Clinical cases of frontal lobe lesions have been significantly associated with acquired aggressive behaviour. Restoring neuronal and cognitive faculties of aggressive individuals through invasive brain intervention raises ethical questions in general. However, more questions have to be addressed in cases where individuals refuse surgical treatment. The ethical desirability and permissibility of using intrusive surgical brain interventions for involuntary or voluntary treatment of acquired aggressiveness is highly questionable. This article engages with the description of acquired aggressiveness in general, (...) and presents a rare clinical case to illustrate the difficulties of treating this population. To expand the debate further, this article explores the ethics related to invasive brain surgery in three parts: a) it examines coercive involuntary invasive brain surgery for the benefit of protecting others on individuals suffering from acquired aggressiveness who lack decision-making capacities to consent; b) it addresses voluntary psychosurgery on individuals suffering from acquired aggressiveness who are competent to consent; and, c) it questions whether acquired aggressive individuals, who are legally competent, have a duty to consent to invasive brain surgery, in order to maintain their autonomy by reducing or even eliminate their aggressive drives. Ensuring the safety and efficacy of surgical brain interventions could increase the ethical permissibility of voluntary treatment, but it would not necessarily entail ethical justification for proceeding with invasive brain surgery for treatment of intractable acquired aggressive behaviour. (shrink)

Bioethics, Volume 36, Issue 1, Page 25-41, January 2022.

Background: Patients undergoing invasive neurosurgical procedures offer researchers unique opportunities to study the brain. Deep brain stimulation patients, for example, may participate in research during the surgical implantation of the stimulator device. Although this research raises many ethical concerns, little attention has been paid to basic studies, which offer no therapeutic benefits, and the value of patient-participant perspectives.Methods: Semi-structured interviews were conducted with fourteen individuals across two studies who participated in basic intraoperative research during their deep (...) class='Hi'>brain stimulator surgery. Interviews explored interpretations of risks and benefits, enrollment motivations, and experiences of participating in awake brain research. Reflexive thematic analysis was conducted.Results: Seven themes were identified from participant narratives, including robust attitudes of trust, high valuations of basic science research, impacts of the surgical context, and mixed experiences of participation.Conclusion: We argue that these narratives raise the potential for a translational misconception and motivate intraoperative re-consent procedures. (shrink)

This is the first article in a two-part series describing subject and family perspectives from the central thalamic deep brain stimulation for the treatment of traumatic brain injury using the Medtronic PC + S first-in-human invasive neurological device trial to achieve cognitive restoration in moderate to severe traumatic brain injury, with subjects who were deemed capable of providing voluntary informed consent. In this article, we report on interviews conducted prior to surgery wherein we asked participants (...) about their experiences recovering from brain injury and their perspectives on study enrollment and participation. We asked how risks and benefits were weighed, what their expectations and fears were, and how decisions were reached about trial participation. We found that informed consent and enrollment decisions are fraught. Subjects and families were often split, with subjects more focused on putative benefits and families concerned about incremental risk. Both subjects and families viewed brain injury as disruptive to personal identity and relationships. As decisions were made about study enrollment, families struggled with recognizing the re-emergent agency of subjects and ceding decision-making authority to subjects who had previously been dependent upon them for protection and guidance. Subjects and family members reported a hope for the relief of cognitive disabilities, improved quality of life, normalization of interpersonal interactions, and a return to work or school as reasons for study participation, along with altruism and a desire to advance science. Despite these aspirations, both subjects and families appreciated the risks of the intervention and did not suffer from a therapeutic misconception. A second essay to be published in the next issue of Cambridge Quarterly of Healthcare Ethics—Clinical Neuroethics will describe interviews conducted after surgery, the effects of cognitive restoration for subjects, families, and challenges presented to the social structures they will call upon to support them through recovery. This subsequent article will be available online prior to its formal publication in October 2023. (shrink)

