scholarly journals Effect of Methylphenidate on Resting-State Connectivity in Adolescents With a Disruptive Behavior Disorder: A Double-Blind Randomized Placebo-Controlled fMRI Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Louise Pape ◽  
Koen van Lith ◽  
Dick Veltman ◽  
Moran Cohn ◽  
Reshmi Marhe ◽  
...  

Some studies suggest that methylphenidate (MPH) might be an effective treatment for antisocial and aggressive behavior in adolescence. However, little is known about the mechanism of action of MPH in adolescents with this kind of psychopathology. MPH is a dopamine and norepinephrine reuptake inhibitor and thus it is likely to affect dopaminergic mesocorticolimbic pathways. This is the first study to investigate the effect of MPH on resting-state connectivity of three mesolimbic seed regions with the rest of the brain in clinical referred male adolescents with a disruptive behavior disorder (DBD). Thirty-six male DBD adolescents and 31 male healthy controls (HCs) were included. DBD subjects were randomly allocated to a single dose of MPH (DBD-MPH, n = 20) or placebo (DBD-PCB, n = 16). Seed-based resting-state functional connectivity of the nucleus accumbens (NAcc), amygdala, and ventral tegmental area (VTA) with the rest of the brain was compared between groups. The NAcc seed showed increased connectivity in DBD-PCB compared to HC with the occipital cortex, posterior cingulate cortex (PCC), precuneus, and inferior parietal lobule (IPL) and increased connectivity in DBD-PCB compared to DBD-MPH with occipital cortex, IPL, and medial frontal gyrus. The amygdala seed showed increased connectivity in DBD-PCB compared to HC with the precuneus and PCC. The VTA seed showed increased connectivity in the DBD-MPH compared to the DBD-PCB group with a cluster in the postcentral gyrus and a cluster in the supplementary motor cortex/superior frontal gyrus. Both NAcc and amygdala seeds showed no connectivity differences in the DBD-MPH compared to the HC group, indicating that MPH normalizes the increased functional connectivity of mesolimbic seed regions with areas involved in moral decision making, visual processing, and attention.

2021 ◽  
Vol 15 ◽  
Author(s):  
Na Xu ◽  
Wei Shan ◽  
Jing Qi ◽  
Jianping Wu ◽  
Qun Wang

Epilepsy is caused by abnormal electrical discharges (clinically identified by electrophysiological recording) in a specific part of the brain [originating in only one part of the brain, namely, the epileptogenic zone (EZ)]. Epilepsy is now defined as an archetypical hyperexcited neural network disorder. It can be investigated through the network analysis of interictal discharges, ictal discharges, and resting-state functional connectivity. Currently, there is an increasing interest in embedding resting-state connectivity analysis into the preoperative evaluation of epilepsy. Among the various neuroimaging technologies employed to achieve brain functional networks, magnetoencephalography (MEG) with the excellent temporal resolution is an ideal tool for estimating the resting-state connectivity between brain regions, which can reveal network abnormalities in epilepsy. What value does MEG resting-state functional connectivity offer for epileptic presurgical evaluation? Regarding this topic, this paper introduced the origin of MEG and the workflow of constructing source–space functional connectivity based on MEG signals. Resting-state functional connectivity abnormalities correlate with epileptogenic networks, which are defined by the brain regions involved in the production and propagation of epileptic activities. This paper reviewed the evidence of altered epileptic connectivity based on low- or high-frequency oscillations (HFOs) and the evidence of the advantage of using simultaneous MEG and intracranial electroencephalography (iEEG) recordings. More importantly, this review highlighted that MEG-based resting-state functional connectivity has the potential to predict postsurgical outcomes. In conclusion, resting-state MEG functional connectivity has made a substantial progress toward serving as a candidate biomarker included in epileptic presurgical evaluations.


2016 ◽  
Author(s):  
Jiahui Wang ◽  
Yudan Ren ◽  
Xintao Hu ◽  
Vinh Thai Nguyen ◽  
Lei Guo ◽  
...  

