Angie Kehagia
King's College London, Dept. Neuroimaging, Faculty Member
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
In an effort to provide timely clinical input for people with Parkinson’s disease (PD) in the face of increasing demand and resource limitation in our UK based service, we introduced remote management in place of clinic appointment,... more
In an effort to provide timely clinical input for people with Parkinson’s disease (PD) in the face of increasing demand and resource limitation in our UK based service, we introduced remote management in place of clinic appointment, including the use of the Parkinson’s KinetiGraph (PKG™), a wrist-worn device that provides a continuous measure of movement. We evaluated our reporting methods and findings, the nature of unmet need we identified, our treatment recommendations and the degree of their implementation in our patients whose feedback guided our service developments. Our evaluation highlighted opportunities and challenges associated with incorporating digital data into care traditionally delivered via in-person contact.
Research Interests:
Anaïs Nin, diarist and author of autobiographical novellas and erotica, and gregarious socialite, was known for her exotic persona and stormy personal life. The concept of personality disorder and the underlying assumption of the... more
Anaïs Nin, diarist and author of autobiographical novellas and erotica, and gregarious socialite, was known for her exotic persona and stormy personal life. The concept of personality disorder and the underlying assumption of the buffering capacity that personality affords to stressors are discussed. Against this background, evidence drawn from Nin’s diaries, short stories and two biographies suggests that she conformed
Research Interests:
Research Interests:
Research Interests: Neuroscience, Psychology, Neuropsychology, Categorization, Medicine, and 15 morePrefrontal Cortex, Humans, Female, Male, Names, Aged, Middle Aged, Control Reconfiguration, Frontal Lobe, Parkinson Disease, Brain injuries, Neuropsychological Tests, Attention deficit disorder with hyperactivity, photic stimulation, and Medical and Health Sciences
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Research Interests:
Research Interests:
Research Interests:
Research Interests: Neuroscience, Psychology, Cognitive Science, Dementia, Cognition, and 14 moreMedicine, Executive Function, Neurodegenerative Diseases, Humans, Impulse Control Disorders, Disease, Clinical Sciences, Brain Chemistry, Parkinson´s Disease, Neurosciences, Parkinson Disease, Cognition disorders, Mirroring, and Neuro-Degenerative Diseases
Research Interests:
Research Interests: Psychology, Neuropsychology, Dementia, Cognition, Medicine, and 14 moreHumans, Genetic Testing, Disease, Cognitive Therapy, Executive Functions, Clinical Sciences, Cognitive impairment, Parkinson´s Disease, Neurosciences, Dementia With Lewy Bodies, Parkinson Disease, Cognition disorders, Cholinergic agents, and Neuropsychological Tests
Research Interests: Cognitive Science, Computer Science, Metaphysics, Philosophy Of Language, Consciousness, and 14 moreCognitive Neuroscience, Medicine, Behavioral Neuroscience, Emergence, Bayesian Inference, Brain, Computational Models, Oscillators, Integrated Information Theory, Weak Emergence, Psychology and Cognitive Sciences, Medical and Health Sciences, Free Energy Principle, and strong emergence
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Cognitive enhancement is signified by adaptive behavioural change following an intervention that targets the brain. Although much of the discussion and research into cognitive enhancement focuses on the effects of neural interventions in... more
Cognitive enhancement is signified by adaptive behavioural change following an intervention that targets the brain. Although much of the discussion and research into cognitive enhancement focuses on the effects of neural interventions in healthy individuals, it is useful to consider evidence from clinical populations. Diseases of the central nervous system represent the primary and richest source of evidence on the effects of brain manipulations, which are in the first instance therapeutic. Parkinson’s disease (PD) is used as a model for understanding the effects of pharmacological agents that target systems with a central role in cognition. The mixed outcomes of deep brain stimulation on cognition will also be discussed. By illustrating the psychopharmacological principle of diverse and malleable neurochemical optima for different cognitive functions, and the role of individual differences, it will be argued that the entire spectrum of cognitive effects in any one individual following any given manipulation, such as the administration of a drug, often includes enhancement as well as impairment. Predicting these effects represents a complex multivariate problem, and the accuracy of this predictive effort, as well as the harm prevention it connotes, is determined by our evolving understanding of the brain and cognition. A manipulation can be said to confer cognitive enhancement; however, it is argued that using the global term cognitive enhancer to refer to such a manipulation without qualification is of limited utility.
