2024
Xiao, Xiang; Hammond, Christopher; Salmeron, Betty Jo; Wang, Danni; Gu, Hong; Zhai, Tianye; Nguyen, Hieu; Lu, Hanbing; Ross, Thomas J; Yang, Yihong
Brain Functional Connectome Defines a Transdiagnostic Dimension Shared by Cognitive Function and Psychopathology in Preadolescents Journal Article
In: Biol Psychiatry, vol. 95, no. 12, pp. 1081–1090, 2024, ISSN: 1873-2402.
@article{pmid37769982b,
title = {Brain Functional Connectome Defines a Transdiagnostic Dimension Shared by Cognitive Function and Psychopathology in Preadolescents},
author = {Xiang Xiao and Christopher Hammond and Betty Jo Salmeron and Danni Wang and Hong Gu and Tianye Zhai and Hieu Nguyen and Hanbing Lu and Thomas J Ross and Yihong Yang},
url = {https://pubmed.ncbi.nlm.nih.gov/37769982/},
doi = {10.1016/j.biopsych.2023.08.028},
issn = {1873-2402},
year = {2024},
date = {2024-06-01},
urldate = {2024-06-01},
journal = {Biol Psychiatry},
volume = {95},
number = {12},
pages = {1081--1090},
abstract = {BACKGROUND: Cognitive function and general psychopathology are two important classes of human behavior dimensions that are individually related to mental disorders across diagnostic categories. However, whether these two transdiagnostic dimensions are linked to common or distinct brain networks that convey resilience or risk for the development of psychiatric disorders remains unclear.nnMETHODS: The current study is a longitudinal investigation with 11,875 youths from the Adolescent Brain Cognitive Development (ABCD) Study at ages 9 to 10 years at the onset of the study. A machine learning approach based on canonical correlation analysis was used to identify latent dimensional associations of the resting-state functional connectome with multidomain behavioral assessments including cognitive functions and psychopathological measures. For the latent resting-state functional connectivity factor showing a robust behavioral association, its ability to predict psychiatric disorders was assessed using 2-year follow-up data, and its genetic association was evaluated using twin data from the same cohort.nnRESULTS: A latent functional connectome pattern was identified that showed a strong and generalizable association with the multidomain behavioral assessments (5-fold cross-validation: ρ = 0.68-0.73 for the training set [n = 5096]; ρ = 0.56-0.58 for the test set [n = 1476]). This functional connectome pattern was highly heritable (h = 74.42%, 95% CI: 56.76%-85.42%), exhibited a dose-response relationship with the cumulative number of psychiatric disorders assessed concurrently and at 2 years post-magnetic resonance imaging scan, and predicted the transition of diagnosis across disorders over the 2-year follow-up period.nnCONCLUSIONS: These findings provide preliminary evidence for a transdiagnostic connectome-based measure that underlies individual differences in the development of psychiatric disorders during early adolescence.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Cognitive function and general psychopathology are two important classes of human behavior dimensions that are individually related to mental disorders across diagnostic categories. However, whether these two transdiagnostic dimensions are linked to common or distinct brain networks that convey resilience or risk for the development of psychiatric disorders remains unclear.nnMETHODS: The current study is a longitudinal investigation with 11,875 youths from the Adolescent Brain Cognitive Development (ABCD) Study at ages 9 to 10 years at the onset of the study. A machine learning approach based on canonical correlation analysis was used to identify latent dimensional associations of the resting-state functional connectome with multidomain behavioral assessments including cognitive functions and psychopathological measures. For the latent resting-state functional connectivity factor showing a robust behavioral association, its ability to predict psychiatric disorders was assessed using 2-year follow-up data, and its genetic association was evaluated using twin data from the same cohort.nnRESULTS: A latent functional connectome pattern was identified that showed a strong and generalizable association with the multidomain behavioral assessments (5-fold cross-validation: ρ = 0.68-0.73 for the training set [n = 5096]; ρ = 0.56-0.58 for the test set [n = 1476]). This functional connectome pattern was highly heritable (h = 74.42%, 95% CI: 56.76%-85.42%), exhibited a dose-response relationship with the cumulative number of psychiatric disorders assessed concurrently and at 2 years post-magnetic resonance imaging scan, and predicted the transition of diagnosis across disorders over the 2-year follow-up period.nnCONCLUSIONS: These findings provide preliminary evidence for a transdiagnostic connectome-based measure that underlies individual differences in the development of psychiatric disorders during early adolescence.
