dual functional near-infrared spectroscopy (2): an …...autistic traits and neo-ffi for personality...

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Dual functional near-infrared spectroscopy (2): An application in face-to-face conversation Masanobu Shindo 1 , Hideaki Kitamura 1,2 , Akira Tachibana 1 , Toshiyuki Someya 1,2 1.Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan 2.Section of Disaster Medicine, Research Institute for Natural Hazards and Disaster Recovery, Niigata University, Niigata, Japan Objective: Conversation can be affected by a variety of psychiatric conditions such as psychosis, depression, autism, some personality traits, and especially social anxiety. However, the gender difference is a most powerful demographic variable and the related gender-specific brain responses should be examined in non-clinical population. Thus, we attempted to use two unconstraint near-infrared spectroscopy (NIRS) instruments for male/male or female/female pairs of talking healthy subjects. We investigated the gender difference of the relationships between social anxiety and the prefrontal responses measured by NIRS during face-to-face conversation. Methods: Subjects: Fifty healthy right-handed Japanese subjects without any history of psychiatric disorders and psychological traumas participated. To assess the individual differences, we use the following self-rated questionnaires (Japanese version): LSAS for social anxiety, IES-R for post- traumatic symptoms, K10 for depressive and anxiety symptoms, AQ for autistic traits and NEO-FFI for personality style. This study has been approved by the ethics committee of Niigata University School of Medicine and Dental Sciences, and all subjects have provided written informed consent. Total subjects gen nder p-value subjects (n=50) male (n=26) female (n=24) p-value (t-test) Age (mean±SD) 22.5±3.1 23.8±3.3 21.1±2.2 .0011 LSAS (Liebowitz Social A Anxiety Scale) (mean±SD) 37.2±19.9 35.7±20.1 38.9±20.0 n.s. IES-R (Impact of Event S Scale-Revised) (mean±SD) 8.6±10.2 8.2±11.3 9.0±9.0 n.s. K10 (mean±SD) 5.1±5.0 3.8±3.9 6.4±5.7 n.s. AQ (Autism-spectrum Q Quotient) (mean±SD) 19.5±6.7 19.2±5.9 19.8±7.5 n.s. NEO-FFI Neuroticism 46.9±11.9 46.7±13.2 47.2±10.7 n.s. (NEO-Five Extraversion 52.1±9.1 53.1±7.9 50.9±10.3 n.s. Factor Inventory) Openness 47.5±10.5 48.4±10.6 46.6±10.5 n.s. (mean±SD) Agreeableness 57.4±9.1 57.4±9.5 57.5±9.0 n.s. Conscientiousness 53.6±11.5 56.2±12.6 50.8±9.7 n.s. Face-to-face conversation task: After viewing the 4-minutes video clip of the 2011 Great East Japan Earthquake as a common topic, a pair of subjects seated face to face was asked to talk about the topic alternately for 4 minutes. Pre task • Repeat aloud “a,i,u,e,o” alternately as baseline for 30 sec Conversa=on • Talk about the topic for 240 sec • Change the interviewer and the interviewee in the halfD=me Post task • Repeat aloud “a,i,u,e,o” alternately as baseline for 60 sec !0.5 0 0.5 1 1.5 2 0 30 150 270 NIRS measurements and data processing: The relative changes of oxygenated hemoglobin concentration (Δ[Oxy-Hb]) in prefrontal cortices of two subjects were simultaneously measured with 10- channel WOT-100 (HITACHI) attached foreheads, sampling time is 0.2 sec. Baseline correction was made by using linear fitting based on the two baseline data, i.e. the mean [Oxy-Hb] across the last 10seconds-data in the pre-task and post-task baseline. We adopt the laterality index (Left-Right/Left+Right) of the average Δ[Oxy- Hb] across 4 channels for each hemisphere as the main index. Statistical analyses: All statistical analyses were performed with SAS JMP10 and the statistical significance level was set at 5%. Results: Pearson’s correlation analyses: Only in male, LSAS