This is the second paper in a two-part series describing subject and family perspectives from the CENTURY-S (CENtral Thalamic Deep Brain Stimulation for the Treatment of Traumatic Brain InjURY-Safety) first-in-human invasive neurological device trial to achieve cognitive restoration in moderate to severe traumatic brain injury (msTBI). To participate, subjects were independently assessed to formally establish decision-making capacity to provide voluntary informed consent. Here, we report on post-operative interviews conducted after a successful trial of thalamic stimulation. All (...) five msTBI subjects met a pre-selected primary endpoint of at least a 10% improvement in completion time on Trail-Making-Test Part B, a marker of executive function. We describe narrative responses of subjects and family members, refracted against that success. Interviews following surgery and the stimulation trial revealed the challenge of adaptation to improvements in cognitive function and emotional regulation as well as altered (and restored) relationships and family dynamics. These improvements exposed barriers to social reintegration made relevant by recoveries once thought inconceivable. The study’s success sparked concerns about post-trial access to implanted devices, financing of device maintenance, battery replacement, and on-going care. Most subjects and families identified the need for supportive counseling to adapt to the new trajectory of their lives. (shrink)

Neuromodulatory effects of non-invasive brain stimulation (NIBS) have been extensively studied in chronic pain. A hypothetic mechanism of action would be to prevent or revert the ongoing maladaptive plasticity within the pain matrix. In this review, the authors discuss the mechanisms underlying the development of an abnormal plasticity in patients with chronic pain and the putative mechanisms of NIBS in modulating synaptic plasticity in neuropathic pain conditions.

Non-invasive brain stimulation promises innovative experimental possibilities for psychology and neurosci- ence as well as new therapeutic and palliative measures in medicine. Because of its good risk–benefit ratio, non-invasiveness and reversibility as well as its low effort and cost it has good chances of becoming a wide- spread tool in science, medicine and even in lay use. While most issues in medical and research ethics such as informed consent, safety, and potential for misuse can be handled with manageable (...) effort, the real promise of brain stimulation does raise one prominent moral worry: it may lay the foundation of reliable, precise and stable manipulations of the mind. This article addresses this worry and concludes that it is not the possibility of manipulation, but the shift in our understanding of our mind which stands in need of careful consideration. (shrink)

This mini-review provides a detailed outline of studies that have used multimodal approaches in non-invasive brain stimulation to investigate the pathophysiology of the three common movement disorders, namely, essential tremor, Parkinson’s disease, and dystonia. Using specific search terms and filters in the PubMed®database, we finally shortlisted 27 studies in total that were relevant to this review. While two-thirds (Brittain et al., 2013) of these studies were performed on Parkinson’s disease patients, we could find only three studies that were (...) conducted in patients with essential tremor. We clearly show that although multimodal non-invasive brain stimulation holds immense potential in unraveling the physiological mechanisms that are disrupted in movement disorders, the technical challenges and pitfalls of combining these methods may hinder their widespread application by movement disorder specialists. A multidisciplinary team with clinical and technical expertise may be crucial in reaping the fullest benefits from such novel multimodal approaches. (shrink)

While research to improve memory or counter decay caused by neurodegenerative diseases has a fairly long history, scientific attempts to erase memories are very recent. The use of non-invasive brain stimulation for memory modulation represents a new and promising application for the treatment of certain disorders [such as Post-Traumatic Stress Disorder ]. However, numerous ethical issues are related to memory intervention. In particular, the possibility of using forms of non-invasive brain stimulation requires to distinguish treatment interventions (...) from the enhancement of the healthy. Furthermore, a range of important societal and legal concerns arise when manipulating memories. In this short contribution, we address some of the most significant ethical, social, and legal implications surrounding the application of memory-modulation techniques and offer a series of reflections and considerations, which we hope can be of use to guide -and perhaps regulate- their potential, future implementation in society. (shrink)

