1. Neuroscience

Alcoholism gender differences in brain responsivity to emotional stimuli

  1. Kayle S Sawyer  Is a corresponding author
  2. Nasim Maleki
  3. Trinity Urban
  4. Ksenija Marinkovic
  5. Steven Karson
  6. Susan M Ruiz
  7. Gordon J Harris
  8. Marlene Oscar-Berman
  1. VA Healthcare System, United States
  2. Boston University School of Medicine, United States
  3. Massachusetts General Hospital, United States
  4. Sawyer Scientific, LLC, United States
  5. San Diego State University, United States
  6. Dartmouth College, United States
https://doi.org/10.7554/eLife.41723
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Cite this article
  1. Kayle S Sawyer
  2. Nasim Maleki
  3. Trinity Urban
  4. Ksenija Marinkovic
  5. Steven Karson
  6. Susan M Ruiz
  7. Gordon J Harris
  8. Marlene Oscar-Berman
(2019)
Alcoholism gender differences in brain responsivity to emotional stimuli
eLife 8:e41723.
https://doi.org/10.7554/eLife.41723
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6 figures, 9 tables and 1 additional file

Figures

Figure 1 with 1 supplement
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Schematic of task presentation, and examples of stimuli.

As described in the text, participants were shown pictures from the International Affective Picture System (Lang et al., 1988) and asked to report how the pictures made them feel (good, bad, or neutral). Note the pictures in this figure are not the exact pictures shown to participants from the International Affective Picture System as these are not to be made available online (https://csea.phhp.ufl.edu/media/iapsmessage.html). The erotic (https://www.flickr.com/photos/103039225@N05/14964085720) and happy (https://www.flickr.com/photos/moonjazz/2684228420) images are in the public domain and are reproduced here under a Public Domain Mark 1.0 licence (https://creativecommons.org/publicdomain/mark/1.0/). The gruesome (https://commons.wikimedia.org/wiki/File:Amputation_surgery_01.JPG) and neutral (https://commons.wikimedia.org/wiki/File:Herstal_Y1944_med_tiltbar_skjerm-1.JPG) images are in the public domain and are reproduced here under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication (https://creativecommons.org/publicdomain/zero/1.0/deed.en). The aversive image was taken from the National Archives Catalog (https://catalog.archives.gov/id/6366489) where it was made available with no restrictions on its use.

https://doi.org/10.7554/eLife.41723.003
Figure 1—figure supplement 1
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Conceptual model of emotional integration and evaluation, adapted from Halgren and Marinković (1995), and informed more recently by results of a meta-analytic analysis by Riedel et al. (2018).

Widespread and focal dynamic corticolimbic neural networks embody a broad scope of circuitries linked to distinct functional systems for amalgamating cognitive with feeling aspects of emotions: Attention and orientation to a salient stimulus occurs in insular, anterior cingulate, prefrontal, and posterior parietal cortices; Emotional event appraisal, integration, and evaluation (as influenced by the ongoing emotional context and the perceiver’s personality), takes place in posterior cingulate, orbital and medial prefrontal cortex, and other neocortical sites (e.g., fusiform gyrus and superior temporal sulcus), and limbic structures (hippocampus and amygdala); Volition and decisions, which determine response choice, are generated in cingulate, precentral, premotor, and supplementary cortices.

https://doi.org/10.7554/eLife.41723.004
Figure 2
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Participants’ characteristics and drinking measures.

The boxplot represents participant characteristics. Appendix 1—table 1 shows the means, standard deviations, and significant differences. In the boxplot above, blue diamonds indicate mean values. Age, education, DHD, and LOS are expressed in years and DD is in ounces of ethanol per day (approximating daily drinks). LOS values were not applicable for two nonalcoholic control men and four nonalcoholic control women who reported never drinking. Abbreviations: DHD = Duration of Heavy Drinking (>21 drinks per week) in years; DD = Daily drinks; LOS = Length of sobriety in years. HRSD = Hamilton Rating Scale for Depression (Hamilton, 1960); VIQ = Wechsler Adult Intelligence Scale, 3rd ed. Verbal Intelligence Quotient; PIQ = Wechsler Adult Intelligence Scale, 3rd ed. Performance Intelligence Quotient; WMS_DMI = Wechsler Memory Scale, 3rd ed. Delayed (General) Memory Index.

https://doi.org/10.7554/eLife.41723.005
Figure 3 with 1 supplement
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Percentage of behavioral ratings by condition, rating, group, and gender.

