P300 as an auxiliary method in clinical practice: A review of literature

Cognitive functions can be assessed and followed up over a period of time with cognitive evoked potentials (CEP) P300. In this context, brainstem auditory evoked potentials (BAEP) are most commonly used, but visual evoked potentials (VEP) are utilized as well. The research in this area has demonstrated that these techniques could be used as a supplemental method in diagnostics of numerous diseases such as Alzheimer's disease, mild cognitive impairment, vascular dementia, epilepsy, craniocerebral trauma, Parkinson's disease, multiple sclerosis, and other degenerative diseases. In addition, P300 can also be used as an auxiliary method in the diagnostics of mental disorders conditions such as schizophrenia, panic disorders, narcotic drug addiction, nicotinism, alcoholism, etc. The method assists in monitoring the course of diseases leading to encephalopathy, such as liver and kidney damage and grave anaemia. The advantages of P300 testing are easy application, non-invasiveness, and an unlimited number of potential applications. Moreover, the results obtained with this method are measurable and can be compared

EEG and Evoked Potential Measured of Age and Sex Differences in Central Nervous System Processing

Age and gender differences in CNS information processing were investigated with EEG measures of power spectral analysis and cortical coupling , and evoked potential measures of brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs), pattern reversal evoked potentials (PREPs) , and P300 evoked potentials . Eighty normal volunteers comprised four subgroups of 20 subjects: young females and young males (25-35 years); old females and old males (55-70 years). Trends were generally consistent across evoked potential measures: women and young people produced faster latency responses; females and oldsters produced larger amplitude responses. Old age was associated with reduced variability of electrophysiological responding across recording sites. Significant age and gender findings may be related to CNS excitatory /inhibitory equilibrium. Females and oldsters reportedly experience reduction of some neurotransmitters believed to be inhibitory in function. Furthermore, old age is accompanied by neuropathological changes which could result in heightened CNS excitability

The utility of latency and spectral analysis methods in evoked potential recordings from patients with hepatic encephalopathy

Evoked potentials (EPs) are small phasic potentials that are elicited in conjunction with sensory, motor and cognitive events. EP variables have been assessed in patients with cirrhosis but in general, methods were inadequately standardized and study populations incompletely characterized, leading to some studies questioning the validity of EP’s in diagnosing and monitoring hepatic encephalopathy, while other studies indicated that there is only a low positive yield with these investigations. Few studies have attempted tri-modal sensory and cognitive recordings. Recorded waveforms may demonstrate altered morphology while possessing broadly normal latencies. Since EP analysis is usually performed solely in the time domain, latency measurements do not therefore highlight morphological changes to the waveform and so abnormalities may go unreported. The aim of this study was twofold (i) to measure sensory and cognitive EPs in patients with cirrhosis in relation to their neuropsychiatric status and (ii) to address frequency content in relation to neuropsychiatric status by examining EPs with two spectral techniques, the Fourier Transform (FT) and the Power Spectral Density Estimate (PSD). Seventy patients with biopsy–proven cirrhosis were classified using clinical, psychometric and EEG criteria as unimpaired or as having minimal or overt hepatic encephalopathy (HE). Forty-eight healthy individuals served as controls. Visual (VEPs), brainstem auditory (BAEPs) somatosensory (SSEPs) and cognitive auditory (P300) EPs were recorded under standardized conditions. Significant latency differences were observed in sensory EPs between patients and controls with patient subgroups differences being less significant. The cognitive auditory P300 however, distinguished the patient subpopulations from one another. Frequency shifts are observed in all EP modalities with significant differences also occurring between patient groups. The sensitivity and specificity of the frequency-domain is comparable to that of the time-domain. Paired EP investigations analysed by latency indicate BAEP and P300 best discriminate any degree of encephalopathy; in the frequency domain it is the VEP combined with SEP and in the time-frequency domain it is the SEP. These findings suggest that EPs, when performed as a bank of multimodal tests and with spectral analysis, could provide a sensitive and specific method for the diagnosis and monitoring of hepatic encephalopathy