Research Interests:
Research Interests:
a b s t r a c t This study sought to disambiguate the impact of Parkinson's disease (PD) on cognitive control as indexed by task set switching, by addressing discrepancies in the literature pertaining to disease severity and paradigm... more
a b s t r a c t This study sought to disambiguate the impact of Parkinson's disease (PD) on cognitive control as indexed by task set switching, by addressing discrepancies in the literature pertaining to disease severity and paradigm heterogeneity. A task set is governed by a rule that determines how relevant stimuli (stimulus set) map onto specific responses (response set). Task set switching may entail reconfiguration in either or both of these components. Although previous studies have shown that PD patients are impaired at switching between stimuli, in the present study not all patients were impaired at switching entire task sets, that is, both stimulus and response sets: compared with controls, patients with unilateral signs (Hoehn & Yahr Stage I) demonstrated intact switching, even following withdrawal from dopaminergic medication, while bilaterally affected Stage II patients were impaired. The parametric measure of Unified Parkinson's Disease Rating Scale (UPDRS) sc...
In recent years, there have been many computational simulations of spontaneous neural dynamics. Here, we explore a model of spontaneous neural dynamics and allow it to control a virtual agent moving in a simple environment. This setup... more
In recent years, there have been many computational simulations of spontaneous neural dynamics. Here, we explore a model of spontaneous neural dynamics and allow it to control a virtual agent moving in a simple environment. This setup generates interesting brain-environment feedback interactions that rapidly destabilize neural and behavioral dynamics and suggest the need for homeostatic mechanisms. We investigate roles for both local homeostatic plasticity (local inhibition adjusting over time to balance excitatory input) as well as macroscopic task negative activity (that compensates for task positive, sensory input) in regulating both neural activity and resulting behavior (trajectories through the environment). Our results suggest complementary functional roles for both local homeostatic plasticity and balanced activity across brain regions in maintaining neural and behavioral dynamics. These findings suggest important functional roles for homeostatic systems in maintaining neura...
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Background: Recruitment and retention of participants in clinical trials for Parkinson’s disease (PD) is challenging. A qualitative study embedded in the PD STAT multi-centre randomised controlled trial of simvastatin for neuroprotection... more
Background: Recruitment and retention of participants in clinical trials for Parkinson’s disease (PD) is challenging. A qualitative study embedded in the PD STAT multi-centre randomised controlled trial of simvastatin for neuroprotection in PD explored the motivators, barriers and challenges of participants, care partners and research staff. Objective: To outline a set of considerations informing a patient-centred approach to trial recruitment, retention, and delivery. Method: We performed semi-structured interviews and focus groups with a subset of trial participants and their care partners. Quantitative and qualitative data were obtained through surveys circulated among the 235 participants across 23 UK sites at the beginning, middle and end of the 2-year trial. We also interviewed and surveyed research staff at trial closure. Results: Twenty-seven people with PD, 6 care partners and 9 researchers participated in interviews and focus groups. A total of 463 trial participant survey...
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Noradrenergic dysfunction may play a significant role in cognition in Parkinson’s disease due to the early degeneration of the locus coeruleus. Converging evidence from patient and animal studies points to the role of noradrenaline in... more
Noradrenergic dysfunction may play a significant role in cognition in Parkinson’s disease due to the early degeneration of the locus coeruleus. Converging evidence from patient and animal studies points to the role of noradrenaline in dopaminergically insensitive aspects of the parkinsonian dysexecutive syndrome, yet the direct effects of noradrenergic enhancement have not to date been addressed. Our aim was to directly investigate these, focusing on impulsivity during response inhibition and decision making. To this end, we administered 40 mg atomoxetine, a selective noradrenaline re-uptake inhibitor to 25 patients with Parkinson’s disease (12 female /13 male; 64.4 6.9 years old) in a double blind, randomized, placebo controlled design. Patients completed an extensive battery of neuropsychological tests addressing response inhibition, decision-making, attention, planning and verbal short term memory. Atomoxetine improved stopping accuracy on the Stop Signal Task [F(1,19) = 4.51, P ...
Research Interests:
Research Interests:
Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson’s disease
In follow-up to a large-scale ethics survey of neuroscientists whose research involves neuroimaging, brain stimulation and imaging genetics, we conducted focus groups and interviews to explore their sense of responsibility about... more
In follow-up to a large-scale ethics survey of neuroscientists whose research involves neuroimaging, brain stimulation and imaging genetics, we conducted focus groups and interviews to explore their sense of responsibility about integrating ethics into neuroimaging and readiness to adopt new ethics strategies as part of their research. Safety, trust and virtue were key motivators for incorporating ethics into neuroimaging research. Managing incidental findings emerged as a predominant daily challenge for faculty, while student reports focused on the malleability of neuroimaging data and scientific integrity. The most frequently cited barrier was time and administrative burden associated with the ethics review process. Lack of scholarly training in ethics also emerged as a major barrier. Participants constructively offered remedies to these challenges: development and dissemination of best practices and standardized ethics review for minimally invasive neuroimaging protocols. Students in particular, urged changes to curricula to include early, focused training in ethics.