The boxplot represents the significant condition x rating x group interaction, and the significant condition x rating x gender interaction, for percentage rating of the pictures p<0.05 (Appendix 1—table 3). The group interaction is most clearly evident for the difference in the good and neutral ratings of the erotic pictures, with the alcoholic participants rating the pictures good less frequently; other picture types were rated more similarly by both the alcoholic and control groups. The gender interaction indicated that men rated erotic pictures as good more frequently than women. Blue diamonds indicate mean values. Figure 3—figure supplement 1 shows the reaction times. Abbreviations: ALC = Alcoholic participants; NC = Nonalcoholic Control participants.

https://doi.org/10.7554/eLife.41723.006
Figure 3—figure supplement 1
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Reaction times of behavioral ratings by condition, rating, group, and gender.

The boxplot represents the significant rating x gender interaction for reaction times of the pictures p<0.05 (Appendix 1—table 4). The difference in the good rating of the erotic pictures by alcoholics vs. nonalcoholic controls. The ratings for other conditions were qualitatively similar for alcoholics and nonalcoholic control subjects. Blue diamonds indicate mean values. Figure 3 shows the reaction times. ALC = alcoholic participants; NC = nonalcoholic control participants.

https://doi.org/10.7554/eLife.41723.007
Figure 4 with 3 supplements
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Erotic vs. neutral stimuli elicited abnormal activation of the limbic system and cerebellum in alcoholic men.

A significant group x gender interaction in response to erotic vs. neutral stimuli was identified and is displayed as a green outline indicated by arrows. All inferior arrows designate the amygdala. Group mean contrast values are displayed in the four brain images located in the corners of the figure, and group comparisons are indicated by minus signs. Contrast values are overlaid on coronal cross sections. Images are displayed in radiological convention with the right hemisphere shown on the left. (Sagittal and axial views are shown in Figure 4—figure supplement 1 and Figure 4—figure supplement 2; Figure 4—figure supplement 3 shows the magnitude of cluster differences.) Abbreviations: ALCM = Alcoholic men; ALCW = Alcoholic women; NCM = Nonalcoholic men; NCW = Nonalcoholic women.

https://doi.org/10.7554/eLife.41723.008
Figure 4—figure supplement 1
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Erotic vs. neutral stimuli elicited abnormal activation of the limbic system and cerebellum in alcoholic men (sagittal view).

A group x gender interaction in response to erotic vs. neutral stimulation was identified and is displayed as a green outline. Group mean values are displayed in the four brain images located in the corners of the figure, and group comparisons are indicated by minus signs. Contrast effect sizes are overlaid on sagittal cross sections. (Coronal and axial views are shown in Figure 4 and Figure 4—figure supplement 2; Figure 4—figure supplement 3 shows the magnitude of cluster differences.) Abbreviations: ALCM = alcoholic men; ALCW = alcoholic women; NCM = nonalcoholic men; NCW = nonalcoholic women.

https://doi.org/10.7554/eLife.41723.009
Figure 4—figure supplement 2
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Erotic vs. neutral stimuli elicited abnormal activation of the limbic system and cerebellum in alcoholic men (axial view).

A group x gender interaction in response to erotic vs. neutral stimulation was identified and is displayed as a green outline. Group mean values are displayed in the four brain images located in the corners of the figure, and group comparisons are indicated by minus signs. Contrast effect sizes are overlaid on axial cross sections. Images are displayed in radiological convention with the right hemisphere shown on the left. (Coronal and sagittal views are shown in Figure 4 and Figure 4—figure supplement 1; Figure 4—figure supplement 3 shows the magnitude of cluster differences.) Abbreviations: ALCM = alcoholic men; ALCW = alcoholic women; NCM = nonalcoholic men; NCW = nonalcoholic women.

https://doi.org/10.7554/eLife.41723.010
Figure 4—figure supplement 3
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Contrast values observed in the cluster for erotic vs. neutral conditions.

The split violin plot represents the Contrast Effect Size (CES; equivalent to ‘CON’ in SPM or ‘COPE’ in FSL) for the cluster in which a significant group x gender interaction was identified for the erotic vs. neutral contrast (p<0.05 after correction for multiple comparisons). Positive values indicate erotic >neutral, while negative values indicate erotic <neutral. Each point represents a single participant’s average CES for vertices within the cluster. This figure is meant to convey the variability in CES across participants that is not visible in Figure 4. Nonalcoholic control men had greater activation to erotic stimuli than neutral stimuli, and the contrast was more positive than was observed for alcoholic men. The pattern was reversed for women: Alcoholic women had lower contrast values than nonalcoholic women. Abbreviations: ALC = alcoholic participants; NC = nonalcoholic control participants.

https://doi.org/10.7554/eLife.41723.011
Figure 5 with 6 supplements
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Aversive vs. neutral stimuli elicited more abnormally negative responses in alcoholic men.

