Transcranial Direct Current Stimulation, Smoking, Cigarette, Schizophrenia
Conditions
Keywords
Transcranial Direct Current Stimulation, Smoking, Schizophrenia
Brief summary
This study is being done to develop new methods to help smokers with schizophrenia to successfully reduce their smoking and/or quit. This is not a treatment study, but will help find new techniques to create better treatments. Specifically, the investigators are interested in learning more about how thoughts and attention problems associated with schizophrenia might play a role in smoking, as well as the impact of cognitive (thinking, reasoning, and remembering) training and brain stimulation on these symptoms and on actual smoking.
Detailed description
Adults with severe mental illness (SMI) are three times more likely to smoke than non-SMI adults, consuming 35-44% of all cigarettes in the U.S.; and, the highest rates of tobacco-related illnesses and death are among smokers with schizophrenia. Unfortunately, not only are patients with schizophrenia less likely to receive smoking treatments, but cessation medications are only modestly effective in helping this subset of smokers quit. Therefore, it is vital to discover new treatment adjuncts that specifically aid this high-risk subset of smokers to achieve successful abstinence. Toward that end, the investigators propose a novel non-pharmacologic technique that directly targets both cognitive impairment, an avenue considerable past research suggests may be particularly effective to exploit in smokers with schizophrenia, and reactivity to prepotent stimuli, shown to be enhanced in smokers with schizophrenia. Combining a subset of cognitive enhancement therapy known as Cognitive Remediation (CR), with another safe and effective technique, Transcranial Direct Current Stimulation (tDCS), the investigators propose a new cognitive training method aimed at enabling smokers with schizophrenia to gain greater control over smoking and stimuli-induced reactivity (e.g., craving). Recent studies have found significant tDCS-induced cognitive enhancement, as well as reduction in both cue-induced craving and smoking behavior among healthy smokers. This combined with knowledge of the cognitive deficits that exist among individuals with schizophrenia, and clear evidence of a relationship between cognitive function and smoking treatment success, provides the rationale for testing novel CR + tDCS to target underlying mechanisms of smoking among individuals with schizophrenia. Specifically, the proposed study will examine the extent to which targeted cognitive enhancement with CR + tDCS, leads to changes in cognitive control, cue-provoked craving, reaction time and ERP measures of attentional bias; as well as the impact of these changes on smoking behavior and intention and confidence to quit among 80 smokers with schizophrenia. The goal of this study is to inform the development of new non-medication, noninvasive, therapeutic techniques to specifically target smoking among patients with schizophrenia. The long term goal is to establish an effective treatment adjunct to help smokers with schizophrenia successfully achieve abstinence.
Interventions
OTHERTranscranial Direct Current Stimulation
Transcranial direct current stimulation targeting the right inferior frontal gyrus
BEHAVIORALCognitive Remediation (CR)
Cognitive exercises on a computer designed to increase attention, memory, and processing speed.
Sponsors
National Institute on Drug Abuse (NIDA)
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Participants were not informed of their randomization group until debreifing.