Evaluation of Chronic Kidney Disease by Using Visual Evoked Potential and Uremic Markers

BACK GROUND: Chronic Kidney Disease is often unrecognized health problem due to less awareness, less health care facilities. Due to its progressive and irreversible course it may presents with serious complications involving all systems including the central nervous system of our body. AIM AND OBJECTIVE: The aim of the present study was to “evaluate the involvement of central nervous system (CNS) in Chronic kidney disease (CKD) patients by doing Visual Evoked Potentials (VEP) and the estimation of blood levels of uremic markers (Uremic neurotoxins) like Blood Urea, Serum Creatinine. Serum Parathyroid hormone (PTH) in comparison with age matched controls”. The objectives of the study were to determine the subclinical involvement of central nervous system in CKD patients by doing Visual Evoked Potentials and compare it with controls, to assess the uremic neurotoxin’s role in uremic encephalopathy by measuring the blood levels of uremic markers (uremic neurotoxins) like Blood Urea, Serum Creatinine, Serum Parathyroid hormone in CKD patients and compare it with controls, to find out the most vulnerable group of CKD patients by comparing the VEP parameters and blood levels of uremic markers (uremic neurotoxins) among the two CKD groups (CKD3-5 on medical therapy, CKD5D on dialysis and to find the correlation between the Visual Evoked Potential (VEPs) parameters and blood level of uremic marker in Chronic Kidney Disease (CKD) patients. MATERIAL AND METHODOLOGY: 60 diagonsed as CKD (30-CKD3-5, 30-CKD5D) were recruited from Department of Nephrology ,Stanley medical college,Chennai.30 normal subjects were recruited from Master health checkup, Stanley Medical College, Chennai. Ethical committee approval was obtained .Informed and written consent was obtained. After explaining the procedure, VEP recording was done with the RMS Polyrite apparatus. The blood investigation done for the measurement of uremic markers. RESULTS: Means, standard deviations, chi square and 'p' values were calculated by One way ANOVA and ‘t’ test. Chi-square test was used to experiment the importance of disparity among the consolidated (quantitative) variables. Prolonged latencies with highly significant p-value (p<0.0001) of all VEP parameters and reduced amplitude with significant p-value (<0.05) was noticed. Elevated blood levels of all uremic markers was noticed. This altered variables was higher among CKD3-5 with significant p-value(p<0.05) in comparison with CKD 5D. Correlation was noticed but not significant between VEP parameters and blood levels of uremic markers. DISCUSSION: The altered parameters of VEP and Uremic markers may predict the subclinical involvement of central nervous system involvement in CKD patients. CONCLUSION: In order to reduce the morbidity and mortality in CKD patients, VEP recording and the estimation of blood levels of uremic markers may used as a screening tool to identify the subclinical involvement of central nervous system in future

