Projects

Current Projects

Funding Institutions

Fundació, LA MARATÓ de TV3
AJUTS A PROJECTES DE RECERCA EN L'ÀMBIT DE SALUT MARATÓ DE TV3,
ref. 202219-30-31


Participating Institutions

Universitat Politècnica de Catalunya

Universidad De Valladolid

Duration

May 2023 to May 2026

Abstract

The project ‘Definition of biotypes within psychotic syndrome based on cognitive performance and cortical inhibitory activity’ is a consortium with la ‘Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León’, concretely with the team of Vicente Molina at the ‘Hospital Clínico Universitario de Valladolid’ that will have a duration of 3 years and it is funded by ‘Fundació LaMarató de TV3’ and It arises from the problematic of identifying the causes of severe psychiatric disorders, such as schizophrenia and bipolar disorder, due to the heterogeneity of patients within each diagnosis.

This heterogeneity also leads to a non-personalized treatment, making it only partially effective. Therefore, the project proposes to define biotypes in the psychotic syndrome that serve to improve diagnostic practices and treatments by means of their personalization based on the pathophysiological factors. In fact, during the last decade we have reported a subgroup of schizophrenic and bipolar disorders patients characterized by a very poor cognitive performance, anatomical deficits and a hyperactive brain that cannot modulate adequately its activity during cognitive tasks. Nevertheless, more research is needed.

Consequently, the project aims to extend the sample that allowed the aforementioned characterization to improve it and, in particular, to add a direct study of cortical inhibitory function using transcranial magnetic stimulation (TMS) along with electroencephalography (EEG, altogether TMS-EEG), as a possible target for personalized treatments. In addition, cognitive evaluations (an auditory oddball task) will serve as a basis for the search for biotypes, collecting the clinical data with EEG and magnetic resonance (MRI, structural and diffusion). With the processing of the aforementioned data, we expect to, at least, obtain a biotype characterized by severe cognitive deficit, grey matter deficit, basal cortical hyperactivity and GABA transmission deficits, and this group would show a selective response to clozapine.

Mental or brain disorders are characterized by a significant disturbance in a person’s cognition, emotional regulation or behavior, that can be occasional or chronic. Usually, mental disorders are connected to distress or impairment in important areas of functioning. In fact, 1 in every 8 people was living with a mental disorder in 2019; being anxiety and depressive disorders the most common. Despite the availability of effective prevention and treatment options, a large majority of those with mental disorders lack access to adequate care. Additionally, individuals with mental health issues often face stigma, discrimination, and human rights violations.

Notwithstanding the evident genetic substrate and the many cerebral alterations identified during the last decades, there is still little knowledge about the causes of severe psychiatric disorders, such as schizophrenia and bipolar disorder; which leads to a non-targeted treatment that is only partially efficacious. On top of that, there exists a large heterogeneity within each diagnosis, being the patients too different among themselves, suggesting that each diagnostic label includes different biologically substrates. Thus, segregating valid clusters of cases may help in identifying causal mechanisms that may be very useful in both diagnosis and in defining targets for new more tolerable and efficacious treatments. In the last decade, we have reported the possibility of identifying the aforementioned clusters based on the cerebral structure, the cognitive performance and the pattern of bioelectrical activity of patients. Concretely, we have reported a subgroup across schizophrenia and bipolar disorder characterized by a very poor cognitive performance, anatomical deficits and a hyperactive brain that cannot modulate adequately its activity during cognitive tasks.

A deficit in the inhibitory systems of the brain, which are based on the GABA neurotransmitter, is thought to contribute significantly to this group. Therefore, we propose examining its function using transcranial magnetic stimulation (TMS), since it is thought to modulate them. Moreover, we have been using it during the last years. We have already collected a sample of more than 200 cases and 200 controls studied with magnetic resonance, electroencephalography (EEG), clinical and cognitive assessments and, in part, transcranial magnetic stimulation. We need to increase this sample to approximately 500 subjects per group to be able to identify subgroups of patients based on the causal mechanisms contributing to their illness. Finally, we also expect that the patients with a significant cerebral inhibitory deficit would respond to a particular treatment (clozapine) selectively, since this drug improves GABA function in the cortex.