AbstractFunctional connectivity analysis has become a powerful tool for probing the human brain function and its breakdown in neuropsychiatry disorders. So far, most studies adopted resting state paradigm to examine functional connectivity networks in the brain, thanks to its low demand and high tolerance that are essential for clinical studies. However, the test-retest reliability of resting state connectivity measures is moderate, potentially due to its low behavioral constraint. On the other hand, naturalistic neuroimaging paradigms, an emerging approach for cognitive neuroscience with high ecological validity, could potentially improve the reliability of functional connectivity measures. To test this hypothesis, we characterized the test-retest reliability of functional connectivity measures during a natural viewing condition, and benchmarked it against resting state connectivity measures acquired within the same functional magnetic resonance imaging (fMRI) session. We found that the reliability of connectivity and graph theoretical measures of brain networks is significantly improved during natural viewing conditions over resting state conditions, with an average increase of almost 50% across various connectivity measures. Not only sensory networks for audio-visual processing become more reliable, higher order brain networks, such as default mode and attention networks, also appear to show higher reliability during natural viewing. Our results support the use of natural viewing paradigms in estimating functional connectivity of brain networks, and have important implications for clinical application of fMRI.


2020 ◽  
Author(s):  
Matthew B. Wall ◽  
Tom P. Freeman ◽  
Chandni Hindocha ◽  
Lysia Demetriou ◽  
Natalie Ertl ◽  
...  

AbstractCannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are two major constituents of cannabis with contrasting mechanisms of action. THC is the major psychoactive, addiction-promoting, and psychotomimetic compound, while CBD may have somewhat opposite effects. The brain effects of these drugs alone and in combination are poorly understood. In particular the striatum is implicated in the pathophysiology of several psychiatric disorders, but it is unclear how THC and CBD influence striato-cortical connectivity. Across two placebo-controlled, double-blind studies, we examine the effects of THC, CBD, and THC+CBD on the functional connectivity of striatal sub-divisions (associative, limbic, and sensorimotor) using resting-state functional Magnetic Resonance Imaging (fMRI) and seed-based functional connectivity analyses. Study 1 (N=17; inhaled 8mg THC, 8mg THC+10mg CBD, placebo) showed strong disruptive effects of both THC and THC+CBD conditions on connectivity in the associative and sensorimotor networks, but a specific effect of THC in the limbic striatum, which was alleviated in the THC+CBD condition such that it did not differ from placebo. In Study 2 (N=23, oral 600mg CBD, placebo) CBD increased connectivity in the associative network, but relatively minor decreases/disruptions were found in the limbic and sensorimotor. In conclusion, THC strongly disrupts striato-cortical networks, and this effect is selectively mitigated in the limbic striatum when co-administered with CBD. When administered alone, 600mg oral CBD has a more complex effect profile of relative increases and decreases in connectivity. The insula emerges as a key region affected by cannabinoid-induced changes in functional connectivity, with potential implications for understanding cannabis related disorders, and the development of cannabinoid therapeutics.


2017 ◽  
Vol 41 (S1) ◽  
pp. S99-S99
Author(s):  
J. Rössler ◽  
L. Unterrassner ◽  
T. Wyss ◽  
H. Haker ◽  
P. Brugger ◽  
...  

IntroductionAccording to the dopamine hypothesis functional brain abnormalities and neurochemical alterations may converge to cause psychosis through aberrant salience attribution. Indeed, resting-state functional magnetic resonance imaging (rs-fMRI) has revealed widespread brain disconnectivity across the psychotic spectrum.ObjectivesTo advance the understanding of the dopaminergic involvement in intrinsic functional connectivity (iFC) and its putative relationship to the development of psychotic disorders we aimed to investigate the link between L-Dopa, a dopamine precursor, and its modulation of striatal iFC in subthreshold psychosis, i.e. non-clinical psychosis.MethodsWe used a randomized, double-blind placebo controlled study design including in our sample 56 healthy, male, right-handed, subjects with no familiar risk factors for psychosis who were assessed with the Schizotypal Personality Questionnaire (SPQ) and underwent 10 minutes of rs-fMRI scanning. All subjects received either 250 mg of Madopar DR®(200 mg L-Dopa plus 50 mg benserazid, dual release form) or a placebo. We analysed resting-state iFC of 6 striatal seeds, known to evoke dopamine related networks.ResultsThe main effect of L-Dopa presented itself (FWE-corrected) as a significant decrease in iFC from the right ventral striatum to the cerebellum and the precuneus cortex, and an increase in iFC to the occipital cortex. Subjects with high SPQ positive symptom sub-scores showed a significant increase of L-Dopa induced connectivity.ConclusionWe identified striatal functional connectivity being modulated by augmented dopamine availability, and in support of the dopamine hypothesis, we found that those iFC patterns are associated to high scores of psychotic like experiences.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2019 ◽  
Vol 9 (1) ◽  
pp. 11 ◽  
Author(s):  
Ángel Romero-Martínez ◽  
Macarena González ◽  
Marisol Lila ◽  
Enrique Gracia ◽  
Luis Martí-Bonmatí ◽  
...  

