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Article ; Online: Theta oscillatory dynamics of inhibitory control, error processing, and post-error adjustments: Neural underpinnings and alcohol-induced dysregulation in social drinkers.

Marinkovic, Ksenija / Rosen, Burke Q

Alcoholism, clinical and experimental research

2022 Volume 46, Issue 7, Page(s) 1220–1232

Abstract: Background: Alcohol intoxication impairs inhibitory control, resulting in disinhibited, impulsive behavior. The anterior cingulate cortex (ACC) plays an essential role in a range of executive functions and is sensitive to the effects of alcohol, which ... ...

Abstract	Background: Alcohol intoxication impairs inhibitory control, resulting in disinhibited, impulsive behavior. The anterior cingulate cortex (ACC) plays an essential role in a range of executive functions and is sensitive to the effects of alcohol, which contributes to the top-down cognitive dysregulation. This study used a multimodal approach to examine the acute effects of alcohol on the neural underpinnings of inhibitory control, inhibition failures, and neurobehavioral optimization as reflected in trial-to-trial dynamics of post-error adjustments. Methods: Adult social drinkers served as their own controls by participating in the Go/NoGo task during acute alcohol and placebo conditions in a multi-session, counterbalanced design. Distributed source modeling of the magnetoencephalographic signal was combined with structural magnetic resonance imaging to characterize the spatio-temporal dynamics of inhibitory control in the time-frequency domain. Results: Successful response inhibition (NoGo) elicited right-lateralized event-related theta power (4 to 7 Hz). Errors elicited a short-latency increase in theta power in the dorsal (dACC), followed by activity in the rostral (rACC), which may underlie an affective "oh, no!" orienting response to errors. Error-related theta in the dACC was associated with subsequent activity of the motor areas on the first post-error trial, suggesting the occurrence of post-error output adjustments. Importantly, a gradual increase of the dACC theta across post-error trials closely tracked improvements in accuracy under placebo, which may reflect cognitive control engagement to optimize response accuracy. In contrast, alcohol increased NoGo commission errors, dysregulated theta during correct NoGo withholding, and abolished the post-error theta enhancement of cognitive control. Conclusions: Confirming the sensitivity of frontal theta to inhibitory control and error monitoring, the results support functional and temporal dissociation along the dorso-rostral axis of the ACC and the deleterious effects of alcohol on the frontal circuitry subserving top-down regulation. Over time, alcohol-induced disinhibition may give rise to compulsive drinking and contribute to alcohol misuse.
MeSH term(s)	Adult ; Alcohol Drinking/psychology ; Alcoholic Intoxication/psychology ; Ethanol/adverse effects ; Humans ; Inhibition, Psychological ; Magnetic Resonance Imaging ; Magnetoencephalography/methods ; Theta Rhythm
Chemical Substances	Ethanol (3K9958V90M)
Language	English
Publishing date	2022-05-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	428999-7
ISSN	1530-0277 ; 0145-6008
ISSN (online)	1530-0277
ISSN	0145-6008
DOI	10.1111/acer.14856
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Article: Alterations of theta power and synchrony during encoding in young adult binge drinkers: Subsequent memory effects associated with retrieval after 48 h and 6 months.

Huang, Siyuan / White, David R / Marinkovic, Ksenija

Frontiers in psychology

2022 Volume 13, Page(s) 1061016

Abstract: Introduction: Young emerging adults commonly engage in binge drinking which is associated with a range of neurocognitive deficits, including memory impairments. However, evidence on neural oscillations mediating episodic memory in this population is ... ...