2023
Johnson, Jessica T E; Irfanoglu, M Okan; Manninen, Eppu; Ross, Thomas J; Yang, Yihong; Laun, Frederik B; Martin, Jan; Topgaard, Daniel; Benjamini, Dan
In vivo disentanglement of diffusion frequency-dependence, tensor shape, and relaxation using multidimensional MRI Miscellaneous
2023, ISSN: 2692-8205.
@misc{pmid37987005,
title = {In vivo disentanglement of diffusion frequency-dependence, tensor shape, and relaxation using multidimensional MRI},
author = {Jessica T E Johnson and M Okan Irfanoglu and Eppu Manninen and Thomas J Ross and Yihong Yang and Frederik B Laun and Jan Martin and Daniel Topgaard and Dan Benjamini},
url = {https://pubmed.ncbi.nlm.nih.gov/37987005/},
doi = {10.1101/2023.10.10.561702},
issn = {2692-8205},
year = {2023},
date = {2023-10-01},
urldate = {2023-10-01},
journal = {bioRxiv},
abstract = {Diffusion MRI with free gradient waveforms, combined with simultaneous relaxation encoding, referred to as multidimensional MRI (MD-MRI), offers microstructural specificity in complex biological tissue. This approach delivers intravoxel information about the microstructure, local chemical composition, and importantly, how these properties are coupled within heterogeneous tissue containing multiple microenvironments. Recent theoretical advances incorporated diffusion time dependency and integrated MD-MRI with concepts from oscillating gradients. This framework probes the diffusion frequency, , in addition to the diffusion tensor, , and relaxation, , , correlations. A clinical imaging protocol was then introduced, with limited brain coverage and 3 mm voxel size, which hinder brain segmentation and future cohort studies. In this study, we introduce an efficient, sparse MD-MRI acquisition protocol providing whole brain coverage at 2 mm voxel size. We demonstrate its feasibility and robustness using a well-defined phantom and repeated scans of five healthy individuals. Additionally, we test different denoising strategies to address the sparse nature of this protocol, and show that efficient MD-MRI encoding design demands a nuanced denoising approach. The MD-MRI framework provides rich information that allows resolving the diffusion frequency dependence into intravoxel components based on their distribution, enabling the creation of microstructure-specific maps in the human brain. Our results encourage the broader adoption and use of this new imaging approach for characterizing healthy and pathological tissues.},
keywords = {},
pubstate = {published},
tppubtype = {misc}
}
Diffusion MRI with free gradient waveforms, combined with simultaneous relaxation encoding, referred to as multidimensional MRI (MD-MRI), offers microstructural specificity in complex biological tissue. This approach delivers intravoxel information about the microstructure, local chemical composition, and importantly, how these properties are coupled within heterogeneous tissue containing multiple microenvironments. Recent theoretical advances incorporated diffusion time dependency and integrated MD-MRI with concepts from oscillating gradients. This framework probes the diffusion frequency, , in addition to the diffusion tensor, , and relaxation, , , correlations. A clinical imaging protocol was then introduced, with limited brain coverage and 3 mm voxel size, which hinder brain segmentation and future cohort studies. In this study, we introduce an efficient, sparse MD-MRI acquisition protocol providing whole brain coverage at 2 mm voxel size. We demonstrate its feasibility and robustness using a well-defined phantom and repeated scans of five healthy individuals. Additionally, we test different denoising strategies to address the sparse nature of this protocol, and show that efficient MD-MRI encoding design demands a nuanced denoising approach. The MD-MRI framework provides rich information that allows resolving the diffusion frequency dependence into intravoxel components based on their distribution, enabling the creation of microstructure-specific maps in the human brain. Our results encourage the broader adoption and use of this new imaging approach for characterizing healthy and pathological tissues.
2022
Angebrandt, Alexanndra; Abulseoud, Osama A.; Kisner, Mallory; Diazgranados, Nancy; Momenan, Reza; Yang, Yihong; Stein, Elliot A.; Ross, Thomas J.
Dose-dependent Relationship between Social Drinking and Brain Aging Journal Article
In: Neurobiology of Aging, vol. 111, pp. 71–81, 2022, ISSN: 0197-4580.