A significant group x gender interaction revealed several clusters (see Appendix 1—table 6), which are indicated by arrows on the lateral surface of the left hemisphere, overlaid on contrast values between aversive and neutral stimuli. Group mean contrast values (for aversive vs. neutral) are displayed in the four brain images located in the corners of the figure, and group comparisons are indicated by minus signs. (Figure 5—figure supplement 1 shows the medial surface, while the right hemisphere is shown in Figure 5—figure supplement 2 for the lateral and Figure 5—figure supplement 3 for the medial surface; Figure 5—figure supplement 4 shows the magnitude of cluster differences.) Although not shown here, the activation patterns across the four subgroups for contrasts of other emotional stimuli (i.e., happy, gruesome, and erotic) with neutral stimuli were similar to those shown above, and likewise, the general locations of the activation regions were similar for the four subgroups. Abbreviations: ALCM = Alcoholic men; ALCW = Alcoholic women; NCM = Nonalcoholic men; NCW = Nonalcoholic women.

https://doi.org/10.7554/eLife.41723.012
Figure 5—figure supplement 1
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Aversive vs. neutral stimuli elicited more abnormally negative responses in alcoholic men (left medial surface).

A group x gender interaction revealed several clusters (see Appendix 1—table 6), which are displayed as outlines and indicated by arrows on the medial surface of the left hemisphere, overlaid on contrast values between aversive and neutral stimuli. Group mean values (for aversive vs. neutral) are displayed in the four brain images located in the corners of the figure, and group comparisons are indicated by minus signs. (Figure 5 shows the lateral surface, while the right hemisphere is shown in Figure 5—figure supplement 2 for the lateral and Figure 5—figure supplement 3 for the medial surface; Figure 5—figure supplement 4 shows the magnitude of cluster differences.) Although not shown here, the activation patterns across the four subgroups for contrasts of other emotional stimuli (i.e., happy, gruesome, and erotic) with neutral stimuli were similar to those shown above, and likewise, the general locations of the activation regions were similar for the four subgroups. Abbreviations: ALCM = alcoholic men; ALCW = alcoholic women; NCM = nonalcoholic men; NCW = nonalcoholic women.

https://doi.org/10.7554/eLife.41723.013
Figure 5—figure supplement 2
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Aversive vs. neutral stimuli elicited more abnormally negative responses in alcoholic men (right lateral surface).

A group x gender interaction revealed several clusters (see Appendix 1—table 6), which are displayed as outlines and indicated by arrows on the lateral surface of the right hemisphere, overlaid on contrast values between aversive and neutral stimuli. Group mean values (for aversive vs. neutral) are displayed in the brain images located in the four corners of the figure, and group comparisons are indicated by minus signs. (Figure 5 and Figure 5—figure supplement 1 show the lateral and medial surfaces of the left hemisphere, while the medial surface of the right hemisphere is shown in Figure 5—figure supplement 3; Figure 5—figure supplement 4 shows the magnitude of cluster differences.) Although not shown here, the activation patterns across the four subgroups for contrasts of other emotional stimuli (i.e., happy, gruesome, and erotic) with neutral stimuli were similar to those shown above, and likewise, the general locations of the activation regions were similar for the four subgroups. Abbreviations: ALCM = alcoholic men; ALCW = alcoholic women; NCM = nonalcoholic men; NCW = nonalcoholic women.

https://doi.org/10.7554/eLife.41723.014
Figure 5—figure supplement 3
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Aversive vs. neutral stimuli elicited more abnormally negative responses in alcoholic men (right medial surface).

A group x gender interaction revealed several clusters (see Appendix 1—table 6), which are displayed as outlines and indicated by arrows on the medial surface of the right hemisphere, overlaid on contrast values between aversive and neutral stimuli. Group mean values (for aversive vs. neutral) are displayed in the brain images located in the four corners of the figure, and group comparisons are indicated by minus signs. (Figure 5 and Figure 5—figure supplement 1 show the lateral and medial surfaces of the left hemisphere, while the lateral surface of the right hemisphere is shown in Figure 5—figure supplement 2; Figure 5—figure supplement 4 shows the magnitude of cluster differences.) Although not shown here, the activation patterns across the four subgroups for contrasts of other emotional stimuli (i.e., happy, gruesome, and erotic) with neutral stimuli were similar to those shown above, and likewise, the general locations of the activation regions were similar for the four subgroups. Abbreviations: ALCM = alcoholic men; ALCW = alcoholic women; NCM = nonalcoholic men; NCW = nonalcoholic women.

https://doi.org/10.7554/eLife.41723.015
Figure 5—figure supplement 4
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Contrast values observed in each cluster for aversive vs. neutral conditions.

