The neurophysiology of ESSENCE

Overview of the research programme

The different neurodevelopmental conditions that constitute ESSENCE affect brain functioning, and our research program uses different tools with the aim of objectively measuring the differences that may be present between ESSENCE individuals and typically developing ones.

There are many ways to look at brain structure and function, and they include anatomical magnetic resonance imaging (MRI), functional MRI, magneto-encephalography (MEG), electro-encephalography (EEG/ERP), as well as eye tracking, which gives information both on behaviour (gaze) and on the level of arousal (pupillometry) and that can be associated with other measures of arousal as well (heart rate, skin conductance), and psychophysical tests that are reflecting the balance between Excitation and Inhibition (E/I) in the brain (e.g. paradoxical motion perception test). All these tests are complemented by questionnaires that indicate, for example, the level of sensitivity to sensory stimuli, or more generally psychological traits that have been related to an autism or other ESSENCE diagnosis.

We are also interested in a leading hypothesis in the field of autism – one that may also be relevant to other conditions – which stipulates that some of the symptoms observed may result from an E/I imbalance in the brain.

Finally, we are interested in neuroinflammation and its role in different conditions, including Paediatric Acute-onset Neuropsychiatric Syndrome (PANS), a condition defined by sudden onset psychiatric symptoms, including obsessive-compulsive behaviour, as well as cognitive, behavioural, or neurological symptoms; we are aiming to test the hypothesis that these symptoms are associated with neuroinflammation in the basal ganglia.

Past research projects

Over the past years we have published a number of papers that have demonstrated differences in brain functions in individuals with autism, including a hypersensitivity to eye contact (Hadjikhani et al., 2017; Galazka et al., 2018; Lassalle et al., 2017) that can be alleviated by bumetanide treatment (Hadjikhani et al., 2018; see also Hadjikhani et al., 2015). Using MEG, we have shown that gamma suppression can provide a non-invasive measure of inhibitory-based gain control in the healthy and diseased brain (Orekhova et al., 2018), and that differences in gamma oscillations related to hypersensitivity (Orekhova et al., 2019). In addition, we have shown that eye tracking can provide precious information regarding faces and social processing (Frost-Karlsson et al., 2019; Galazka et al., 2019; Åsberg Johnels et al., 2017). Finally, we have explored how underlying electrophysiological (EEG/ERP) patterns associate with behavioural measures of executive problems in children and adolescents with ADHD (Hager et al., 2020).

Ongoing projects

We are currently testing the E/I imbalance hypothesis in a clinical study where autistic individuals will receive a treatment with a diuretic (bumetanide) which, through its action on the intracellular chloride levels, acts on restoring the inhibitory function of GABA. Our previous imaging work has shown promising results on this treatment in a small group of individuals, and our current efforts aim to use different methods in a larger group of participants to further test this hypothesis.

We are also interested in Interpersonal motor and autonomic synchrony in ESSENCE, and will investigate the base of difficulties in social interactions and communications, which are pervasive within ESSENCE, and test the hypothesis that they may be related to difficulties in synchronization and mimicry, both at the motor level (facial mimicry, body posture mimicry, eye gaze synchrony, eye contact) as well as the autonomic level (pupil mimicry, changes in stress levels, heart rate synchronization). In addition, research on the underlying electrophysiological bases to ESSENCE symptoms is ongoing.

References

ASBERG JOHNELS, J., HOVEY, D., ZURCHER, N., HIPPOLYTE, L., LEMONNIER, E., GILLBERG, C. & HADJIKHANI, N. 2017. Autism and emotional face-viewing. Autism Res, 10, 901-910.

FROST-KARLSSON, M., GALAZKA, M. A., GILLBERG, C., GILLBERG, C., MINISCALCO, C., BILLSTEDT, E., HADJIKHANI, N. & ASBERG JOHNELS, J. 2019. Social scene perception in autism spectrum disorder: An eye-tracking and pupillometric study. J Clin Exp Neuropsychol, 41, 1024-1032.

GALAZKA, M. A., ASBERG JOHNELS, J., ZURCHER, N. R., HIPPOLYTE, L., LEMONNIER, E., BILLSTEDT, E., GILLBERG, C. & HADJIKHANI, N. 2018. Pupillary Contagion in Autism. Psychol Sci, 956797618809382.

GALAZKA, M. A., ASBERG JOHNELS, J., ZURCHER, N. R., HIPPOLYTE, L., LEMONNIER, E., BILLSTEDT, E., GILLBERG, C. & HADJIKHANI, N. 2019. Pupillary Contagion in Autism. Psychol Sci, 30, 309-315.

HADJIKHANI, N., ÅSBERG JOHNELS, J., LASSALLE, A., ZÜRCHER, N. R., HIPPOLYTE, L., GILLBERG, C., LEMONNIER, E. & BEN-ARI, Y. 2018. Bumetanide for autism: more eye contact, less amygdala activation. Scientific Reports, 8, 3602.

HADJIKHANI, N., ASBERG JOHNELS, J., ZURCHER, N. R., LASSALLE, A., GUILLON, Q., HIPPOLYTE, L., BILLSTEDT, E., WARD, N., LEMONNIER, E. & GILLBERG, C. 2017. Look me in the eyes: constraining gaze in the eye-region provokes abnormally high subcortical activation in autism. Scientific Reports, 7, 3163.

HADJIKHANI, N., ZURCHER, N. R., ROGIER, O., RUEST, T., HIPPOLYTE, L., BEN-ARI, Y. & LEMONNIER, E. 2015. Improving emotional face perception in autism with diuretic bumetanide: A proof-of-concept behavioral and functional brain imaging pilot study. Autism, 19, 149-57.

HAGER, L. A., OGRIM, G., DANIELSEN, M., BILLSTEDT, E., GILLBERG, C. & ASBERG JOHNELS, J. 2020. Indexing Executive Functions with Test Scores, Parent Ratings and ERPs: How Do the Measures Relate in Children versus Adolescents with ADHD? Neuropsychiatr Dis Treat, 16, 465-477.

LASSALLE, A., ASBERG JOHNELS, J., ZURCHER, N., HIPPOLYTE, L., BILLSTEDT, E., WARD, N., LEMONNIER, E., GILLBERG, C. & HADJIKHANI, N. 2017. Hypersensitivity to low intensity fearful faces in people with autism focusing on the eye region. In: F1000RESEARCH (ed.).

OREKHOVA, E. V., STROGANOVA, T. A., SCHNEIDERMAN, J. F., LUNDSTROM, S., RIAZ, B., SAROVIC, D., SYSOEVA, O. V., BRANT, G., GILLBERG, C. & HADJIKHANI, N. 2019. Neural gain control measured through cortical gamma oscillations is associated with sensory sensitivity. Hum Brain Mapp, 40, 1583-1593.

OREKHOVA, E. V., SYSOEVA, O. V., SCHNEIDERMAN, J. F., LUNDSTROM, S., GALUTA, I. A., GOIAEVA, D. E., PROKOFYEV, A. O., RIAZ, B., KEELER, C., HADJIKHANI, N., GILLBERG, C. & STROGANOVA, T. A. 2018. Input-dependent modulation of MEG gamma oscillations reflects gain control in the visual cortex. Sci Rep, 8, 8451.