were significantly correlated positively with the laterality index during the interviewer (r=0.43, p=0.03). Multiple regression analyses: The laterality index of male during the interviewer, as a dependent variable, was affected by LSAS(β=0.55), AQ(β=-0.40), Extraversion(β=-0.46), and Agreeableness(β=0.36). This models’s adjusted R 2 was 0.41, and p-value was 0.0043. Conclusion: The result of present study about relationships between social anxiety and right frontal hypo-activation during social anxiety-provoking situation in male is consistent to the previous study. The content analysis of conversation may be useful to validate this interpretation of the hemispheric gender difference. pre interviewer interviewee post Δ[Oxy-Hb] Discussion: The higher social anxiety, the more predominant the left prefrontal cortices activity during interviewer only in male. Patients with social anxiety disorder showed hyperactivity in the amygdalae, parahippocampal gyrus, fusiform gyrus, globus pallidus, insula, inferior frontal gyrus, and superior temporal gyrus. (A.Etkin, T.Wager. 2007. Meta-analyses) While the amygdala region was activated by the stressful public speaking task, the failure to activate cortical areas could indicate that top-down inhibitory influences corresponding to self regulatory processes are compromised in social anxiety disorder. (M.Tillfors et al. 2001. PET study) Males showed more lateralization of emotional activity, by contrast, females showed more brainstem activation. (T. Wager et al. 2003. Meta-analyses) The lower AQ, the lower Extraversion and the higher Agreeableness is also the same result in male. Genetic factors that influence individual variation in low extraversion and high neuroticism appear to account entirely for the genetic liability to social phobia. (O.Bienvenu et al. 2007. Twin study) The frontopolar activity during conversation negatively correlated with Cooperativeness assessed using the Temperament and Character Inventory. And the left superior temporal sulcus activity negatively correlated with AQ, especially in males. (M.Suda et al. 2010, 2011. NIRS study) Regarding the content, between-male conversations might be solution- dominant, while between-female conversations might be sympathy- dominant, yielding to the hemispheric gender differences. Limitation: The sample size is small. The lack of clarity as to whether differences in activation patterns represent pathological manifestations or compensatory responses. Because of evaluating social anxiety in the healthy subjects, it’s not clear whether current results could apply to social anxiety disorder patients. -0.5 0 0.5 1 laterality index during interviewer 0 10 20 30 40 50 60 70 80 LSAS female male gender LSAS laterality index Variable 38.875 0.100695 Mean 19.99633 0.288363 Std Dev -0.05308 Correlation 0.8054 Signif. Prob 24 Number Correlation gender=="female" LSAS laterality index Variable 35.69231 -0.00312 Mean 20.06942 0.252174 Std Dev 0.426359 Correlation 0.0299* Signif. Prob 26 Number Correlation gender=="male" RSquare RSquare Adj Root Mean Square Error Mean of Response Observations (or Sum Wgts) 0.500427 0.40527 0.194473 -0.00312 26 Summary of Fit -0.49499 AICc 2.632533 BIC Model Error C. Total Source 4 21 25 DF 0.7955742 0.7942177 1.5897919 Sum of Squares 0.198894 0.037820 Mean Square 5.2590 F Ratio 0.0043* Prob > F F Ratio Analysis of Variance Intercept LSAS AQ E A Term 0.319197 0.0068913 -0.01722 -0.014817 0.0095592 Estimate 0.365879 0.0021 0.007129 0.005429 0.004463 Std Error 0.87 3.28 -2.42 -2.73 2.14 t Ratio 0.3928 0.0036* 0.0249* 0.0126* 0.0441* Prob>|t| 0 0.548446 -0.40268 -0.46185 0.358351 Std Beta . 1.1745247 1.168143 1.2035868 1.1766617 VIF Parameter Estimates seconds

