency test data. Behavioral Research Methods, https://doi.org/10.3758/s13428-022-02007-y (open access)
van Leeuwen TM, Wilsson L, Nobel Norrman H, Dingemanse M, Bölte S & Neufeld J (2021): Perceptual processing links autism and synesthesia: a co-twin control study. Cortex, 145, 236-249, PMID: 34763130; https://www.sciencedirect.com/science/article/pii/S001094522100321X?via%3Dihub (open access)
van Leeuwen TM, Neufeld J, Hughes J, & Ward J (2020): Synaesthesia and autism: Different developmental outcomes from overlapping mechanisms? Cognitive Neuropsychology, 37(7-8), 433-449, PMID: 32845799; https://www.tandfonline.com/doi/full/10.1080/02643294.2020.1808455 (open access)
Riedel, A, Maier, S, Wenzler, K, Feige, B, Tebartz van Elst, L, Bölte, S, & Neufeld J (2020). A case of co-occuring synesthesia, autism, prodigious talent and strong structural brain connectivity. BMC psychiatry, 20(1), 1-11, PMID: 32605557; https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-020-02722-w#Fun (open access)
2. Submitted articles
Taylor MJ, Leeuwen TM, Kuja-Halkola R, Lundström S, Larsson H, Lichtenstein P, Bölte S & Neufeld J: Genetic and environmental architecture of synesthesia and its association with the autism spectrum - A twin study. Submitted to Nature Human Behaviour.
3. Conference papers & abstracts
- 2023 – 14th Scientific Congress on the Autism Spectrum, Freiburg; https://wgas-autismus.org/wp-content/uploads/2023/03/Tagungsband-WTAS-2023.pdf
- 2021 – 29th European Congress of Psychiatry (EPA); https://info.kenes.com/epa21/index.html
- 2020 - Annual meeting of the International Society for Autism Research (INSAR), virtual meeting; https://insar.confex.com/insar/2020/meetingapp.cgi/Search/0?sort=Relevance&size=10&page=1&searchterm=neufeld
- 2019 – 42nd edition of the European Conference on Visual Perception, Leuven, Belgium; https://journals.sagepub.com/doi/pdf/10.1177/0301006619863862
- 2019 - 49th Annual Meeting of the Behavior Genetics Association, Stockholm, Sweden; https://bga19.exordo.com/programme/presentation/126
4. Popular science contributions
- Interview on synesthesia and autism in Special nest; https://www.specialnest.se/liv-hem/hon-forskar-om-synestesi-de-upplever-varlden-pa-ett-annat-satt
- Talk about synesthesia, Färgcentrum Stockholm, 2022; https://www.facebook.com/svensktfargcentrum/
- Contribution to the podcast “Allt Du velat veta” 2021; https://play.acast.com/s/alltduvelatveta/313omsynestesimedjaninaneufeld
- Talk at the 2021 Aha-festival, Chalmers, Göteborg
- Interview in Medicinsk Vetenskap, 2020: https://ki.se/forskning/en-fargstark-formaga-synestesi
- Article on synesthesia and autism in the journal Speciellt, 2017 & 2019; https://www.autism.se/stockholms-lan/om-oss/medlemstidningen-speciellt/
Own websites
https://medarbetare.ki.se/people/janina-neufeld
https://ki.se/kind/synestesi-och-koppling-till-autism-perception-och-mental-halsa