Nicotine Addiction and Nicotine's Actions Are Associated with Separate Cingulate Cortex Functional Circuits methods
Aim. Evidence-backed execution summary for Nicotine Addiction and Nicotine's Actions Are Associated with Separate Cingulate Cortex Functional Circuits methods from Nicotine Addiction and Nicotine's Actions Are Associated with Separate Cingulate Cortex Functional Circuits.
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human
Subject model for the experiment.
- Use
- confirm full cohort details in the source paper
Methods
reagent used in the protocol.
- Use
- Nineteen (5 female) healthy smokers (10 or more cigarettes per day) participated in the study. Subjects gave written informed consent approved by both University of Maryland and National Institute on Drug Abuse IRB panels. Subjects were 18-50 years of age, right handed, and were recruited through media adverti...
Nicotine addiction severity by drug interaction on cingulate connectivity
reagent used in the protocol.
- Use
- We first investigated interactions between addiction severity (FTND) and nicotinic effect on functional connectivity using the regression model: V' i(diff) = ß' 0 + ß'X + ε', where V' was the z score of the arithmetic difference between nicotine vs. placebo condition on the i th voxel, X was the cente...
Cingulate connectivity and nicotine addiction severity
reagent used in the protocol.
- Use
- Voxel-wise regression analyses showed no significant interaction between FTND score and drug condition in any cingulate functional circuit. In contrast, voxel-wise regression analyses for the main effect of FTND score showed that FTND was significantly ( p corrected < 0.05, corresponding to p uncorrected < 0.001 and...
Figures and Tables
reagent used in the protocol.
- Use
- Significant main effect of drug on cingulate circuitry based on paired t-tests. Seven resting-state functional connectivity pathways were statistically enhanced by nicotine administration (red) when compared to placebo. See for the coordinates and the extents of each significant cluster. There was never a statistica...
Figures and Tables
reagent used in the protocol.
- Use
- A comparison of nicotine vs. placebo related measurements. There was no significant bias on smoking level prior to each condition based on similar CO levels prior to placebo vs. nicotine patch applications. Post-scan nicotine levels confirmed robust differences in drug levels during placebo vs. nicotine scanning.
Design
Subjects were instructed to maintain their normal smoking routine prior to patch application, and then abstain for about 4.5 hours following patch administration, including 2.5 hours prior to scanning, and 2 hours inside the scanner. The 4.5 hour window was chosen to avoid confounds induced by withdrawal, which gene...
- Use
- Subjects were instructed to maintain their normal smoking routine prior to patch application, and then abstain for about 4.5 hours following patch administration, including 2.5 hours prior to scanning, and 2 hours inside the scanner. The 4.5 hour window was chosen to avoid confounds induced by withdrawal, which gene...
MRI acquisition
Data were collected on a 3 Tesla Siemens Allegra scanner equipped with a quadrature volume head coil. Subjects were given a simple instruction to rest and keep their eyes open. A static neutral image (the projector's logo) was presented on the screen during the resting scan. A bite bar was used to minimize head moti...
- Use
- Data were collected on a 3 Tesla Siemens Allegra scanner equipped with a quadrature volume head coil. Subjects were given a simple instruction to rest and keep their eyes open. A static neutral image (the projector's logo) was presented on the screen during the resting scan. A bite bar was used to minimize head moti...
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Main Outcome Measure(s)
Correlation of nicotine addiction severity and cingulate resting state functional connectivity, and effects of acute nicotine on connectivity strength.
Context
Understanding the mechanisms underlying nicotine addiction in order to develop more effective treatment is a public health priority. Research consistently shows that nicotine transiently improves multiple cognitive functions. However, using nicotine replacement to treat nicotine addiction yields generally inconsistent results. While this dichotomy is well known, the reasons are unclear. Imaging studies showed that nicotine challenges almost always involve cingulate cortex, suggesting that this loci may be a key region associated with nicotine addiction and its treatment.
Intervention(s)
Single dose (21/35mg) nicotine patch.