The split violin plot represents the Contrast Effect Size (CES; equivalent to ‘CON’ in SPM or ‘COPE’ in FSL) for left hemisphere clusters in which a significant group x gender interaction was identified for the aversive vs. neutral contrast (p<0.05 after correction for multiple comparisons). Positive values indicate aversive >neutral, while negative values indicate aversive <neutral. Each point represents a single participant’s average CES for vertices within the cluster. This figure is meant to convey the variability in CES across participants that is not visible in Figure 5. In each of the four clusters, nonalcoholic control men had greater activation to aversive stimuli than neutral stimuli, and the contrast was more positive than was observed for alcoholic men. The pattern was reversed for women: Alcoholic women had higher contrast values than nonalcoholic women. Abbreviations: ALC = alcoholic participants; NC = nonalcoholic participants.

https://doi.org/10.7554/eLife.41723.016
Figure 5—figure supplement 5
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Aversive vs.neutral stimuli elicited more abnormally negative responses in alcoholic men (left lateral surface), cluster-forming threshold p<0.001.

A group x gender interaction revealed two clusters (see Appendix 1—table 8), which are displayed as outlines and indicated by arrows on the lateral surface of the left hemisphere, overlaid on contrast values between aversive and neutral stimuli. Group mean values (for aversive vs. neutral) are displayed in the four brain images located in the corners of the figure, and group comparisons are indicated by minus signs. (The lateral surface of the right hemisphere is shown in Figure 5—figure supplement 6; no clusters were visible on medial surfaces). Abbreviations: ALCM = alcoholic men; ALCW = alcoholic women; NCM = nonalcoholic men; NCW = nonalcoholic women.

https://doi.org/10.7554/eLife.41723.017
Figure 5—figure supplement 6
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Aversive vs.neutral stimuli elicited more abnormally negative responses in alcoholic men (right lateral surface), cluster-forming threshold p<0.001.

A group x gender interaction revealed two clusters (see Appendix 1—table 8), which are displayed as outlines and indicated by arrows on the lateral surface of the right hemisphere, overlaid on contrast values between aversive and neutral stimuli. Group mean values (for aversive vs. neutral) are displayed in the four brain images located in the corners of the figure, and group comparisons are indicated by minus signs. (The lateral surface of the left hemisphere is shown in Figure 5—figure supplement 5; no clusters were visible on medial surfaces). Abbreviations: ALCM = alcoholic men; ALCW = alcoholic women; NCM = nonalcoholic men; NCW = nonalcoholic women.

https://doi.org/10.7554/eLife.41723.018
Figure 6
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Interaction of group x gender for aversive, erotic, gruesome, and happy stimuli vs. neutral stimuli.

Significant clusters are indicated by arrows shown on interaction maps of contrast values for each of the four emotions vs. neutral (similar to the center image in Figure 4 and Figure 5). All four brain surfaces are shown (from left: left lateral, left medial, right lateral, and right medial). Blue regions indicate less activation contrast (emotion vs. neutral) for ALCM relative to NCM vs. ALCW relative to NCW. Abbreviations: RH = Right Hemisphere; LH = Left Hemisphere.

https://doi.org/10.7554/eLife.41723.019

Tables

Table 1
Peak voxel or vertex labels of significant clusters for group contrasts of each emotion vs. neutral condition.

Significant clusters (p<0.05 after correction for multiple comparisons) were observed for comparisons between alcoholic and control groups (for the entire sample and for men and women separately), along with group x gender interactions, for each of the four contrasts between each emotion condition compared to the neutral condition. Cortical regions were determined from the peak voxel or vertex. Overall, the table shows that the ALCM had widespread abnormalities in response to emotional stimuli, and that these effects were significantly different than the effects for the ALCW. Details are described in the text, Figure 4, Figure 5, and Figure 6, and in Appendix 1—tables 5, 6 and 7. Abbreviations: ACC = anterior cingulate cortex; L = left hemisphere; R = right hemisphere; ALCW = alcoholic women; ALCM = alcoholic men; NCW = nonalcoholic control women; NCM = nonalcoholic control men; ns = not significant; BanksSTS = banks, superior temporal sulcus.