Abstract	Introduction: Young emerging adults commonly engage in binge drinking which is associated with a range of neurocognitive deficits, including memory impairments. However, evidence on neural oscillations mediating episodic memory in this population is lacking. To address this gap, we recorded theta oscillatory activity in young binge (BDs) and light drinkers (LDs) during memory encoding and analyzed it prospectively as a function of subsequent retrieval. Theta underlies successful encoding of novel items in memory through corticolimbic integration. Subsequent memory effects (SMEs) are reflected in stronger theta activity during encoding of the items that are later remembered compared to those that are later forgotten. Methods: In the present study, 23 BDs (age: 23.3 ± 3.3) and 24 LDs (age: 23.4 ± 3.3) rated emotionally evocative images with negative, positive, and neutral themes during implicit encoding. They performed a recognition memory task on two follow-up occasions after a short (48 h), and long retention delay (6 months). Electroencephalography (EEG) signal was recorded during the encoding session and analyzed in time-frequency domain with Morlet wavelets in theta band (4-7 Hz). To evaluate SMEs, the event-related theta oscillations acquired during encoding were analyzed based on recognition outcomes after the two retention intervals. Results: The BD and LD groups did not differ on recognition memory. However, BDs showed attenuated event-related theta power during encoding of images that were successfully retained after 6 months compared to LDs. In addition, theta synchronous activity between frontal and left posterior regions during encoding successfully predicted recognition of the images after both retention delays in LDs but not in BDs. These SMEs on theta power and synchrony correlated negatively with high-intensity drinking in the previous 6 months. No differences between men and women were observed for any analysis. Discussion: It has been well established that long-range neural synchrony between cortical and limbic nodes underlies successful memory encoding and retention which, in turn, depends on neural excitation/inhibition (E/I) balance. Given that binge drinking is associated with E/I dysregulation, the observed SME deficiencies are consistent with other evidence of neural hyperexcitability in BDs, and may be indicative of increased risk of developing alcohol use disorders.
Language	English
Publishing date	2022-12-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2563826-9
ISSN	1664-1078
ISSN	1664-1078
DOI	10.3389/fpsyg.2022.1061016
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Article: Recall and Self-Relevance of Emotional Words Predict Subjective Self-Evaluation of Cognition in Patients with MTLE with or without Depressive Symptoms.

Preglej, Lidija / Marinkovic, Ksenija / Hećimović, Hrvoje

Brain sciences

2021 Volume 11, Issue 11

Abstract: We examined whether word processing is associated with subjective self-evaluation of cognition in patients with mesial temporal lobe epilepsy (MTLE) as a function of their depressive symptoms. MTLE patients with (MTLE +d, ...

Abstract	We examined whether word processing is associated with subjective self-evaluation of cognition in patients with mesial temporal lobe epilepsy (MTLE) as a function of their depressive symptoms. MTLE patients with (MTLE +d,
Language	English
Publishing date	2021-10-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci11111402
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Article ; Online: Neural indices of multimodal sensory and autonomic hyperexcitability in fibromyalgia.

Marinkovic, Ksenija / Woodruff, Denali / White, David R / Caudle, Morgan M / Cronan, Terry

Neurobiology of pain (Cambridge, Mass.)

2023 Volume 14, Page(s) 100140

Abstract: Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain and psychological distress. Research suggests people with FM experience increased somatosensory sensitization which generalizes to other sensory modalities and may indicate ... ...

Abstract	Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain and psychological distress. Research suggests people with FM experience increased somatosensory sensitization which generalizes to other sensory modalities and may indicate neural hyperexcitability. However, the available evidence is limited, and studies including measures of neural responsivity across sensory domains and both central and peripheral aspects of the neuraxis are lacking. Thirty-nine participants (51.5 ± 13.6 years of age) with no history of neurological disorders, psychosis, visual, auditory, or learning deficits, were recruited for this study. People with FM (N = 19) and control participants (CNT, N = 20) did not differ on demographic variables and cognitive capacity. Participants completed a task that combined innocuous auditory stimuli with electrocutaneous stimulation (ECS), delivered at individually-selected levels that were uncomfortable but not painful. Event-related potentials (ERPs) and electrodermal activity were analyzed to examine the central and sympathetic indices of neural responsivity. FM participants reported greater sensitivity to ECS and auditory stimulation, as well as higher levels of depression, anxiety, ADHD, and an array of pain-related experiences than CNT. In response to ECS, the P50 deflection was greater in FM than CNT participants, reflecting early somatosensory hyperexcitability. The P50 amplitude was positively correlated with the FM profile factor obtained with a principal component analysis. The N100 to innocuous tones and sympathetic reactivity to ECS were greater in FM participants, except in the subgroup treated with gabapentinoids, which aligns with previous evidence of symptomatic improvement with GABA-mimetic medications. These results support the principal tenet of generalized neural hyperexcitability in FM and provide preliminary mechanistic insight into the impact of GABA-mimetic pharmacological therapy on ameliorating the neural excitation dominance.
Language	English
Publishing date	2023-07-22
Publishing country	United States
Document type	Journal Article
ISSN	2452-073X
ISSN (online)	2452-073X
DOI	10.1016/j.ynpai.2023.100140
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Article ; Online: Local and network-level dysregulation of error processing is associated with binge drinking.