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Page 1: Dual functional near-infrared spectroscopy (2): An …...autistic traits and NEO-FFI for personality style. This study has been approved by the ethics committee of Niigata University

Dual functional near-infrared spectroscopy (2):An application in face-to-face conversation

Masanobu Shindo1, Hideaki Kitamura1,2, Akira Tachibana1, Toshiyuki Someya1,2

1.Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan2.Section of Disaster Medicine, Research Institute for Natural Hazards and Disaster Recovery, Niigata University, Niigata, Japan

Objective:Conversation can be affected by a variety of psychiatric conditions such as psychosis, depression, autism, some personality traits, and especially social anxiety. However, the gender difference is a most powerful demographic variable and the related gender-specific brain responses should be examined in non-clinical population. Thus, we attempted to use two unconstraint near-infrared spectroscopy (NIRS) instruments for male/male or female/female pairs of talking healthy subjects. We investigated the gender difference of the relationships between social anxiety and the prefrontal responses measured by NIRS during face-to-face conversation.

Methods:Subjects:

Fifty healthy right-handed Japanese subjects without any history of psychiatric disorders and psychological traumas participated.To assess the individual differences, we use the following self-rated questionnaires (Japanese version): LSAS for social anxiety, IES-R for post-traumatic symptoms, K10 for depressive and anxiety symptoms, AQ for autistic traits and NEO-FFI for personality style.This study has been approved by the ethics committee of Niigata University School of Medicine and Dental Sciences, and all subjects have provided written informed consent.

Total subjects(n=50)

gendergenderp-value(t-test)

Total subjects(n=50)

male(n=26)

female(n=24)

p-value(t-test)

Age (mean±SD)Age (mean±SD) 22.5±3.1 23.8±3.3 21.1±2.2 .0011LSAS (Liebowitz Social Anxiety Scale) (mean±SD)LSAS (Liebowitz Social Anxiety Scale) (mean±SD) 37.2±19.9 35.7±20.1 38.9±20.0 n.s.IES-R (Impact of Event Scale-Revised) (mean±SD)IES-R (Impact of Event Scale-Revised) (mean±SD) 8.6±10.2 8.2±11.3 9.0±9.0 n.s.K10 (mean±SD)K10 (mean±SD) 5.1±5.0 3.8±3.9 6.4±5.7 n.s.AQ (Autism-spectrum Quotient) (mean±SD)AQ (Autism-spectrum Quotient) (mean±SD) 19.5±6.7 19.2±5.9 19.8±7.5 n.s.NEO-FFI Neuroticism 46.9±11.9 46.7±13.2 47.2±10.7 n.s.(NEO-Five Extraversion 52.1±9.1 53.1±7.9 50.9±10.3 n.s.

Factor Inventory) Openness 47.5±10.5 48.4±10.6 46.6±10.5 n.s.(mean±SD) Agreeableness 57.4±9.1 57.4±9.5 57.5±9.0 n.s.

Conscientiousness 53.6±11.5 56.2±12.6 50.8±9.7 n.s.

Face-to-face conversation task:After viewing the 4-minutes video clip of the 2011 Great East Japan Earthquake as a common topic, a pair of subjects seated face to face was asked to talk about the topic alternately for 4 minutes.

Pre$task�

• Repeat$aloud$“a,i,u,e,o”$alternately$as$baseline$for$30$sec�

Conversa=on�

• Talk$about$the$topic$for$240$sec�• Change$the$interviewer$and$the$interviewee$in$the$halfD=me�

Post$task�

• Repeat$aloud$“a,i,u,e,o”$alternately$as$baseline$for$60$sec�

!0.5%

0%

0.5%

1%

1.5%

2%

0% 30% 150% 270%

NIRS measurements and data processing:The relative changes of oxygenated hemoglobin concentration (Δ[Oxy-Hb]) in prefrontal cortices of two subjects were simultaneously measured with 10-channel WOT-100 (HITACHI) attached foreheads, sampling time is 0.2 sec.Baseline correction was made by using linear fitting based on the two baseline data, i.e. the mean [Oxy-Hb] across the last 10seconds-data in the pre-task and post-task baseline.We adopt the laterality index (Left-Right/Left+Right) of the average Δ[Oxy-Hb] across 4 channels for each hemisphere as the main index.

