Comparative efficacy of seven nonpharmacological interventions on global cognition in older adults with and without mild cognitive impairment: a network meta-analysis of randomized controlled trials.

To maintain current cognitive function and access greater cognitive reserves, nonpharmacological interventions may be a viable alternative for older adults with or without cognitive impairment. This study aimed to compare different nonpharmacological interventions for enhancing global cognition, including mind-body exercise, physical exercise, non-invasive brain stimulation, cognitive training intervention (CTI), acutherapy (ACU), meditation, and music therapy, by applying a network meta-analysis (NMA). Sixty-one randomized controlled trials evaluating the efficacy of interventions on global cognition in older adults with or without mild cognitive decline were selected. An NMA was conducted to compare the efficacy of different nonpharmacological interventions. The NMA revealed that mind-body exercise (standardized mean difference, 1.384; 95% confidence interval, 0.777-1.992); ACU (1.283; 0.478-2.088); meditation (0.910; 0.097-1.724); non-invasive brain stimulation (1.242; 0.254-2.230); CTI (1.269; 0.736-1.802); and physical exercise (0.977; 0.212-1.742), showed positive effects compared to passive controls. There were no significant differences between the efficacies of other interventions. Nonpharmacological interventions may potentially enhance and maintain global cognition through various pathways, such as memorizing movements and enhancing brain plasticity by reducing stress in the older adult population. Additional studies are needed to clarify the impact of other variables, including intervention methods or psychological variables.

Psychopharmacological treatment of disruptive behavior in youths: systematic review and network meta-analysis.

To conduct a systematic review of the comparative efficacy of various psychotropic medications for the treatment of disruptive behavior (DBs) in youths. To this aim, we systematically reviewed randomized clinical trials (RCTs) of various psychotropic medications targeting symptoms of DBs and applied network meta-analysis to investigate their relative efficacy. Fifty-five RCTs meeting the inclusion criteria were selected. To predict and interpret relative treatment efficacy, we compared the efficacy of various psychotropic medications prescribed for DB symptoms based on their mechanism of action. Network meta-analysis revealed that for reducing DBs, second-generation antipsychotics, stimulants, and non-stimulant ADHD medications were more efficacious than placebo, and second-generation antipsychotics were the most efficacious. The dopaminergic modulation of top-down inhibitory process by these medications is discussed in this review. This study offers information on the relative efficacy of various psychotropic medications for the treatment of DB, and insight into a potential neurobiological underpinning for those symptoms. It also illustrates the potential utility of these neurobiological mechanisms as a target for future treatment studies.

Structural atrophy of the right superior frontal gyrus in adolescents with severe irritability.

Severe irritability is common in youths with psychiatric disorders and results in significant dysfunction across domains (academic, social, and familial). Prior structural MRI studies in the pediatric population demonstrated that aberrations of cortical thickness (CT) and gray matter volume (GMV) in the fronto-striatal-temporal regions which have been associated with irritability. However, the directions of the correlations between structural alteration and irritability in the individual indices were not consistent. Thus, we aim to address this by implementing comprehensive assessments of CT, GMV, and local gyrification index (LGI) simultaneously in youths with severe levels of irritability by voxel-based morphometry and surface-based morphometry. One hundred and eight adolescents (46 youths with severe irritability and 62 healthy youths, average age = 14.08 years, standard deviation = 2.36) were scanned with a T1-weighted MRI sequence. The severity of irritability was measured using the affective reactivity index. In youths with severe irritability, there was decreased CT, GMV, and LGI in the right superior frontal gyrus (SFG) compared to healthy youths, and negative correlations between these indices of the SFG and irritability. Our findings suggest that structural deficits in the SFG, potentially related to its role in inhibitory control, may be critical for the neurobiology of irritability.

Altered Effective Connectivity within the Fronto-Limbic Circuitry in Response to Negative Emotional Task in Female Patients with Major Depressive Disorder.

Background: Major depressive disorder (MDD) is a mood disorder associated with disruptions in emotional control. Previous studies have investigated abnormal regional activity and connectivity within the fronto-limbic circuit. However, condition-specific connectivity changes and their association with the pathophysiology of MDD remain unexplored. This study investigated effective connectivity in the fronto-limbic circuit induced by negative emotional processing from patients with MDD. Methods: Thirty-four unmedicated female patients with MDD and 28 healthy participants underwent event-related functional magnetic resonance imaging at 7T while viewing emotionally negative and neutral images. Brain regions whose dynamics are driven by experimental conditions were identified by using statistical parametric mapping. Effective connectivity among regions of interest was then estimated by using dynamic causal modeling. Results: Patients with MDD had lower activation of the orbitofrontal cortex (OFC) and higher activation of the parahippocampal gyrus (PHG) than healthy controls (HC). In association with these regional changes, we found that patients with MDD did not have significant modulatory connections from the primary visual cortex (V1) to OFC, whereas those connections of HC were significantly positively modulated during negative emotional processing. Regarding the PHG activity, patients with MDD had greater modulatory connection from the V1, but reduced negative modulatory connection from the OFC, compared with healthy participants. Conclusions: These results imply that disrupted effective connectivity among regions of the OFC, PHG, and V1 may be closely associated with the impaired regulation of negative emotional processing in the female patients with MDD.