Introduction: There is growing scientific interest in understanding the biological mechanisms affecting and/or underlying violent behaviors in order to develop effective treatment and prevention programs. In recent years, neuroscientific research has tried to demonstrate whether the intrinsic activity within the brain at rest in the absence of any external stimulation (resting-state functional connectivity; RSFC) could be employed as a reliable marker for several cognitive abilities and personality traits that are important in behavior regulation, particularly, proneness to violence. Aims: This review aims to highlight the association between the RSFC among specific brain structures and the predisposition to experiencing anger and/or responding to stressful and distressing situations with anger in several populations. Methods: The scientific literature was reviewed following the PRISMA quality criteria for reviews, using the following digital databases: PubMed, PsycINFO, Psicodoc, and Dialnet. Results: The identification of 181 abstracts and retrieval of 34 full texts led to the inclusion of 17 papers. The results described in our study offer a better understanding of the brain networks that might explain the tendency to experience anger. The majority of the studies highlighted that diminished RSFC between the prefrontal cortex and the amygdala might make people prone to reactive violence, but that it is also necessary to contemplate additional cortical (i.e. insula, gyrus [angular, supramarginal, temporal, fusiform, superior, and middle frontal], anterior and posterior cingulated cortex) and subcortical brain structures (i.e. hippocampus, cerebellum, ventral striatum, and nucleus centralis superior) in order to explain a phenomenon as complex as violence. Moreover, we also described the neural pathways that might underlie proactive violence and feelings of revenge, highlighting the RSFC between the OFC, ventral striatal, angular gyrus, mid-occipital cortex, and cerebellum. Conclusions. The results from this synthesis and critical analysis of RSFC findings in several populations offer guidelines for future research and for developing a more accurate model of proneness to violence, in order to create effective treatment and prevention programs.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi224-vi225
Author(s):  
Katharina Rosengarth ◽  
Katharina Hense ◽  
Tina Plank ◽  
Mark Greenlee ◽  
Christina Wendl ◽  
...  

Abstract OBJECTIVE Space-occupying brain lesions as brain tumors in the occipital lobe have only been sparsely investigated so far, as this localization is extremely rare with only 1% of cases. It is still unclear how this affects the overall organization of the visual system. We investigated functional connectivity of functional networks associated with higher visual processing between patients with occipital space-occupying lesion in the occipital cortex and healthy controls. METHODS 12 patients with brain tumors, 7 patients with vascular lesions in the occipital cortex and 19 healthy subjects matched for age and sex were included. During functional MRI patients and subjects performed a visual excentricity mapping task. Data analysis was done using CONN toolbox based on Matlab. See-to-ROI connectivities of 23 Regions of Interest (ROIs) implemented in the CONN toolbox which were assigned to the Default Mode, Visual, Salience, Dorsal Attention, and Frontoparietal network were assessed. For each subject, connectivity was calculated using Fischer transformed pairwise correlations. These correlations were first considered separately for each group in one-sample analyses and then compared between the groups. RESULTS Main results show, that compared to control subjects and vascular patients, tumor patients showed weaker intra-network connectivity of components of all networks except the default-network. Tumor patients showed even stronger between-network connectivity in the default-mode network compared to the other groups. Weaker connectivity was observed within the salience network in both patient groups compared to controls. CONCLUSION The results indicate that in the course of the disease, compensatory countermeasures take place in the brain against a brain tumor or a space-occupying brain lesion with the aim of maintaining the performance level and cognitive processes for as long as possible. However, more research is needed in this area to understand the mechanisms and effects of brain tumors and space-consuming brain lesions on surrounding tissue.