Alderson Myers, Austin B / Arienzo, Donatello / Molnar, Sean M / Marinkovic, Ksenija

NeuroImage. Clinical

2021 Volume 32, Page(s) 102879

Abstract: Binge drinking refers to the pattern of alcohol consumption that brings blood alcohol levels to or above legal intoxication levels. Commonly practiced by young adults, it is associated with neurofunctional alterations, raising health-related concerns. ... ...

Abstract	Binge drinking refers to the pattern of alcohol consumption that brings blood alcohol levels to or above legal intoxication levels. Commonly practiced by young adults, it is associated with neurofunctional alterations, raising health-related concerns. Executive deficits may contribute to the inability to refrain from excessive alcohol intake. As a facet of cognitive control, error processing allows for flexible modification of behavior to optimize future outcomes. It is highly relevant to addiction research, as a failure to inhibit excessive drinking results in relapses, which is a hallmark of alcohol use disorder. However, research on local and system-level neural underpinnings of inhibition failures as a function of binge drinking is limited. To address these gaps, functional magnetic resonance imaging (fMRI) was used to examine local changes and interregional functional connectivity during response inhibition errors on a Go/NoGo task. Young adult binge drinkers (BDs) performed equally well as light drinkers (LDs), a group of demographically matched individuals who drink regularly but in low-risk patterns. In contrast, BDs exhibited greater fMRI activity to inhibition errors contrasted with correct NoGo trials in the rostral anterior (rACC) and posterior cingulate cortices (PCC), as well as right middle frontal gyrus (R-MFG). Furthermore, BDs showed increased connectivity between the rACC and right lateral prefrontal cortex, in addition to greater connectivity between the R-MFG and the left ventrolateral and superior frontal cortices. Imaging indices were positively correlated only with alcohol-related measures, but not with those related to moods, disposition, or cognitive capacity. Taken together, greater error-related activity and expanded functional connectivity among prefrontal regions may serve a compensatory role to maintain efficiency of inhibitory control. Aligned with prominent models of addiction, these findings accentuate the importance of top-down control in maintaining low-risk drinking levels. They provide insight into potentially early signs of deteriorating cognitive control functions in BDs and may help guide intervention strategies aimed at preventing excessive drinking habits.
MeSH term(s)	Alcohol Drinking ; Binge Drinking ; Ethanol ; Humans ; Inhibition, Psychological ; Magnetic Resonance Imaging ; Young Adult
Chemical Substances	Ethanol (3K9958V90M)
Language	English
Publishing date	2021-11-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2021.102879
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Article ; Online: Cortical GABA levels are reduced in young adult binge drinkers: Association with recent alcohol consumption and sex.

Marinkovic, Ksenija / Alderson Myers, Austin B / Arienzo, Donatello / Sereno, Martin I / Mason, Graeme F

NeuroImage. Clinical

2022 Volume 35, Page(s) 103091

Abstract: Binge drinking refers to a pattern of alcohol intake that raises blood alcohol concentration to or above legal intoxication levels. It is common among young adults and is associated with health risks that scale up with alcohol intake. Acute intoxication ... ...

Abstract	Binge drinking refers to a pattern of alcohol intake that raises blood alcohol concentration to or above legal intoxication levels. It is common among young adults and is associated with health risks that scale up with alcohol intake. Acute intoxication depresses neural activity via complex signaling mechanisms by enhancing inhibition mediated by gamma-amino butyric acid (GABA), and by decreasing excitatory glutamatergic effects. Evidence primarily rooted in animal research indicates that the brain compensates for the acute depressant effects under the conditions of habitual heavy use. These neuroadaptive changes are reflected in neural hyperexcitability via downregulated inhibitory signaling, which becomes apparent as withdrawal symptoms. However, human evidence on the compensatory reduction in GABA signaling is scant. The neurochemical aspect of this mechanistic model was evaluated in the present study with proton magnetic resonance spectroscopy (
MeSH term(s)	Alcohol Drinking ; Binge Drinking ; Blood Alcohol Content ; Brain ; Child, Preschool ; Ethanol ; Female ; Humans ; Male ; Young Adult ; gamma-Aminobutyric Acid
Chemical Substances	Blood Alcohol Content ; Ethanol (3K9958V90M) ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2022-06-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2022.103091
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Article: Cortical GABA Levels Are Reduced in Post-Acute COVID-19 Syndrome.