Research Interests:
Research Interests:
In an effort to provide timely clinical input for people with Parkinson’s disease (PD) in the face of increasing demand and resource limitation in our UK based service, we introduced remote management in place of clinic appointment,... more
In an effort to provide timely clinical input for people with Parkinson’s disease (PD) in the face of increasing demand and resource limitation in our UK based service, we introduced remote management in place of clinic appointment, including the use of the Parkinson’s KinetiGraph (PKG™), a wrist-worn device that provides a continuous measure of movement. We evaluated our reporting methods and findings, the nature of unmet need we identified, our treatment recommendations and the degree of their implementation in our patients whose feedback guided our service developments. Our evaluation highlighted opportunities and challenges associated with incorporating digital data into care traditionally delivered via in-person contact.
Research Interests:
Research Interests:
Research Interests:
Cognitive control has traditionally been associated with pFC based on observations of deficits in patients with frontal lesions. However, evidence from patients with Parkinson's disease indicates that subcortical regions also... more
Cognitive control has traditionally been associated with pFC based on observations of deficits in patients with frontal lesions. However, evidence from patients with Parkinson's disease indicates that subcortical regions also contribute to control under certain conditions. We scanned 17 healthy volunteers while they performed a task-switching paradigm that previously dissociated performance deficits arising from frontal lesions in comparison with Parkinson's disease, as a function of the abstraction of the rules that are switched. From a multivoxel pattern analysis by Gaussian Process Classification, we then estimated the forward (generative) model to infer regional patterns of activity that predict Switch/Repeat behavior between rule conditions. At 1000 permutations, Switch/Repeat classification accuracy for concrete rules was significant in the BG, but at chance in the frontal lobe. The inverse pattern was obtained for abstract rules, whereby the conditions were successful...
Research Interests:
Research Interests:
Cognitive enhancement is signified by adaptive behavioural change following an intervention that targets the brain. Although much of the discussion and research into cognitive enhancement focuses on the effects of neural interventions in... more
Cognitive enhancement is signified by adaptive behavioural change following an intervention that targets the brain. Although much of the discussion and research into cognitive enhancement focuses on the effects of neural interventions in healthy individuals, it is useful to consider evidence from clinical populations. Diseases of the central nervous system represent the primary and richest source of evidence on the effects of brain manipulations, which are in the first instance therapeutic. Parkinson's disease (PD) is used as a model for understanding the effects of pharmacological agents that target systems with a central role in cognition. The mixed outcomes of deep brain stimulation on cognition will also be discussed. By illustrating the psychopharmacological principle of diverse and malleable neurochemical optima for different cognitive functions, and the role of individual differences, it will be argued that the entire spectrum of cognitive effects in any one individual following any given manipulation, such as the administration of a drug, often includes enhancement as well as impairment. Predicting these effects represents a complex multivariate problem, and the accuracy of this predictive effort, as well as the harm prevention it connotes, is determined by our evolving understanding of the brain and cognition. A manipulation can be said to confer cognitive enhancement; however, it is argued that using the global term cognitive enhancer to refer to such a manipulation without qualification is of limited utility.
Research Interests:
Anaïs Nin, diarist and author of autobiographical novellas and erotica, and gregarious socialite, was known for her exotic persona and stormy personal life. The concept of personality disorder and the underlying assumption of the... more
Anaïs Nin, diarist and author of autobiographical novellas and erotica, and gregarious socialite, was known for her exotic persona and stormy personal life. The concept of personality disorder and the underlying assumption of the buffering capacity that personality affords to stressors are discussed. Against this background, evidence drawn from Nin’s diaries, short stories and two biographies suggests that she conformed
Research Interests:
This study sought to disambiguate the impact of... more
This study sought to disambiguate the impact of Parkinson's disease (PD) on cognitive control as indexed by task set switching, by addressing discrepancies in the literature pertaining to disease severity and paradigm heterogeneity. A task set is governed by a rule that determines how relevant stimuli (stimulus set) map onto specific responses (response set). Task set switching may entail reconfiguration in either or both of these components. Although previous studies have shown that PD patients are impaired at switching between stimuli, in the present study not all patients were impaired at switching entire task sets, that is, both stimulus and response sets: compared with controls, patients with unilateral signs (Hoehn & Yahr Stage I) demonstrated intact switching, even following withdrawal from dopaminergic medication, while bilaterally affected Stage II patients were impaired. The parametric measure of Unified Parkinson's Disease Rating Scale (UPDRS) score predicted increasing switch costs within the patient group. These findings suggest that switching entire task sets may be a function of extrastriatal, possibly non-dopaminergic pathology which increases as the disease progresses.