https://doi.org/10.7554/eLife.41723.020
LobeRegion at peakALC vs. NCALCW vs. NCWALCM vs. NCMInteraction
FrontalCaudal Middle Frontalnsnsnsaversive (L)
Medial OrbitofrontalnsnsALCM > NCM: aversive (R)ns
Rostral ACCALC > NC: aversive (L)nsALCM > NCM: aversive (L)ns
Rostral Middle FrontalnsnsALCM < NCM: happy (R)happy (L,R), aversive (R)
PrecentralnsnsALCM < NCM: aversive (L,R), happy (L,R), erotic (R)aversive (L), happy (L,R), erotic (R)
Superior FrontalnsALCW > NCW: happy (L)ALCM < NCM: aversive (R), erotic (R)aversive (L), happy (R)
Caudal ACCnsnsnshappy (L)
ParietalInferior ParietalALC < NC: happy (L)nsALCM < NCM: aversive (L,R), happy (L)aversive (L), happy (L)
PostcentralALC > NC: erotic (L)nsnsns
Precuneusnsnsnshappy (L)
Superior ParietalnsnsALCM < NCM: happy (R)ns
SupramarginalnsALCW > NCW: aversive (L)nsns
TemporalBanksSTSnsnsALCM < NCM: gruesome (L)gruesome (L)
Parahippocampalnsnsnserotic (L)
Cuneusnsnsnshappy (R)
Pericalcarinensnsnshappy (L)
SubcorticalThalamusnsnsALCM < NCM: happy (R)ns
CerebellumCerebellumnsnsnshappy (L), aversive (L)
Appendix 1—table 1
Participants’ characteristics and drinking measures.

Values presented as mean ± standard deviation. Abbreviations: ALCW = Alcoholic women; ALCM = Alcoholic men; NCW = Nonalcoholic control women; NCM = Nonalcoholic control men; DHD = Duration of Heavy Drinking (>21 drinks per week) in years; DD = Daily drinks; LOS = Length of sobriety in years. HRSD = Hamilton Rating Scale for Depression (Hamilton, 1960); VIQ = Wechsler Adult Intelligence Scale, 3rd ed. Verbal Intelligence Quotient; PIQ = Wechsler Adult Intelligence Scale, 3rd ed. Performance Intelligence Quotient; WMS DMI = Wechsler Memory Scale, 3rd ed. Delayed (General) Memory Index. Significant differences: a(ALCM > NCM, p<0.05); b(ALCM > NCM, p<0.001); c(ALCW > NCW, p<0.01); d(ALCW > NCW, p<0.001); e(ALCW > ALCM, p<0.001); f(ALCM > ALCW, p<0.05); g(NCW >NCM, p<0.05); h(NCW >NCM, p<0.01); i(group x gender interaction, p<0.05). jLOS values were not applicable for two NCM and four NCW who reported never drinking.

https://doi.org/10.7554/eLife.41723.023
MeasureALCW
N = 25		ALCM
N = 17		NCW
N = 24		NCM
N = 22
Age52.0±10.653.2±9.754.4±15.455.0±12.4
Educationg15.3±2.313.8±2.516.1±2.614.8±1.9
VIQ110.4±16.6107.0±15.0113.2±17.8109.9±11.1
PIQ106.9±17.7100.1±12.5111.2±16.9107.1±11.8
WMS DMIe,h119.1±15.999.0±10.3117±17.3105.0±14.0
HRSDa,c3.4±3.53.6±4.71.2±2.21.0±1.2
DHDb,d13.3±6.414.6±6.20.0±0.00.0±0.0
DDb,d,f,i6.9±6.312.9±9.60.2±0.30.4±0.5
LOSj7.3±8.97.5±11.96.2±11.80.9±1.5
Appendix 1—table 2
Neuropsychological and affect scores for alcoholic men and women.

Values presented as mean ± standard deviation. Abbreviations: ALCW = alcoholic women; ALCM = alcoholic men; NCW = nonalcoholic control women; NCM = nonalcoholic control men; Abbreviations: FSIQ = Wechsler Adult Intelligence Scale, 3rd ed. Full Scale Intelligence Quotient; WMS IMI = Wechsler Memory Scale, 3rd ed. Immediate Memory Index; WMS WMI = Wechsler Memory Scale, 3rd ed. Working Memory Index; POMS = Profile of Mood States (McNair, 1971); MAACL = Multiple Affective Adjective Checklist (Zuckerman and Lubin, 1985). Significant differences: a(ALCM >NCM, p<0.05); b(ALCW > NCW, p<0.05); c(ALCW > ALCM, p<0.05); d(ALCW < ALCM, p<0.05); e(ALCM <ALCW, p<0.001); f(NCM >NCW, p<0.05); g(NCM <NCW, p<0.05); h(NCM <NCW, p<0.01).