Marinkovic, Ksenija / White, David R / Alderson Myers, Austin / Parker, Katie S / Arienzo, Donatello / Mason, Graeme F

Brain sciences

2023 Volume 13, Issue 12

Abstract: After recovering from the acute COVID-19 illness, a substantial proportion of people continue experiencing post-acute sequelae of COVID-19 (PASC), also termed "long COVID". Their quality of life is adversely impacted by persistent cognitive dysfunction ... ...

Abstract	After recovering from the acute COVID-19 illness, a substantial proportion of people continue experiencing post-acute sequelae of COVID-19 (PASC), also termed "long COVID". Their quality of life is adversely impacted by persistent cognitive dysfunction and affective distress, but the underlying neural mechanisms are poorly understood. The present study recruited a group of mostly young, previously healthy adults (24.4 ± 5.2 years of age) who experienced PASC for almost 6 months following a mild acute COVID-19 illness. Confirming prior evidence, they reported noticeable memory and attention deficits, brain fog, depression/anxiety, fatigue, and other symptoms potentially suggestive of excitation/inhibition imbalance. Proton magnetic resonance spectroscopy (
Language	English
Publishing date	2023-12-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci13121666
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Article: Neurodynamic correlates of response inhibition from emerging to mid adulthood.

Knežević, Martina / Marinković, Ksenija

Cognitive development

2017 Volume 43, Page(s) 106–118

Abstract: Response inhibition, a key executive function, continues to develop in early adulthood in parallel with maturational processes of the underlying prefrontal regions known to support it. The current study examined behavioral and neurophysiological ... ...

Abstract	Response inhibition, a key executive function, continues to develop in early adulthood in parallel with maturational processes of the underlying prefrontal regions known to support it. The current study examined behavioral and neurophysiological correlates of response inhibition during a visual Go/No-Go task in a large sample (N = 120) comprised of participants in their Early 20s (ages 19-21), Mid 20s (ages 23-27), and Early 30s (ages 28-42). The two younger groups had lower accuracy, shorter reaction times, and made more premature responses compared to Early 30s. These impulsive behavioral tendencies were reflected in a delayed N2 latency and reduced P2 and P3 amplitudes for Early 20s compared to Early 30s and were associated with personality traits such as impulsivity in an age-dependent manner. The results suggest that response inhibition may not develop fully before the approximate age of 25, as the refinement of the primarily prefrontal cognitive control network follows a protracted developmental trajectory throughout young adulthood.
Language	English
Publishing date	2017-03-21
Publishing country	United States
Document type	Journal Article
ISSN	0885-2014
ISSN	0885-2014
DOI	10.1016/j.cogdev.2017.03.002
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Article ; Online: The "when" and "where" of the interplay between attentional capture and response inhibition during a Go/NoGo variant.

Happer, Joseph P / Wagner, Laura C / Beaton, Lauren E / Rosen, Burke Q / Marinkovic, Ksenija

NeuroImage

2021 Volume 231, Page(s) 117837

Abstract: Inhibitory control relies on attention, inhibition, and other functions that are integrated across neural networks in an interactive manner. Functional MRI studies have provided excellent spatial mapping of the involved regions. However, finer temporal ... ...

