Altered thalamocortical structural connectivity in persons with schizophrenia and healthy siblings

Schizophrenia has long been framed as a disorder of altered brain connectivity, with dysfunction in thalamocortical circuity potentially playing a key role in the development of the illness phenotype, including psychotic symptomatology and cognitive impairments. There is emerging evidence for functional and structural hypoconnectivity between thalamus and prefrontal cortex in persons with schizophrenia spectrum disorders, as well as hyperconnectivity between thalamus and sensory and motor cortices. However, it is unclear whether thalamocortical dysconnectivity is a general marker of vulnerability to schizophrenia or a specific mechanism of schizophrenia pathophysiology. This study aimed to answer this question by using diffusion-weighted imaging to examine thalamocortical structural connectivity in 22 persons with schizophrenia or schizoaffective disorder (SZ), 20 siblings of individuals with a schizophrenia spectrum disorder (SIB), and 44 healthy controls (HC) of either sex. Probabilistic tractography was used to quantify structural connectivity between thalamus and six cortical regions of interest. Thalamocortical structural connectivity was compared among the three groups using cross-thalamic and voxel-wise approaches. Thalamo-prefrontal structural connectivity was reduced in both SZ and SIB relative to HC, while SZ and SIB did not differ from each other. Thalamo-motor structural connectivity was increased in SZ relative to SIB and HC, while SIB and HC did not differ from each other. Hemispheric differences also emerged in thalamic connectivity with motor, posterior parietal, and temporal cortices across all groups. The results support the hypothesis that altered thalamo-prefrontal structural connectivity is a general marker of vulnerability to schizophrenia, whereas altered connectivity between thalamus and motor cortex is related to illness expression or illness-related secondary factors

Human Fronto-Tectal and Fronto-Striatal-Tectal Pathways Activate Differently During Anti-Saccades

Almost all cortical areas in the vertebrate brain take part in recurrent connections through the subcortical basal ganglia (BG) nuclei, through parallel inhibitory and excitatory loops. It has been suggested that these circuits can modulate our reactions to external events such that appropriate reactions are chosen from many available options, thereby imposing volitional control over behavior. The saccade system is an excellent model system to study cortico-BG interactions. In this study two possible pathways were investigated that might regulate automaticity of eye movements in the human brain; the cortico-tectal pathway, running directly between the frontal eye fields (FEF) and superior colliculus (SC) and the cortico-striatal pathway from the FEF to the SC involving the caudate nucleus (CN) in the BG. In an event-related functional magnetic resonance imaging (fMRI) paradigm participants made pro- and anti-saccades. A diffusion tensor imaging (DTI) scan was made for reconstruction of white matter tracts between the FEF, CN and SC. DTI fiber tracts were used to divide both the left and right FEF into two sub-areas, projecting to either ipsilateral SC or CN. For each of these FEF zones an event-related fMRI timecourse was extracted. In general activity in the FEF was larger for anti-saccades. This increase in activity was lateralized with respect to anti-saccade direction in FEF zones connected to the SC but not for zones only connected to the CN. These findings suggest that activity along the contralateral FEF–SC projection is responsible for directly generating anti-saccades, whereas the pathway through the BG might merely have a gating function withholding or allowing a pro-saccade

Забезпечення розвитку інноваційності промислових підприємств при активізації інтелектуального капіталу суспільства

Проаналізовано стан і умови інноваційної діяльності підприємств в Україні. Досліджено проблеми неефективності державної політики в економічній сфері щодо розвитку інноваційності промислових підприємств. Розроблено пропозиції з удосконалення структури і напрямів діяльності державної політики щодо розвитку інноваційності промислових підприємств при активізації інтелектуального капіталу суспільства.Проанализированы состояние и условия инновационной деятельности предприятий в Украине. Исследованы проблемы неэффективности государственной политики в экономической сфере относительно развития инновационности промышленных предприятий. Разработаны предложения по усовершенствованию структуры и направлений деятельности государственной политики относительно развития инновационности промышленных предприятий при активизации интеллектуального капитала.The state and terms of innovative activity of enterprises in Ukraine are analyzed. Problems of inefficiency of public policy are investigated in an economic sphere in relation to innovativeness development of industrial enterprises. Suggestions for the improvement of structure and directions public policy activity in relation to innovativeness development of the industrial enterprises during activation of the society intellectual capital are worked out