https://doi.org/10.7554/eLife.41723.024
MeasureALCW
N = 25		ALCM
N = 17		NCW
N = 24		NCM
N = 22
FSIQ109.7±17.2104.3±13.5113.5±17.6109.4±10.3
WMS IMIe,h117.4±17.494.8±11.0116.2±17.5102.9±14.2
WMS WMI103.9±15.9104.6±11.3110.2±15.0102.9±10.3
POMS Tensiona,b38.7±9.339.1±6.433.6±6.334.9±5.9
POMS Depressiona,b,f38.9±8.242.4±7.034.5±4.237.5±4.1
POMS Angera,b43.1±6.844.5±7.339.8±3.539.9±4.0
POMS Vigorb59.4±11.360.8±7.766.3±10.261.9±7.7
POMS Fatigue44.1±9.246.4±8.541.0±6.642.7±5.6
POMS Confusionb41.3±8.242.3±7.636.7±5.238.6±6.6
MAACL Anxiety51.6±17.047.1±11.844.3±13.044.1±6.8
MAACL Depression56.9±26.657.4±32.247.5±12.946.8±7.7
MAACL Hostility49.4±12.345.3±6.246.9±13.043.5±3.2
MAACL Positive Affectc,g62.2±8.457.6±4.664.9±7.060.6±6.9
MAACL Sensation Seekingd51.4±6.849.1±8.155.5±6.850.3±6.8
MAACL Dysphoria53.8±22.847.6±17.444.7±16.342.7±6.5
MAACL Positive Affect Sensation Seekingc,f59.7±8.055.5±4.763.3±6.658.5±6.3
Appendix 1—table 3
Analysis of variance for percentage of pictures rated.

Abbreviations: DF = degrees of freedom. Significance codes: ***p<0.001; *p<0.05

https://doi.org/10.7554/eLife.41723.025
Sum of squaresMean squareNumerator DFDenominator DFFp-value
Condition004108001.00
Rating1615280762108024.474.04E-11***
Group001108001.00
Gender001108001.00
Condition x Rating120871515108981080457.842.20E-16***
Condition x Group004108001.00
Rating x Group1880940210802.850.06
Condition x Gender004108001.00
Rating x Gender832641632108012.623.84E-06***
Group x Gender001108001.00
Condition x Rating x Group5200650810801.970.02*
Condition x Rating x Gender3469443378108013.142.20E-16***
Condition x Group x Gender004108001.00
Rating x Group x Gender1525762210802.310.10
Condition x Rating x Group x Gender4762595810801.80.07
Appendix 1—table 4
Analysis of variance for reaction times of pictures rated.

Abbreviations: DF = degrees of freedom. Significance codes: ***p<0.001

https://doi.org/10.7554/eLife.41723.026
Sum of squaresMean squareNumerator DFDenominator DFFp-value
Condition26144206536054746.224.8437.34E-04***
Rating753693137684652750.6927.9212.01E-12***
Group4680746807180.480.3470.56
Gender119106119106180.480.8820.35
Condition x Rating4943108661788868744.5345.7792.20E-16***
Condition x Group5402971350744746.221.0010.41
Rating x Group4284012142012750.691.5870.20
Condition x Gender9006602251654746.221.6680.15
Rating x Gender215229010761452750.697.9733.75E-04***
Group x Gender37213721180.480.0280.87
Condition x Rating x Group12304351538048744.531.140.33
Condition x Rating x Gender19504932438128744.531.8060.07
Condition x Group x Gender286187715474746.220.530.71
Rating x Group x Gender2204411102212750.690.8170.44
Condition x Rating x Group x Gender12485921560748744.531.1560.32
Appendix 1—table 5
Cortical brain activation differences between alcoholic and nonalcoholic control participants.

MNI305 coordinates for peak voxel within significant clusters of activation showing difference between alcoholic and nonalcoholic control participants determined by surface-based whole brain analyses in (a) all subjects, (b) women only, and (c) men only. Abbreviations: LH = left hemisphere; RH = right hemisphere; Max = maximum −log10(p-value) in the cluster; VtxMax = vertex number at the maximum; size = surface area of cluster; XYZ = the MNI coordinates of the maximum; CWP = clusterwise p-value further corrected for the three spaces of left cortex, right cortex, and volume; CWPLow and CWPHi = 90% confidence interval for CWP; NVtxs = number of vertices in the cluster; ALC = alcoholic participants; NC = nonalcoholic Control participants.