Abstract	Inhibitory control relies on attention, inhibition, and other functions that are integrated across neural networks in an interactive manner. Functional MRI studies have provided excellent spatial mapping of the involved regions. However, finer temporal resolution is needed to capture the underlying neural dynamics and the pattern of their functional contributions. Here, we used anatomically-constrained magnetoencephalography (aMEG) which combines MEG with structural MRI to examine how the spatial ("where") and temporal ("when") processing stages and interregional co-oscillations unfold in real time to contribute to inhibitory control. Healthy participants completed a modified Go/NoGo paradigm in which a subset of stimuli was modified to be visually salient (SAL). Compared to the non-modified condition, the SAL manipulation facilitated response withholding on NoGo trials and hindered responding to Go stimuli, reflecting attentional capture effectuated by an orienting response to SAL stimuli. aMEG source estimates indicate SAL stimuli elicited the attentional "circuit breaker" effect through early activity within a right-lateralized network centered around the lateral temporal cortex with additional activity in the pre-supplementary motor area (preSMA) and anterior insula (aINS/FO). Activity of the bilateral inferior frontal cortex responded specifically to inhibitory demands and was generally unaffected by the attentional manipulation. In contrast, early aINS/FO activity was sensitive to stimulus salience while subsequent activity was specific to inhibitory control. Activity estimated to the medial prefrontal cortex including the dorsal anterior cingulate cortex and preSMA reflected an integrative role that was sensitive to both inhibitory and attentional stimulus properties. At the level of neurofunctional networks, neural synchrony in the theta band (4-7 Hz) revealed interactions between principal cortical regions subserving attentional and inhibitory processes. Together, these results underscore the dynamic, integrative processing stages underlying inhibitory control.
MeSH term(s)	Adult ; Attention/physiology ; Brain/diagnostic imaging ; Brain/physiology ; Brain Mapping/methods ; Female ; Humans ; Inhibition, Psychological ; Magnetic Resonance Imaging/methods ; Magnetoencephalography/methods ; Male ; Nerve Net/diagnostic imaging ; Nerve Net/physiology ; Photic Stimulation/methods ; Psychomotor Performance/physiology ; Reaction Time/physiology ; Young Adult
Language	English
Publishing date	2021-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1147767-2
ISSN	1095-9572 ; 1053-8119
ISSN (online)	1095-9572
ISSN	1053-8119
DOI	10.1016/j.neuroimage.2021.117837
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Zs.A 3664: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: When the brain changes its mind: Oscillatory dynamics of conflict processing and response switching in a flanker task during alcohol challenge.

Beaton, Lauren E / Azma, Sheeva / Marinkovic, Ksenija

PloS one

2018 Volume 13, Issue 1, Page(s) e0191200

Abstract: Despite the subjective experience of being in full and deliberate control of our actions, our daily routines rely on a continuous and interactive engagement of sensory evaluation and response preparation streams. They unfold automatically and ... ...

Abstract	Despite the subjective experience of being in full and deliberate control of our actions, our daily routines rely on a continuous and interactive engagement of sensory evaluation and response preparation streams. They unfold automatically and unconsciously and are seamlessly integrated with cognitive control which is mobilized by stimuli that evoke ambiguity or response conflict. Methods with high spatio-temporal sensitivity are needed to provide insight into the interplay between automatic and controlled processing. This study used anatomically-constrained MEG to examine the underlying neural dynamics in a flanker task that manipulated S-R incongruity at the stimulus (SI) and response levels (RI). Though irrelevant, flankers evoked automatic preparation of motor plans which had to be suppressed and reversed following the target presentation on RI trials. Event-related source power estimates in beta (15-25 Hz) frequency band in the sensorimotor cortex tracked motor preparation and response in real time and revealed switching from the incorrectly-primed to the correctly-responding hemisphere. In contrast, theta oscillations (4-7 Hz) were sensitive to the levels of incongruity as the medial and ventrolateral frontal cortices were especially activated by response conflict. These two areas are key to cognitive control and their integrated contributions to response inhibition and switching were revealed by phase-locked co-oscillations. These processes were pharmacologically manipulated with a moderate alcohol beverage or a placebo administered to healthy social drinkers. Alcohol selectively decreased accuracy to response conflict. It strongly attenuated theta oscillations during decision making and partly re-sculpted relative contributions of the frontal network without affecting the motor switching process subserved by beta band. Our results indicate that motor preparation is initiated automatically even when counterproductive but that it is monitored and regulated by the prefrontal cognitive control processes under conflict. They further confirm that the regulative top-down functions are particularly vulnerable to alcohol intoxication.
MeSH term(s)	Adult ; Alcohol Drinking/physiopathology ; Alcohol Drinking/psychology ; Alcoholic Intoxication/physiopathology ; Alcoholic Intoxication/psychology ; Beta Rhythm/drug effects ; Beta Rhythm/physiology ; Brain/diagnostic imaging ; Brain/drug effects ; Brain/physiology ; Brain Mapping ; Cognition/drug effects ; Cognition/physiology ; Conflict (Psychology) ; Ethanol/adverse effects ; Female ; Functional Neuroimaging ; Humans ; Magnetic Resonance Imaging ; Magnetoencephalography ; Male ; Prefrontal Cortex/diagnostic imaging ; Prefrontal Cortex/drug effects ; Prefrontal Cortex/physiology ; Psychomotor Performance/drug effects ; Psychomotor Performance/physiology ; Theta Rhythm/drug effects ; Theta Rhythm/physiology ; Young Adult
Chemical Substances	Ethanol (3K9958V90M)
Language	English
Publishing date	2018
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0191200
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