Research Interests: Cognitive Science, Cognitive Control, Cognition, Attention, Dopamine, and 15 moreHumans, Judgment, Cognitive Mapping, Female, Male, Disease Severity, Mental processes, Cognitive processes, Aged, Middle Aged, Analysis of Variance, Neuropsychologia, Disease Progression, Indexation, and Neuropsychological Tests
This study sought to disambiguate the impact of... more
This study sought to disambiguate the impact of Parkinson's disease (PD) on cognitive control as indexed by task set switching, by addressing discrepancies in the literature pertaining to disease severity and paradigm heterogeneity. A task set is governed by a rule that determines how relevant stimuli (stimulus set) map onto specific responses (response set). Task set switching may entail reconfiguration in either or both of these components. Although previous studies have shown that PD patients are impaired at switching between stimuli, in the present study not all patients were impaired at switching entire task sets, that is, both stimulus and response sets: compared with controls, patients with unilateral signs (Hoehn & Yahr Stage I) demonstrated intact switching, even following withdrawal from dopaminergic medication, while bilaterally affected Stage II patients were impaired. The parametric measure of Unified Parkinson's Disease Rating Scale (UPDRS) score predicted increasing switch costs within the patient group. These findings suggest that switching entire task sets may be a function of extrastriatal, possibly non-dopaminergic pathology which increases as the disease progresses.
Research Interests: Cognitive Science, Cognitive Control, Cognition, Attention, Dopamine, and 15 moreHumans, Judgment, Cognitive Mapping, Female, Male, Disease Severity, Mental processes, Cognitive processes, Aged, Middle Aged, Analysis of Variance, Neuropsychologia, Disease Progression, Indexation, and Neuropsychological Tests
Noradrenergic dysfunction may play a significant role in cognition in Parkinson's disease due to the early degeneration of the locus coeruleus. Converging evidence from patient and animal studies points to the role of noradrenaline in... more
Noradrenergic dysfunction may play a significant role in cognition in Parkinson's disease due to the early degeneration of the locus coeruleus. Converging evidence from patient and animal studies points to the role of noradrenaline in dopaminergically insensitive aspects of the parkinsonian dysexecutive syndrome, yet the direct effects of noradrenergic enhancement have not to date been addressed. Our aim was to directly investigate these, focusing on impulsivity during response inhibition and decision making. To this end, we administered 40 mg atomoxetine, a selective noradrenaline re-uptake inhibitor to 25 patients with Parkinson's disease (12 female /13 male; 64.4 ± 6.9 years old) in a double blind, randomized, placebo controlled design. Patients completed an extensive battery of neuropsychological tests addressing response inhibition, decision-making, attention, planning and verbal short term memory. Atomoxetine improved stopping accuracy on the Stop Signal Task [F(1,19) ...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Learning in a constant environment, and adapting flexibly to a changing one, through changes in reinforcement contingencies or valence-free cues, depends on overlapping circuitry that interconnects the prefrontal cortex (PFC) with the... more
Learning in a constant environment, and adapting flexibly to a changing one, through changes in reinforcement contingencies or valence-free cues, depends on overlapping circuitry that interconnects the prefrontal cortex (PFC) with the striatum and is subject to several forms of neurochemical modulation. We present evidence from recent studies in animals employing electrophysiological, pharmacological and lesion techniques, and neuroimaging, neuropsychological and pharmacological investigations of healthy humans and clinical patients. Dopamine (DA) neurotransmission in the medial striatum and PFC is critical for basic reinforcement learning and the integration of negative feedback during reversal learning, whilst orbitofrontal 5-hydroxytryptamine (5-HT) likely mediates this type of low level flexibility, perhaps by reducing interference from salient stimuli. The role of prefrontal noradrenaline (NA) in higher order flexibility indexed through attentional set-shifting has recently received significant empirical support, and similar avenues appear promising in the field of task switching.