Frequency-specific network activity predicts bradykinesia severity in Parkinson's disease

Objective Bradykinesia has been associated with beta and gamma band interactions in the basal ganglia-thalamo-cortical circuit in Parkinson’s disease. In this present cross-sectional study, we aimed to search for neural networks with electroencephalography whose frequency-specific actions may predict bradykinesia. Methods Twenty Parkinsonian patients treated with bilateral subthalamic stimulation were first prescreened while we selected four levels of contralateral stimulation (0: OFF, 1–3: decreasing symptoms to ON state) individually, based on kinematics. In the screening period, we performed 64-channel electroencephalography measurements simultaneously with electromyography and motion detection during a resting state, finger tapping, hand grasping tasks, and pronation-supination of the arm, with the four levels of contralateral stimulation. We analyzed spectral power at the low (13–20 Hz) and high (21–30 Hz) beta frequency bands and low (31–60 Hz) and high (61–100 Hz) gamma frequency bands using the dynamic imaging of coherent sources. Structural equation modelling estimated causal relationships between the slope of changes in network beta and gamma activities and the slope of changes in bradykinesia measures. Results Activity in different subnetworks, including predominantly the primary motor and premotor cortex, the subthalamic nucleus predicted the slopes in amplitude and speed while switching between stimulation levels. These subnetwork dynamics on their preferred frequencies predicted distinct types and parameters of the movement only on the contralateral side. Discussion Concurrent subnetworks affected in bradykinesia and their activity changes in the different frequency bands are specific to the type and parameters of the movement; and the primary motor and premotor cortex are common nodes

Network substrates of cognitive impairment in Alzheimer's Disease

This is the final version. Available on open access from Elsevier via the DOI in this recordObjectives: Functional and structural disconnection of the brain is a prevailing hypothesis to explain cognitive impairment in Alzheimer's Disease (AD). We aim to understand the link between alterations to networks and cognitive impairment using functional connectivity analysis and modelling. Methods: EEG was recorded from 21 AD patients and 26 controls, mapped into source space using eLORETA, and functional connectivity was calculated using phase locking factor. The mini-mental state exam (MMSE) was used to assess cognitive impairment. A computational model was used to uncover mechanisms of altered functional connectivity. Results: Small-worldness (SW) of functional networks decreased in AD and was positively correlated with MMSE score and the language sub-score. Reduced SW was a result of increased path lengths, predominantly localized to the temporal lobes. Combining observed differences in local oscillation frequency with reduced temporal lobe effective connectivity in the model could account for observed functional network differences. Conclusions: Temporal lobe disconnection plays a key role in cognitive impairment in AD. Significance: We combine electrophysiology, neuropsychological scores, and computational modelling to provide novel insight into the relationships between the disconnection hypothesis and cognitive decline in AD.Engineering and Physical Sciences Research Council (EPSRC)Wellcome TrustAlzheimer's SocietyGarfield Weston FoundationUniversity of Bristo

Correlatos neurales del déficit de memoria asociativa en el deterioro cognitivo leve: efecto del gen APOE y conversión a la enfermedad de Alzheimer