Design
This was a double-blind, placebo controlled, cross-over, randomized fMRI study comparing nicotine vs. placebo patch effect on resting-state functional connectivity. Subjects were scanned on two occasions approximately one week apart, within 5-14 days. They received either a nicotine patch (Nicoderm CQ, SmithKline Beecham) or an identical placebo patch on each occasion. We used a two-dose strategy to better match the regular nicotine intakes: 21mg for individuals who smoked 10-15 cigarettes/day (n=6) and 35 mg for individuals who smoked more than 15 cigarettes/day (n=13).
Design
Subjects were instructed to maintain their normal smoking routine prior to patch application, and then abstain for about 4.5 hours following patch administration, including 2.5 hours prior to scanning, and 2 hours inside the scanner. The 4.5 hour window was chosen to avoid confounds induced by withdrawal, which generally begins 6-12 hours after abstinence. In the scanner, each subject underwent 1 hour of smooth pursuit eye movement/fixation tasks (data not shown), followed by a 5-minute resting scan and an 8-minute structural scan. Resting scan data were therefore collected about 3.5 hours after patch administration, which is within the window of steady plasma nicotine levels. A self-reported symptom checklist and a self-reported mood change questionnaire were administered before patch application and after scan. Breath CO was measured immediately prior to patch application. P...
MRI acquisition
Data were collected on a 3 Tesla Siemens Allegra scanner equipped with a quadrature volume head coil. Subjects were given a simple instruction to rest and keep their eyes open. A static neutral image (the projector's logo) was presented on the screen during the resting scan. A bite bar was used to minimize head motion. Resting-state fMRI were acquired over 39, 4 mm axial, interleaving slices using a gradient-echo EPI sequence (150 volumes, TE/TR = 27/2000 ms; FA = 80°; FOV = 220 × 220 mm 2; image matrix = 64 × 64). High-resolution (1 × 1 × 1 mm 3 ) T1-weighted MPRAGE images were acquired after each resting scan.
Data Processing
Data were analyzed in AFNI and MATLAB (The MathWorks, Inc., Natick, MA). Volumes were slice-timing aligned and motion corrected to the base volume that minimally deviated from other volumes using an AFNI built-in algorithm. After linear detrending of the time course of each voxel, volumes were spatially normalized and resampled to Talairach space at 3 × 3 × 3 mm 3, spatially smoothed (FWHM 6 mm), and temporally low-pass filtered ( f cutoff = 0.1 Hz) -. Correlation analyses were performed by calculating the cross-correlation coefficient (CC) between each voxel's time course and the template time course extracted by averaging time courses of all the voxels in the defined regions of interest ("seed ROI"), including the six rigid head-motion parameter time courses and the average time course in white matter as nuisance covariates;. The white matter mask was generate...
Regions of interest (ROIs)
Each subject's cingulate was partitioned into 7 ROIs per hemisphere: 3 subregions for ACC; a middle cingulate cortex (MCC); and 3 subregions for the posterior cingulate cortex (PCC). ROIs were manually drawn on the grey matter at the coronal and sagittal planes of each subject's T1 image volume based on prior conventions when available, supplemented by histological, structural, and functional evidence ( ): ACC. ACC was divided into dorsal ACC (dACC), rostral ACC (oACC), and subcallosal ACC (sACC): a) dACC was separated from the rostral ACC by drawing a coronal plane that was one slice forward from the disappearance of the juncture of the anterior corpus callosum from both hemispheres;. The posterior end of dACC was the first vertical slice posterior to the anterior commissure, as proposed by Fornito et al. This is more anterior to that defined by McCormick et al, but is close to t...
Measurement outputs
What raw and processed outputs should exist?
Correlation of nicotine addiction severity and cingulate resting state functional connectivity, and effects of acute nicotine on connectivity strength.
- Raw artifact
- Per-sample or per-animal endpoint measurements collected during the experiment
- Processed artifact
- Structured table with cleaned measurements ready for comparison
- Reported as
- Summary statistics and between-group or across-timepoint comparisons
Nineteen (5 female) healthy smokers (10 or more cigarettes per day) participated in the study. Subjects gave written informed consent approved by both University of Maryland and...
- Raw artifact
- Per-sample or per-animal endpoint measurements collected during the experiment
- Processed artifact
- Structured table with cleaned measurements ready for comparison
- Reported as
- Summary statistics and between-group or across-timepoint comparisons
Data were collected on a 3 Tesla Siemens Allegra scanner equipped with a quadrature volume head coil. Subjects were given a simple instruction to rest and keep their eyes open....