@article{ross_T_DoseDependentRelationship2022,
title = {Dose-dependent Relationship between Social Drinking and Brain Aging},
author = {Alexanndra Angebrandt and Osama A. Abulseoud and Mallory Kisner and Nancy Diazgranados and Reza Momenan and Yihong Yang and Elliot A. Stein and Thomas J. Ross},
url = {https://pubmed.ncbi.nlm.nih.gov/34973470/},
doi = {10.1016/j.neurobiolaging.2021.11.008},
issn = {0197-4580},
year = {2022},
date = {2022-03-01},
urldate = {2022-03-01},
journal = {Neurobiology of Aging},
volume = {111},
pages = {71--81},
abstract = {Low-level alcohol consumption is commonly perceived as being inconsequential or even beneficial for overall health, with some reports suggesting that it may protect against dementia or cardiovascular risks. However, these potential benefits do not preclude the concurrent possibility of negative health outcomes related to alcohol consumption. To examine whether casual, non-heavy drinking is associated with premature brain aging, we utilized the Brain-Age Regression Analysis and Computational Utility Software package to predict brain age in a community sample of adults [n~=~240, mean age 35.1 ($pm$10.7) years, 48% male, 49% African American]. Accelerated brain aging was operationalized as the difference between predicted and chronological age (``brain age gap''). Multiple regression analysis revealed a significant association between previous 90-day alcohol consumption and brain age gap ($beta~$=~0.014, p~=~0.023). We replicated these results in an independent cohort [n~=~231 adults, mean age 34.3 ($pm$11.1) years, 55% male, 28% African American: $beta~$=~0.014, p~=~0.002]. Our results suggest that even low-level alcohol consumption is associated with premature brain aging. The clinical significance of these findings remains to be investigated.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Low-level alcohol consumption is commonly perceived as being inconsequential or even beneficial for overall health, with some reports suggesting that it may protect against dementia or cardiovascular risks. However, these potential benefits do not preclude the concurrent possibility of negative health outcomes related to alcohol consumption. To examine whether casual, non-heavy drinking is associated with premature brain aging, we utilized the Brain-Age Regression Analysis and Computational Utility Software package to predict brain age in a community sample of adults [n~=~240, mean age 35.1 ($pm$10.7) years, 48% male, 49% African American]. Accelerated brain aging was operationalized as the difference between predicted and chronological age (``brain age gap''). Multiple regression analysis revealed a significant association between previous 90-day alcohol consumption and brain age gap ($beta~$=~0.014, p~=~0.023). We replicated these results in an independent cohort [n~=~231 adults, mean age 34.3 ($pm$11.1) years, 55% male, 28% African American: $beta~$=~0.014, p~=~0.002]. Our results suggest that even low-level alcohol consumption is associated with premature brain aging. The clinical significance of these findings remains to be investigated.
Deshpande, Harshawardhan U.; Fedota, John R.; Castillo, Juan; Salmeron, Betty Jo; Ross, Thomas J.; Stein, Elliot A.
Not All Smokers Are Alike: The Hidden Cost of Sustained Attention during Nicotine Abstinence Journal Article
In: Neuropsychopharmacology, pp. 1–10, 2022, ISSN: 1740-634X.
@article{stein_E_NotAllSmokers2022,
title = {Not All Smokers Are Alike: The Hidden Cost of Sustained Attention during Nicotine Abstinence},
author = {Harshawardhan U. Deshpande and John R. Fedota and Juan Castillo and Betty Jo Salmeron and Thomas J. Ross and Elliot A. Stein},
url = {https://pubmed.ncbi.nlm.nih.gov/35091674/},
doi = {10.1038/s41386-022-01275-8},
issn = {1740-634X},
year = {2022},
date = {2022-01-28},
urldate = {2022-01-28},
journal = {Neuropsychopharmacology},
pages = {1--10},
publisher = {Nature Publishing Group},
abstract = {Nicotine Withdrawal Syndrome (NWS)-associated cognitive deficits are notably heterogeneous, suggesting underlying endophenotypic variance. However, parsing this variance in smokers has remained challenging. In this study, we identified smoker subgroups based on response accuracy during a Parametric Flanker Task (PFT) and then characterized distinct neuroimaging endophenotypes using a nicotine state manipulation. Smokers completed the PFT in two fMRI sessions (nicotine sated, abstinent). Based on response accuracy in the stressful, high cognitive demand PFT condition, smokers split into high (HTP},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Nicotine Withdrawal Syndrome (NWS)-associated cognitive deficits are notably heterogeneous, suggesting underlying endophenotypic variance. However, parsing this variance in smokers has remained challenging. In this study, we identified smoker subgroups based on response accuracy during a Parametric Flanker Task (PFT) and then characterized distinct neuroimaging endophenotypes using a nicotine state manipulation. Smokers completed the PFT in two fMRI sessions (nicotine sated, abstinent). Based on response accuracy in the stressful, high cognitive demand PFT condition, smokers split into high (HTP
2021
Korponay, Cole; Stein, Elliot A; Ross, Thomas J
Laterality Hotspots in the Striatum Journal Article
In: Cereb Cortex, 2021, ISSN: 1460-2199.
