Scientists discover response to anxiety linked to movement control areas in brain

Media Release: European College of Neuropsychopharmacology (ECNP)
“For the science and treatment of disorders of the brain”

Scientists discover response to anxiety linked to movement control areas in brain
Embargo until: Sunday 18th September, 2016, 00.01 CEST (Vienna)

Researchers have discovered that the response to anxiety in teenagers may include not only the parts of the brain which deal with emotions (the limbic system), as has been long understood, but also movement control centres in the brain, which may be associated with movement inhibition when stressed (“freezing”). This is a small longitudinal study, presented at the ECNP conference in Vienna.
A group of Italian and Canadian researchers have followed a selection of socially anxious and control group children from childhood to adolescence. The researchers tested 150 children at the ages of 8/9, for signs of social inhibition. Some of these were shown to have early signs of social anxiety, and showed an increased tendency to withdraw from social situations. They also had more difficulty in recognising emotions, and particularly angry faces.
The anxious children, plus controls, were then followed into adolescence. At the ages of 14-15 they were tested again to see if signs of social anxiety had developed. The researchers also used fMRI brain scans to test how the teenage brains responded to angry facial expressions.
As lead researcher, Laura Muzzarelli said:
“We found that when presented with an angry face the brain of socially anxious adolescents showed increased activity in the amygdala, which is the brain area concerned with emotions, memory and how we respond to threats. Surprisingly, we also found this produced inhibition of some motor areas of the brain, the premotor cortex. This is an area which ‘prepares the body for action’, and for specific movements. This is the first hard proof that strong emotions produce a response in brain areas concerned with movement. Adolescents who don’t show social anxiety tend not to show the inhibition in the movement centres. We don’t yet know how this inhibition feeds into movement – it may be that this has something to do with why we sometimes ‘freeze’ when we are frightened or under strong emotional stress, this still has to be tested. What it does give us is a possible explanation for some motor inhibition associated with emotional stress.
We need to acknowledge that there are some limitations to this work. We started this 6-year study with 150 children, but by the time we reached adolescence we had narrowed down the field to just 5 children with social anxiety, and 5 with less severe (subthreshold) social anxiety, so it’s a small sample”.
Social Anxiety is a mental health condition characterised by excessive fear and avoidance of the judgement of others. It is the most common anxiety disorder, affecting around 6% to 8% people during their life*, meaning around 50m** Europeans are affected by the condition. It can occur at any age, but most commonly the onset is in adolescence, with early signs already visible during infancy. In early stages, social anxiety can be mistaken for shyness.
See notes for conference abstract, funding, and other details.
ENDS

Notes for editors
Please mention the European College of Neuropsychopharmacology Congress in any stories which result from this press release.

Contacts
Laura Muzzarelli laura.muzzarelli.rodrigues@gmail.com
ECNP Press Officer, Tom Parkhill press@ecnp.eu tel +39 349 238 8191 (Italy)

The European College of Neuropsychopharmacology (ECNP)
The ECNP is an independent scientific association dedicated to the science and treatment of disorders of the brain. It is the largest non-institutional supporter of applied and translational neuroscience research and education in Europe. Website: www.ecnp.eu
The annual ECNP Congress takes place from 17th to 20th September in Vienna. It is Europe’s premier scientific meeting for disease-oriented brain research, annually attracting between 4,000 and 6,000 neuroscientists, psychiatrists, neurologists and psychologists from around the world. Congress website: http://www.ecnp-congress.eu/
*EMA, Social Anxiety guideline p5 http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003490.pdf
**The population of Europe is around 740m, "World Population Prospects: The 2012 Revision". UN — Department of Economic and Social Affairs.

