To understand how pharmacological interventions can exert their powerful effects on brain functio... more To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs’ effects on brain function and multiple neurotransmitter systems. The effects of both anesthetics and psychedelics on brain function are organized along hierarchical gradie...
Hypnosis has been shown to be of clinical utility; however, its underlying neural mechanisms rema... more Hypnosis has been shown to be of clinical utility; however, its underlying neural mechanisms remain unclear. This study aims to investigate altered brain dynamics during the non-ordinary state of consciousness induced by hypnosis. We studied high-density EEG in 9 healthy participants during eyes-closed wakefulness and during hypnosis, induced by a muscle relaxation and eyes fixation procedure. Using hypotheses based on internal and external awareness brain networks, we assessed region-wise brain connectivity between 6 ROI (right and left frontal, right and left parietal, upper and lower midline regions) at the scalp level and compared across conditions. Data-driven, graph-theory analyses were also carried out to characterize brain network topology in terms of brain network segregation and integration. During hypnosis, we observed (1) increased delta connectivity between left and right frontal, as well as between right frontal and parietal regions, (2) decreased connectivity for alph...
Patients with disorders of consciousness (DoC) represent a group of severely brain-injured patien... more Patients with disorders of consciousness (DoC) represent a group of severely brain-injured patients with varying capacities for consciousness in terms of both wakefulness and awareness. The current state-of-theart for assessing these patients is through standardised behavioural examinations, but inaccuracies are commonplace. Neuroimaging and electrophysiological techniques have revealed vast insights into the relationships between neural alterations, andcognitive and behavioural features of consciousness in patients with DoC. This has led to the establishment of neuroimaging paradigms for the clinical assessment of DoC patients. Here, we review selected neuroimaging findings on the DoC population, outlining key findings of the dysfunction underlying DoC and presenting the current clinical utility of neuroimaging tools. We discuss that whilst individual brain areas play instrumental roles in generating and supporting consciousness, activation of these areas alone is not sufficient for conscious experience. Instead, for consciousness to arise, we need preserved thalamo-cortical circuits, in addition to sufficient connectivity between distinctly differentiated brain networks, underlined by connectivity both within, and between such brain networks. Finally, we present recent advances and future perspectives in computational methodologies applied to DoC, supporting the notion that progress in the science of DoC will be driven by a symbiosis of these data-driven analyses, and theory-driven research. Both perspectives will work in tandem to provide mechanistic insights contextualised within theoretical frameworks which ultimately inform the practice of clinical neurology.
Brain states are frequently represented using a unidimensional scale measuring the richness of su... more Brain states are frequently represented using a unidimensional scale measuring the richness of subjective experience (level of consciousness). This description assumes a mapping between the high-dimensional space of whole-brain configurations and the trajectories of brain states associated with changes in consciousness, yet this mapping and its properties remain unknown. We combined whole-brain modelling, data augmentation and deep learning for dimensionality reduction to determine a mapping representing states of consciousness in a low-dimensional space, where distances parallel similarities between states. An orderly trajectory from wakefulness to brain injured patients is revealed in a latent space whose coordinates represent metrics related to functional modularity and structure-function coupling, both increasing alongside loss of consciousness. Finally, we investigated the effects of model perturbations, providing geometrical interpretation for the stability and reversibility o...
Cannabis use is highly prevalent in adolescents however little is known about its effects on adol... more Cannabis use is highly prevalent in adolescents however little is known about its effects on adolescent brain function. Resting-state functional Magnetic Resonance Imaging was used in matched groups of adolescents (16-17 years old, N=70, 35 users/35 controls) and young adults (26-29 years old, N=70, 35 users/35 controls). Pre-registered analyses examined the connectivity of cortical and sub-cortical brain networks. Cannabis users (across both age-groups) showed localised increases in connectivity in the default mode, executive, and limbic striatum networks. Localised decreases in connectivity were seen in the salience network, and the sensorimotor striatal network showed both localised increases and decreases in connectivity. Mean connectivity across entire networks was significantly decreased in the default mode network in cannabis users. There were no significant interactions found between age-group and user-group. Cannabis use is associated with changes to connectivity in cortica...
Patients with locked-in syndrome (LIS) may suffer from pain, which can significantly affect their... more Patients with locked-in syndrome (LIS) may suffer from pain, which can significantly affect their daily life and well-being. In this study, we aim to investigate the presence and the management of pain in LIS patients. Fifty-one participants completed a survey collecting socio-demographic information and detailed reports regarding pain perception and management (type and frequency of pain, daily impact of pain, treatments). Almost half of the LIS patients reported experiencing pain (49%) that affected their quality of life, sleep and cognition. The majority of these patients reported that they did not communicate their pain to clinical staff. Out of the 25 patients reporting pain, 18 (72%) received treatment (60% pharmacological, 12% non-pharmacological) and described the treatment efficacy as ‘moderate’. In addition, 14 (56%) patients were willing to try other non-pharmacological treatments, such as hypnosis or meditation. This study provides a comprehensive characterization of pai...