@article{pmid34727171,
title = {Laterality Hotspots in the Striatum},
author = {Cole Korponay and Elliot A Stein and Thomas J Ross},
url = {https://pubmed.ncbi.nlm.nih.gov/34727171/},
doi = {10.1093/cercor/bhab392},
issn = {1460-2199},
year = {2021},
date = {2021-11-01},
urldate = {2021-11-01},
journal = {Cereb Cortex},
abstract = {Striatal loci are connected to both the ipsilateral and contralateral frontal cortex. Normative quantitation of the dissimilarity between striatal loci's hemispheric connection profiles and its spatial variance across the striatum, and assessment of how interindividual differences relate to function, stands to further the understanding of the role of corticostriatal circuits in lateralized functions and the role of abnormal corticostriatal laterality in neurodevelopmental and other neuropsychiatric disorders. A resting-state functional connectivity fingerprinting approach (n = 261) identified "laterality hotspots"-loci whose profiles of connectivity with ipsilateral and contralateral frontal cortex were disproportionately dissimilar-in the right rostral ventral putamen, left rostral central caudate, and bilateral caudal ventral caudate. Findings were replicated in an independent sample and were robust to both preprocessing choices and the choice of cortical atlas used for parcellation definitions. Across subjects, greater rightward connectional laterality at the right ventral putamen hotspot and greater leftward connectional laterality at the left rostral caudate hotspot were associated with higher performance on tasks engaging lateralized functions (i.e., response inhibition and language, respectively). In sum, we find robust and reproducible evidence for striatal loci with disproportionately lateralized connectivity profiles where interindividual differences in laterality magnitude are associated with behavioral capacities on lateralized functions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Striatal loci are connected to both the ipsilateral and contralateral frontal cortex. Normative quantitation of the dissimilarity between striatal loci's hemispheric connection profiles and its spatial variance across the striatum, and assessment of how interindividual differences relate to function, stands to further the understanding of the role of corticostriatal circuits in lateralized functions and the role of abnormal corticostriatal laterality in neurodevelopmental and other neuropsychiatric disorders. A resting-state functional connectivity fingerprinting approach (n = 261) identified "laterality hotspots"-loci whose profiles of connectivity with ipsilateral and contralateral frontal cortex were disproportionately dissimilar-in the right rostral ventral putamen, left rostral central caudate, and bilateral caudal ventral caudate. Findings were replicated in an independent sample and were robust to both preprocessing choices and the choice of cortical atlas used for parcellation definitions. Across subjects, greater rightward connectional laterality at the right ventral putamen hotspot and greater leftward connectional laterality at the left rostral caudate hotspot were associated with higher performance on tasks engaging lateralized functions (i.e., response inhibition and language, respectively). In sum, we find robust and reproducible evidence for striatal loci with disproportionately lateralized connectivity profiles where interindividual differences in laterality magnitude are associated with behavioral capacities on lateralized functions.
2020
Lesage, E.; Sutherland, M. T.; Ross, T. J.; Salmeron, B. J.; Stein, E. A.
In: Neuropsychopharmacology, vol. 45, no. 5, pp. 857–865, 2020, ISSN: 1740-634X.