Statistical analyses:All statistical analyses were performed with SAS JMP10 and the statistical significance level was set at 5%.

Results:Pearson’s correlation analyses:

Only in male, LSAS were significantly correlated positively with the laterality index during the interviewer (r=0.43, p=0.03).

Multiple regression analyses:

The laterality index of male during the interviewer, as a dependent variable, was affected by LSAS(β=0.55), AQ(β=-0.40), Extraversion(β=-0.46), and Agreeableness(β=0.36). This models’s adjusted R2 was 0.41, and p-value was 0.0043.

Conclusion:✓The result of present study about relationships between social anxiety and

right frontal hypo-activation during social anxiety-provoking situation in male is consistent to the previous study.

✓The content analysis of conversation may be useful to validate this interpretation of the hemispheric gender difference.

pre interviewer interviewee post

Δ[Oxy-Hb]

Discussion:✓The higher social anxiety, the more predominant the left prefrontal cortices

activity during interviewer only in male.• Patients with social anxiety disorder showed hyperactivity in the

amygdalae, parahippocampal gyrus, fusiform gyrus, globus pallidus, insula, inferior frontal gyrus, and superior temporal gyrus. (A.Etkin, T.Wager. 2007. Meta-analyses)

• While the amygdala region was activated by the stressful public speaking task, the failure to activate cortical areas could indicate that top-down inhibitory influences corresponding to self regulatory processes are compromised in social anxiety disorder. (M.Tillfors et al. 2001. PET study)

• Males showed more lateralization of emotional activity, by contrast, females showed more brainstem activation. (T. Wager et al. 2003. Meta-analyses)

✓The lower AQ, the lower Extraversion and the higher Agreeableness is also the same result in male.• Genetic factors that influence individual variation in low extraversion and

high neuroticism appear to account entirely for the genetic liability to social phobia. (O.Bienvenu et al. 2007. Twin study)

• The frontopolar activity during conversation negatively correlated with Cooperativeness assessed using the Temperament and Character Inventory. And the left superior temporal sulcus activity negatively correlated with AQ, especially in males. (M.Suda et al. 2010, 2011. NIRS study)

✓Regarding the content, between-male conversations might be solution-dominant, while between-female conversations might be sympathy-dominant, yielding to the hemispheric gender differences.

Limitation:✓The sample size is small.✓The lack of clarity as to whether differences in activation patterns represent

pathological manifestations or compensatory responses.✓Because of evaluating social anxiety in the healthy subjects, it’s not clear

whether current results could apply to social anxiety disorder patients.

-0.5

0

0.5

1

late

rality

inde

x du

ring

inte

rvie

wer

0 10 20 30 40 50 60 70 80LSAS

femalemale

gender

LSASlaterality index

Variable38.875

0.100695

Mean19.996330.288363

Std Dev-0.05308

Correlation0.8054

Signif.Prob

24Number

Correlation gender=="female"

LSASlaterality index

Variable35.69231-0.00312

Mean20.069420.252174

Std Dev0.426359

Correlation0.0299*

Signif.Prob

26Number

Correlation gender=="male"

RSquareRSquare AdjRoot Mean Square ErrorMean of ResponseObservations (or Sum Wgts)

0.5004270.40527

0.194473-0.00312

26

Summary of Fit

-0.49499AICc

2.632533BIC

ModelErrorC. Total

Source4

2125

DF0.79557420.79421771.5897919

Sum ofSquares

0.1988940.037820

Mean Square5.2590

F Ratio

0.0043*Prob > F

F Ratio

Analysis of Variance

InterceptLSASAQEA

Term0.319197

0.0068913-0.01722

-0.0148170.0095592

Estimate0.365879

0.00210.0071290.0054290.004463

Std Error0.873.28

-2.42-2.732.14

t Ratio0.39280.0036*0.0249*0.0126*0.0441*

Prob>|t|0

0.548446-0.40268-0.461850.358351

Std Beta.

1.17452471.168143

1.20358681.1766617

VIF

Parameter Estimates

seconds