https://doi.org/10.7554/eLife.41723.027
StructureMaxVtxMaxSize (mm2)XYZCWPCWPLowCWPHiNVtxsContrastComparison
A. All
Participants
Inferior Parietal
Gyrus (LH)		−3.307104494876.17−40.6−76.121.60.001800.000900.002701560happyALC < NC
Rostral Anterior Cingulate (LH)3.49737787784.55−6.624.1−9.70.011060.008670.013441397aversiveALC > NC
Postcentral Gyrus (LH)4.46029054798.38−48.8−25.147.10.010460.008380.012841852eroticALC > NC
B. Women
Superior Frontal Gyrus (LH)4.39273009838.05−7.439.130.00.006590.004790.008382333.2happyALCW > NCW
Supramarginal Gyrus (LH)3.3996263662.10−51.5−52.825.60.034690.030580.038791457aversiveALCW > NCW
C. Men
Inferior Parietal (LH)−4.829117735640.53−26.7−63.234.50.042870.03850.047241366aversiveALCM < NCM
Inferior Parietal (LH)−4.124478111371.62−40.1−7522.20.000300.00062633happyALCM < NCM
Inferior Parietal Gyrus (RH)−3.35157480916.2130.7−6339.60.003890.00270.005391717aversiveALCM < NCM
Inferior Parietal (RH)−4.21268984714.1244.1−5714.70.023220.019970.026461489aversiveALCM < NCM
Medial Orbitofrontal (RH)3.771125131874.6511.845.8−4.10.005090.00360.006591476aversiveALCM > NCM
Precentral (LH)−4.165302891617.73−40.80.927.50.000300.00063248aversiveALCM < NCM
Precentral (LH)−4.782665521845.52−39.51.426.30.000300.00063529happyALCM < NCM
Precentral (RH)−4.2656026480851.23.930.90.010460.008380.012841668aversiveALCM < NCM
Precentral (RH)−2.771118687831.4623.6−6.546.40.009270.007180.011361810happyALCM < NCM
Precentral (RH)−3.442925621459.9740.3−9.3600.000300.00063278eroticALCM < NCM
Rostral Anterior Cingulate (LH)3.937117327739.44−6.333.3−7.80.017890.014930.020851373aversiveALCM > NCM
Rostral Middle
Frontal (RH)		−3.6151167651340.9633.630.132.80.000300.00062268happyALCM < NCM
Rostral Middle
Frontal (RH)		−4.17103943775.7822.462.220.012840.010460.01522996happyALCM < NCM
Superior Frontal (RH)−5.827938971018.425.824.138.90.00090.00030.00152033aversiveALCM < NCM
Superior Frontal (RH)−3.97135035639.3317.756.217.30.046360.041710.05101977aversiveALCM < NCM
Superior Frontal (RH)−3.71835035774.0817.756.217.30.013740.011060.016411212eroticALCM < NCM
Superior Parietal (RH)−4.1474265791.4924.9−77.734.20.011360.008970.013741313happyALCM < NCM
Banks, Superior Temporal Sulcus (LH)−3.17427674637.52−55.7−46−1.40.043750.039370.04841387gruesomeALCM < NCM
Appendix 1—table 6
Cortical brain activation regions corresponding to the interactions between gender and alcoholism.

MNI305 coordinates for peak voxel within significant clusters of activation showing group x gender interaction for emotion (happy, aversive, gruesome, and erotic vs. neutral) from surface-based, and volumetric whole brain analyses. Abbreviations: LH = left hemisphere; RH = right hemisphere; Max = maximum −log10(p-value) in the cluster; VtxMax = vertex number at the maximum; Size = surface area of cluster; XYZ = Montreal Neurological Institute (MNI) coordinates of the maximum; CWP = clusterwise p-value further corrected for the three spaces of left cortex, right cortex, and volume; CWPLow and CWPHi = 90% confidence interval for CWP; NVtxs = number of vertices in the cluster.