@article{lesageNicotineDependenceTrait2020,
title = {Nicotine Dependence (Trait) and Acute Nicotinic Stimulation (State) Modulate Attention but Not Inhibitory Control: Converging fMRI Evidence from Go–Nogo and Flanker Tasks},
author = {E. Lesage and M. T. Sutherland and T. J. Ross and B. J. Salmeron and E. A. Stein},
url = {https://pubmed.ncbi.nlm.nih.gov/31995811/},
doi = {10.1038/s41386-020-0623-1},
issn = {1740-634X},
year = {2020},
date = {2020-04-01},
urldate = {2020-04-01},
journal = {Neuropsychopharmacology},
volume = {45},
number = {5},
pages = {857--865},
publisher = {Nature Publishing Group},
abstract = {Cognitive deficits during nicotine withdrawal may contribute to smoking relapse. However, interacting effects of chronic nicotine dependence and acute nicotine withdrawal on cognitive control are poorly understood. Here we examine the effects of nicotine dependence (trait; smokers (n,=,24) vs. non-smoking controls; n,=,20) and acute nicotinic stimulation (state; administration of nicotine and varenicline, two FDA-approved smoking cessation aids, during abstinence), on two well-established tests of inhibitory control, the Go– Nogo task and the Flanker task, during fMRI scanning. We compared performance and neural responses between these four pharmacological manipulations in a double-blind, placebo-controlled crossover design. As expected, performance in both tasks was modulated by nicotine dependence, abstinence, and pharmacological manipulation. However, effects were driven entirely by conditions that required less inhibitory control. When demand for inhibitory control was high, abstinent smokers showed no deficits. By contrast, acutely abstinent smokers showed performance deficits in easier conditions and missed more trials. Go– Nogo fMRI results showed decreased inhibition-related neural activity in right anterior insula and right putamen in smokers and decreased dorsal anterior cingulate cortex activity on nicotine across groups. No effects were found on inhibition-related activity during the Flanker task or on error-related activity in either task. Given robust nicotinic effects on physiology and behavioral deficits in attention, we are confident that pharmacological manipulations were effective. Thus findings fit a recent proposal that abstinent smokers show decreased ability to divert cognitive resources at low or intermediate cognitive demand, while performance at high cognitive demand remains relatively unaffected, suggesting a primary attentional deficit during acute abstinence.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cognitive deficits during nicotine withdrawal may contribute to smoking relapse. However, interacting effects of chronic nicotine dependence and acute nicotine withdrawal on cognitive control are poorly understood. Here we examine the effects of nicotine dependence (trait; smokers (n,=,24) vs. non-smoking controls; n,=,20) and acute nicotinic stimulation (state; administration of nicotine and varenicline, two FDA-approved smoking cessation aids, during abstinence), on two well-established tests of inhibitory control, the Go– Nogo task and the Flanker task, during fMRI scanning. We compared performance and neural responses between these four pharmacological manipulations in a double-blind, placebo-controlled crossover design. As expected, performance in both tasks was modulated by nicotine dependence, abstinence, and pharmacological manipulation. However, effects were driven entirely by conditions that required less inhibitory control. When demand for inhibitory control was high, abstinent smokers showed no deficits. By contrast, acutely abstinent smokers showed performance deficits in easier conditions and missed more trials. Go– Nogo fMRI results showed decreased inhibition-related neural activity in right anterior insula and right putamen in smokers and decreased dorsal anterior cingulate cortex activity on nicotine across groups. No effects were found on inhibition-related activity during the Flanker task or on error-related activity in either task. Given robust nicotinic effects on physiology and behavioral deficits in attention, we are confident that pharmacological manipulations were effective. Thus findings fit a recent proposal that abstinent smokers show decreased ability to divert cognitive resources at low or intermediate cognitive demand, while performance at high cognitive demand remains relatively unaffected, suggesting a primary attentional deficit during acute abstinence.
Abulseoud, Osama A; Ross, Thomas J; Nam, Hyung Wook; Caparelli, Elisabeth C; Tennekoon, Michael; Schleyer, Brooke; Castillo, Juan; Fedota, John; Gu, Hong; Yang, Yihong; Stein, Elliot
In: Neuropsychopharmacology, vol. 45, no. 11, pp. 1920–1930, 2020, ISBN: 1740-634X.