Objective:This study aimed to investigate the effect of robot-assisted gait training therapy combined with non-invasive brain stimulation on lower limb function in patients with stroke and spinal cord injury.Data sourcesPubMed, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, and Web of Science were searched.Study selectionRandomized controlled trials published as of 3 March 2021. RCTs evaluating RAGT combined with NIBS, such as transcranial direct current stimulation and repetitive transcranial magnetic stimulation, for lower limb function and activities in patients with (...) stroke and SCI were included.Data extractionTwo reviewers independently screened the records, extracted the data, and assessed the risk of bias.Data synthesisA meta-analysis of five studies and risk of bias were conducted. Pooled estimates demonstrated that RAGT combined with NIBS significantly improved lower limb function [standardized mean difference = 0.52; 95% confidence interval = 0.06–0.99] but not lower limb activities. Subgroup analyses also failed to find a greater improvement in lower limb function of RAGT with tDCS compared to sham stimulation. No significant differences between participant characteristics or types of NIBS were observed.ConclusionThis meta-analysis demonstrated that RAGT therapy in combination with NIBS was effective in patients with stroke and SCI. However, a greater improvement in lower limb function and activities were not observed using RAGT with tDCS compared to sham stimulation. (shrink)

Recent advances in second-person neuroscience have allowed the underlying neural mechanisms involved in teaching-learning interactions to be better understood. Teaching is not merely a one-way transfer of information from teacher to student; it is a complex interaction that requires metacognitive and mentalizing skills to understand others’ intentions and integrate information regarding oneself and others. Physiotherapy involving therapists instructing patients on how to improve their motor skills is a clinical field in which teaching-learning interactions play a central role. Accumulating evidence suggests (...) that non-invasive brain stimulation modulates cognitive functions; however, NIBS approaches to teaching-learning interactions are yet to be utilized in rehabilitation. In this review, I evaluate the present research into NIBS and its role in enhancing metacognitive and mentalizing abilities; I then review hyperscanning studies of teaching-learning interactions and explore the potential clinical applications of NIBS in rehabilitation. Dual-brain stimulation using NIBS has been developed based on findings of brain-to-brain synchrony in hyperscanning studies, and it is delivered simultaneously to two individuals to increase inter-brain synchronized oscillations at the stimulated frequency. Artificial induction of brain-to-brain synchrony has the potential to promote instruction-based learning. The brain-to-brain interface, which induces inter-brain synchronization by adjusting the patient’s brain activity, using NIBS, to the therapist’s brain activity, could have a positive effect on both therapist-patient interactions and rehabilitation outcomes. NIBS based on second-person neuroscience has the potential to serve as a useful addition to the current neuroscientific methods used in complementary interventions for rehabilitation. (shrink)

Functional human brain mapping is commonly performed during invasive monitoring with intracranial electroencephalographic electrodes prior to resective surgery for drug­ resistant epilepsy. The current gold standard, electrocortical stimulation mapping, is time ­consuming, sometimes elicits pain, and often induces after discharges or seizures. Moreover, there is a risk of overestimating eloquent areas due to propagation of the effects of stimulation to a broader network of language cortex. Passive iEEG spatial-temporal functional mapping has recently emerged as a potential alternative (...) to ESM. However, investigators have observed less correspondence between STFM and ESM maps of language than between their maps of motor function. We hypothesized that incongruities between ESM and STFM of language function may arise due to propagation of the effects of ESM to cortical areas having strong effective connectivity with the site of stimulation. We evaluated five patients who underwent invasive monitoring for seizure localization, whose language areas were identified using ESM. All patients performed a battery of language tasks during passive iEEG recordings. To estimate the effective connectivity of stimulation sites with a broader network of task-activated cortical sites, we measured cortico-cortical evoked potentials elicited across all recording sites by single-pulse electrical stimulation at sites where ESM was performed at other times. With the combination of high gamma power as well as CCEPs results, we trained a logistic regression model to predict ESM results at individual electrode pairs. The average accuracy of the classifier using both STFM and CCEPs results combined was 87.7%, significantly higher than the one using STFM alone, indicating that the correspondence between STFM and ESM results is greater when effective connectivity between ESM stimulation sites and task-activated sites is taken into consideration. These findings, though based on a small number of subjects to date, provide preliminary support for the hypothesis that incongruities between ESM and STFM may arise in part from propagation of stimulation effects to a broader network of cortical language sites activated by language tasks, and suggest that more studies, with larger numbers of patients, are needed to understand the utility of both mapping techniques in clinical practice. (shrink)