Correction to: Functional dissociation of hippocampal subregions corresponding to memory types and stages.

An amendment to this paper has been published and can be accessed via the original article.

Functional dissociation of hippocampal subregions corresponding to memory types and stages.

BACKGROUND: The hippocampus reportedly plays a crucial role in memory. However, examining individual human hippocampal-subfield function remains challenging because of their small sizes and convoluted structures. Here, we identified hippocampal subregions involved in memory types (implicit and explicit memory) and stages (encoding and retrieval). METHODS: We modified the serial reaction time task to examine four memory types, i.e. implicit encoding, explicit encoding, implicit retrieval, and explicit retrieval. During this task, 7-T functional magnetic resonance imaging was used to compare brain activity evoked by these memory types. RESULTS: We found hippocampal activation according to all memory types and stages and identified that the hippocampus subserves both implicit and explicit memory processing. Moreover, we confirmed that cornu ammonis (CA) regions 1-3 were implicated in both memory encoding and retrieval, whereas the subiculum was implicated only in memory retrieval. We also found that CA 1-3 was activated more for explicit than implicit memory. CONCLUSIONS: These results elucidate human hippocampal-subfield functioning underlying memory and may support future investigations into hippocampal-subfield functioning in health and neurodegenerative disease.

Gray Matter Deficits and Dysfunction in the Insula Among Individuals With Intermittent Explosive Disorder.

Although numerous neuroimaging studies have evaluated the characteristics of intermittent explosive disorder (IED), studies on the structural alterations and focal dysfunction in the brain in this condition are limited. This study aimed to identify gray matter deficits and functional alterations in individuals with IED using voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) analyses. Fifteen men with IED and 15 age- and sex-matched healthy controls participated in this study. Gray matter volume and brain activation while viewing the anger-inducing films were measured using 7T MRI. VBM results indicated that individuals with IED had significantly reduced gray matter volume in the insula, amygdala, and orbitofrontal area, relative to controls. Gray matter volume in the left insula was negatively correlated with composite aggression scores. fMRI results demonstrated that relative to healthy controls, individuals with IED showed greater activation in the insula, putamen, anterior cingulate cortex, and amygdala during anger processing. Left insular activity was positively correlated with composite aggression scores. Collectively, these findings suggest that structural and functional alterations in the left insula are linked to IED; this provides insight into the neural mechanisms underlying IED.

Response inhibition during processing of sexual stimuli in males with problematic hypersexual behavior.

BACKGROUND AND AIMS: Individuals with problematic hypersexual behavior (PHB) are unable to control their sexual cravings, regardless of other situational factors. This inability to control cravings is a common trait in patients with neurological pathologies related to response inhibition. Until recently, however, it was unclear whether individuals with PHB have decreased inhibition and altered neural responses in the brain regions associated with inhibition compared to healthy control individuals, especially in the presence of distracting sexual stimuli. In this study, we examined the neural and psychological underpinnings of inhibition in individuals with PHB. METHODS: Thirty individuals with PHB and 30 healthy subjects underwent functional magnetic resonance imaging while performing a modified go/no-go task with neutral or sexual backgrounds used as distractors. RESULTS: Individuals with PHB showed poorer response inhibition than healthy subjects, especially when sexual distractors were present. Further, compared to healthy control subjects, individuals with PHB showed decreased activation in the right inferior frontal gyrus (IFG) and reduced functional connectivity between the IFG and the pre-supplementary motor area (preSMA) when response inhibition was required. Finally, the reduced activation and connectivity were more pronounced in the presence of sexual distractors than in the presence of neutral distractors. DISCUSSION: These findings suggest that individuals with PHB show reduced ability to inhibit responses that might be related to lower IFG activation and IFG-preSMA connectivity during response inhibition. Our results provide insights into the neurobiological underpinnings of poor response inhibition in individuals with PHB.

Dynamic Causal Modeling of Effective Connectivity During Anger Experience in Healthy Young Men: 7T Magnetic Resonance Imaging Study.