To understand how pharmacological interventions can exert their powerful effects on brain functio... more To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically induced macroscale functional reorganization, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from positron emission tomography, and the regional changes in functional magnetic resonance imaging connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, lysergic acid diethylamide (LSD), psilocybin, N,N-Dimethyltryptamine (DMT), ayahuasca, 3,4-methylenedioxymethamphetamine (MDMA), modafinil, and methylphenidate. Our results reveal a many-to-many mapping between psychoactive drugs’ effects on brain function and multiple neurotransmitter systems. The effects of both anesthetics and psychedelics on brain function are organized along hierarchical gradie...
Hypnosis has been shown to be of clinical utility; however, its underlying neural mechanisms rema... more Hypnosis has been shown to be of clinical utility; however, its underlying neural mechanisms remain unclear. This study aims to investigate altered brain dynamics during the non-ordinary state of consciousness induced by hypnosis. We studied high-density EEG in 9 healthy participants during eyes-closed wakefulness and during hypnosis, induced by a muscle relaxation and eyes fixation procedure. Using hypotheses based on internal and external awareness brain networks, we assessed region-wise brain connectivity between 6 ROI (right and left frontal, right and left parietal, upper and lower midline regions) at the scalp level and compared across conditions. Data-driven, graph-theory analyses were also carried out to characterize brain network topology in terms of brain network segregation and integration. During hypnosis, we observed (1) increased delta connectivity between left and right frontal, as well as between right frontal and parietal regions, (2) decreased connectivity for alph...
Patients with disorders of consciousness (DoC) represent a group of severely brain-injured patien... more Patients with disorders of consciousness (DoC) represent a group of severely brain-injured patients with varying capacities for consciousness in terms of both wakefulness and awareness. The current state-of-theart for assessing these patients is through standardised behavioural examinations, but inaccuracies are commonplace. Neuroimaging and electrophysiological techniques have revealed vast insights into the relationships between neural alterations, andcognitive and behavioural features of consciousness in patients with DoC. This has led to the establishment of neuroimaging paradigms for the clinical assessment of DoC patients. Here, we review selected neuroimaging findings on the DoC population, outlining key findings of the dysfunction underlying DoC and presenting the current clinical utility of neuroimaging tools. We discuss that whilst individual brain areas play instrumental roles in generating and supporting consciousness, activation of these areas alone is not sufficient for conscious experience. Instead, for consciousness to arise, we need preserved thalamo-cortical circuits, in addition to sufficient connectivity between distinctly differentiated brain networks, underlined by connectivity both within, and between such brain networks. Finally, we present recent advances and future perspectives in computational methodologies applied to DoC, supporting the notion that progress in the science of DoC will be driven by a symbiosis of these data-driven analyses, and theory-driven research. Both perspectives will work in tandem to provide mechanistic insights contextualised within theoretical frameworks which ultimately inform the practice of clinical neurology.
Brain states are frequently represented using a unidimensional scale measuring the richness of su... more Brain states are frequently represented using a unidimensional scale measuring the richness of subjective experience (level of consciousness). This description assumes a mapping between the high-dimensional space of whole-brain configurations and the trajectories of brain states associated with changes in consciousness, yet this mapping and its properties remain unknown. We combined whole-brain modelling, data augmentation and deep learning for dimensionality reduction to determine a mapping representing states of consciousness in a low-dimensional space, where distances parallel similarities between states. An orderly trajectory from wakefulness to brain injured patients is revealed in a latent space whose coordinates represent metrics related to functional modularity and structure-function coupling, both increasing alongside loss of consciousness. Finally, we investigated the effects of model perturbations, providing geometrical interpretation for the stability and reversibility o...
Cannabis use is highly prevalent in adolescents however little is known about its effects on adol... more Cannabis use is highly prevalent in adolescents however little is known about its effects on adolescent brain function. Resting-state functional Magnetic Resonance Imaging was used in matched groups of adolescents (16-17 years old, N=70, 35 users/35 controls) and young adults (26-29 years old, N=70, 35 users/35 controls). Pre-registered analyses examined the connectivity of cortical and sub-cortical brain networks. Cannabis users (across both age-groups) showed localised increases in connectivity in the default mode, executive, and limbic striatum networks. Localised decreases in connectivity were seen in the salience network, and the sensorimotor striatal network showed both localised increases and decreases in connectivity. Mean connectivity across entire networks was significantly decreased in the default mode network in cannabis users. There were no significant interactions found between age-group and user-group. Cannabis use is associated with changes to connectivity in cortica...
Patients with locked-in syndrome (LIS) may suffer from pain, which can significantly affect their... more Patients with locked-in syndrome (LIS) may suffer from pain, which can significantly affect their daily life and well-being. In this study, we aim to investigate the presence and the management of pain in LIS patients. Fifty-one participants completed a survey collecting socio-demographic information and detailed reports regarding pain perception and management (type and frequency of pain, daily impact of pain, treatments). Almost half of the LIS patients reported experiencing pain (49%) that affected their quality of life, sleep and cognition. The majority of these patients reported that they did not communicate their pain to clinical staff. Out of the 25 patients reporting pain, 18 (72%) received treatment (60% pharmacological, 12% non-pharmacological) and described the treatment efficacy as ‘moderate’. In addition, 14 (56%) patients were willing to try other non-pharmacological treatments, such as hypnosis or meditation. This study provides a comprehensive characterization of pai...
Uploads
Papers by Naji Alnagger