Why are we not flooded by involuntary thoughts about the past and future? Testing the cognitive inhibition dependency hypothesis

© The Author(s) 2018In everyday life, involuntary thoughts about future plans and events occur as often as involuntary thoughts about the past. However, compared to involuntary autobiographical memories (IAMs), such episodic involuntary future thoughts (IFTs) have become a focus of study only recently. The aim of the present investigation was to examine why we are not constantly flooded by IFTs and IAMs given that they are often triggered by incidental cues while performing undemanding activities. One possibility is that activated thoughts are suppressed by the inhibitory control mechanism, and therefore depleting inhibitory control should enhance the frequency of both IFTs and IAMs. We report an experiment with a between-subjects design, in which participants in the depleted inhibition condition performed a 60-min high-conflict Stroop task before completing a laboratory vigilance task measuring the frequency of IFTs and IAMs. Participants in the intact inhibition condition performed a version of the Stroop task that did not deplete inhibitory control. To control for physical and mental fatigue resulting from performing the 60-min Stroop tasks in experimental conditions, participants in the control condition completed only the vigilance task. Contrary to predictions, the number of IFTs and IAMs reported during the vigilance task, using the probe-caught method, did not differ across conditions. However, manipulation checks showed that participants’ inhibitory resources were reduced in the depleted inhibition condition, and participants were more tired in the experimental than in the control conditions. These initial findings suggest that neither inhibitory control nor physical and mental fatigue affect the frequency of IFTs and IAMs.Peer reviewedFinal Published versio

Generation and validation of a novel multitarget small molecule in glioblastoma

The development of multitarget small molecules (MSMs) has emerged as a powerful strategy for the treatment of multifactorial diseases such as cancer. Glioblastoma is the most prevalent and malignant primary brain tumor in adults, which is characterized by poor prognosis and a high heterogeneity. Current standards of treatment present limited effectiveness, as patients develop therapy resistance and recur. In this work, we synthesized and characterized a novel multi-target molecule (named DDI199 or contilistat), which is a polyfunctionalized indole derivative developed by juxtaposing selected pharmacophoric moieties of the parent compounds Contilisant and Vorinostat (SAHA) to act as multifunctional ligands that inhibit histone deacetylases (HDACs), monoamine oxidases (MAOs) and cholinesterases (ChEs), and modulate histamine H3 (H3R) and Sigma 1 Receptor (S1R) receptors. DDI199 exerts high cytotoxic activity in conventional glioblastoma cell lines and patient-derived glioma stem cells in vitro. Importantly, it significantly reduces tumor growth in vivo, both alone and in combination with temozolomide (TMZ). The comparison with SAHA showed higher target specificity and antitumor activity of the new molecule. Transcriptomic and proteomic analyses of patient-derived glioma stem cells revealed a deregulation in cell cycle, DNA remodeling and neurotransmission activity by the treatment with DDI199. In conclusion, our data reveal the efficacy of a novel MSM in glioblastoma pre-clinical setting.A.A-Z received a predoctoral fellowship from the Education Department of the Basque Government (PRE_2020_1_0130). N.I-R is the recipient of a Sara Borrell postdoctoral contract (CD22/00076) and V. M-A by Miguel Servet contract (CP23/ 00111) from Carlos III Institute of Health. LSH wants to gratefully acknowledge experimental support by Philipp Stegen. The authors thank the Neurooncology Committee of the Donostia Hospital and the Animal facility and Pathology Service of Biogipuzkoa Institute for their help. This work was supported by grants from Carlos III Institute of Health and the European Regional Development Fund (PI19/01355, PI22/ 01905, DTS24/00153) and Health Department of the Basque Country (2022333034, 2023333012) to AM, AEI (PID2019-105813RB-C21) and UCJC (MITOPI) (2022) to JMC, and Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) −GRK2873 (494832089) to L.S-H and FK.H

From mind-pops to hallucinations? : A study of involuntary semantic memories in schizophrenia

Involuntary semantic memories or mind-pops consist of isolated fragments of one's semantic knowledge (e.g., a word or a sentence, proper name, image or a melody) that come to mind unexpectedly, without any deliberate attempt to recall them. They can be experienced as alien and uncontrollable, and may share some phenomenological similarities with hallucinations. The aim of the present study was to investigate the nature and frequency of mind-pops in people with schizophrenia (N=37), as well as clinically depressed (N=31) and non-clinical controls (N=31). Results showed that schizophrenia patients reported experiencing mind-pops more frequently than both depressed and non-clinical controls. Schizophrenia patients also reported a wider range of different types of mind-pops than non-clinical controls. The depressed group did not differ from non-clinical controls in the frequency and range of mind-pops, indicating that mind-pops are not characteristic of clinical populations in general, but may be particularly prevalent in patients with schizophrenia. The possible implications of this finding to current models of auditory verbal hallucinations are discussed and the need for future research in this area is emphasized. (C) 2012 Elsevier Ireland Ltd. All rights reserved.Peer reviewedFinal Accepted Versio