Programa de Doctorado en NeurocienciasEl daño sináptico, debido fundamentalmente a la presencia de oligómeros solubles de beta amiloide (Aß), es uno de los primeros eventos que caracteriza a la enfermedad de Alzheimer (EA). Estos fallos en la transmisión sináptica alteran los mecanismos de sincronización neuronal desencadenando cambios en las oscilaciones electroencefalográficas (EEG). Las oscilaciones neuronales en diferentes rangos de frecuencia facilitan el procesamiento y el flujo de información tanto a nivel local como entre regiones cerebrales distantes, y por ello constituyen un elemento fundamental de la cognición. Dado que la memoria episódica es una de las funciones cognitivas más afectadas en las fases prodrómicas de la EA, el presente trabajo pretende evaluar en pacientes con deterioro cognitivo leve de tipo amnésico (DCLa) el posible efecto que pueda ejercer el genotipo APOE4, considerado el mayor factor de riesgo genético para la EA de tipo esporádico, sobre las oscilaciones EEG asociadas a una tarea de memoria episódica. Además, se evaluará si dichas oscilaciones, ya sea de forma aislada o en combinación con otros marcadores estructurales de resonancia magnética (RM) cerebral, son capaces de predecir la conversión de DCLa a EA. Para abordar estos objetivos se ha adoptado una aproximación multimodal y longitudinal que incluye: i) diferentes índices de memoria, uno relacionado con la memoria asociativa y otro relacionado con el beneficio que supone para la memoria episódica presentar claves semánticas durante la codificación, ii) diferentes parámetros de las oscilaciones EEG (potencia espectral, frecuencia y distribución topográfica) evaluadas a nivel de sensor y a nivel de fuentes generadoras, y iii) diversos marcadores de la estructura cerebral, como el espesor cortical y el volumen del hipocampo y la amígdala. En el estudio participaron 26 personas mayores cognitiva y neurológicamente normales que no portaban el genotipo APOE4 (controles) y 34 pacientes con DCLa, 18 de los cuales portaban el APOE4 (¿4-) y 16 no (¿4+). Transcurridos 2 años, 16 DCLa convirtieron a EA (DCLa-c) y 18 permanecieron estables (DCLa-e). Las oscilaciones EEG se registraron en la línea base durante la codificación y recuperación de nuevas memorias. En la fase de codificación, los participantes fueron expuestos a caras de personas famosas en una determinada localización espacial, la mitad precedidas por claves semánticas congruentes y la otra mitad por claves incongruentes. En la fase de recuperación se esperaba que el reconocimiento de la cara en una localización particular estuviera facilitado para las caras codificadas en condiciones de congruencia semántica. La memoria asociativa fue mejor en los controles y peor en los DCLa ¿4+ y en los DCLa-c, mientras que los DCLa ¿4- y los DCLa-e se situaron a medio camino. El daño asociativo mostrado por los DCLa ¿4+ y los DCLa-c estuvo asociado a la incapacidad para beneficiarse de la congruencia semántica durante la codificación. A nivel estructural, el principal predictor de la memoria asociativa en los DCLa ¿4+ fue el volumen del hipocampo derecho, mientras que el volumen de la amígdala derecha emergió como el mejor predictor de la conversión a EA. Desde un punto de vista funcional, los DCLa ¿4+ y los DCLa-c mostraron una menor desincronización de alfa en amplias regiones de la corteza en comparación con los DCLa ¿4- y los DCLa-e, respectivamente. Este déficit funcional asociado a las oscilaciones alfa no solo fue capaz de predecir la conversión de DCLa a EA, sino que además mejoró la capacidad de la amígdala para predecir la progresión de la enfermedad. Aunque los mejores resultados se obtuvieron cuando se combinaron ambos marcadores (i.e., déficit funcional en el rango de alfa y volumen de la amígdala) en un único modelo. En el caso de los DCLa ¿4+, la menor desincronización de alfa fue un reflejo de su incapacidad para reclutar mecanismos compensatorios. En concreto, los análisis de mediación revelaron que la disminución de volumen del hipocampo en los DCLa impactó de manera diferente sobre la memoria en función de que los pacientes fueran portadores del genotipo APOE4. Mientras que este efecto fue directo en los DCLa ¿4+, en los DCLa ¿4- estuvo mediado por la capacidad para reclutar regiones temporales en el rango de theta y regiones parieto-temporales en el rango de alfa/beta, todo ello condicionado por el grado de integridad cortical del lóbulo temporal. Estos hallazgos ponen de manifiesto que las oscilaciones alfa asociadas a una tarea de memoria episódica son un buen predictor de la progresión de la EA, sobre todo si se combinan con otros marcadores estructurales del lóbulo temporal medial. Además, nos permiten entender mejor cómo el genotipo APOE4 modula el impacto de la atrofia del hipocampo sobre la memoria en pacientes con DCLa. En conjunto, los resultados del presente estudio aportan evidencias que podrían mejorar el diagnóstico temprano de la EA, su pronóstico y el diseño de intervenciones terapéuticas adaptadas al daño cerebral de cada individuo y a su potencial para compensarlo.Universidad Pablo de Olavide. Departamento de Fisiología, Anatomía y Biología CelularPostprin

