A central debate in philosophy and neuroscience pertains to whether PFC activity plays an essential role in the neural basis of consciousness. Neuroimaging and electrophysiology studies have revealed that the contents of conscious perceptual experience can be successfully decoded from PFC activity, but these findings might be confounded by post- perceptual cognitive processes, such as thinking, reasoning, and decision-making, that are not necessary for con- sciousness. To clarify the involvement of the PFC in consciousness, we present a synthesis of research (...) that has used intracranial electrical stimulation (iES) for the causal modulation of neural activity in the human PFC. This research provides compelling evidence that iES of only certain prefrontal regions (i.e., orbitofrontal cortex and anterior cingu- late cortex) reliably perturbs conscious experience. Conversely, stimulation of anterolateral prefrontal sites, often con- sidered crucial in higher-order and global workspace theories of consciousness, seldom elicits any reportable alterations in consciousness. Furthermore, the wide variety of iES-elicited effects in the PFC (e.g., emotions, thoughts, and olfactory and visual hallucinations) exhibits no clear relation to the immediate environment. Therefore, there is no evidence for the kinds of alterations in ongoing perceptual experience that would be predicted by higher-order or global workspace theories. Nevertheless, effects in the orbitofrontal and anterior cingulate cortices suggest a specific role for these PFC subregions in supporting emotional aspects of conscious experience. Overall, this evidence presents a challenge for higher-order and global workspace theories, which commonly point to the PFC as the basis for con- scious perception based on correlative and possibly confounded information. (shrink)

Libet demonstrated that a substantial duration (>0.5-1.0 s) of direct electrical stimulation of the surface of a sensory cortex at a threshold or liminal current is required before a subject can experience a percept. Libet and his co-workers originally proposed that the result could be due either to spatial and temporal facilitation of the underlying neurons or additionally to a prolonged central processing time. However, over the next four decades, Libet chose to attribute the prolonged latency for evoking (...) conscious experience to a prolonged central processing time. In my view, Libet has not provided any convincing evidence, either on the basis of his own past work or in his critique of my paper, for his hypothesis of a central processing time exceeding 0.5s before conscious experience emerges following direct electrical threshold stimulation of the cortical surface. I stand by my original results and conclusion that such prolonged latencies are largely the consequence of a dynamically increasing cortical facilitatory process that begins hundreds of milliseconds before there is a sustained neuronal activation. In some cases, the facilitatory process must overcome an initial stimulus-induced inhibition before neuronal firing commences. (shrink)

Cranial electrical stimulation has been applied at various current levels in both adults and children with neurological conditions with seemingly promising but somewhat inconsistent results. Stimulation-induced spatial electric fields within a specific brain region are likely a significant contributing factor for the biological effects. Although several simulation models have been used to predict EF distributions in the brain, these models actually have not been validated by in vivo CES-induced EF measurements in the live human (...) class='Hi'>brain. This study directly measured the CES-induced voltage changes with implanted stereotactic-electroencephalographic electrodes in twenty-one epilepsy participants and then compared these measured values with the simulated ones obtained from the personalized models. In addition, we further investigated the influence of stimulation frequency, intensity, electrode montage and age on EFs in parts of participants. We found both measured voltages and EFs obtained in vivo are highly correlated with the predicted ones in our cohort. In white matter and gray matter, the measured voltages linearly increased when the stimulation intensity increased from 5 to 500 μA but showed no significant changes with changing stimulation frequency from 0.5 to 200 Hz. Electrode montage, but not age, significantly affects the distribution of the EFs. Our in vivo measurements demonstrate that the individualized simulation model can reliably predict the CES-induced EFs in both adults and children. It also confirms that the CES-induced EFs highly depend on the electrode montages and individual anatomical features. (shrink)

Deep Brain Stimulation (DBS) is an invasive therapeutic method involving the implantation of electrodes and the electrical stimulation of specific areas of the brain to modulate their activity. DBS brings therapeutic benefits, but can also have adverse side effects. Recently, neuroethicists have recognized that DBS poses a threat to the very fabric of human existence, namely, to the selves of patients. This article provides a review of the neuroethical literature examining this issue, and identifies the (...) crucial dimensions related to the self which DBS may endanger—personal identity, authenticity, and autonomy. The most influential theories accounting for these dimensions are analyzed herein, and it is argued that most of these theories require further refinement. This paper also demonstrates the interrelation between personal identity, authenticity, and autonomy, and concludes that one can only fully understand the impact of DBS on the self when all of these factors are taken into account. (shrink)