Intervention model description
2 (CR, Control CR) x 2 (tDCS xSham tDCS)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Currently meets DSM-5 criteria for Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder, or Delusional Disorder. * Ability to provide written informed consent * Smoke ≥ 7 cigarettes per day * Expired breath CO ≥ 10 ppm at screening * Stable medication regimen for ≥ 4 weeks (If on more than one psychotropic medication, main antipsychotic will be considered for stability)
Exclusion criteria
* Epilepsy or Current Seizure Disorder * Alcohol or Substance Dependence past 3 months (caffeine allowed, nicotine is part of inclusion criteria). * Pregnant or lactating * Psychiatric hospitalization in past 3 months * Suicidal and/or aggressive behavior past 3 months * Implanted cardiac or brain medical devices * Latex allergy * Scalp irritation or recent shaving of scalp * Use of other smoking cessation medication * History of head trauma * History of ECT
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS™): MATRICS Consensus Cognitive Battery (MCCB) | Baseline to approximately 4 weeks | the MATRICS Consensus battery (MCCB) is a cognitive battery of tests for assessing cognition-enhancing treatments for schizophrenia through a broadly based scientific evaluation of measures. Change in cognitive measures of MATRICS Consensus Cognitive Battery (MCCB). Post-intervention minus baseline. Scale is scored 0-100. Difference score range is (-100 to 100) with positive scores reflecting improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cigarette Puff Volume | Baseline and at approximately 4 weeks | Change in mean cigarette puff volume |
| Latency to First Cigarette Puff | Baseline to approximately 4 weeks | Change in mean latency to first cigarette puff |
| AX Version of the Continuous Performance Task (AX-CPT) Reaction Time | Baseline to approximately 4 weeks | AX version of the CPT measures a participant's active maintenance and cognitive control. In this task, the participant is presented with a series of trials in which they are instructed to make a response which distinguishes between stimuli. Here the stimuli included are: smoking, nonsmoking, person, non-person). Assessment is of Post - Pre intervention difference in reaction time to respond to stimuli on the AX Version of the Continuous Performance Task (AX-CPT) |
| AX Version of the Continuous Performance Task (AX-CPT) Reaction Time Variability | Baseline to approximately 4 weeks | Post minus pre-intervention difference Reaction time variability for hits on the AX Version of the Continuous Performance Task (AX-CPT). A negative value indicates improvement. |
| Cue-Reactivity | Baseline to approximately 4 weeks | Change in cue-induced craving indexed as change in self-report craving on the questionnaire of smoking urges, 4-item version (QSU-4) from baseline to end of intervention. Craving rating range = 0-100. Difference scores range from (-100 to 100) with a negative score reflecting improvement. |
| EEG (Electroencephalogram) Contingent Negative Variation (CNV) | Baseline to approximately 4 weeks | Difference in CNV between the A and X in the AX-CPT Task. More negative indicates larger CNV. |
| EEG (Electroencephalogram) Beta-Band Event-Related Desynchronization (ERD) | Baseline to approximately 4 weeks | Difference in ERD between the A and X in AX-CPT during EEG assessment of Beta-Band Event-Related Desynchronization (ERD). More negative values indicate greater Beta-band ERD at post-intervention. |
| Attention & Smoking Cue Exposure Task (ASCET) | Baseline to approximately 4 weeks | Post minus Pre-intervention difference in Reaction time between smoking and neutral images presented with the ASCET task. A negative RT indicates improvement. |
| Total Number of Puffs | Baseline to approximately 4 weeks | Change in number of puffs on cigarettes assessment during smoking topography measurement during the cue reactivity task. Number of puffs was assessed during pre-training cue reactivity and again during post-training cue reactivity. |
| EEG (Electroencephalogram) N170 Amplitude | Baseline to approximately 4 weeks | Difference in change scores (post minus pre-intervention) in N170 Amplitude between smoking and neutral images. A more negative score indicates greater improvement. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CR + tDCS Cognitive Remediation (CR) and Transcranial Direct Current Stimulation (tDCS)
Transcranial Direct Current Stimulation: Transcranial direct current stimulation targeting the right inferior frontal gyrus
Cognitive Remediation (CR): Cognitive exercises on a computer designed to increase attention, memory, and processing speed. | 7 |
| CR + Sham tDCS Cognitive Remediation (CR) and Sham Transcranial Direct Current Stimulation (tDCS)
Cognitive Remediation (CR): Cognitive exercises on a computer designed to increase attention, memory, and processing speed. | 6 |
| Control CR + tDCS Control Cognitive Remediation (CR) and Transcranial Direct Current Stimulation (tDCS)
Transcranial Direct Current Stimulation: Transcranial direct current stimulation targeting the right inferior frontal gyrus | 9 |
| Control CR + Sham tDCS Control Cognitive Remediation (CR) and Sham Transcranial Direct Current Stimulation (tDCS) | 8 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Did not meet eligibility ctriteria | 0 | 0 | 3 | 2 |
| Overall Study | Hospitalized for COVID | 1 | 0 | 0 | 0 |
| Overall Study | Lab shut down due to COVID-19 | 0 | 0 | 0 | 1 |