- Raw artifact
- Per-sample or per-animal endpoint measurements collected during the experiment
- Processed artifact
- Structured table with cleaned measurements ready for comparison
- Reported as
- Summary statistics and between-group or across-timepoint comparisons
Data were analyzed in AFNI and MATLAB (The MathWorks, Inc., Natick, MA). Volumes were slice-timing aligned and motion corrected to the base volume that minimally deviated from o...
- Raw artifact
- Per-sample or per-animal endpoint measurements collected during the experiment
- Processed artifact
- Structured table with cleaned measurements ready for comparison
- Reported as
- Summary statistics and between-group or across-timepoint comparisons
Analysis plan
How should the outputs become interpretable results?
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
inferred from protocolPreprocessing / cleaning
The connectivity maps of each cingulate "seed ROI" ( p corrected < 0.05, corresponding to p uncorrected < 0.001 and a cluster size of 810 mm 3 ) are presented in.
from paperScoring or quantification
Quantify the primary readouts for this experiment: Correlation of nicotine addiction severity and cingulate resting state functional connectivity, and effects of acute nicotine on connectivity strength.; Nineteen (5 female) healthy smokers (10 or more cigarettes per day) participated in the study. Subjects gave written informed consent approved by both University of Maryland and...; Data were collected on a 3 Tesla Siemens Allegra scanner equipped with a quadrature volume head coil. Subjects were given a simple instruction to rest and keep their eyes open....; Data were analyzed in AFNI and MATLAB (The MathWorks, Inc., Natick, MA). Volumes were slice-timing aligned and motion corrected to the base volume that minimally deviated from o....
from paperStatistical comparison
The connectivity maps of each cingulate "seed ROI" ( p corrected < 0.05, corresponding to p uncorrected < 0.001 and a cluster size of 810 mm 3 ) are presented in. I...; We first investigated interactions between addiction severity (FTND) and nicotinic effect on functional connectivity using the regression model: V' i(diff) = ß' 0 + ß'...; In the event of no significant interaction, we applied a second regression model: V i(mean) = ß 0 + ßX + ε, where V was the z score of the mean of nicotine and pl...; Voxel-wise regression analyses showed no significant interaction between FTND score and drug condition in any cingulate functional circuit. In contrast, voxel-wise regression an...
from paperReporting output
Report representative outputs alongside summary comparisons for Correlation of nicotine addiction severity and cingulate resting state functional connectivity, and effects of acute nicotine on connectivity strength., Nineteen (5 female) healthy smokers (10 or more cigarettes per day) participated in the study. Subjects gave written informed consent approved by both University of Maryland and..., Data were collected on a 3 Tesla Siemens Allegra scanner equipped with a quadrature volume head coil. Subjects were given a simple instruction to rest and keep their eyes open...., Data were analyzed in AFNI and MATLAB (The MathWorks, Inc., Natick, MA). Volumes were slice-timing aligned and motion corrected to the base volume that minimally deviated from o....
inferred from protocolStructured statistical methods
The connectivity maps of each cingulate "seed ROI" ( p corrected < 0.05, corresponding to p uncorrected < 0.001 and a cluster size of 810 mm 3 ) are presented in. I...; We first investigated interactions between addiction severity (FTND) and nicotinic effect on functional connectivity using the regression model: V' i(diff) = ß' 0 + ß'...; In the event of no significant interaction, we applied a second regression model: V i(mean) = ß 0 + ßX + ε, where V was the z score of the mean of nicotine and pl...; Voxel-wise regression analyses showed no significant interaction between FTND score and drug condition in any cingulate functional circuit. In contrast, voxel-wise regression an...
source structuredSource and audit
What supports the facts on this page?
Evidence quotes (8)
Correlation of nicotine addiction severity and cingulate resting state functional connectivity, and effects of acute nicotine on connectivity strength.
Understanding the mechanisms underlying nicotine addiction in order to develop more effective treatment is a public health priority. Research consistently shows that nicotine transiently improves multiple cognitive functions. However, using nicotine replacement to treat nicotine addiction yields generally inconsistent results. While this dichotomy is well known, the reasons are unclear. Imaging studies showed that nicotine challenges almost always involve cingulate cortex, suggesting that this loci may be a key region associated with nicotine addiction and its treatment.