Non‐invasive brain stimulation is used to modulate brain excitation and inhibition and to improve cognitive functioning. The effectiveness of the enhancement due to transcranial direct current stimulation (tDCS) is still controversial, but the technique seems to have large potential for improvement and more specific applications. In particular, it has recently been used by athletes, both beginners and professionals. This paper analyses the ethical issues related to tDCS enhancement, which depend on its specific features: ease of use, (...) immediate effect, non‐detectability and great variability of effects. If tDCS were to become widespread, there could be some potential side effects, especially the rise of inequality in many selective competitive contexts. I discuss two possible scenarios to counter this effect: that of prohibition and that of compensation, each supported by reasons and arguments that seem plausible and worthy of consideration. In conclusion, I show why I think the scenario of compensation is the preferable one. (shrink)

Despite technological and interpretative advances, the non-invasive modalities used for pre-surgical evaluation of patients with drug-resistant epilepsy, fail to generate a concordant anatomo-electroclinical hypothesis for the location of the seizure onset zone in many patients. This requires chronic monitoring with intracranial electroencephalography, which facilitates better localization of the seizure onset zone, and allows evaluation of the functional significance of cortical regions-of-interest by electrical stimulation mapping. There are two principal modalities for intracranial EEG, namely subdural electrodes and stereotactic depth (...) electrodes. Although ESM is considered the gold standard for functional mapping with subdural electrodes, there have been concerns about its utility with stereo-EEG. This is mainly because subdural electrodes allow contiguous sampling of the dorsolateral convexity of cerebral hemispheres, and permit delineation of the extent of eloquent functional areas on the cortical surface. Stereo-EEG, while having relatively sparse sampling on the cortical surface, offers the ability to access the depth of sulci, mesial and basal surfaces of cerebral hemispheres, and deep structures such as the insula, which are largely inaccessible to subdural electrodes. As stereo-EEG is increasingly the preferred modality for intracranial monitoring, we find it opportune to summarize the literature for ESM with stereo-EEG in this narrative review. Emerging evidence shows that ESM for defining functional neuroanatomy is feasible with stereo-EEG, but probably requires a different approach for interpretation and clinical decision making compared to ESM with subdural electrodes. We have also compared ESM with stereo-EEG and subdural electrodes, for current thresholds required to evoke desired functional responses vs. unwanted after-discharges. In this regard, there is preliminary evidence that ESM with stereo-EEG may be safer than ESM with subdural grids. Finally, we have highlighted important unanswered clinical and scientific questions for ESM with stereo-EEG in the hope to encourage future research and collaborative efforts. (shrink)

People suffering from Obsessive-Compulsive Disorder (OCD) do things they do not want to do, and/or they think things they do not want to think. In about 10 percent of OCD patients, none of the available treatment options is effective. A small group of these patients is currently being treated with deep brain stimulation (DBS). Deep brain stimulation involves the implantation of electrodes in the brain. These electrodes give a continuous electrical pulse to the (...) class='Hi'>brain area in which they are implanted. It turns out that patients may experience profound changes as a result of DBS treatment. It is not just the symptoms that change; patients rather seem to experience a different way of being in the world. These global effects are insufficiently captured by traditional psychiatric scales, which mainly consist of behavioural measures of the severity of the symptoms. In this article we aim to capture the changes in the patients’ phenomenology and make sense of the broad range of changes they report. For that we introduce an enactive, affordance-based model that fleshes out the dynamic interactions between person and world in four aspects. The first aspect is the patients’ experience of the world. We propose to specify the patients’ world in terms of a field of affordances, with the three dimensions of broadness of scope (‘width’ of the field), temporal horizon (‘depth’), and relevance of the perceived affordances (‘height’). The second aspect is the person-side of the interaction, that is, the patients’ self-experience, notably their moods and feelings. Thirdly, we point to the different characteristics of the way in which patients relate to the world. And lastly, the existential stance refers to the stance that patients take towards the changes they experience: the second-order evaluative relation to their interactions and themselves. With our model we intend to specify the notion of being in the world in order to do justice to the phenomenological effects of DBS treatment. (shrink)

In order to make an attempt at grouping the various aspects of brain functional imaging (fMRI, MRS, EEG-MEG, ...) within a coherent frame, we implemented a model consisting of a system of differential equations, that includes: (1) sodium membrane transport, (2) Na/K ATPase, (3) neuronal energy metabolism (i.e. glycolysis, buffering effect of phosphocreatine, and mitochondrial respiration), (4) blood-brain barrier exchanges and (5) brain hemodynamics, all the processes which are involved in the activation of brain areas. We (...) assumed that the correlation between brain activation and metabolism could be due to either changes in the concentrations of ATP and ADP following activation of Na/K ATPase that result from the changes in ion concentrations, or the involvement, in different phases of metabolism, of a second messenger such as calcium. In this article, we show how this type of model enables interpretation of MRS and fMRI published data that were obtained during prolonged stimulations. (shrink)