Repetitive Transcranial Magnetic Stimulation by Theta Burst

Transcranial magnetic stimulation (TMS) is a non-invasive diagnostic and therapeutic technique used to stimulate the brain in several neurological and psychiatric diseases, even though the main bases underlying its action are not fully understood. Theta Burst Stimulation (TBS), a patterned form of repetitive TMS, has been assuming particular importance due to its faster application. Research of TBS effects on some higher cortical functions such as cognition after stimulation of the prefrontal cortex (PFC), or its possible influence in some less studied cortical regions (as the temporal cortex) has been limited and revealed inconsistent results. One of the problems assessing the cognitive TBS after-effects relates to the use of multiple evaluation methods, with different sensitivities. In this matter, the use of neurophysiology studies such as the auditory P300, a cognitive evoked potential, may be of particular importance. To date, studies addressing the association between auditory P300 and TBS are scarce, and some contradictory results were found. The study of other higher cognitive domains such as creativity is even rarer, but it may be relevant given that part of the neural networks involved in creative processing are associated with the PFC. The effect of TMS over the PFC, studying the modulation of functions mediated by the autonomic nervous system has also been reported, but there is still a significant disagreement between the rare studies performed. So far, the extent of the modulatory effects associated with TBS at the sensory level is still poorly known, and research with TBS over the auditory cortex, despite showing some positive results, remains inconclusive, with some reports of sound hypersensitivity after sessions with higher intensity stimulation. It should also be noted that a significant part of the knowledge about the effects of TBS derives from studies in patients, with dysfunctional neuronal networks or hemispheric lesions, which add challenges to the search for scientific evidence in healthy individuals. Given the uncertainties that remain regarding the extent of the neuromodulatory effects of TBS, the primary objective of this thesis focused on increasing the scientific knowledge related to the use of TBS in the healthy brain. Therefore, we intended to study the neurophysiological responses (such as auditory P300), the functional responses (such as auditory thresholds), and the physiological responses (such as cerebral oximetry and blood pressure) associated with the application of TBS in the prefrontal and temporal cortices. All studies used a target population of healthy young adults, with an average age of approximately 23 years, and similar education. TBS was performed accordingly to the 600-pulse paradigm described by Huang et al. (continuous and intermittent). Sham-controlled, double-blind intervention protocols were used, with random distribution by the respective groups. The main objective of the study in chapter III was to evaluate the effect of TBS on the dorsolateral prefrontal cortex (DLPFC) of both cerebral hemispheres in cognitive processing. The objective was to assess if the auditory P300 would be influenced by the stimulation type. Results revealed that the mean P300 peak latency after TBS decreased only after leftward iTBS. A significant delay in P300 latency was originated from both right and left cTBS. Amplitude response did not change significantly. The results covered in chapter IV derived from the use of TBS on the left DLPFC, studying the possibility of a relationship between the post-TBS auditory P300 and the post-TBS neuropsychological tests: Trail Making Test (TMT) and the Stroop Test of Words and Colours. Results revealed that cTBS led to a delay of the P300, also significantly influencing the expected performance on Stroop C and Stroop Interference when compared to the groups submitted to iTBS and sham stimulation. No significant results were found in the TMT tests for any type of TBS stimulation. In Chapter V, we studied the cerebral oximetry using Near Infra-Red Spectroscopy, blood pressure, and heart rate, after applying TBS to the right and left DLPFC. We found a significant reduction in oximetry in the left frontal region after ipsilateral cTBS and a significant decrease in systolic blood pressure after cTBS to the right DLPFC. Chapter VI covered the evaluation of the effects of TBS over the left temporal cortex, specifically studying the auditory thresholds in the ear closest to the coil. Results showed no major side effects after iTBS, cTBS, or sham stimulation. It was also found that iTBS led to lower hearing thresholds, especially when comparing the iTBS and sham groups at 500Hz and between the iTBS and cTBS groups at 4000Hz. Chapter VII addresses a patent concerning the technique and possible use of iTBS as a method to influence creative processing. After iTBS over the right DLPFC, results of an adapted selection of the Torrance Tests of Creative Thinking suggest that divergent thinking, originality and fluency improved significantly compared to the sham group. An integrative analysis of the results shows that TBS seems to effectively influence the underlying cortical neurons and cortico-subcortical networks. The findings thus support the existence of a trans-synaptic effect advocated initially for the classic repetitive TMS, which after the publication of our research can continue to be extended with greater confidence to TBS protocols. Our results also support the most consensual theory about the modulatory effects of the two main forms of TBS – intermittent (excitatory) and continuous (inhibitory) – particularly on the prefrontal and temporal cortices. The effects of TBS seem to be intrinsically correlated with the hemispheric lateralization and this may be related to the specific functions or dominance of each hemisphere and the specific stimulated cortical regions. The combined results of this investigation also seem to suggest that the inhibition induced by cTBS seems more effective when compared to the excitatory effect of iTBS, which seemed stronger in the left hemisphere. After all our research with TBS in more than one cortical region, we can infer that this is a safe technique, with rare and incipient side effects. The encouraging results after using iTBS in the auditory cortex opens new perspectives regarding future implementations of the technique and should be replicated in patients, particularly with mild