Brain areas involved in spatial working memory

Spatial working memory entails the ability to keep spatial information active in working memory over a short period of time. To study the areas of the brain that are involved in spatial working memory, a group of stroke patients was tested with a spatial search task. Patients and healthy controls were asked to search through a number of boxes shown at different locations on a touch-sensitive computer screen in order to find a target object. In subsequent trials, new target objects were hidden in boxes that were previously empty. Within-search errors were made if a participant returned to an already searched box; between-search errors occurred if a participant returned to a box that was already known to contain a target item. The use of a strategy to remember the locations of the target objects was calculated as well. Damage to the right posterior parietal and right dorsolateral prefrontal cortex impaired the ability to keep spatial information [`]on-line', as was indicated by performance on the Corsi Block-Tapping task and the within-search errors. Moreover, patients with damage to the right posterior parietal cortex, the right dorsolateral prefrontal cortex and the hippocampal formation bilaterally made more between-search errors, indicating the importance of these areas in maintaining spatial information in working memory over an extended time period.http://www.sciencedirect.com/science/article/B6T0D-4HM7WH2-2/1/b6b13c7b404377bae2b8cf632eb61fe

The position of combined medical treatment in acromegaly

Advances in combination medical treatment have offer new perspectives for acromegaly patients with persistent disease activity despite receiving the available medical monotherapies. The outcomes of combination medical treatment may reflect both additive and synergistic effects. This review focuses on combination medical treatment and its current position in acromegaly, based on clinical studies evaluating the efficacy and safety of combined medical treatment(s) and our own experiences with combination therapy. Arch Endocrinol Metab. 2019;63(6):646-52

Altered effective connectivity within an oculomotor control network in individuals with schizophrenia

Rapid inhibition or modification of actions is a crucial cognitive ability, which is impaired in persons with schizophrenia (SZP). Primate neurophysiology studies have identified a network of brain regions that subserves control over gaze. Here, we examine effective connectivity within this oculomotor control network in SZP and healthy controls (HC). During fMRI, participants performed a stop-signal task variant in which they were instructed to saccade to a visual target (no-step trials) unless a second target appeared (redirect trials); on redirect trials, participants were instructed to inhibit the planned saccade and redirect to the new target. We compared functional responses on redirect trials to no-step trials and used dynamic causal modelling (DCM) to examine group differences in network effective connectivity. Behaviorally, SZP were less efficient at inhibiting, which was related to their employment status. Compared to HC, they showed a smaller difference in activity between redirect trials and no-step trials in frontal eye fields (FEF), supplementary eye fields (SEF), inferior frontal cortex (IFC), thalamus, and caudate. DCM analyses revealed widespread group differences in effective connectivity across the task, including different patterns of self-inhibition in many nodes in SZP. Group differences in how effective connectivity was modulated on redirect trials revealed differences between the FEF and SEF, between the SEF and IFC, between the superior colliculus and the thalamus, and self-inhibition within the FEF and caudate. These results provide insight into the neural mechanisms of inefficient inhibitory control in individuals with schizophrenia

A novel concurrent TMS-fMRI method to reveal propagation patterns of prefrontal magnetic brain stimulation

Major depressive disorder (MDD) is a severe mental disorder associated with high morbidity and mortality rates, which remains difficult to treat, as both resistance and recurrence rates are high. Repetitive transcranial magnetic stimulation (TMS) of the left dorsolateral prefrontal cortex (DLPFC) provides a safe and effective treatment for selected patients with treatment-resistant MDD. Little is known about the mechanisms of action of TMS provided to the left DLPFC in MDD and we can currently not predict who will respond to this type of treatment, precluding effective patient selection. In order to shed some light on the mechanism of action, we applied single pulse TMS to the left DLPFC in 10 healthy participants using a unique TMS-fMRI set-up, in which we could record the direct effects of TMS. Stimulation of the DLPFC triggered activity in a number of connected brain regions, including the subgenual anterior cingulate cortex (sgACC) in four out of nine participants. The sgACC is of particular interest, because normalization of activity in this region has been associated with relief of depressive symptoms in MDD patients. This is the first direct evidence that TMS pulses delivered to the DLPFC can propagate to the sgACC. The propagation of TMS-induced activity from the DLPFC to sgACC may be an accurate biomarker for rTMS efficacy. Further research is required to determine whether this method can contribute to the selection of patients with treatment resistant MDD who will respond to rTMS treatment

Excellent response to pasireotide therapy in an aggressive and dopamine-resistant prolactinoma.