The main objectives are:

  • To identify a group of patients with psychotic disorders (possibly including a majority of patients with schizophrenia, but also cases of bipolar disorders) characterized primarily by a significant cognitive deficit, which will be accompanied by abnormal ego experiences, functional cortical hyperactivation, decreased regional cortical thickness and decreased mean fractional anisotropy.
  • To assess cortical GABA hypofunction of GABA-A or/and GABA-B type with TMS in patients and controls and its relation to cognition.
  • To assess the relation between inhibitory deficits and cognitive task-induced variation (modulation) of bioelectrical activity, assessed with EEG.
  • To compare treatment resistance between patients with or without inhibitory activity deficits, and the degree of response to clozapine
  • To compare treatment resistance between patients with or without inhibitory activity deficits, and the degree of response to clozapine

In order to achieve the aforementioned objectives, different procedures are going to be implemented. First, we will use TMS-EEG data to assess the cortical inhibitory systems of the brain of both pathological and non-pathological populations. To assess this function, two different paired-pulses paradigms will be employed: the long-interval intracortical inhibition (LICI) protocol, that is thought to be mediated by GABA-B receptor and the short-interval intracortical inhibition (SICI), mediated by GABA-A receptor. For the evaluation of the cognitive performance, an auditory oddball task will be used. Three different tones (a distractor, a target and a standard tones) will be presented to the participant, who will have to press a button each time they hear the target one. The cortical activity during the task will be recorded with EEG. Both, TMS-EEG and EEG data will be analyzed to characterize the cortical activity of the participants and to extract the features needed to perform the clustering and the assessing of the cortical GABA hypofunction and the relation between the inhibitory deficits and the cognitive performance.

Publications
Fernández-Linsenbarth I, Mijancos-Martínez G, Bachiller A, Núñez P, Rodríguez-González V, Beño-Ruiz-de-la-Sierra RM, Roig-Herrero A, Arjona-Valladares A, Poza J, Mañanas MÁ, Molina V. Relation between task-related activity modulation and cortical inhibitory function in schizophrenia and healthy controls: a TMS-EEG study. Eur Arch Psychiatry Clin Neurosci. 2024 Jan 19. doi: /10.1007/s00406-023-01745-0 . Epub ahead of print. PMID: 38243018.

In this pilot study the authors aim to explore the association between EEG modulation during a cognitive task (using and auditory task) and the inhibitory system function (employing TMS-EEG) in vivo in a sample including healthy controls and patients with schizophrenia. Results replicated the task-related cortical activity modulation deficit in schizophrenia patients. Moreover, they showed higher cortical reactivity compared to healthy controls. Cortical reactivity was inversely associated with EEG modulation, supporting the idea that a hypofunction of the inhibitory system could hamper the task-related modulation of EEG activity.


Díez Á, Gomez-Pilar J, Poza J, Beño-Ruiz-de-la-Sierra R, Fernández-Linsenbarth I, Recio-Barbero M, Núñez P, Holgado-Madera P, Molina V. Functional network properties in schizophrenia and bipolar disorder assessed with high-density electroencephalography. Prog Neuropsychopharmacol Biol Psychiatry. 2024 Feb 8;129:110902. doi: 10.1016/j.pnpbp.2023.110902. Epub 2023 Nov 29. PMID: 38036032.

This study investigates cortical functional networks in schizophrenia (SCZ) using graph theory parameters applied to high-density EEG. Connectivity Strength (CS) measures global network synchrony, and Shannon Graph Complexity (SGC) assesses network distribution of link weights, allowing to distinguish between primary and secondary pathways. Brain activity of the participants (healthy controls -HC-, SCZ patients and bipolar disorder -BD- patietns) during a P300 oddball task was recorded using EEG. SCZ patients had higher pre-stimulus CS values and lower theta-band CS modulation compared to HC. Both SCZ and BD patients showed reduced theta-band CS modulation. Chronic SCZ patients also exhibited reduced SGC modulation. Relationships were found between theta-band SGC modulation and CS measures, which correlated with cognitive outcomes and negative symptoms. The study concluded that SCZ and BD patients have hyperactive, hypomodulatory networks, particularly in secondary pathways, independent of antipsychotic effects.


Beño-Ruiz-de-la-Sierra RM, Arjona-Valladares A, Hernández-García M, Fernández-Linsenbarth I, Díez Á, Fondevila Estevez S, Castaño C, Muñoz F, Sanz-Fuentenebro J, Roig-Herrero A, Molina V. Corollary Discharge Dysfunction as a Possible Substrate of Anomalous Self-experiences in Schizophrenia. Schizophr Bull. 2023 Nov 10:sbad157. doi: 10.1093/schbul/sbad157 . Epub ahead of print. PMID: 37951230.

The study explores the dysfunction of the corollary discharge mechanism in schizophrenia (SCZ), which suppresses the perception of self-generated speech and reduces the auditory N1 event-related potential during EEG recordings. A dysfunction in this mechanism may be linked to anomalous self-experiences (AEs) in SCZ.ERP were recorded with EEG from SCZ patients and healthy control; both during concurrent listening to self-produced vowels (talk condition) and and non-concurrent listening to the same vowels (listen condition). AEs and symptomatology were scored with IPASE, PANSS and BNSS. N1 amplitude was lower during talk conditions compared to listen condition in both populations. However, the difference in N1 amplitude between both conditions was significantly higher in controls than in schizophrenia patients. These differences in patients correlated significantly and negatively with the IPASE, PANSS, and BNSS scores. The findings suggest that corollary discharge dysfunction may underlie ASEs in schizophrenia.


