Mechanisms of cognitive-behavioral therapy for obsessive-compulsive disorder involve robust and extensive increases in brain network connectivity.

Cognitive-behavioral therapy (CBT) is effective for obsessive compulsive disorder (OCD); however, little is understood about its mechanisms related to brain network connectivity. We examined connectivity changes from resting-state functional magnetic resonance imaging data pre-to-post-CBT in 43 OCD participants, randomized to receive either 4 weeks of intensive CBT or 4 weeks waitlist followed by 4 weeks of CBT, and 24 healthy controls before and after 4 weeks of no treatment. Network-based-statistic analysis revealed large-magnitude increases in OCD connectivity in eight networks. Strongest increases involved connectivity between the cerebellum and caudate/putamen, and between the cerebellum and dorsolateral/ventrolateral prefrontal cortices. Connectivity increases were associated with increased resistance to compulsions. Mechanisms of CBT may involve enhanced cross-network integration, both within and outside of classical cortico-striatal-thalamo-cortical regions; those involving cerebellar to striatal and prefrontal regions may reflect acquisition of new non-compulsive goal-directed behaviors and thought patterns. Our findings have implications for identifying targets for enhancing treatment efficacy and monitoring treatment progress

Characterization of brain blood flow and the amplitude of low-frequency fluctuations in major depressive disorder: A multimodal meta-analysis.

Background In healthy subjects, there is an association between amplitude of low-frequency fluctuations (ALFF) and regional cerebral blood flow (rCBF). To date, no published meta-analysis has investigated changes in the regional ALFF in medication-free depressed patients. Methods In this study, we aimed to explore whether resting-state rCBF and ALFF changes co-occur in the depressed brain without the potential confound of medication. Using signed differential mapping (SDM), we conducted two meta-analyses, one of rCBF studies and one of ALFF studies, involving medication-free patients with major depressive disorder (MDD). In addition, we conducted a multimodal meta-analysis to identify brain regions that showed abnormalities in both rCBF and ALFF. Results A total of 16 studies were included in this series. We identified abnormalities in resting-state rCBF and ALFF in the left insula in medication-free MDD patients compared with healthy controls (HC). In addition, we observed altered resting-state rCBF in the limbic-subcortical-cortical circuit and altered ALFF in the default mode network (DMN) and some motor-related brain regions. Limitations The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous. Conclusions The conjoint alterations in ALFF and rCBF in the left insula may represent core neuropathological changes in medication-free patients with MDD and merit further studying

Conjoint and dissociated structural and functional abnormalities in first-episode drug-naive patients with major depressive disorder: a multimodal meta-analysis

Published MRI evidence of structural and resting-state functional brain abnormalities in MDD has been inconsistent. To eliminate interference by repeated disease episodes and antidepressant treatment, we conducted the first multimodal voxel-wise meta-analysis of studies of voxel-based morphometry (VBM) and the amplitude of low-frequency fluctuation (ALFF) in first-episode drug-naive MDD patients, using the Seed-based d Mapping method (SDM). Fifteen VBM data sets and 11 ALFF data sets were included. SDM-based multimodal meta-analysis was used to highlight brain regions with both structural and functional abnormalities. This identified conjoint structural and functional abnormalities in left lateral orbitofrontal cortex and right supplementary motor area, and also dissociated abnormalities of structure (decreased grey matter in right dorsolateral prefrontal cortex and right inferior temporal gyrus; increased grey matter in right insula, right putamen, left temporal pole, and bilateral thalamus) and function (increased brain activity in left supplementary motor area, left parahippocampal gyrus, and hippocampus; decreased brain activity in right lateral orbitofrontal cortex). This study reveals a complex pattern of conjoint and dissociated structural and functional abnormalities, supporting the involvement of basal ganglia-thalamocortical circuits, representing emotional, cognitive and psychomotor abnormalities, in the pathophysiology of early-stage MDD. Specifically, this study adds to Psychoradiology, an emerging subspecialty of radiology, which seems primed to play a major clinical role in guiding diagnostic and treatment planning decisions in patients with mental disorder

Aberrant neural activity in patients with bipolar depressive disorder distinguishing to the unipolar depressive disorder: a resting-state functional magnetic resonance imaging study

This study aims to explore the intrinsic patterns of spontaneous activity of bipolar depression (BD) patients by analyzing the fractional amplitude of low frequency fluctuation (fALFF) that help differentiate BD from unipolar depressive disorder(UD). Twenty eight patients with BD, 47 patients with UD and 29 healthy controls were enrolled to receive the resting-state functional magnetic resonance imaging (rs-fMRI) scans. The group differences of fALFF values were calculated among three groups. In addition, the correlations between the clinical variables and mfALFF values were estimated. The brain regions with activation discrepancies among three groups are located in precuneus, the left middle temporal gyrus (MTG) and left inferior parietal lobe (IPL) and lingual gyrus. Compared with HC group, BD group shows decreased fALFF in precuneus, the left IPL and increased fALFF in lingual gyrus remarkably; UD group shows significantly decreased fALFF in precuneus, the left MTG and the left IPL. On the contrast of patients with UD, patients with BD have significantly increased fALFF value in the left precuneus, the left MGT and lingual gyrus. Furthermore, a negative correlation is found between the mfALFF values in precuneus and the scores of cognitive impairment factor in the UD group. The similar pattern of intrinsic activity in PCC suggests depressive state-dependent change. The aberrant patterns of intrinsic activity in precuneus, the IPL and lingual gyrus might be provide quantitative nodes that help to conduct further study for better distinguishing between BD and UD