Little is known about how anger-associated brain regions integrate and modulate external input. Therefore, we investigated the neural connectivity architecture of anger processing using a dynamic causal modeling (DCM) approach. Thirteen subjects underwent functional magnetic resonance imaging (fMRI) while viewing anger-inducing film clips. Conventional fMRI and DCM analyses were conducted to identify a dominant connectivity model. Viewing anger-inducing film clips led to activation in the left superior temporal gyrus, left insula, and left orbitofrontal cortex (OFC). The results of a group-level comparison of eight connectivity models based on conventional fMRI findings showed superiority of the model including reciprocal effective connectivities between the left insula, left superior temporal gyrus, and left orbitofrontal gyrus and bottom-up connectivity from the left superior temporal gyrus to the left orbitofrontal gyrus. Positive coupling effects were identified for connectivities between the left superior temporal gyrus and left insula and the left superior temporal gyrus and left OFC. A negative coupling effect was identified for connectivity between the left OFC and left insula. In conclusion, we propose a model of effective connectivity associated with the anger experience based on dynamic causal modeling. The findings have implications for various psychiatric disorders related to abnormalities in anger processing.

Altered Prefrontal and Inferior Parietal Activity During a Stroop Task in Individuals With Problematic Hypersexual Behavior.

Accumulating evidence suggests a relationship between problematic hypersexual behavior (PHB) and diminished executive control. Clinical studies have demonstrated that individuals with PHB exhibit high levels of impulsivity; however, relatively little is known regarding the neural mechanisms underlying impaired executive control in PHB. This study investigated the neural correlates of executive control in individuals with PHB and healthy controls using event-related functional magnetic resonance imaging (fMRI). Twenty-three individuals with PHB and 22 healthy control participants underwent fMRI while performing a Stroop task. Response time and error rates were measured as surrogate indicators of executive control. Individuals with PHB exhibited impaired task performance and lower activation in the right dorsolateral prefrontal cortex (DLPFC) and inferior parietal cortex relative to healthy controls during the Stroop task. In addition, blood oxygen level-dependent responses in these areas were negatively associated with PHB severity. The right DLPFC and inferior parietal cortex are associated with higher-order cognitive control and visual attention, respectively. Our findings suggest that individuals with PHB have diminished executive control and impaired functionality in the right DLPFC and inferior parietal cortex, providing a neural basis for PHB.

Altered Gray Matter Volume and Resting-State Connectivity in Individuals With Internet Gaming Disorder: A Voxel-Based Morphometry and Resting-State Functional Magnetic Resonance Imaging Study.

Neuroimaging studies on the characteristics of individuals with Internet gaming disorder (IGD) have been accumulating due to growing concerns regarding the psychological and social problems associated with Internet use. However, relatively little is known about the brain characteristics underlying IGD, such as the associated functional connectivity and structure. The aim of this study was to investigate alterations in gray matter (GM) volume and functional connectivity during resting state in individuals with IGD using voxel-based morphometry and a resting-state connectivity analysis. The participants included 20 individuals with IGD and 20 age- and sex-matched healthy controls. Resting-state functional and structural images were acquired for all participants using 3 T magnetic resonance imaging. We also measured the severity of IGD and impulsivity using psychological scales. The results show that IGD severity was positively correlated with GM volume in the left caudate (p < 0.05, corrected for multiple comparisons), and negatively associated with functional connectivity between the left caudate and the right middle frontal gyrus (p < 0.05, corrected for multiple comparisons). This study demonstrates that IGD is associated with neuroanatomical changes in the right middle frontal cortex and the left caudate. These are important brain regions for reward and cognitive control processes, and structural and functional abnormalities in these regions have been reported for other addictions, such as substance abuse and pathological gambling. The findings suggest that structural deficits and resting-state functional impairments in the frontostriatal network may be associated with IGD and provide new insights into the underlying neural mechanisms of IGD.

Gray matter deficits and altered resting-state connectivity in the superior temporal gyrus among individuals with problematic hypersexual behavior.

Neuroimaging studies on the characteristics of hypersexual disorder have been accumulating, yet alternations in brain structures and functional connectivity in individuals with problematic hypersexual behavior (PHB) has only recently been studied. This study aimed to investigate gray matter deficits and resting-state abnormalities in individuals with PHB using voxel-based morphometry and resting-state connectivity analysis. Seventeen individuals with PHB and 19 age-matched healthy controls participated in this study. Gray matter volume of the brain and resting-state connectivity were measured using 3T magnetic resonance imaging. Compared to healthy subjects, individuals with PHB had significant reductions in gray matter volume in the left superior temporal gyrus (STG) and right middle temporal gyrus. Individuals with PHB also exhibited a decrease in resting-state functional connectivity between the left STG and left precuneus and between the left STG and right caudate. The gray matter volume of the left STG and its resting-state functional connectivity with the right caudate both showed significant negative correlations with the severity of PHB. The findings suggest that structural deficits and resting-state functional impairments in the left STG might be linked to PHB and provide new insights into the underlying neural mechanisms of PHB.

Neural substrates of sexual arousal in heterosexual males: event-related fMRI investigation.