Beño-Ruiz-de-la-Sierra RM, Arjona-Valladares A, Fondevila Estevez S, Fernández-Linsenbarth I, Díez Á, Molina V. Corollary discharge function in healthy controls: Evidence about self-speech and external speech processing. Eur J Neurosci. 2023 Oct;58(7):3705-3713. doi: 10.1111/ejn.16125. Epub 2023 Aug 27. PMID: 37635264.

The study examines corollary discharge in healthy individuals, which reduces perception of self-generated speech and attenuates the auditory N1 component. Event-related potentials were recorded in a healthy population in three conditions: self-spoken vowels (talk condition), played-back vowels of their own voice (listen-self condition), and played-back vowels of an external voice (listen-other condition). The N1 amplitude was smaller for self-spoken vowels compared to both played-back conditions, with no differences between the two listen conditions. The P2 component and peak latencies showed no differences across conditions. These results confirm that corollary discharge dampens sensory responses to self-generated speech and provide new neurophysiological evidence about the similarities in the processing of played-back vowels with our own voice (ownership experience) and with an external voice.



Congresses proceedings

2024 SIRS Congress (Schizophrenia International Research Society), 3-7 April, Florence, Italy.
Fernández-Linsenbarth, I; Mijancos-Martínez, G; Bachiller, A; Beño-Ruis-de-la-Sierra, R; Arjona-Valladares, A; Roig-Herrero, A; Mañanas, A; Molina, V. Cortical reactivity and task-related activity modulation in schizophrenia and healthy controls: A TMS-EEG study.


Beño-Ruiz-de-la-Sierra, Arjona-Valladares, A; R; G; Fondevila-Estévez, S; Fernández-Linsenbarth, I; Roig-Herrero, A; Díez, A; Molina, V. Corollary discharge dysfunction as a potential underlying mechanism for Abnormal Self-Experiences and its association with clinical symptoms in schizophrenia.


2023 EMBC Congress (45th Annual International Conference of the IEEE Engineering in Medicine and Biology Society), 24-27 July, Sydney, Australia
Mijancos-Martinez G, Bachiller A, Fernandez-Linsenbarth I, Romero S, Alonso JF, Molina V, Mañanas MA. Cortical inhibition on TMS-EEG: interstimulus interval effect on short-interval paired-pulse. Annu Int Conf IEEE Eng Med Biol Soc. 2023 Jul;2023:1-4. doi: 10.1109/EMBC40787.2023.10340654 . PMID: 38083290.

Funding Institutions

ACCIÓ, Generalitat de Catalunya
Tecniospring INDUSTRY, RIS3CAT,
ref. ACE026/21/000035

European Commission
Marie Slodowska-Curie,
Grant Agreement no. 801342

Participating Institutions

Universitat Politècnica de Catalunya

Duration

Feb 2022 to Feb 2024

Abstract

MyoArm is a device designed for the treatment of musculoskeletal disorders of the forearm. It uses high density EMG to measure muscle activity during the rehabilitation, providing biofeedback to the subject on his/her control of the muscle and allowing to obtaining quantitative indexes of the muscular function. Such indexes can be used by clinicians as support tool for diagnostics and follow up. Moreover, unique information extracted from subjects own particular activation, can be used to designed personalized interventions, helping patients to recover better and faster.

 

 



 

 

Funding Institutions

CaixaImpulse CI18-00083

Participating Institutions

Technical University of Catalonia
"la Caixa" Foundation
Caixa Capital Risc

Duration

From January 2019 to March 2020

 

Funding Institutions

MINECO (DPI2017-83989-R)

Participating Institutions

Technical University of Catalonia

Duration

From January 2018 to December 2020

 

Funding Institutions

FBBVA

 

Duration

From October 2016 to October 2018

 

Past Projects

Funding Institutions

European Commission (ref. 643535-WOMEN-UP), Strategic objective: PHC-26-2014 - Self management of health and disease: citizen engagement and mHealth (HORIZON 2020)

Participating Institutions

Technical University of Catalonia, Mega Electronics, Hospital Universitario de Kuopio, Hospital Clinic, Academic Medical Center, Asociación Europea de Uroginecología, Universidad Babes Bolyai, YouRehab, BAP Health outcomes research

Duration

From December 2014 to May 2018

 