Deep brain stimulation is a clinical intervention for the treatment of movement disorders. It has also been applied to the treatment of psychiatric disorders such as depression, anorexia nervosa, obsessive-compulsive disorder, and schizophrenia. Psychiatric disorders including schizophrenia, bipolar disorder, and major depression can lead to psychosis, which can cause patients to lose touch with reality. The ventral tegmental area, located near the midline of the midbrain, is an important region involved in psychosis. However, the clinical application of (...) class='Hi'>electrical stimulation of the VTA to treat psychotic diseases has been limited, and related mechanisms have not been thoroughly studied. In the present study, hyperlocomotion and stereotyped behaviors of the mice were employed to mimic and evaluate the positive-psychotic-like behaviors. We attempted to treat positive psychotic-like behaviors by electrically stimulating the VTA in mice and exploring the neural mechanisms behind behavioral effects. Local field potential recording and in vivo fiber photometry to observe the behavioral effects and changes in neural activities caused by DBS in the VTA of mice. Optogenetic techniques were used to verify the neural mechanisms underlying the behavioral effects induced by DBS. Our results showed that electrical stimulation of the VTA activates local gamma-aminobutyric acid neurons, and dopamine neurons, reduces hyperlocomotion, and relieves stereotyped behaviors induced by MK-801 injection. The results of optogenetic manipulation showed that the activation of the VTA GABA neurons, but not DA neurons, is involved in the alleviation of hyperlocomotion and stereotyped behaviors. We visualized changes in the activity of specific types in specific brain areas induced by DBS, and explored the neural mechanism of DBS in alleviating positive psychotic-like behaviors. This preclinical study not only proposes new technical means of exploring the mechanism of DBS, but also provides experimental justification for the clinical treatment of psychotic diseases by electrical stimulation of the VTA. (shrink)

In the following text, medical, anthropological and ethical issues of deep brain stimulation, a medical technology in which electrodes implanted in the human brain electrically influence specified brain regions, will be discussed. After a brief account of the deep brain stimulation procedure and its chances and risks, anthropological and ethical aspects of the approach will be discussed. These relate to the reversibility of the procedure and to the patient’s capacity to control the effects it (...) exerts in the brain, to modifications and fluctuations in a person’s character traits and individuality brought about by neurostimulation, and to the range of legitimate, adequate uses of the deep brain stimulation approach. The paper concludes that deep brain stimulation should be confined to therapeutic contexts and to severe, otherwise treatment-refractory disorders in which the aim is to normalize brain functioning. Apart from this, it should not be used to modify a person’s individual character traits and behaviour or to enhance human traits. (shrink)

Using P300-based brain–computer interfaces in daily life should take into account the user’s emotional state because various emotional conditions are likely to influence event-related potentials and consequently the performance of P300-based BCIs. This study aimed at investigating whether external emotional stimuli affect the performance of a P300-based BCI, particularly built for controlling home appliances. We presented a set of emotional auditory stimuli to subjects, which had been selected for each subject based on individual valence scores evaluated a priori, while (...) they were controlling an electric light device using a P300-based BCI. There were four conditions regarding the auditory stimuli, including high valence, low valence, noise, and no sound. As a result, subjects controlled the electric light device using the BCI in real time with a mean accuracy of 88.14%. The overall accuracy and P300 features over most EEG channels did not show a significant difference between the four auditory conditions. When we measured emotional states using frontal alpha asymmetry and compared FAA across the auditory conditions, we also found no significant difference. Our results suggest that there is no clear evidence to support a hypothesis that external emotional stimuli influence the P300-based BCI performance or the P300 features while people are controlling devices using the BCI in real time. This study may provide useful information for those who are concerned with the implementation of a P300-based BCI in practice. (shrink)