Augmentation of Brain Function: Facts, Fiction and Controversy. Volume III: From Clinical Applications to Ethical Issues and Futuristic Ideas

The final volume in this tripartite series on Brain Augmentation is entitled “From Clinical Applications to Ethical Issues and Futuristic Ideas”. Many of the articles within this volume deal with translational efforts taking the results of experiments on laboratory animals and applying them to humans. In many cases, these interventions are intended to help people with disabilities in such a way so as to either restore or extend brain function. Traditionally, therapies in brain augmentation have included electrical and pharmacological techniques. In contrast, some of the techniques discussed in this volume add specificity by targeting select neural populations. This approach opens the door to where and how to promote the best interventions. Along the way, results have empowered the medical profession by expanding their understanding of brain function. Articles in this volume relate novel clinical solutions for a host of neurological and psychiatric conditions such as stroke, Parkinson’s disease, Huntington’s disease, epilepsy, dementia, Alzheimer’s disease, autism spectrum disorders (ASD), traumatic brain injury, and disorders of consciousness. In disease, symptoms and signs denote a departure from normal function. Brain augmentation has now been used to target both the core symptoms that provide specificity in the diagnosis of a disease, as well as other constitutional symptoms that may greatly handicap the individual. The volume provides a report on the use of repetitive transcranial magnetic stimulation (rTMS) in ASD with reported improvements of core deficits (i.e., executive functions). TMS in this regard departs from the present-day trend towards symptomatic treatment that leaves unaltered the root cause of the condition. In diseases, such as schizophrenia, brain augmentation approaches hold promise to avoid lengthy pharmacological interventions that are usually riddled with side effects or those with limiting returns as in the case of Parkinson’s disease. Brain stimulation can also be used to treat auditory verbal hallucination, visuospatial (hemispatial) neglect, and pain in patients suffering from multiple sclerosis. The brain acts as a telecommunication transceiver wherein different bandwidth of frequencies (brainwave oscillations) transmit information. Their baseline levels correlate with certain behavioral states. The proper integration of brain oscillations provides for the phenomenon of binding and central coherence. Brain augmentation may foster the normalization of brain oscillations in nervous system disorders. These techniques hold the promise of being applied remotely (under the supervision of medical personnel), thus overcoming the obstacle of travel in order to obtain healthcare. At present, traditional thinking would argue the possibility of synergism among different modalities of brain augmentation as a way of increasing their overall effectiveness and improving therapeutic selectivity. Thinking outside of the box would also provide for the implementation of brain-to-brain interfaces where techniques, proper to artificial intelligence, could allow us to surpass the limits of natural selection or enable communications between several individual brains sharing memories, or even a global brain capable of self-organization. Not all brains are created equal. Brain stimulation studies suggest large individual variability in response that may affect overall recovery/treatment, or modify desired effects of a given intervention. The subject’s age, gender, hormonal levels may affect an individual’s cortical excitability. In addition, this volume discusses the role of social interactions in the operations of augmenting technologies. Finally, augmenting methods could be applied to modulate consciousness, even though its neural mechanisms are poorly understood. Finally, this volume should be taken as a debate on social, moral and ethical issues on neurotechnologies. Brain enhancement may transform the individual into someone or something else. These techniques bypass the usual routes of accommodation to environmental exigencies that exalted our personal fortitude: learning, exercising, and diet. This will allow humans to preselect desired characteristics and realize consequent rewards without having to overcome adversity through more laborious means. The concern is that humans may be playing God, and the possibility of an expanding gap in social equity where brain enhancements may be selectively available to the wealthier individuals. These issues are discussed by a number of articles in this volume. Also discussed are the relationship between the diminishment and enhancement following the application of brain-augmenting technologies, the problem of “mind control” with BMI technologies, free will the duty to use cognitive enhancers in high-responsibility professions, determining the population of people in need of brain enhancement, informed public policy, cognitive biases, and the hype caused by the development of brain- augmenting approaches