https://doi.org/10.7554/eLife.41723.028
StructureMaxVtxMaxSize (mm2)XYZCWPCWPLowCWPHiNVtxsContrast
Superior Frontal (LH)−2.349152510675.48−19.76.857.10.032930.029110.037031451aversive
Superior Frontal (RH)−3.90067995825.3316.458.514.10.009570.007480.011651204happy
Rostral Middle Frontal (LH)−4.06934073086.86−25.847.015.30.000300.000000.000605250happy
Rostral Middle Frontal (LH)−3.46749071022.51−40.328.420.70.000900.000300.001501907happy
Rostral Middle Frontal (RH)−3.254116765984.3133.630.132.80.002100.001200.003001677happy
Rostral Middle Frontal (RH)−4.62442522753.5822.954.417.00.015220.012550.017891119aversive
Caudal Middle Frontal (LH)−4.250760292047.63−43.12.847.20.000300.000000.000604069aversive
Caudal Middle Frontal (LH)−6.08447079957.26−27.321.336.00.001800.000900.002701728aversive
Inferior Parietal (LH)−3.00368612660.83−38.8−55.121.40.037330.033230.041411423aversive
Inferior Parietal (LH)−2.82212076689.53−29.4−65.240.40.027940.024400.031461405happy
Precentral (LH)−4.363802541602.74−46.4−2.038.60.000300.000000.000603292happy
Precentral (RH)−4.268269421245.0350.93.431.00.000300.000000.000602436aversive
Precentral (RH)−3.3521446923.3923.5−5.546.50.003890.002700.005392049happy
Precentral (RH)−3.2111452331749.6036.1−20.152.80.000300.000000.000603917erotic
Pericalcarine (LH)−5.885129101431.93−5.0−69.911.40.000300.000000.000601866happy
Precuneus (LH)−2.59469252653.39−16.0−47.834.80.039370.034980.043751285happy
Cuneus (RH)−3.366861771658.665.4−84.319.60.000300.000000.000602305happy
Caudal Anterior Cingulate (LH)−3.72237463670.38−6.729.122.10.033520.029700.037621297happy
Banks, Superior Temporal Sulcus (LH)−4.42886543625.34−56−44.7−2.60.047820.043160.052461361gruesome
Appendix 1—table 7
Significant brain activation differences determined through volumetric based comparisons.

MNI305 coordinates for peak voxel within significant clusters of activation determined through volumetric whole brain analyses. Abbreviations: LH = left hemisphere; RH = right hemisphere; Max = maximum −log10(p-value) in the cluster; XYZ = Montreal Neurological Institute (MNI) coordinates of the maximum; CWP = clusterwise p-value further corrected for the three spaces of left cortex, right cortex, and volume.

https://doi.org/10.7554/eLife.41723.029
StructureSize (mm3)XYZCWPMaxComparisonContrast
Parahippocampal Cortex (LH)15920−34−23−270.0007912−5.62445Group x Gendererotic
Accumbens (LH)50016−105-90.0000005.49738Control: male vs. femaleerotic
Cerebellum Cortex (LH)15960−14−39−230.00020−3.790Group x Genderhappy
Cerebellum Cortex (LH)7224-8−45−130.04676733.25617Control: male vs. femalehappy
Thalamus (RH)123846−19110.0016394−3.93561Male: alc vs. controlhappy
Cerebellum Cortex (LH)18648−22−79−290.00008314.05785Control: male vs. femaleaversive
Cerebellum Cortex (LH)15240-6−41−190.00049−3.409Group x Genderaversive
Appendix 1—table 8
Brain activation clusters identified using a cluster forming threshold of p<0.001.

MNI305 coordinates for peak voxel within significant clusters of activation for emotion (happy, aversive, gruesome, and erotic vs. neutral) from surface-based and volumetric whole brain analyses. Abbreviations: LH = left hemisphere; RH = right hemisphere; Max = maximum −log10(p-value) in the cluster; VtxMax = vertex number at the maximum; Size = surface area of cluster; XYZ = Montreal Neurological Institute (MNI) coordinates of the maximum; CWP = clusterwise p-value further corrected for the three spaces of left cortex, right cortex, and volume; CWPLow and CWPHi = 90% confidence interval for CWP; NVtxs = number of vertices in the cluster; NC = nonalcoholic control group; ALC = alcoholic group.

https://doi.org/10.7554/eLife.41723.030
StructureMaxVtxMaxSize (mm2)XYZCWPCWPLowCWPHiNVtxsComparisonContrast
Superior Frontal (RH)4.346132708151.42846.643.50.006290.004490.00808243NC: Men > Womenaversive
Caudal Middle Frontal (RH)4.12937195128.8638.69.543.70.016410.013740.01937191NC: Men > Womenaversive
Supramarginal (RH)4.11874592112.5554.4−28.841.40.03440.030290.0385283NC: Men > Womenaversive
Rostral Middle Frontal (RH)−4.62442522108.7722.954.4170.033810.030.03791144Group x Genderaversive
Caudal Middle Frontal (LH)−6.08447079106.95−27.321.3360.044620.039960.04927230Group x Genderaversive
Inferior Parietal (LH)−3.86112079107.78−28.8−65.740.30.042870.03850.04724193Men: ALC < NChappy

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  1. Kayle S Sawyer
  2. Nasim Maleki
  3. Trinity Urban
  4. Ksenija Marinkovic
  5. Steven Karson
  6. Susan M Ruiz
  7. Gordon J Harris
  8. Marlene Oscar-Berman
(2019)
Alcoholism gender differences in brain responsivity to emotional stimuli
eLife 8:e41723.
https://doi.org/10.7554/eLife.41723