The use of transcranial Electrical Stimulation in the modulation of cognitive brain functions to improve neuropsychiatric conditions has extensively increased over the decades. tES techniques have also raised new challenges associated with study design, stimulation protocol, functional specificity, and dose-response relationship. In this paper, we addressed challenges through the emerging methodology to investigate the dose-response relationship of High Definition-transcranial Direct Current Stimulation, identifying the role of negative valence in tinnitus perception. In light of the neurofunctional (...) testable framework and tES application, hypotheses were formulated to measure clinical and surrogate endpoints. We posited that conscious pairing adequately pleasant stimuli with tinnitus perception results in correction of the loudness misperception and would be reinforced by concurrent active HD-tDCS on the left Dorsolateral Prefrontal Cortex. The dose-response relationship between HD-tDCS specificity and the loudness perception is also modeled. We conducted a double-blind, randomized crossover pilot study with six recruited tinnitus patients. Accrued data was utilized to design a well-controlled adaptive seamless Bayesian dose-response study. The sample size and optimum interims were anticipated for adaptive decision-making about efficacy, safety, and single session dose parameters. Furthermore, preliminary pilot study results were sufficient to show a significant difference within the longitudinally detected self-report tinnitus loudness between before and under positive emotion induction. This study demonstrated a research methodology used to improve emotion regulation in tinnitus patients. In the projected method, positive emotion induction is essential for promoting functional targeting under HD-tDCS anatomical specificity to indicate the efficacy and facilitate the dose-finding process. The continuous updating of prior knowledge about efficacy and dose during the exploratory stage adapts the anticipated dose-response model. Consequently, the effective dose range to make superiority neuromodulation in correcting loudness misperception of tinnitus will be redefined. Highly effective dose adapts the study to a standard randomized trial and transforms it into the confirmatory stage in which active HD-tDCS protocol is compared with a sham trial. Establishing the HD-tDCS intervention protocols relying on this novel method provides reliable evidence for regulatory agencies to approve or reject the efficacy and safety. Furthermore, this paper supports a technical report for designing multimodality data-driven complementary investigations in emotion regulation, including EEG-driven neuro markers, Stroop-driven attention biases, and neuroimaging-driven brain network dynamics. (shrink)

Déjà vu and involuntary autobiographical memories (IAM) can be induced by intracranial electric brain stimulation in epileptic patients, sometimes in the same individual. We suggest that there may be different types of IAM which should be taken into account and provide several ideas to test the hypothesis of a continuity between IAM and déjà vu phenomena.

Due to the individual differences controlling brain-computer interfaces, the applicability and accuracy of BCIs based on motor imagery are limited. To improve the performance of BCIs, this article examined the effect of transcranial electrical stimulation on brain activity during MI. This article designed an experimental paradigm that combines tES and MI and examined the effects of tES based on the measurements of electroencephalogram features in MI processing, including the power spectral density and dynamic event-related desynchronization. Finally, (...) we investigated the effect of tES on the accuracy of MI classification using linear discriminant analysis. The results showed that the ERD of the μ and β rhythms in the left-hand MI task was enhanced after electrical stimulation with a significant effect in the tDCS group. The average classification accuracy of the transcranial alternating current stimulation group and transcranial direct current stimulation group were improved significantly compared to the pre-and pseudo stimulation groups. These findings indicated that tES can improve the performance and applicability of BCI and that tDCS was a potential approach in regulating brain activity and enhancing valid features during noninvasive MI-BCI processing. (shrink)

Precision targeting of specific white matter bundles that traverse the subcallosal cingulate has been linked to efficacy of deep brain stimulation for treatment resistant depression. Methods to confirm optimal target engagement in this heterogenous region are now critical to establish an objective treatment protocol. As yet unexamined are the time-frequency features of the SCC evoked potential, including spectral power and phase-clustering. We examined these spectral features—evoked power and phase clustering—in a sample of TRD patients with implanted SCC stimulators. (...) Electroencephalogram was recorded during wakeful rest. Location of electrical stimulation in the SCC target region was the experimental manipulation. EEG was analyzed at the surface level with an average reference for a cluster of frontal sensors and at a time window identified by prior study. Morlet wavelets generated indices of evoked power and inter-trial phase clustering. Enhanced phase clustering at theta frequency was observed in every subject and was significantly correlated with SCC-EP magnitude, but only during left SCC stimulation. Stimulation to dorsal SCC evinced stronger phase clustering than ventral SCC. There was a weak correlation between phase clustering and white matter density. An increase in evoked delta power was also coincident with SCC-EP, but was less consistent across participants. DBS evoked time-frequency features index mm-scale changes to the location of stimulation in the SCC target region and correlate with structural characteristics implicated in treatment optimization. Results also imply a shared generative mechanism between evoked potentials evinced by electrical stimulation and evoked potentials evinced by auditory/visual stimuli and behavioral tasks. Understanding how current injection impacts downstream cortical activity is essential to building new technologies that adapt treatment parameters to individual differences in neurophysiology. (shrink)