| Overall Study | multiple technical issues | 1 | 0 | 0 | 0 |
| Overall Study | Schedule change unable to attend sessions | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | CR + tDCS | Total | Control CR + Sham tDCS | Control CR + tDCS | CR + Sham tDCS |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 30 Participants | 8 Participants | 9 Participants | 6 Participants |
| Age, Continuous | 44.7 years STANDARD_DEVIATION 13 | 49.1 years STANDARD_DEVIATION 10.2 | 48.4 years STANDARD_DEVIATION 10.5 | 50.9 years STANDARD_DEVIATION 8.3 | 52.5 years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 26 Participants | 7 Participants | 8 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 1 Participants | 1 Participants | 0 Participants |
| Nicotine Dependence Score | 4.7 units on a scale STANDARD_DEVIATION 1.7 | 5.3 units on a scale STANDARD_DEVIATION 1.6 | 5.8 units on a scale STANDARD_DEVIATION 2 | 5.0 units on a scale STANDARD_DEVIATION 1.1 | 5.8 units on a scale STANDARD_DEVIATION 1.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 17 Participants | 5 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 11 Participants | 3 Participants | 4 Participants | 1 Participants |
| Region of Enrollment United States | 7 Participants | 30 Participants | 8 Participants | 9 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 12 Participants | 2 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 5 Participants | 18 Participants | 6 Participants | 5 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 12 | 0 / 11 |
| other Total, other adverse events | 1 / 10 | 0 / 6 | 0 / 12 | 0 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 12 | 0 / 11 |
Outcome results
Primary
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS™): MATRICS Consensus Cognitive Battery (MCCB)
the MATRICS Consensus battery (MCCB) is a cognitive battery of tests for assessing cognition-enhancing treatments for schizophrenia through a broadly based scientific evaluation of measures. Change in cognitive measures of MATRICS Consensus Cognitive Battery (MCCB). Post-intervention minus baseline. Scale is scored 0-100. Difference score range is (-100 to 100) with positive scores reflecting improvement.
Time frame: Baseline to approximately 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CR + tDCS | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS™): MATRICS Consensus Cognitive Battery (MCCB) | 3.6 score on a scale | Standard Deviation 4 |
| CR + Sham tDCS | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS™): MATRICS Consensus Cognitive Battery (MCCB) | 2.3 score on a scale | Standard Deviation 8.6 |
| Control CR + tDCS | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS™): MATRICS Consensus Cognitive Battery (MCCB) | 3.1 score on a scale | Standard Deviation 3.6 |
| Control CR + Sham tDCS | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS™): MATRICS Consensus Cognitive Battery (MCCB) | 1.8 score on a scale | Standard Deviation 3.7 |
Comparison: Test of between-subjects effectsp-value: 0.781ANOVA
Secondary
Attention & Smoking Cue Exposure Task (ASCET)
Post minus Pre-intervention difference in Reaction time between smoking and neutral images presented with the ASCET task. A negative RT indicates improvement.
Time frame: Baseline to approximately 4 weeks
Population: The baseline data for one subject in CR + tDCS did not save.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CR + tDCS | Attention & Smoking Cue Exposure Task (ASCET) | -21.9 milliseconds | Standard Deviation 19.6 |
| CR + Sham tDCS | Attention & Smoking Cue Exposure Task (ASCET) | -21.7 milliseconds | Standard Deviation 23 |
| Control CR + tDCS | Attention & Smoking Cue Exposure Task (ASCET) | -10.5 milliseconds | Standard Deviation 23.3 |
| Control CR + Sham tDCS | Attention & Smoking Cue Exposure Task (ASCET) | -8.6 milliseconds | Standard Deviation 32.8 |
Comparison: Tests of between-subjects effectsp-value: 0.998ANOVA
Secondary
AX Version of the Continuous Performance Task (AX-CPT) Reaction Time
AX version of the CPT measures a participant's active maintenance and cognitive control. In this task, the participant is presented with a series of trials in which they are instructed to make a response which distinguishes between stimuli. Here the stimuli included are: smoking, nonsmoking, person, non-person). Assessment is of Post - Pre intervention difference in reaction time to respond to stimuli on the AX Version of the Continuous Performance Task (AX-CPT)
Time frame: Baseline to approximately 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CR + tDCS | AX Version of the Continuous Performance Task (AX-CPT) Reaction Time | -59.5 milliseconds | Standard Deviation 62.9 |
| CR + Sham tDCS | AX Version of the Continuous Performance Task (AX-CPT) Reaction Time | -37.8 milliseconds | Standard Deviation 47.4 |
| Control CR + tDCS | AX Version of the Continuous Performance Task (AX-CPT) Reaction Time | 4.3 milliseconds | Standard Deviation 29.8 |
| Control CR + Sham tDCS | AX Version of the Continuous Performance Task (AX-CPT) Reaction Time | -7.2 milliseconds | Standard Deviation 30.8 |
Comparison: Test of between-subjects effectsp-value: 0.185ANOVA
Secondary
AX Version of the Continuous Performance Task (AX-CPT) Reaction Time Variability
Post minus pre-intervention difference Reaction time variability for hits on the AX Version of the Continuous Performance Task (AX-CPT). A negative value indicates improvement.