sensorineural hearing loss, in order to assess whether this stimulation protocol can be a valid therapeutic technique in these cases. We also conclude that the techniques used to study TBS-related effects, as the P300 or the NIRS, can be very useful in the future, as an attempt to identify the effectiveness of the therapeutic use of TBS protocols, possibly allowing to adapt and modify the idealized interventions, leading to a personalized patient intervention. Our findings provide relevant information, necessary to increase the technical and scientific credibility required for achieving a more comprehensive and reliable clinical use of TBS. This is crucial at a time when transcranial magnetic stimulation use as an off-label therapy for numerous neurological and psychiatric diseases grows unregulated, and the patient best interests must be defended.A estimulação magnética transcraniana (EMT) é uma técnica de diagnóstico e terapêutica não invasiva, que tem vindo a evoluir nos últimos 35 anos. A aplicação terapêutica da forma repetitiva da EMT (EMTr), tem vindo a demonstrar a sua utilidade científica e clínica, com aplicação em várias doenças neurológicas e psiquiátricas como a depressão major, a perturbação obsessivo-compulsiva, dor e reabilitação em doentes com acidentes vasculares cerebrais, ainda que as principais bases subjacentes à sua acção não sejam totalmente compreendidas. A EMT baseia-se no princípio da indução magnética e na sua capacidade de induzir correntes elétricas no tecido cortical. Esses campos magnéticos (pulsos) originados por uma bobina adjacente ao couro cabeludo originam um fluxo iónico intracraniano que irá provocar a despolarização da membrana neuronal, desencadeando assim um potencial de ação. Embora a EMT exerça os seus efeitos predominantemente na área cortical adjacente à bobina, os potenciais de ação induzidos espalham-se trans-sinapticamente, originando a propagação da ativação para regiões corticais e subcorticais vizinhas pertencentes à rede neuronal em questão. Parece ocorrer ainda a aparente capacidade de influenciar a função do hemisfério contralateral à estimulação possivelmente por mediação calossal. Os efeitos da EMTr ao nível da modulação da excitabilidade neuronal estão intrinsecamente dependentes das características da estimulação, nomeadamente ao nível da frequência e padronização dos estímulos. A aplicação de frequências inferiores ou iguais a 1 Hz (EMTr de baixa frequência) são associadas à indução de um efeito inibitório neuronal, enquanto que a aplicação de frequências acima de 1 Hz, normalmente acima dos 5 Hz (EMTr de alta frequência), podem induzir um efeito excitatório. Em 2005 surgiu uma forma padronizada de aplicação dos pulsos magnéticos, denominada Theta Burst Stimulation (TBS), na qual grupos de 3 pulsos com alta frequência (bursts de 50Hz) são enviados a cada 200 milissegundos (5 Hz – frequência teta), implicando normalmente a aplicação de 600 pulsos por cada sessão de estimulação. Este é um protocolo que assume particular importância pela sua rápida aplicação, levando menos de 3 minutos a executar, sendo significativamente mais célere do que os protocolos clássicos de EMTr (que podem exceder 30 minutos). Efeitos neuromodulatórios opostos podem ser igualmente induzidos com TBS, sendo que a aplicação ininterrupta da estimulação durante 40 segundos – TBS contínua (cTBS) – parece originar uma diminuição na excitabilidade cortical com uma duração de até 50 minutos pós-estimulação, enquanto que a aplicação de apenas 2 segundos de TBS intervalada por 8 segundos de pausa – TBS intermitente (iTBS) – durante 190 segundos, terá a capacidade de induzir aumento na excitabilidade cortical até cerca de 60 minutos pós-estimulação. Apesar do volume significativo de investigação acumulada na estimulação com EMTr e TBS, demonstrando a sua capacidade modulatória e a sua aplicabilidade na prática clínica, a investigação dos seus efeitos sobre algumas funções corticais superiores como a cognição ou os efeitos da aplicação em algumas regiões corticais menos estudadas como a região temporal tem sido mais limitada (principalmente com a TBS) e apresentado alguns resultados contraditórios. O córtex pré-frontal assume particular importância associado à aplicação da EMTr/TBS dada a extensa rede de conexões com outras regiões corticais (como o córtex motor, o córtex sensitivo, a amígdala, o tálamo e o hipocampo), importantes em doenças como a depressão (desequilíbrio inter-hemisférico pré-frontal verificado por neuroimagem), e ainda pela sua aparente capacidade de influenciar funções autonómicas e cardiovasculares. Meta-análises como a de Lowe et al. 2018, avaliando os efeitos da TBS sobre o córtex pré-frontal, revelam que parece existir um efeito negativo no desempenho das tarefas de função executiva após estimulação com cTBS e um efeito positivo mas em menor grau após estimulação com iTBS. No entanto, o efeito mais definido da estimulação sobre as várias dimensões cognitivas permanece envolto em alguma dúvida, dado que por um lado têm surgido alguns resultados negativos e por outro lado a maioria dos estudos tem usado populações relativamente pequenas, com infrequente recurso a grupos sham. Um dos principais problemas na avaliação dos possíveis efeitos da estimulação magnética repetitiva prende-se com o uso de diversos métodos de avaliação, com diferentes sensibilidades para o estudo das várias dimensões cognitivas, ou ainda com técnicas com menor resolução temporal (como os estudos de imagem cerebral funcional) comparativamente a técnicas neurofisiológicas. Neste ponto, a utilização de estudos no âmbito da neurofisiologia, como os potenciais de longa latência, pode assumir particular importância. O P300 auditivo, é um potencial evocado cognitivo, dependente da atenção e capacidade de discriminação do sujeito, traduzindo estadios mais superiores ou avançados de processamento associado a uma tarefa. As origens neuronais do P300 são múltiplas e bi-hemisféricas, associando-se a regiões como o hipocampo, o córtex pré-frontal ventrolateral e o córtex cingulado posterior. Até à data, são raros os estudos que abordaram a associação entre o P300 auditivo e a EMTr e ainda mais raros combinando a estimulação com TBS e o P300. A avaliação dos resultados prévios sugere que a estimulação magnética pode ser capaz de influenciar o processamento cognitivo e que as alterações podem ser monitorizadas pelo P300, mas são encontrados alguns resultados contraditórios, existindo significativas discrepâncias na metodologia usada. […