The increasing attention to the brain in science and the media, and people’s continuing quest for a better life, have resulted in a successful self-help industry for brain enhancement. Apart from brain books, foods and games, there are several devices on the market that people can use to stimulate their brains and become happier, healthier or more successful. People can, for example, switch their brain state into relaxation or concentration with a light-and-sound machine, they can train (...) their brainwaves to cure their Attention Deficit Hyperactivity Disorder (ADHD) or solve their sleeping problems with a neurofeedback device, or they can influence the firing of their neurons with electric or magnetic stimulation to overcome their depression and anxieties. Working on your self with a brain device can be seen as a contemporary form of Michel Foucault’s ‘technologies of the self’. Foucault described how since antiquity people had used techniques such as reading manuscripts, listening to teachers, or saying prayers to ‘act on their selves’ and control their own thoughts and behaviours. Different techniques, Foucault stated, are based on different precepts and constitute different selves. I follow Foucault by stating that using a brain device for self-improvement indeed constitutes a new self. Drawing on interviews with users of brain devices and observations of the practices in brain clinics, I analyse how a new self takes shape in the use of brain devices; not a monistic (neuroscientific) self, but a ‘layered’ self of all kinds of entities that exchange and control each other continuously. (shrink)

Direct electrical stimulation has been widely applied in both guidance of lesion resection and scientific research; however, the design and selection of intraoperative cognitive mapping tasks have not been updated in a very long time. We introduce updated mapping tasks for language and non-language functions and provide recommendations for optimal design and selection of intraoperative mapping tasks. In addition, with DES becoming more critical in current neuroscientific research, a task design that has not been widely used in DES (...) yet was introduced for more delicate mapping of brain functions especially for research purposes. We also illustrate the importance of designing a common task series for DES and other non-invasive mapping techniques. This review gives practical updated guidelines for advanced application of DES in clinical and neuroscientific research. (shrink)

Patients with advanced Alzheimer's disease experience cognitive impairment and physical disabilities in daily life. Currently, there are no treatments available to slow down the course of the disease, and limited treatments exist only to treat symptoms. However, deep brain stimulation of the nucleus basalis of Meynert has been reported to improve cognitive function in individuals with AD. Here, we report the effects of NBM-DBS on cognitive function in a subject with severe AD. An 80-year-old male with severe AD (...) underwent surgery for bilateral NBM-DBS electrode placement. After 10 weeks of stimulation, Mini-Mental State Examination assessment improved from a score of 5 to 9 points, and assessment using the Alzheimer's Disease Assessment Scale–Cognitive Subscale showed a marked reduction in total score from 43 to 33 points, suggesting cognitive benefits from NBM-DBS. The patient's postoperative course was complicated by a subdural effusion that occurred several days after surgery, with complete recovery. Interestingly, the subject also displayed abnormal thermoregulation with stimulation initiation and stimulation parameter modifications. NBM-DBS may serve as a potential therapy for severe AD patients.Clinical Trial Registration: ChiCTR1900022324. (shrink)

Deep brain stimulation (DBS) of the globus pallidus interna and subthalamic nucleus has restored some degree of motor control in many patients in advanced stages of Parkinson’s disease. DBS has also been used to treat dystonia, essential tremor (progressive neurological condition causing trembling), chronic pain, obsessive-compulsive disorder, Tourette’s syndrome, major depressive disorder, obesity, cerebral palsy, and the minimally conscious state. Although the underlying mechanisms of the technique are still not clear, DBS can modulate underactive or overactive neural circuits (...) and restore disrupted communication between and among groups of neurons in interacting regions of the brain. This can control and relieve many symptoms associated with a range of neurological and psychiatric disorders.But the procedures of implanting and stimulating the electrodes are brain-invasive and entail significant risks. Some patients receiving DBS have experienced intracerebral hemorrhage, infection, cognitive disturbances such as impulsive behavior, and affective disturbances such as mania. It is not known whether continuous electrical stimulation of the brain would reshape synaptic connectivity and permanently alter neural circuits in ways that may not be salutary. The risk of these effects indicates that DBS should be used only when a patient’s condition is refractory to all other interventions and when there is a high probability that the technique will benefit the patient and improve his or her quality of life. If a patient’s quality of life is poor and all other treatment options have been exhausted, then the likelihood of benefit can justify physicians’ exposing patients to some risk. The clinical and ethical significance of the risk in DBS underscores the obligation of physicians to obtain fully informed consent from patients undergoing the procedure. (shrink)