Funding Institutions

MINECO (DPI2014-59049-R)

Participating Institutions

Technical University of Catalonia

Duration

From January 2015 to December 2017

 

Funding Institutions

Generalitat de Catalunya/European Commission (TECSPR14-2-0038)

Participating Institutions

Technical University of Catalonia

Duration

From October 2015 to October 2017

 

Funding Institutions

Fondo Nacional de Regalías de la República de Colombia

Participating Institutions

Universidad de Antioquia, Hospital Universitario San Vicente Fundación, IPS Universitaria – Clínica Leon XIII, Escuela de Ingenieros de Antioquia (EIA), Hospital General de Medellín, Bioin Soluciones SAS

Duration

From October 2014 to September 2016

 

Funding Institutions

Centro de Investigación Biomédica en Red. Bioingeniería, Biomateriales y Nanoingeniería (CIBER-BBN)

Participating Institutions

Universitat Politècnica de Catalunya (Barcelona- Spain), Universidad Miguel Hernández (Valencia- Spain), Hospital Vega Baja

Duration

From June 2014 to May 2016

 

Funding Institutions

Fondo Nacional de Regalías de la República de Colombia

Participating Institutions

Universidad de Antioquia, Hospital Universitario San Vicente Fundación, Comercializadora Internacional Primer AP SAS, TEKVO SAS, Technical University of Catalonia

Duration

From February 2013 to December 2015

 

Funding Institutions

Fondo Nacional de Regalías de la República de Colombia

Participating Institutions

Universidad de Antioquia, Universidad Pontificia Bolivariana, Hospital Universitario San Vicente Fundación, Technical University of Catalonia

Duration

From November 2013 to November 2015

 

Funding Institutions

AECID. MAAEE (C/032085/10)

Participating Institutions

Technical University of Catalonia, Universidad de Antioquia

Duration

From June 2011 June 2012

 

Funding Institutions

MICINN (TEC2008-02274)

Participating Institutions

Technical University of Catalonia

Duration

From January 2009 to December 2012

 

Funding Institutions

ACC1Ó (CIDEM), Generalitat de Catalunya (VALTEC09-1-0060)

Participating Institutions

Universitat Politècnica de Catalunya

Duration

From October 2009 to June 2012

 

Funding Institutions

Centro de Cooperación para el Desarrollo (Technical University of Catalonia) (U-013,U-014)

Participating Institutions

Technical University of Catalonia-Universidad de Antioquia

Duration

2008 to 2010

 

Funding Institutions

Centro de Cooperación para el De Center for Cooperation and Development (CCD-UPC) (ref. U-017)

Participating Institutions

Universidad Politécnica de Catalunya, Universidad de Antioquia

Duration

From September 2007 to July 2008

 

Funding Institutions

AECID. MAAEE (C/032085/10)

Participating Institutions

Technical University of Catalonia, Universidad de Antioquia

Duration

From June 2011 June 2012

 

Funding Institutions

Institute for Older Persons and Social Services (IMSERSO). Ministerio de Trabajo y Asuntos Sociales (Proyecto 102-06).

Participating Institutions

Consorcio entre Hospital de Neurorehabilitación Institut Guttmann-Universidad Politécnica de Cataluña-Fatronik

Duration

From 2006 to 2007

 

Funding Institutions

Ministerio Ciencia y Tecnología Acción Integrada (ref. HI2003-0186)

Participating Institutions

Technical University of Catalonia-Mútua Egarsat-Politécnico de Turín

Duration

From 2004 to 2005

 

Funding Institutions

MEC, CICYT (TEC2004-02274)

Participating Institutions

Technical University of Catalonia

Duration

From 2004 to 2007

 

Funding Institutions

CICYT (ref. TIC2001-2167-C02-01)

Participating Institutions

Technical University of Catalonia-Universidad de Zaragoza

Duration

From 2002 to 2004

 

Funding Institutions

FEDER, (ref. 2FD97-1197-C02-02)

Participating Institutions

Technical University of Catalonia-Universidad de Zaragoza

Duration

From 1999 to 2001

 

Funding Institutions

CICYT (ref. TIC 97-0945-C02-01)

Participating Institutions

Technical University of Catalonia-Universidad de Zaragoza

Duration

From 1997 to 2000

 

Funding Institutions

CICYT (ref. TIC 94-0608-C02-01)

Participating Institutions

Technical University of Catalonia-Universidad de Zaragoza

Duration

From 2004 to 2007

Abstract

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Funding Institutions

Consejo Superior de Investigaciones Científicas - Hungarian Academy of Sciences

Participating Institutions

Technical University of Catalonia-PC-Eötvos University de Budapest (Hungria)

Duration

From 1992 to 1996

Abstract

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