Time frame: Baseline to approximately 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CR + tDCS | AX Version of the Continuous Performance Task (AX-CPT) Reaction Time Variability | -49463.5 milliseconds | Standard Deviation 71684.1 |
| CR + Sham tDCS | AX Version of the Continuous Performance Task (AX-CPT) Reaction Time Variability | 12828.3 milliseconds | Standard Deviation 63752.7 |
| Control CR + tDCS | AX Version of the Continuous Performance Task (AX-CPT) Reaction Time Variability | 22570.7 milliseconds | Standard Deviation 83194.9 |
| Control CR + Sham tDCS | AX Version of the Continuous Performance Task (AX-CPT) Reaction Time Variability | 8292.96 milliseconds | Standard Deviation 74462.3 |
Comparison: Test of between-measures effectsp-value: 0.198ANOVA
Secondary
Cigarette Puff Volume
Change in mean cigarette puff volume
Time frame: Baseline and at approximately 4 weeks
Population: Participants who did not smoke at baseline during cue reactivity were excluded from the analyses. This included 1 from arm CR + tDCS, 2 from CR + sham tDCS, and 2 from control CR + tDCS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CR + tDCS | Cigarette Puff Volume | -218.8 Milliliters | Standard Deviation 450.9 |
| CR + Sham tDCS | Cigarette Puff Volume | -90.7 Milliliters | Standard Deviation 345 |
| Control CR + tDCS | Cigarette Puff Volume | -9.9 Milliliters | Standard Deviation 268 |
| Control CR + Sham tDCS | Cigarette Puff Volume | 27.4 Milliliters | Standard Deviation 623.5 |
Comparison: Test of between-subjects effectsp-value: 0.697ANOVA
Secondary
Cue-Reactivity
Change in cue-induced craving indexed as change in self-report craving on the questionnaire of smoking urges, 4-item version (QSU-4) from baseline to end of intervention. Craving rating range = 0-100. Difference scores range from (-100 to 100) with a negative score reflecting improvement.
Time frame: Baseline to approximately 4 weeks
Population: Three subjects were removed from analyses due to misunderstanding the computerized rating system.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CR + tDCS | Cue-Reactivity | -6.4 score on a scale | Standard Deviation 38.1 |
| CR + Sham tDCS | Cue-Reactivity | -6.2 score on a scale | Standard Deviation 14.3 |
| Control CR + tDCS | Cue-Reactivity | -3.0 score on a scale | Standard Deviation 24.5 |
| Control CR + Sham tDCS | Cue-Reactivity | 2.6 score on a scale | Standard Deviation 29.5 |
Comparison: Test of between-subjects effectsp-value: 0.409ANOVA
Secondary
EEG (Electroencephalogram) Beta-Band Event-Related Desynchronization (ERD)
Difference in ERD between the A and X in AX-CPT during EEG assessment of Beta-Band Event-Related Desynchronization (ERD). More negative values indicate greater Beta-band ERD at post-intervention.
Time frame: Baseline to approximately 4 weeks
Population: Subjects were removed from analysis if their data was too noisy from excessive coughing or moving around.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CR + tDCS | EEG (Electroencephalogram) Beta-Band Event-Related Desynchronization (ERD) | -3.8 microvolts squared | Standard Deviation 2.6 |
| CR + Sham tDCS | EEG (Electroencephalogram) Beta-Band Event-Related Desynchronization (ERD) | -2.6 microvolts squared | Standard Deviation 3.1 |
| Control CR + tDCS | EEG (Electroencephalogram) Beta-Band Event-Related Desynchronization (ERD) | -3.6 microvolts squared | Standard Deviation 6.2 |
| Control CR + Sham tDCS | EEG (Electroencephalogram) Beta-Band Event-Related Desynchronization (ERD) | -0.2 microvolts squared | Standard Deviation 4.6 |
Comparison: Test of between-subjects effectsp-value: 0.564ANOVA
Secondary
EEG (Electroencephalogram) Contingent Negative Variation (CNV)
Difference in CNV between the A and X in the AX-CPT Task. More negative indicates larger CNV.