Cephalalgia ◽  
2021 ◽  
pp. 033310242110466
Author(s):  
Roberta Messina ◽  
Maria A Rocca ◽  
Paola Valsasina ◽  
Paolo Misci ◽  
Massimo Filippi

Objective To elucidate the hypothalamic involvement in episodic migraine and investigate the association between hypothalamic resting state functional connectivity changes and migraine patients’ clinical characteristics and disease progression over the years. Methods Ninety-one patients with episodic migraine and 73 controls underwent interictal resting state functional magnetic resonance imaging. Twenty-three patients and controls were re-examined after a median of 4.5 years. Hypothalamic resting state functional connectivity changes were investigated using a seed-based correlation approach. Results At baseline, a decreased functional interaction between the hypothalamus and the parahippocampus, cerebellum, temporal, lingual and orbitofrontal gyrus was found in migraine patients versus controls. Increased resting state functional connectivity between the hypothalamus and bilateral orbitofrontal gyrus was demonstrated in migraine patients at follow-up versus baseline. Migraine patients also experienced decreased right hypothalamic resting state functional connectivity with ipsilateral lingual gyrus. A higher migraine attack frequency was associated with decreased hypothalamic-lingual gyrus resting state functional connectivity at baseline, while greater headache impact at follow-up correlated with decreased hypothalamic-orbitofrontal gyrus resting state functional connectivity at baseline. At follow-up, a lower frequency of migraine attacks was associated with higher hypothalamic-orbitofrontal gyrus resting state functional connectivity. Conclusions During the interictal phase, the hypothalamus modulates the activity of pain and visual processing areas in episodic migraine patients. The hypothalamic-cortical interplay changes dynamically over time according to patients’ clinical features.


2020 ◽  
pp. 1-21
Author(s):  
Alexandra Anagnostopoulou ◽  
Charis Styliadis ◽  
Panagiotis Kartsidis ◽  
Evangelia Romanopoulou ◽  
Vasiliki Zilidou ◽  
...  

Understanding the neuroplastic capacity of people with Down syndrome (PwDS) can potentially reveal the causal relationship between aberrant brain organization and phenotypic characteristics. We used resting-state EEG recordings to identify how a neuroplasticity-triggering training protocol relates to changes in the functional connectivity of the brain’s intrinsic cortical networks. Brain activity of 12 PwDS before and after a 10-week protocol of combined physical and cognitive training was statistically compared to quantify changes in directed functional connectivity in conjunction with psychosomatometric assessments. PwDS showed increased connectivity within the left hemisphere and from left-to-right hemisphere, as well as increased physical and cognitive performance. Our findings reveal a strong adaptive neuroplastic reorganization as a result of the training that leads to a less-random network with a more pronounced hierarchical organization. Our results go beyond previous findings by indicating a transition to a healthier, more efficient, and flexible network architecture, with improved integration and segregation abilities in the brain of PwDS. Resting-state electrophysiological brain activity is used here for the first time to display meaningful relationships to underlying Down syndrome processes and outcomes of importance in a translational inquiry. This trial is registered with ClinicalTrials.gov Identifier NCT04390321.


2019 ◽  
Author(s):  
Milou Straathof ◽  
Michel R.T. Sinke ◽  
Theresia J.M. Roelofs ◽  
Erwin L.A. Blezer ◽  
R. Angela Sarabdjitsingh ◽  
...  

AbstractAn improved understanding of the structure-function relationship in the brain is necessary to know to what degree structural connectivity underpins abnormal functional connectivity seen in many disorders. We integrated high-field resting-state fMRI-based functional connectivity with high-resolution macro-scale diffusion-based and meso-scale neuronal tracer-based structural connectivity, to obtain an accurate depiction of the structure-function relationship in the rat brain. Our main goal was to identify to what extent structural and functional connectivity strengths are correlated, macro- and meso-scopically, across the cortex. Correlation analyses revealed a positive correspondence between functional connectivity and macro-scale diffusion-based structural connectivity, but no correspondence between functional connectivity and meso-scale neuronal tracer-based structural connectivity. Locally, strong functional connectivity was found in two well-known resting-state networks: the sensorimotor and default mode network. Strong functional connectivity within these networks coincided with strong short-range intrahemispheric structural connectivity, but with weak heterotopic interhemispheric and long-range intrahemispheric structural connectivity. Our study indicates the importance of combining measures of connectivity at distinct hierarchical levels to accurately determine connectivity across networks in the healthy and diseased brain. Distinct structure-function relationships across the brain can explain the organization of networks and may underlie variations in the impact of structural damage on functional networks and behavior.


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