Hit the lights and jump in the fire, you’re about to enter the School of Rock! Today’s lecture will be a crash course in brain surgery. This hard and fast lesson is taught by instructors who graduated from the old school—they actually paid $5.98 for _The $5.98 EP_. But back before these philosophy professors cut their hair, they were lieutenants in the Metal Militia. A provocative study of the ‘thinking man’s’ metal band Maps out the connections between Aristotle, (...) Nietzsche, Marx, Kierkegaard, and Metallica, to demonstrate the band’s philosophical significance Uses themes in Metallica’s work to illuminate topics such as freedom, truth, identity, existentialism, questions of life and death, metaphysics, epistemology, the mind-body problem, morality, justice, and what we owe one another Draws on Metallica’s lyrical content, Lars Ulrich’s relationship with Napster, as well as the documentary _Some Kind of Monster_ Serves as a guide for thinking through the work of one of the greatest rock bands of all time Compiled by the editor of _Seinfeld and Philosophy: A Book about Everything and Nothing_ and _The Simpsons and Philosophy: The D’oh! of Homer_. (shrink)

ObjectiveTo examine measurement agreement between a vocabulary test that is administered in the standardized manner and a version that is administered with a brain-computer interface.MethodThe sample was comprised of 21 participants, ages 9–27, mean age 16.7 years, 61.9% male, including 10 with congenital spastic cerebral palsy, and 11 comparison peers. Participants completed both standard and BCI-facilitated alternate versions of the Peabody Picture Vocabulary Test - 4. The BCI-facilitated PPVT-4 uses items identical to the unmodified PPVT-4, but each quadrant forced-choice (...) item is presented on a computer screen for use with the BCI.ResultsMeasurement agreement between instruments was excellent, including an intra-class correlation coefficient of 0.98, and Bland-Altman plots and tests indicating adequate limits of agreement and no systematic test version bias. The mean standard score difference between test versions was 2.0 points.ConclusionThese results demonstrate that BCI-facilitated quadrant forced-choice vocabulary testing has the potential to measure aspects of language without requiring any overt physical or communicative response. Thus, it may be possible to identify the language capabilities and needs of many individuals who have not had access to standardized clinical and research instruments. (shrink)

The dorsal anterior cingulate cortex is a key node in the human salience network. It has been ascribed motor, pain-processing and affective functions. However, the dynamics of information flow in this complex region and how it responds to inputs remain unclear and are difficult to study using non-invasive electrophysiology. The area is targeted by neurosurgery to treat neuropathic pain. During deep brain stimulation surgery, we recorded local field potentials from this region in humans during a decision-making task (...) requiring motor output. We investigated the spatial and temporal distribution of information flow within the dACC. We demonstrate the existence of a distributed network within the anterior cingulate cortex where discrete nodes demonstrate directed communication following inputs. We show that this network anticipates and responds to the valence of feedback to actions. We further show that these network dynamics adapt following learning. Our results provide evidence for the integration of learning and the response to feedback in a key cognitive region. (shrink)

This chapter examines five emulation methods, drawing a distinction between structure replication and reconstruction (SR) methods, and reverse brain engineering (RBE) methods. It argues that we need reasons to claim a particular procedure does or does not maintain identity, independently of whether the procedure is destructive or nondestructive. The chapter proposes that whole brain emulation (WBE) research be aimed primarily at cybernetics and possibility of replacing a biological brain in steps that involve very small parts with no (...) psychologically relevant structure. It also argues that methods reliant on structure replication and reconstruction will not preserve personal identity, based on a neo‐Lockean definition of personal identity according to which the self is a relatively autonomous self‐perpetuating substance whose psychological continuity through time is ensured primarily by immanent causation. All SR methods involve too much transeunt causation. (shrink)

Implanting deep brain stimulation (DBS) electrodes in patients with Parkinson’s disease often results in the appearance of a non-infectious, delayed-onset edema that disappears over time. However, the time window between the DBS electrode and DBS stimulating device implant is often used to record local field potentials (LFPs) which are used both to better understand basal ganglia pathophysiology and to improve DBS therapy. In this work, we investigated whether the presence of post-surgery edema correlates with the quality of LFP (...) recordings in eight patients with advanced Parkinson’s disease implanted with subthalamic DBS electrodes. The magnetic resonance scans of the brain after 8.5 ± 1.5 days from the implantation surgery were segmented and the peri-electrode edema volume was calculated for both brain hemispheres. We found a correlation (ρ = −0.81, p < 0.0218, Spearman’s correlation coefficient) between left side local field potentials of the low beta band (11–20 Hz) and the edema volume of the same side. No other significant differences between the hemispheres were found. Despite the limited sample size, our results suggest that the effect on LFPs may be related to the edema localization, thus indicating a mechanism involving brain networks instead of a simple change in the electrode-tissue interface. (shrink)