BACKGROUND: Sexual behavior is an important role for the survival of species. The advancement of brain imaging methods has enabled the understanding of the brain mechanism related to sexual arousal. The previous studies on the brain mechanism related to sexual arousal have mostly conducted on block design paradigm. METHODS: Despite its requirement for stricter experimental control, the event-related paradigm is known to be more efficient in detecting instant emotional and cognitive responses. The paradigm also enables the observation of hemodynamic responses through time. Therefore, this study used the event-related fMRI to examine the brain activation in various areas associated with sexual arousal as well as changes in hemodynamic responses with time. RESULTS: Strong activations were observed in the various areas associated with sexual arousal comprised of various factors: (1) activation areas related to cognitive factors: the occipital lobe and parietal lobe; (2) activation areas related to emotional factors: the thalamus and amygdala; (3) activation areas related to motivational factors: the anterior cingulate gyrus, orbitofrontal cortex, and insula; and (4) activation areas related to physiological factors: the precentral gyrus, putamen, and globus pallidus. We also identified the activation of the putamen and globus pallidus that were not well observed in previous block design studies. In the result of the hemodynamic response, the neural activity in those areas showed more transient aspects of the hemodynamic responses relative to the neural activity of other areas. CONCLUSIONS: These results suggested that the event-related paradigm is better at detecting the neural activity of the brain regions, which tend to appear suddenly, but disappear soon.

Neural Substrates of Sexual Desire in Individuals with Problematic Hypersexual Behavior.

Studies on the characteristics of individuals with hypersexual disorder have been accumulating due to increasing concerns about problematic hypersexual behavior (PHB). Currently, relatively little is known about the underlying behavioral and neural mechanisms of sexual desire. Our study aimed to investigate the neural correlates of sexual desire with event-related functional magnetic resonance imaging (fMRI). Twenty-three individuals with PHB and 22 age-matched healthy controls were scanned while they passively viewed sexual and nonsexual stimuli. The subjects' levels of sexual desire were assessed in response to each sexual stimulus. Relative to controls, individuals with PHB experienced more frequent and enhanced sexual desire during exposure to sexual stimuli. Greater activation was observed in the caudate nucleus, inferior parietal lobe, dorsal anterior cingulate gyrus, thalamus, and dorsolateral prefrontal cortex in the PHB group than in the control group. In addition, the hemodynamic patterns in the activated areas differed between the groups. Consistent with the findings of brain imaging studies of substance and behavior addiction, individuals with the behavioral characteristics of PHB and enhanced desire exhibited altered activation in the prefrontal cortex and subcortical regions. In conclusion, our results will help to characterize the behaviors and associated neural mechanisms of individuals with PHB.

Neural substrates of risky decision making in individuals with Internet addiction.

OBJECTIVE: With the wide and rapid expansion of computers and smartphones, Internet use has become an essential part of life and an important tool that serves various purposes. Despite the advantages of Internet use, psychological and behavioral problems, including Internet addiction, have been reported. In response to growing concern, researchers have focused on the characteristics of Internet addicts. However, relatively little is known about the behavioral and neural mechanisms that underlie Internet addiction, especially with respect to risky decision making, which is an important domain frequently reported in other types of addictions. METHOD: To examine the neural characteristics of decision making in Internet addicts, Internet addicts and healthy controls were scanned while they performed a financial decision-making task. RESULTS: Relative to healthy controls, Internet addicts showed (1) more frequent risky decision making; (2) greater activation in the dorsal anterior cingulate cortex and the left caudate nucleus, which are brain regions involved in conflict monitoring and reward, respectively; and (3) less activation in the ventrolateral prefrontal cortex, an area associated with cognitive control/regulation. CONCLUSION: These findings suggest that risky decision making may be an important behavioral characteristic of Internet addiction and that altered brain function in regions associated with conflict monitoring, reward and cognitive control/regulation might be critical biological risk factors for Internet addiction.

Effect of emotional arousal on inter-temporal decision-making: an fMRI study.

BACKGROUND: Previous research has shown that emotion can significantly impact decision-making in humans. The current study examined whether or not and how situationally induced emotion influences people to make inter-temporal choices. METHODS: Affective pictures were used as experiment stimuli to provoke emotion, immediately followed by subjects' performance of a delay-discounting task to measure impulsivity during functional magnetic resonance imaging. RESULTS: Results demonstrate a subsequent process of increased impulsive decision-making following a prior exposure to both high positive and negative arousal stimuli, compared to the experiment subjects' experiences with neutral stimuli. Findings indicate that increased impulsive decision-making behaviors can occur with high arousal and can be characterized by decreased activities in the cognitive control regions such as prefronto-parietal regions. CONCLUSIONS: These results suggest that 'stabilization of high emotional arousal' may facilitate a reduction of impulsive decision-making and implementation of longer term goals.