Deep brain stimulation of the subthalamic nucleus is an effective treatment for the motor symptoms of movement disorders including Parkinson's Disease. Despite its therapeutic benefits, STN-DBS has been associated with adverse effects on mood and cognition. Specifically, apathy, which is defined as a loss of motivation, has been reported to emerge or to worsen following STN-DBS. However, it is often challenging to disentangle the effects of STN-DBSper sefrom concurrent reduction of dopamine replacement therapy, from underlying PD pathology or (...) from disease progression. To this end, pre-clinical models allow for the dissociation of each of these factors, and to establish neural substrates underlying the emergence of motivational symptoms following STN-DBS. Here, we performed a systematic analysis of rodent studies assessing the effects of STN-DBS on reward seeking, reward motivation and reward consumption across a variety of behavioral paradigms. We find that STN-DBS decreases reward seeking in the majority of experiments, and we outline how design of the behavioral task and DBS parameters can influence experimental outcomes. While an early hypothesis posited that DBS acts as a “functional lesion,” an analysis of lesions and inhibition of the STN revealed no consistent pattern on reward-related behavior. Thus, we discuss alternative mechanisms that could contribute to the amotivational effects of STN-DBS. We also argue that optogenetic-assisted circuit dissection could yield important insight into the effects of the STN on motivated behavior in health and disease. Understanding the mechanisms underlying the effects of STN-DBS on motivated behavior-will be critical for optimizing the clinical application of STN-DBS. (shrink)

Parkinson´s disease (PD) is a neurodegenerative disorder characterized by motor symptoms following dopaminergic depletion in the substantia nigra. Besides motor impairments however, several non-motor detriments can have the potential to considerably impact subjectively perceived quality of life in patients. Particularly emotion recognition of facial expressions has been shown to be affected in PD, and especially the perception of negative emotions like fear, anger or disgust is impaired. While emotion processing generally refers to automatic implicit as well as conscious explicit processing, (...) the focus of most previous studies in PD was on explicit recognition of emotions only, while largely ignoring implicit processing deficits. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is widely accepted as therapeutic measure in the treatment of PD and has been shown to advantageously influence motor problems. Among various concomitant non-motor effects of STN-DBS, modulation of facial emotion recognition under subthalamic stimulation has been investigated in previous studies with rather heterogeneous results. While there seems to be consensus regarding the processing of disgust which significantly deteriorates under STN stimulation, findings concerning emotions like fear or happiness report heterogeneous data and seem to depend on various experimental settings and measurements. In the present review, we summarized previous investigations focusing on STN-DBS influence on recognition of facial emotional expressions in patients suffering from PD. In a first step, we provide a synopsis of disturbances and problems in facial emotion processing observed in patients with PD. Secondly, we present findings of STN-DBS influence on facial emotion recognition and especially highlight different impacts of stimulation on implicit and explicit emotional processing. (shrink)

Libet discovered that a substantial duration (> 0.5-1.0 s) of direct electrical stimulation of the surface of the somatosensory cortex at threshold currents is required before human subjects can report that a conscious somatosensory experience had occurred. Using a reaction time method we confirm that a similarly long stimulation duration at threshold currents is required for activation of elementary visual experiences (phosphenes) in human subjects following stimulation of the surface of the striate cortex. However, the reaction (...) times for the subject to respond to the cessation of the visual experience after the end of electrical stimulation could be as brief as 225-242 ms. We also carried out extensive studies in cats under a variety of anesthetic conditions using the same electrodes and parameters of stimulation employed in the human studies to study the patterns of neuronal activity beneath the stimulating surface electrode. Whereas sufficiently strong currents can activate neurons within milliseconds, stimulating currents close to threshold activate sustained neural activity only after at least 350-500 ms. When currents are close to threshold, some neurons are inhibited for several hundreds of millisecond before the balance between inhibition and excitation shifts towards excitation. These results suggest that the prolonged latencies, i.e., latencies beyond 200-250 ms, for the emergence of conscious experience following direct cortical stimulation result from a delay in the sustained activation of underlying cortical neurons at threshold currents rather than being due to any unusually long duration in central processing time. Intracellular records from cortical neurological cells during repetitive electrical stimulation of the surface of the feline striate cortex demonstrate that such stimulation induces a profound depolarizing shift in membrane potential that may persist after each stimulus train. Such a depolarization is evidence that extracellular K+ concentrations have increased during electrical stimulation. Such an increase in extracellular K+ progressively increases cortical excitability until the threshold for sustained activation of cortical neurons is reached and then exceeded. Consequently, the long latency for threshold activation of cortical neurons depends upon a dynamically increasing cortical facilatory process that begins hundreds of milliseconds before there is sustained activation of such neurons. In some cases, this facilatory process must overcome an initial stimulus-induced inhibition before neuronal firing commences. (shrink)