peer reviewedProlactinomas are the most commonly encountered pituitary adenomas in the clinical setting. While most can be controlled by dopamine agonists, a subset of prolactinomas are dopamine-resistant and very aggressive. In such tumors, the treatment of choice is neurosurgery and radiotherapy, with or without temozolomide. Here, we report a patient with an highly aggressive, dopamine-resistant prolactinoma, who only achieved biochemical and tumor control during pasireotide long-acting release (PAS-LAR) therapy , a second-generation somatostatin receptor ligand (SRL). Interestingly, cystic degeneration, tumor cell necrosis, or both was observed after PAS-LAR administration suggesting an antitumor effect. This case shows that PAS-LAR therapy holds clinical potential in selective aggressive, dopamine-resistant prolactinomas that express somatostatin (SST) receptor subtype 5 and appears to be a potential new treatment option before starting temozolomide. In addition, PAS-LAR therapy may induce cystic degeneration, tumor cell necrosis, or both in prolactinomas

Multivariable Prediction Model for Biochemical Response to First-Generation Somatostatin Receptor Ligands in Acromegaly

CONTEXT: First-generation somatostatin receptor ligands (fg-SRLs) represent the mainstay of medical therapy for acromegaly, but they provide biochemical control of disease in only a subset of patients. Various pretreatment biomarkers might affect biochemical response to fg-SRLs. OBJECTIVE: To identify clinical predictors of the biochemical response to fg-SRLs monotherapy defined as biochemical response (insulin-like growth factor (IGF)-1 ≤ 1.3 × ULN (upper limit of normal)), partial response (>20% relative IGF-1 reduction without normalization), and nonresponse (≤20% relative IGF-1 reduction), and IGF-1 reduction. DESIGN: Retrospective multicenter study. SETTING: Eight participating European centers. METHODS: We performed a meta-analysis of participant data from 2 cohorts (Rotterdam and Liège acromegaly survey, 622 out of 3520 patients). Multivariable regression models were used to identify predictors of biochemical response to fg-SRL monotherapy. RESULTS: Lower IGF-1 concentration at baseline (odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.72-0.95 IGF-1 ULN, P = .0073) and lower bodyweight (OR = 0.99, 95% CI 0.98-0.99 kg, P = .038) were associated with biochemical response. Higher IGF-1 concentration at baseline (OR = 1.40, (1.19-1.65) IGF-1 ULN, P ≤ .0001), the presence of type 2 diabetes (oral medication OR = 2.48, (1.43-4.29), P = .0013; insulin therapy OR = 2.65, (1.02-6.70), P = .045), and higher bodyweight (OR = 1.02, (1.01-1.04) kg, P = .0023) were associated with achieving partial response. Younger patients at diagnosis are more likely to achieve nonresponse (OR = 0.96, (0.94-0.99) year, P = .0070). Baseline IGF-1 and growth hormo

A Functional and Structural Investigation of the Human Fronto-Basal Volitional Saccade Network

Almost all cortical areas are connected to the subcortical basal ganglia (BG) through parallel recurrent inhibitory and excitatory loops, exerting volitional control over automatic behavior. As this model is largely based on non-human primate research, we used high resolution functional MRI and diffusion tensor imaging (DTI) to investigate the functional and structural organization of the human (pre)frontal cortico-basal network controlling eye movements. Participants performed saccades in darkness, pro- and antisaccades and observed stimuli during fixation. We observed several bilateral functional subdivisions along the precentral sulcus around the human frontal eye fields (FEF): a medial and lateral zone activating for saccades in darkness, a more fronto-medial zone preferentially active for ipsilateral antisaccades, and a large anterior strip along the precentral sulcus activating for visual stimulus presentation during fixation. The supplementary eye fields (SEF) were identified along the medial wall containing all aforementioned functions. In the striatum, the BG area receiving almost all cortical input, all saccade related activation was observed in the putamen, previously considered a skeletomotor striatal subdivision. Activation elicited by the cue instructing pro or antisaccade trials was clearest in the medial FEF and right putamen. DTI fiber tracking revealed that the subdivisions of the human FEF complex are mainly connected to the putamen, in agreement with the fMRI findings. The present findings demonstrate that the human FEF has functional subdivisions somewhat comparable to non-human primates. However, the connections to and activation in the human striatum preferentially involve the putamen, not the caudate nucleus as is reported for monkeys. This could imply that fronto-striatal projections for the oculomotor system are fundamentally different between humans and monkeys. Alternatively, there could be a bias in published reports of monkey studies favoring the caudate nucleus over the putamen in the search for oculomotor functions