@article{Abulseoud:2020aa,
title = {Short-term nicotine deprivation alters dorsal anterior cingulate glutamate concentration and concomitant cingulate-cortical functional connectivity},
author = {Osama A Abulseoud and Thomas J Ross and Hyung Wook Nam and Elisabeth C Caparelli and Michael Tennekoon and Brooke Schleyer and Juan Castillo and John Fedota and Hong Gu and Yihong Yang and Elliot Stein},
url = {https://pubmed.ncbi.nlm.nih.gov/32559759/},
doi = {10.1038/s41386-020-0741-9},
isbn = {1740-634X},
year = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Neuropsychopharmacology},
volume = {45},
number = {11},
pages = {1920--1930},
abstract = {Most cigarette smokers who wish to quit too often relapse within the first few days of abstinence, primarily due to the aversive aspects of the nicotine withdrawal syndrome (NWS), which remains poorly understood. Considerable research has suggested that the dorsal anterior cingulate cortex (dACC) plays a key role in nicotine dependence, with its functional connections between other brain regions altered as a function of trait addiction and state withdrawal. The flow of information between dACC and fronto-striatal regions is secured through different pathways, the vast majority of which are glutamatergic. As such, we investigated dACC activity using resting state functional connectivity (rsFC) with functional magnetic resonance imaging (fMRI) and glutamate (Glu) concentration with magnetic resonance spectroscopy (MRS). We also investigated the changes in adenosine levels in plasma during withdrawal as a surrogate for brain adenosine, which plays a role in fine-tuning synaptic glutamate transmission. Using a double-blind, placebo-controlled, randomized crossover design, nontreatment seeking smoking participants (N = 30) completed two imaging sessions, one while nicotine sated and another after 36 h nicotine abstinence. We observed reduced dACC Glu (P = 0.029) along with a significant reduction in plasma adenosine (P = 0.03) and adenosine monophosphate (AMP; P < 0.0001) concentrations during nicotine withdrawal in comparison with nicotine sated state. This withdrawal state manipulation also led to an increase in rsFC strength (P < 0.05) between dACC and several frontal cortical regions, including left superior frontal gyrus (LSFG), and right middle frontal gyrus (RMFG). Moreover, the state-trait changes in dACC Glu and rsFC strength between the dACC and both SFG and MFG were positively correlated (P = 0.012, and P = 0.007, respectively). Finally, the change in circuit strength between dACC and LSFG was negatively correlated with the change in withdrawal symptom manifestations as measured by the Wisconsin Smoking Withdrawal Scale (P = 0.04) and Tobacco Craving Questionnaire (P = 0.014). These multimodal imaging-behavioral findings reveal the complex cascade of changes induced by acute nicotine deprivation and call for further investigation into the potential utility of adenosine- and glutamate-signaling as novel therapeutic targets to treat the NWS.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Most cigarette smokers who wish to quit too often relapse within the first few days of abstinence, primarily due to the aversive aspects of the nicotine withdrawal syndrome (NWS), which remains poorly understood. Considerable research has suggested that the dorsal anterior cingulate cortex (dACC) plays a key role in nicotine dependence, with its functional connections between other brain regions altered as a function of trait addiction and state withdrawal. The flow of information between dACC and fronto-striatal regions is secured through different pathways, the vast majority of which are glutamatergic. As such, we investigated dACC activity using resting state functional connectivity (rsFC) with functional magnetic resonance imaging (fMRI) and glutamate (Glu) concentration with magnetic resonance spectroscopy (MRS). We also investigated the changes in adenosine levels in plasma during withdrawal as a surrogate for brain adenosine, which plays a role in fine-tuning synaptic glutamate transmission. Using a double-blind, placebo-controlled, randomized crossover design, nontreatment seeking smoking participants (N = 30) completed two imaging sessions, one while nicotine sated and another after 36 h nicotine abstinence. We observed reduced dACC Glu (P = 0.029) along with a significant reduction in plasma adenosine (P = 0.03) and adenosine monophosphate (AMP; P < 0.0001) concentrations during nicotine withdrawal in comparison with nicotine sated state. This withdrawal state manipulation also led to an increase in rsFC strength (P < 0.05) between dACC and several frontal cortical regions, including left superior frontal gyrus (LSFG), and right middle frontal gyrus (RMFG). Moreover, the state-trait changes in dACC Glu and rsFC strength between the dACC and both SFG and MFG were positively correlated (P = 0.012, and P = 0.007, respectively). Finally, the change in circuit strength between dACC and LSFG was negatively correlated with the change in withdrawal symptom manifestations as measured by the Wisconsin Smoking Withdrawal Scale (P = 0.04) and Tobacco Craving Questionnaire (P = 0.014). These multimodal imaging-behavioral findings reveal the complex cascade of changes induced by acute nicotine deprivation and call for further investigation into the potential utility of adenosine- and glutamate-signaling as novel therapeutic targets to treat the NWS.