Time frame: Baseline to approximately 4 weeks
Population: Subjects were removed from analysis if their data was too noisy from excessive coughing or moving around.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CR + tDCS | EEG (Electroencephalogram) Contingent Negative Variation (CNV) | 0.8 microvolts | Standard Deviation 1.7 |
| CR + Sham tDCS | EEG (Electroencephalogram) Contingent Negative Variation (CNV) | 0.6 microvolts | Standard Deviation 1.5 |
| Control CR + tDCS | EEG (Electroencephalogram) Contingent Negative Variation (CNV) | 0.8 microvolts | Standard Deviation 1.3 |
| Control CR + Sham tDCS | EEG (Electroencephalogram) Contingent Negative Variation (CNV) | 1.2 microvolts | Standard Deviation 1.1 |
Comparison: Test of between-subjects effectdp-value: 0.574ANOVA
Secondary
EEG (Electroencephalogram) N170 Amplitude
Difference in change scores (post minus pre-intervention) in N170 Amplitude between smoking and neutral images. A more negative score indicates greater improvement.
Time frame: Baseline to approximately 4 weeks
Population: Subjects were removed from analysis if their data was too noisy from excessive coughing or moving around.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CR + tDCS | EEG (Electroencephalogram) N170 Amplitude | -1.9 microvolts | Standard Deviation 1.8 |
| CR + Sham tDCS | EEG (Electroencephalogram) N170 Amplitude | 0.2 microvolts | Standard Deviation 1.9 |
| Control CR + tDCS | EEG (Electroencephalogram) N170 Amplitude | -0.8 microvolts | Standard Deviation 2.2 |
| Control CR + Sham tDCS | EEG (Electroencephalogram) N170 Amplitude | 0.6 microvolts | Standard Deviation 1.3 |
Comparison: Test of between-subjects effectsp-value: 0.638ANOVA
Secondary
Latency to First Cigarette Puff
Change in mean latency to first cigarette puff
Time frame: Baseline to approximately 4 weeks
Population: Participants who did not smoke at baseline during cue reactivity were excluded from this analysis. This included 1 from arm CR + tDCS, 2 from CR + sham tDCS, and 2 from control CR + tDCS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CR + tDCS | Latency to First Cigarette Puff | 119.0 seconds | Standard Deviation 197.1 |
| CR + Sham tDCS | Latency to First Cigarette Puff | 182.8 seconds | Standard Deviation 243.7 |
| Control CR + tDCS | Latency to First Cigarette Puff | 19.1 seconds | Standard Deviation 65.1 |
| Control CR + Sham tDCS | Latency to First Cigarette Puff | 96.5 seconds | Standard Deviation 188.3 |
Comparison: Test of between subjects effectsp-value: 0.193ANOVA
Secondary
Total Number of Puffs
Change in number of puffs on cigarettes assessment during smoking topography measurement during the cue reactivity task. Number of puffs was assessed during pre-training cue reactivity and again during post-training cue reactivity.
Time frame: Baseline to approximately 4 weeks
Population: Participants who did not smoke at baseline during cue reactivity were excluded from this analysis. This included 1 from arm CR + tDCS, 2 from CR + sham tDCS, and 2 from control CR + tDCS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CR + tDCS | Total Number of Puffs | -7.3 puffs | Standard Deviation 11.3 |
| CR + Sham tDCS | Total Number of Puffs | 0.8 puffs | Standard Deviation 7.8 |
| Control CR + tDCS | Total Number of Puffs | -2.0 puffs | Standard Deviation 11.1 |
| Control CR + Sham tDCS | Total Number of Puffs | 2.0 puffs | Standard Deviation 15.7 |
Comparison: Tests of between-subjecs effectsp-value: 0.348ANOVA