Conference Abstract: P.1.j.009 The emotional processing network at the onset of social anxiety disorder: a combined diffusion tensor imaging and functional connectivity study
L. Muzzarelli1 M. Tettamanti2,3 M. Taddei4 M. Battaglia5,6
1Vita-Salute San Raffaele University, Faculty of Psychology, Milan, Italy 2San Raffaele Hospital, Nuclear Medicine Unit, Milan, Italy 3San Raffaele Scientific Institute, Division of Neuroscience, Milan, Italy 4Istituto Neurologico C. Besta, Developmental Neurology Division, Milan, Italy 5University of Toronto, Department of Psychiatry, Toronto, Canada 6Centre for Addiction and Mental Health, Division of Child and Youth Psychiatry, Toronto, Canada
Background: Angry facial expressions of emotions (EoE) elicit an increase in the activity of the amygdala and of broadly distributed brain regions involved in emotional processing and in defensive reactions to threat. This response is heightened in adolescence, and is further enhanced in social anxiety disorder (SAD), to the point that specific neural responses to angry EoE could constitute a marker for susceptibility to the disorder.
Therefore, based on our previous evidence of an increased amygdala response to angry and neutral EoE in juvenile SAD [1], we aimed at unravelling the structural and functional connectivity architecture underlying both normative anger processing in adolescence, and the specific alterations induced by SAD.
Methods: A sample of 19 adolescents (mean age 14.8±1.1 years; 7 girls), part of a longitudinal study on SAD and emotional recognition [1,2], underwent DSM-IV diagnostic screening (5 SAD, 5 subthreshold-SAD, 9 with no SAD symptoms), and fMRI and DTI scans targeting brain responses to EoE and white matter fractional anisotropy (FA) [1,3]. In the current study, we carried out fMRI BOLD-FA correlation and psychophysiological interaction analyses, in order to elucidate how amygdala reactivity to EoE influences respectively white matter structural and functional connectivity. Furthermore, through DCM Network Discovery analyses, we investigated the functional relationships among a 5-nodes brain network involving known emotional processing regions (fusiform gyrus, bilateral amygdalae, subgenual anterior cingulate cortex) and the premotor cortex, which appeared to be a central hub in anger/threat processing by converging multimodal data. Then, we analysed how the connection strengths in this functional architecture are influenced by SAD and its precursors: particularly Harm Avoidance, an indicator of anxiety, as evaluated at age 7–8.
Results: Both structural and functional connectivity analyses evidenced the influence of amygdalar activity on broadly distributed brain regions (encompassing prefrontal and premotor cortices), and white matter, mostly on dorsal projectional and commissural tracts. The DCM analysis showed that the premotor cortex serves as a functional hub in the EoE processing network, by modulating the activity of the other nodes. Anger processing was shown to be selectively affected by SAD: SAD diagnosis associated with increased feed-forward connectivity from the fusiform gyrus to the amygdala (p = 0.035, ρ = 0.486) and with increased inhibition of the precentral gyrus by the amygdala (p = 0.046, ρ= ˗0.464). Furthermore, the higher was Harm Avoidance during childhood, the stronger were the excitatory influence of fusiform gyrus on subgenual anterior cingulate cortex (p = 0.038, ρ = 0.479), possibly as a compensatory effect to amygdala hyperactivity.
Discussion: Our data provide a first evidence of the involvement of motor-related areas in EoE processing and SAD. Anger, as a threatening social signal, triggers in subjects at risk for SAD both hyperresponsivity of the amygdala, and inhibition of motor responses. Such inhibition parallels the freezing reaction displayed in anxiogenic contexts by infants and primates [4], indicating the translational and developmental stability of this endophenotype. Neurobehavioral responses to angry faces thus characterize the risk for SAD longitudinally, constituting an early and stable functional marker that compounds the ethiopathogenic pathway to the development of the disorder.
References
[1] Battaglia, M., Zanoni, A., Taddei, M., Giorda, R., Bertoletti, E., Lampis, V., … Tettamanti, M., 2012. Cerebral responses to emotional expressions and the development of social anxiety disorder: a preliminary longitudinal study. Depression and Anxiety 29(1), 54–61. http://onlinelibrary.wiley.com/doi/10.1002/da.20896/abstract
[2] Battaglia, M., Ogliari, A., Zanoni, A., Villa, F., Citterio, A., Binaghi, F., … Maffei, C., 2004. Children's discrimination of expressions of emotions: relationship with indices of social anxiety and shyness. Journal of the American Academy of Child and Adolescent Psychiatry 43(3), 358–65.
[3] Taddei, M., Tettamanti, M., Zanoni, A., Cappa, S., & Battaglia, M., 2012. Brain white matter organisation in adolescence is related to childhood cerebral responses to facial expressions and harm avoidance. Neuroimage 61(4), 1394–401.
[4] Shackman, A.J., Fox, A.S., Oler, J.A., Shelton, S.E., Davidson, R.J., & Kalin, N.H., 2013. Neural mechanisms underlying heterogeneity in the presentation of anxious temperament. Proceedings of the National Academy of Sciences 110(15), 6145–50.
This work was supported by the National Alliance for Research in Schizophrenia and Depression 2006 Independent Investigator Award, awarded to Dr. Prof. Marco Battaglia, the principal investigator of the whole longitudinal project.