Fedota, John R; Ross, Thomas J; Castillo, Juan; McKenna, Michael R; Matous, Allison L; Salmeron, Betty Jo; Menon, Vinod; Stein, Elliot A
Time-Varying Functional Connectivity Decreases as a Function of Acute Nicotine Abstinence Journal Article
In: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2020, ISSN: 2451-9022.
@article{FEDOTA2020b,
title = {Time-Varying Functional Connectivity Decreases as a Function of Acute Nicotine Abstinence},
author = {John R Fedota and Thomas J Ross and Juan Castillo and Michael R McKenna and Allison L Matous and Betty Jo Salmeron and Vinod Menon and Elliot A Stein},
url = {https://pubmed.ncbi.nlm.nih.gov/33436331/},
doi = {https://doi.org/10.1016/j.bpsc.2020.10.004},
issn = {2451-9022},
year = {2020},
date = {2020-01-01},
urldate = {2020-01-01},
journal = {Biological Psychiatry: Cognitive Neuroscience and Neuroimaging},
abstract = {\textbf{Background}
The nicotine withdrawal syndrome (NWS) includes affective and cognitive disruptions whose incidence and severity vary across time during acute abstinence. However, most network-level neuroimaging uses static measures of resting-state functional connectivity and assumes time-invariance and is thus unable to capture dynamic brain-behavior relationships. Recent advances in resting-state functional connectivity signal processing allow characterization of time-varying functional connectivity (TVFC), which characterizes network communication between networks that reconfigure over the course of data collection. Therefore, TVFC may more fully describe network dysfunction related to the NWS.
\textbf{Methods}
To isolate alterations in the frequency and diversity of communication across network boundaries during acute nicotine abstinence, we scanned 25 cigarette smokers in the nicotine-sated and abstinent states and applied a previously validated method to characterize TVFC at a network and a nodal level within the brain.
\textbf{Results}
During abstinence, we found brain-wide decreases in the frequency of interactions between network nodes in different modular communities (i.e., temporal flexibility). In addition, within a subset of the networks examined, the variability of these interactions across community boundaries (i.e., spatiotemporal diversity) also decreased. Finally, within 2 of these networks, the decrease in spatiotemporal diversity was significantly related to NWS clinical symptoms.
\textbf{Conclusions}
Using multiple measures of TVFC in a within-subjects design, we characterized a novel set of changes in network communication and linked these changes to specific behavioral symptoms of the NWS. These reductions in TVFC provide a meso-scale network description of the relative inflexibility of specific large-scale brain networks during acute abstinence.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background
The nicotine withdrawal syndrome (NWS) includes affective and cognitive disruptions whose incidence and severity vary across time during acute abstinence. However, most network-level neuroimaging uses static measures of resting-state functional connectivity and assumes time-invariance and is thus unable to capture dynamic brain-behavior relationships. Recent advances in resting-state functional connectivity signal processing allow characterization of time-varying functional connectivity (TVFC), which characterizes network communication between networks that reconfigure over the course of data collection. Therefore, TVFC may more fully describe network dysfunction related to the NWS.
Methods
To isolate alterations in the frequency and diversity of communication across network boundaries during acute nicotine abstinence, we scanned 25 cigarette smokers in the nicotine-sated and abstinent states and applied a previously validated method to characterize TVFC at a network and a nodal level within the brain.
Results
During abstinence, we found brain-wide decreases in the frequency of interactions between network nodes in different modular communities (i.e., temporal flexibility). In addition, within a subset of the networks examined, the variability of these interactions across community boundaries (i.e., spatiotemporal diversity) also decreased. Finally, within 2 of these networks, the decrease in spatiotemporal diversity was significantly related to NWS clinical symptoms.
Conclusions
Using multiple measures of TVFC in a within-subjects design, we characterized a novel set of changes in network communication and linked these changes to specific behavioral symptoms of the NWS. These reductions in TVFC provide a meso-scale network description of the relative inflexibility of specific large-scale brain networks during acute abstinence.