This study describes the results of experiments motivated by an attempt to understand spectral processing in the cerebral cortex (DeValois and DeValois, 1988; Pribram, 1971, 1991). This level of inquiry concerns processing within a restricted cortical area rather than that by which spatially separate circuits become synchronized during certain behavioral and experiential processes. We recorded neural responses for 55 locations in the somatosensory (barrel) cortex of the rat to various combinations of spatial frequency (texture) and temporal frequency stimulation of (...) their vibrissae. The recordings obtained from single and multi-unit bursts of spikes were mapped as surface distributions of local dendritic potentials. The distributions showed a variety of patterns that are asymmetric with respect to the spatial and temporal parameters of stimulation, and were, therefore, not simply reflecting whisker flick rate. Next, a simulation of our results showed that these surface distributions of local dendritic potentials can be described by Gabor-like functions much as in the visual system. The results provide support for a model of distributed cortical processing that imposes a physiologically derived frame (the limited extent of a dendritic patch) and an anatomically derived (axonal) sampling of the distributed process. This combination provides a complex Gabor wavelet that encodes phase, which is necessary to processing such details as edges and texture in a scene. The synchronization across cortical areas that make the Gabor wavelet processes within restricted cortical areas available to one another (the binding problem) proceed at a ''higher order'' level of integration. Both levels of distributed processing accomplish computation in the conjoint spacetime and spectral domain. (shrink)

Most donated organs in the United States come from brain dead donors, while a small percentage come from patients who die in “controlled,” or expected, circumstances, typically after the family or surrogate makes a decision to withdraw life support. The number of organs available for transplant could be substantially if donations were permitted in “uncontrolled” circumstances–that is, from people who die unexpectedly, often outside the hospital. According to projections from the Institute of Medicine, establishing programs permitting “uncontrolled donation after (...) circulatory determination of death,” or uDCDD, throughout the United States has the potential to provide 22,000 more donation opportunities annually. In contrast, U.S. controlled donation after circulatory determination of death, or cDCDD, cases have increased progressively over the past decade from 87 to 848 donors, but currently account for only 10.6 percent of all deceased donors. Following the IOM recommendations, several projects exploring the feasibility of uDCDD were funded by the federal government, including a grant from the Health Resources and Services Administration that supported a pilot project in New York City in which the authors of this article participated.A key feature of our protocol, and indeed of many uDCDD protocols, is the initiation of preservation methods such as chest compressions and extracorporeal membrane oxygenation shortly after death in order to perfuse and preserve the donor's organs. Critics of uDCDD argue that the means of determining death deviates from generally ascribed principles. They assert that reinstituting circulation in order to preserve organs has the effect of “undoing” the prior determination of death. The result is that cDCDD is widely accepted and practiced routinely even though it only marginally increases the number of organs available for transplantation, and uDCDD is widely considered unacceptable despite being ethically embraced and proven to significantly increase organ donation opportunities in other countries. This article explores the evolution of this counterintuitive state of affairs and calls for a policy that, in line with the IOM report, allows for both cDCDD and uDCDD protocols. (shrink)

Medical interventions are usually categorized as “invasive” when they involve piercing the skin or inserting an object into the body. Beyond this standard definition, however, there is little discussion of the concept of invasiveness in the medical literature, despite evidence that the term is used in ways that do not reflect the standard definition of medical invasiveness. We interviewed psychiatrists, patients with depression, and members of the public without depression to better understand their views on the invasiveness of several psychiatric (...) electroceutical interventions (treatments that involve electrical or magnetic stimulation of the brain) for the treatment of depression. Our study shows that people recognize several kinds of invasiveness: physical, emotional, and lifestyle. In addition, several characteristics of therapies influence how invasive they are perceived to be; these include the perceived capacity of an intervention to result in harm; how localized the effects of the intervention are; the amount of control retained by the person receiving the intervention; how permanent its effects are perceived as being; and how familiar it seemed to participants. Our findings contribute to a small literature on the concept of invasiveness, which emphasizes that categorizing an intervention as invasive, or as noninvasive, evokes a variety of other normative considerations, including the potential harm it poses and how it compares to other potential therapies. It may also draw attention away from other salient features of the intervention. (shrink)