SEROTONIN 1B/1A RECEPTOR MODULATION ON BEHAVIORAL FLEXIBILITY IN C57BL/6J MICE

Pharmacological activation of the 5-HT1B and 1A receptors has been implicated in OCD-like behaviors in rodents such as increased perseverative circling, checking behaviors, and locomotor stereotypy. However, little is understood about the effects of 5-HT1B and 1A receptor activation on behavioral inflexibility, a common symptom associated with OCD. The present study utilized the 5-HT1B/1A receptor agonist RU24969 at 0.01, 0.1, and 1.0 mg/kg to test three hypotheses. The first hypothesis predicted RU24969 would lead to a dose-dependent impairment on behavioral flexibility in C57BL/6J mice. It was also predicted that male C57BL/6J mice would be more inflexible than female C57BL/6J mice following RU24969 administration. The second hypothesis stated that RU24969 would have a dose-dependent increase in locomotor activity. Finally, it was hypothesized that RU24969 would increase anxiety-like behaviors in C57BL/6J mice. Results concluded that male mice had impaired behavioral flexibility at all doses of RU24969 while female mice were only impaired at the 1.0 mg/kg dose. For locomotor activity, male mice exhibited reduced distance traveled at the 1.0 mg/kg dose while RU24969 had no significant effect on female locomotion scores. Finally, male mice exhibited greater anxiety-like behaviors at 0.1 and 1.0 mg/kg while female mice were not significantly affected. Overall, the evidence suggests that 5-HT1B and 1A receptor activation could play a role in the manifestation of learning impairments associated with core OCD symptoms

Functional neural correlates of first-episode psychoses during sensory, cognitive, language, and emotional processing

Background. Numerosi studi hanno evidenziato che i pazienti affetti da esordi sindromici dello spettro schizofrenico presentano alterazioni neurofunzionali durante l’esecuzione di compiti che coinvolgono le funzioni sensoriali, cognitive, linguistiche ed emotive. Obiettivo. Paragonare pazienti con esordio psicotico a individui sani al fine di studiare il network neurale coinvolto nelle risposte a compiti sensoriali, cognitive, linguistiche ed emotive, identificando le similarità e le differenze nelle attivazioni cerebrali correlate all’esecuzione degli stessi compiti. Metodo. Abbiamo eseguito una meta-analisi ALE utilizzando il database costruito su ventisei studi di risonanza magnetica funzionale condotti su 516 pazienti con esordio e 546 soggetti sani durante l’esecuzione di task sensoriali, cognitivi, linguistici ed emotivi. Risultati. Le analisi within-group hanno dimostrato che i controlli sani manifestavano in risposta a tutti i task attivazioni significative in un circuito bilaterale fronto-parietale, mentre i pazienti in un circuito bilaterale parietale-precentrale. Le analisi between-groups hanno evidenziato iperattivazioni del lobulo parietale inferiore di destra, del giro medio frontale sinistro e della corteccia temporale destra nei sani e del cingolo di destra nei pazienti. L’analisi condotta separatamente per gruppi di compiti ha evidenziato che la performance di task attentivo-mnestici si correlava ad attivazione di aree prefrontali nei sani e parietali bilaterali negli esordi; l’esecuzione di task emotivi si correlava ad attivazione della corteccia dorsolaterale prefrontale (DLPFC) bilaterale, della corteccia parietale destra, del cingolo di sinistra e dell’amigdala di destra nei sani e del giro fusiforme di destra nei pazienti; solo i sani hanno evidenziato attivazioni in aree corticali di sinistra incentrate sull’insula, la DLPFC e la corteccia temporale in correlazione a compiti linguistici. Conclusioni. Il risultato principale di questa meta-analisi è l’evidenza di deficit funzionale della DLPFC di sinistra in pazienti con esordio psicotico durante l’esecuzione di task sensoriali, cognitivi, linguistici ed emotivi. Il giro del cingolo di destra, le cortecce parietali e la temporale di destra hanno anch’esse un ruolo importante nella neurofisiopatologia degli esordi. Questo studio ha anche evidenziato che i pazienti attivano circuiti cerebrali diversi rispetto ai sani in risposta a compiti attentivo-mnestici (attivazione predominante in aree parietali bilaterali), emotivi (attivazione predominante nel giro fusiforme destro) e linguistici (mancata attivazione di aree corticali di sinistra).Background: Several studies reported neural functional alterations in patients with schizophrenia spectrum first-episode psychosis (FEP) during performance of tasks that involve sensory, attentional memory, language, and emotional (SAMLE) processing. Aim: To compare meta-analytically FEP and healthy control (CTR) samples regarding the circuitries engaged in responding to a set of SAMLE tasks and identifying commonalities and differences in task-related brain activations. Method: We performed an activation likelihood estimation (ALE) meta-analysis using a database built on 26 fMRI studies, conducted on 516 FEP patients and 546 CTRs during SAMLE task performance. Results: Within-Group analyses showed that the CTR group has significant SAMLE task-related cortical activations in the context of a bilateral fronto-parietal network; FEP patients showed taskrelated activations of a bilateral parietal-precentral network. Between-Groups analyses showed hyperactivation of the right inferior parietal lobule, left middle frontal gyrus, and right temporal cortex in CTRs, and hyperactivation of the right cingulate gyrus in FEP. Segregated analyses of tasks showed that brain activations to attentional and memory-related tasks mainly occurred in prefrontal areas in CTRs, and in bilateral parietal areas in FEP; emotional task-related activations concerned the bilateral dorsolateral prefrontal cortex (DLPFC), right parietal cortex, left cingulate cortex and right amygdala in CTRs, whereas in FEP the activation concerned the right fusiform gyrus; we found significant left-sided language task-related activations only in the CTR group, centred on the insula, DLPFC, and temporal cortex. Conclusions: The major finding of this study is the evidence of a functional deficit of the left DLPFC in FEP during the SAMLE task performance. A prominent role in the neuropathophysiology of FEP appears also to be played by the right dorsal anterior cingulate, bilateral parietal, and right temporal cortices. This study also underlined that FEP patients activate different circuits than CTRs in response to attentional- and memory-tasks (predominant activation of bilateral parietal areas), emotional (predominant activation of the right fusiform gyrus), and language (lack of activation of left-sided cortical areas) tasks