Patogênese da encefalopatia hepática: um papel para os receptores de benzodiazepínicos?

A encefalopatia hepática (EH) é uma síndrome multifatorial, na qual a função do sistema nervoso central está alterada devido às conseqüências metabólicas da disfunção hepática. Os dois principais componentes das doenças hepáticas que levam à EH são a diminuição no número de hepatócitos funcionantes e o rearranjo vascular, que leva à diminuição na fração de sangue, efetivamente detoxificado pelo fígado. Os sintomas da EH podem variar de déficits cognitivos leves até o coma profundo. Algum grau de morte neuronal pode ser observado em pacientes com EH, como conseqüência da cirrose hepática, ou, na EH avançada, da presença de edema cerebral. No entanto, a maior parte da síndrome neurológica é reversível com a compensação da doença hepática. A etiologia da EH não é totalmente conhecida e trata-se, provavelmente, de um processo multifatorial. Inicialmente, as teorias apontavam para o acúmulo de neurotoxinas que prejudicariam a função neuronal. Mais recentemente, anormalidades em vários sistemas de neurotransmissão foram propostos como causas potencias da EH como, por exemplo, o aumento observado na neurotransmissão GABAérgica. Existe evidência de que este aumento esteja relacionado com o aumento da potenciação GABAérgica por substâncias de ação similar aos benzodiazepínicos, as quais se encontram aumentadas na EH. Com esta evidência em mente, foi tentada a terapia desta síndrome com flumazenil, um antagonista benzodiazepínico, o qual tem mostrado eficácia clínica em uma porcentagem variável de pacientes em estudos recentes. No entanto, ainda não há evidências conclusivas para sustentar uma relação causal entre o aumento de ligantes ao receptor de benzodiazepínicos e os sintomas da EH. É possível que esta relação exista em alguns, mas não em todos os pacientes com esta síndrome.Hepatic encephalopathy (HE) is a multifactorial syndrome in which the function of the central nervous system is impaired due to the metabolic consequences of liver disease. The two main components of liver pathology which lead to HE are the decrease in the number of functioning hepatocytes and the vascular rearrangement causing blood from the portal vein to bypass the liver. The symptoms of HE range from mild cognitive impairment to deep coma. Some degree of neuronal loss may be found in HE patients as a consequence of chronic cirrhosis and, in advanced HE, of brain edema; however, most of the HE syndrome is reversible with compensation of the liver disease. The pathogenesis of HE is not fully understood and &nbsp;is likely to be multifactorial. The initial theories implicated accumulation of neurotoxins leading to an impairment of neuronal function. With better understanding of the physiology of neuroreceptors, abnormalities in several neurotransmission systems have been put forward as potential causes of HE, such as a reported increase in GABAergic neurotransmission. There is evidence that this enhancement is related to an increase in the potentiation of GABAergic action by ligands to the benzodiazepine receptor (BZR), which are known to be increased in liver disease. With this evidence in mind, therapy with the benzodiazepine antagonist flumazenil has been attempted in HE, yielding clinical benefit in a variable percentage of patients in recent studies. However, there is still a lack of evidence to support a causal relationship between increased levels of benzodiazepine agonist ligands and HE symptoms. It is feasible to think that this relationship exists in some but not all HE patients