Single dose (21/35mg) nicotine patch.
This was a double-blind, placebo controlled, cross-over, randomized fMRI study comparing nicotine vs. placebo patch effect on resting-state functional connectivity. Subjects were scanned on two occasions approximately one week apart, within 5-14 days. They received either a nicotine patch (Nicoderm CQ, SmithKline Beecham) or an identical placebo patch on each occasion. We used a two-dose strategy to better match the regular nicotine intakes: 21mg for individuals who smoked 10-15 cigarettes/day (n=6) and 35 mg for individuals who smoked more than 15 cigarettes/day (n=13).
Subjects were instructed to maintain their normal smoking routine prior to patch application, and then abstain for about 4.5 hours following patch administration, including 2.5 hours prior to scanning, and 2 hours inside the scanner. The 4.5 hour window was chosen to avoid confounds induced by withdrawal, which generally begins 6-12 hours after abstinence. In the scanner, each subject underwent 1 hour of smooth pursuit eye movement/fixation tasks (data not shown), followed by a 5-minute resting scan and an 8-minute structural scan. Resting scan data were therefore collected about 3.5 hours after patch administration, which is within the window of steady plasma nicotine levels. A self-reported symptom checklist and a self-reported mood change questionnaire were administered before patch application and after scan. Breath CO was measured immediately prior to patch application. Plasma nicotine levels were measured at the end of each scan session.
Data were collected on a 3 Tesla Siemens Allegra scanner equipped with a quadrature volume head coil. Subjects were given a simple instruction to rest and keep their eyes open. A static neutral image (the projector's logo) was presented on the screen during the resting scan. A bite bar was used to minimize head motion. Resting-state fMRI were acquired over 39, 4 mm axial, interleaving slices using a gradient-echo EPI sequence (150 volumes, TE/TR = 27/2000 ms; FA = 80°; FOV = 220 × 220 mm 2; image matrix = 64 × 64). High-resolution (1 × 1 × 1 mm 3 ) T1-weighted MPRAGE images were acquired after each resting scan.
Data were analyzed in AFNI and MATLAB (The MathWorks, Inc., Natick, MA). Volumes were slice-timing aligned and motion corrected to the base volume that minimally deviated from other volumes using an AFNI built-in algorithm. After linear detrending of the time course of each voxel, volumes were spatially normalized and resampled to Talairach space at 3 × 3 × 3 mm 3, spatially smoothed (FWHM 6 mm), and temporally low-pass filtered ( f cutoff = 0.1 Hz) -. Correlation analyses were performed by calculating the cross-correlation coefficient (CC) between each voxel's time course and the template time course extracted by averaging time courses of all the voxels in the defined regions of interest ("seed ROI"), including the six rigid head-motion parameter time courses and the average time course in white matter as nuisance covariates;. The white matter mask was generated by segmenting the high-resolution anatomical images in SPM5 and down-gridding the obtained white matter masks to the same resolution as the functional data. These nuisance covariates regress out fluctuations unlikely to be relevant to neuronal activities. CC maps were then converted to z-score ma...
Each subject's cingulate was partitioned into 7 ROIs per hemisphere: 3 subregions for ACC; a middle cingulate cortex (MCC); and 3 subregions for the posterior cingulate cortex (PCC). ROIs were manually drawn on the grey matter at the coronal and sagittal planes of each subject's T1 image volume based on prior conventions when available, supplemented by histological, structural, and functional evidence ( ): ACC. ACC was divided into dorsal ACC (dACC), rostral ACC (oACC), and subcallosal ACC (sACC): a) dACC was separated from the rostral ACC by drawing a coronal plane that was one slice forward from the disappearance of the juncture of the anterior corpus callosum from both hemispheres;. The posterior end of dACC was the first vertical slice posterior to the anterior commissure, as proposed by Fornito et al. This is more anterior to that defined by McCormick et al, but is close to the division of anterior and posterior mid-cingulate cortex (MCC) that was proposed by Vogt et al;. The deepest points of the cingulate and callosal sulci defined the superior and inferior boundaries of dACC, respectively. When the second cingulate; was present, we traced the structure as part of...
Machine-readable layer
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