It has been well documented that the auditory system in the superior temporal cortex is responsible for processing basic auditory sound features, such as sound frequency and intensity, while the prefrontal cortex is involved in higher-order auditory functions, such as language processing and auditory episodic memory. The temporal auditory cortex has vast forward anatomical projections to the prefrontal auditory cortex, connecting with the lateral, medial, and orbital parts of the prefrontal cortex. The connections between the auditory cortex and the prefrontal (...) cortex thus help in localizing, recognizing, and comprehending external auditory inputs. In addition, the medial prefrontal cortex is believed to be a core region of episodic memory retrieval and is one of the most important regions in the default mode network. However, previous neural evidence with regard to the comparison between basic auditory processing and auditory episodic memory retrieval mainly comes from fMRI studies. The specific neural networks and the corresponding critical frequency bands of neuronal oscillations underlying the two auditory functions remain unclear. In the present study, we reported results of direct cortical stimulations during stereo-electro-encephalography recording in a patient with drug-resistant epilepsy. Electrodes covered the superior temporal gyrus, the operculum and the insula cortex of bilateral hemispheres, the prefrontal cortex, the parietal lobe, the anterior and middle cingulate cortex, and the amygdala of the left hemisphere. Two types of auditory hallucinations were evoked with direct cortical stimulations, which were consistent with the habitual seizures. The noise hallucinations, i.e., “I could hear buzzing noises in my head,” were evoked with the stimulation of the superior temporal gyrus. The episodic memory hallucinations “I could hear a young woman who was dressed in a red skirt saying: What is the matter with you?,” were evoked with the stimulation of MPFC. The patient described how she had met this young woman when she was young and that the woman said the same sentence to her. Furthermore, by analyzing the high gamma power induced by direct electrical stimulation, two dissociable neural networks underlying the two types of auditory hallucinations were localized. Taken together, the present results confirm the hierarchical processing of auditory information by showing the different involvements of the primary auditory cortex vs. the prefrontal cortex in the two types of auditory hallucinations. (shrink)

This paper proposed a novel tactile-stimuli P300 paradigm for Brain-Computer Interface, which potentially targeted at people with less learning ability or difficulty in maintaining attention. The new paradigm using only two types of stimuli was designed, and different targets were distinguished by frequency and spatial information. The classification algorithm was developed by introducing filters for frequency bands selection and conducting optimization with common spatial pattern on the tactile evoked EEG signals. It features a combination of spatial and frequency information, (...) with the spatial information distinguishing the sites of stimuli and frequency information identifying target stimuli and disturbances. We investigated both electrical stimuli and vibration stimuli, in which only one target site was stimulated in each block. The results demonstrated an average accuracy of 94.88% for electrical stimuli and 95.21% for vibration stimuli, respectively. (shrink)

Objective: Electrical stimulation potentially delineates epileptogenic cortex through induction of typical seizures. Although frequently employed, its value for epilepsy surgery remains controversial. Similarly, ES is used to identify symptomatogenic zones, but with greater success and a long-standing evidence base. Recent work points to new seizure symptoms such as ictal central apnea that may enhance presurgical hypotheses. The aims of this review are 2-fold: to determine the value of ES-induced seizures in epilepsy surgery and to analyze current evidence on (...) ICA as a new surrogate of symptomatogenic cortex.Methods: Three databases were searched for ESIS. Investigators independently selected studies according to pre-specified criteria. Studies reporting postoperative outcome in patients with ESIS were included in a meta-analysis. For ES-induced apnea, a thorough search was performed and reference list searching was employed.Results: Of 6,314 articles identified for ESIS, 25 were considered eligible to be reviewed in full text. Fourteen studies were included in the qualitative synthesis ; six studies were included in the meta-analysis. The meta-analysis showed that favorable outcome is associated with ESIS prior to surgery. In addition, the overall estimation of the occurrence of favorable outcome among cases with ESIS is 68.13%. On the other hand, recent studies have shown that stimulation of exclusively mesial temporal lobe structures elicits central apnea and represents symptomatogenic anatomic substrates of ICA. This is in variance with traditional teaching that mesial temporal ES is non-symptomatogenic.Conclusions: ES is a tool highly likely to aid in the delineation of the epileptogenic zone, since ESIS is associated with favorable postoperative outcomes. There is an urgent need for prospective evaluation of this technique, including effective stimulation parameters and surgical outcomes, that will provide knowledge base for practice. In addition, ES-induced apnea studies suggest that ICA, especially when it is the first or only clinical sign, is an important semiological feature in localizing the symptomatogenic zone to mesial temporal lobe structures, which must be considered in SEEG explorations where this is planned, and in surgical resection strategies. (shrink)