Advances in Clinical Neurophysiology

Including some of the newest advances in the field of neurophysiology, this book can be considered as one of the treasures that interested scientists would like to collect. It discusses many disciplines of clinical neurophysiology that are, currently, crucial in the practice as they explain methods and findings of techniques that help to improve diagnosis and to ensure better treatment. While trying to rely on evidence-based facts, this book presents some new ideas to be applied and tested in the clinical practice. Advances in Clinical Neurophysiology is important not only for the neurophysiologists but also for clinicians interested or working in wide range of specialties such as neurology, neurosurgery, intensive care units, pediatrics and so on. Generally, this book is written and designed to all those involved in, interpreting or requesting neurophysiologic tests

A Physiological Signal Processing System for Optimal Engagement and Attention Detection.

In today’s high paced, hi-tech and high stress environment, with extended work hours, long to-do lists and neglected personal health, sleep deprivation has become common in modern culture. Coupled with these factors is the inherent repetitious and tedious nature of certain occupations and daily routines, which all add up to an undesirable fluctuation in individuals’ cognitive attention and capacity. Given certain critical professions, a momentary or prolonged lapse in attention level can be catastrophic and sometimes deadly. This research proposes to develop a real-time monitoring system which uses fundamental physiological signals such as the Electrocardiograph (ECG), to analyze and predict the presence or lack of cognitive attention in individuals during task execution. The primary focus of this study is to identify the correlation between fluctuating level of attention and its implications on the physiological parameters of the body. The system is designed using only those physiological signals that can be collected easily with small, wearable, portable and non-invasive monitors and thereby being able to predict well in advance, an individual’s potential loss of attention and ingression of sleepiness. Several advanced signal processing techniques have been implemented and investigated to derive multiple clandestine and informative features. These features are then applied to machine learning algorithms to produce classification models that are capable of differentiating between the cases of a person being attentive and the person not being attentive. Furthermore, Electroencephalograph (EEG) signals are also analyzed and classified for use as a benchmark for comparison with ECG analysis. For the study, ECG signals and EEG signals of volunteer subjects are acquired in a controlled experiment. The experiment is designed to inculcate and sustain cognitive attention for a period of time following which an attempt is made to reduce cognitive attention of volunteer subjects. The data acquired during the experiment is decomposed and analyzed for feature extraction and classification. The presented results show that to a fairly reasonable accuracy it is possible to detect the presence or lack of attention in individuals with just their ECG signal, especially in comparison with analysis done on EEG signals. The continual work of this research includes other physiological signals such as Galvanic Skin Response, Heat Flux, Skin Temperature and video based facial feature analysis