The nicotine withdrawal syndrome (NWS) includes affective and cognitive disruptions whose incidence and severity vary across time during acute abstinence. However, most network-level neuroimaging uses static measures of resting-state functional connectivity and assumes time-invariance and is thus unable to capture dynamic brain-behavior relationships. Recent advances in resting-state functional connectivity signal processing allow characterization of time-varying functional connectivity (TVFC), which characterizes network communication between networks that reconfigure over the course of data collection. Therefore, TVFC may more fully describe network dysfunction related to the NWS.
Methods
To isolate alterations in the frequency and diversity of communication across network boundaries during acute nicotine abstinence, we scanned 25 cigarette smokers in the nicotine-sated and abstinent states and applied a previously validated method to characterize TVFC at a network and a nodal level within the brain.
Results
During abstinence, we found brain-wide decreases in the frequency of interactions between network nodes in different modular communities (i.e., temporal flexibility). In addition, within a subset of the networks examined, the variability of these interactions across community boundaries (i.e., spatiotemporal diversity) also decreased. Finally, within 2 of these networks, the decrease in spatiotemporal diversity was significantly related to NWS clinical symptoms.
Conclusions
Using multiple measures of TVFC in a within-subjects design, we characterized a novel set of changes in network communication and linked these changes to specific behavioral symptoms of the NWS. These reductions in TVFC provide a meso-scale network description of the relative inflexibility of specific large-scale brain networks during acute abstinence.
2019
Flannery, Jessica S; Riedel, Michael C; Poudel, Ranjita; Laird, Angela R; Ross, Thomas J; Salmeron, Betty Jo; Stein, Elliot A; Sutherland, Matthew T
In: Sci Adv, vol. 5, no. 10, pp. eaax2084, 2019, ISSN: 2375-2548 (Electronic); 2375-2548 (Linking).
@article{Flannery:2019aa,
title = {Habenular and striatal activity during performance feedback are differentially linked with state-like and trait-like aspects of tobacco use disorder.},
author = {Jessica S Flannery and Michael C Riedel and Ranjita Poudel and Angela R Laird and Thomas J Ross and Betty Jo Salmeron and Elliot A Stein and Matthew T Sutherland},
url = {https://www.ncbi.nlm.nih.gov/pubmed/31633021},
doi = {10.1126/sciadv.aax2084},
issn = {2375-2548 (Electronic); 2375-2548 (Linking)},
year = {2019},
date = {2019-10-09},
urldate = {2019-10-09},
journal = {Sci Adv},
volume = {5},
number = {10},
pages = {eaax2084},
address = {Department of Psychology, Florida International University, Miami, FL, USA.},
abstract = {The habenula, an epithalamic nucleus involved in reward and aversive processing, may contribute to negative reinforcement mechanisms maintaining nicotine use. We used a performance feedback task that differentially activates the striatum and habenula and administered nicotine and varenicline (versus placebos) to overnight-abstinent smokers and nonsmokers to delineate feedback-related functional brain alterations both as a function of smoking trait (smokers versus nonsmokers) and drug administration state (drug versus placebo). Smokers showed less striatal responsivity to positive feedback, an alteration not mitigated by drug administration, but rather correlated with trait-level addiction severity. Conversely, nicotine administration reduced habenula activity following both positive and negative feedback among abstinent smokers, but not nonsmokers, and increased habenula activity among smokers correlated with elevated state-level tobacco cravings. These outcomes highlight a dissociation between neurobiological processes linked with the dependence severity trait and the nicotine withdrawal state. Interventions simultaneously targeting both aspects may improve currently poor cessation outcomes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The habenula, an epithalamic nucleus involved in reward and aversive processing, may contribute to negative reinforcement mechanisms maintaining nicotine use. We used a performance feedback task that differentially activates the striatum and habenula and administered nicotine and varenicline (versus placebos) to overnight-abstinent smokers and nonsmokers to delineate feedback-related functional brain alterations both as a function of smoking trait (smokers versus nonsmokers) and drug administration state (drug versus placebo). Smokers showed less striatal responsivity to positive feedback, an alteration not mitigated by drug administration, but rather correlated with trait-level addiction severity. Conversely, nicotine administration reduced habenula activity following both positive and negative feedback among abstinent smokers, but not nonsmokers, and increased habenula activity among smokers correlated with elevated state-level tobacco cravings. These outcomes highlight a dissociation between neurobiological processes linked with the dependence severity trait and the nicotine withdrawal state. Interventions simultaneously targeting both aspects may improve currently poor cessation outcomes.