Vliv memantinu a riluzolu na učení ve zvířecím modelu obsedantně-kompulzivní poruchy vyvolaném sensitizací pomocí 8-OH-DPAT

Obsedantně-kompulzivní porucha je chronické psychiatrické onemocnění. Vážně omezuje a mění kvalitu života. Léčba OCD je v této době založena na kombinaci antidepresiv a psychoterapie, presto spoustu pacientů zůstává bez úspěšné léčby, či s přetrvávajícími symptomy. Zvířecí modely založené na genetické, behaviorální, farmakologické a optogenetické manipulaci jsou úspěšným zdrojem pro výzkum tohoto onemocnění i jeho léčby. Chronická senzitizace serotoninových 1A a 7 - receptorů jejich agonistou 8-OH-DPAT ((8- hydroxy-2-(di-npropylamino)-tetralin hydrobromid) indukuje repetitivní a kompulzivní chování, považované za zvířecí analog symptomů OCD. V této práci byl zjišťován jeho vliv na učení a paměť v kolotočovém bludišti během úkolu aktivního vyhýbání se místu. Dalším cílem této práce bylo zjistit, zda společné podávání memantinu nebo riluzolu s 8-OH-DPAT zmírňuje kognitivní účinky a deficity v učení tohoto modelu. Měřená kritéria byla; celková vzdálenost, počet vstupů do zakázaného sektoru, maximální počet šoků a průměrná rychlost po šoku. Během habituační fáze byla zvířata sensitizována 8-OH-DPAT (s kontrolní skupinou, která dostávala pouze fyziologický roztok). Při akvizici byly zvířatům podávány dvě injekce, jedna s memantinem nebo riluzolem nebo fyziologickým roztokem a druhá s 8-OH-DPAT nebo...Obsessive-compulsive disorder is a chronic psychiatric disease. It seriously limits the quality of life of patients. Treatment of OCD is not yet fully successful and still many patients are left with debilitating symptoms without functioning medication. Animal models of genetic, behavioral, pharmacological, and optogenetic origins are beneficial in the achievement of new understandings of the disease. Chronic sensitization of serotonin 1A and 7-receptors with an agonist 8-OH-DPAT ((8- hydroxy-2-(di-propylamino)-tetralin hydrobromide) induces perseverative and compulsive behaviors, which is considered to constitute an animal model of OCD. In this thesis, the 8-OH- DPAT model has been tested in the active place avoidance task on Carousel maze to provide information about the model on learning. Second, this model is used to determine, whether co- administration of memantine or riluzole alleviates the cognitive and learning deficits of this model. To uncover these effects, an active place avoidance task on a Carousel maze was used. Measured criteria were total distance, entrances to the shock sector, total number of shocks, and median speed after the shock. During habituation, the animals were sensitized to 8-OH-DPAT (with a control group that did not receive 8-OH-DPAT but only saline). In an...Katedra fyziologieDepartment of PhysiologyPřírodovědecká fakultaFaculty of Scienc