Objective: To investigate the differences between patients returning to work and those who did not after brain tumor surgery.Methods: Patients were evaluated before surgery and after 3 months. The Montreal Cognitive Assessment test, Trail-Making Test, 15-word Rey–Osterrieth Word List, F-A-S tests, and Karnosfky Performance Status were used to assess cognitive status, attention, executive functions, memory, word fluency, and functional status. Patient-reported outcome measures used to evaluate emotional distress and disability were the Hospital Anxiety and Depression Scale and (...) World Health Organization Disability Assessment Schedule. Clinical and work-related variables, PROMs, and cognitive tests were compared using chi-squared, t-test or Mann–Whitney U test.Results: Sixty patients were included. Patients returning to work were 61.3 and 31.0% among people with meningioma and glioma, respectively. They reported lower postoperative disability and lesser home-to-work travel time. Patients with meningioma also showed better preoperative and postoperative attention and executive functions, better postoperative functional and cognitive status, and lower frequency of treatments.Conclusions: These variables should be considered in a clinical context to plan interventions for people who need support during return to work and in future research to investigate preoperative and postoperative predictive factors of going back to work. (shrink)

Objective: Deep brain stimulation targeted to the ventral intermediate nucleus of the thalamus is effective for motor symptoms in essential tremor, but there is limited data on cognitive outcomes. We examined cognitive outcomes in a large cohort of ET DBS patients.Methods: In a retrospective analysis, we used repeated-measures ANOVA testing to examine whether the age of tremor onset, age at DBS surgery, hemisphere side implanted with lead, unilateral vs. bilateral implantations, and presence of surgical complications influenced the cognitive (...) outcomes. Neuropsychological outcomes of interest were verbal memory, executive functioning, working memory, language functioning, visuospatial functioning, and general cognitive function.Results: We identified 50 ET DBS patients; 29 males; the mean age of tremor onset was 35.84 years with a median age of 38 years. The mean age at DBS was 68.18 years. There were 37 unilateral 30 left, seven right, and 13 bilateral brain implantations. In the subgroup analysis, there was a significant interaction between assessment and age of tremor onset ; F = 4.47; p = 0.043 for working memory. The post hoc testing found improvements for younger onset ET. Similarly, there was a significant interaction between assessment and complications vs. no complications subgroups; F = 4.34; p = 0.043 for verbal memory with worsening scores seen for ET patients with complications. The remaining tests were not significant.Conclusion: In this large cohort of ET patients with, DBS was not accompanied by a significant decline in many cognitive domains. These outcomes were possibly related to the selection of patients with normal cognitive functioning before surgery, unilateral DBS implantations for the majority, and selection of patients with optimal response to DBS. (shrink)

Invasive neurotechnologies are a frequent subject of discussion in neuroethics. Technologies, like deep brain stimulation and implantable brain-computer interfaces, are thought to hold significant promise for human health and well-being, but they also raise important ethical questions about autonomy, safety, stigma, privacy, and agency, among others. The terms ‘invasive’ and ‘invasiveness’ are commonly applied to these and other neurotechnologies, yet the concept of invasiveness itself is rarely defined or delimited. Some have suggested that invasiveness may have (...) multiple meanings – physical, emotional, or lifestyle – and that confusion about how people use the terms may lead to harm, especially for users of invasive devices. It is uncertain if debates in neuroethics contribute to this confusion. To investigate this, we conducted a study of how the term ‘invasiveness’ is used in neuroethics. We found that neuroethicists almost always use ‘invasiveness’ to refer to the physical features of interventions, and rarely to refer to other senses of invasiveness. We also found that referencing invasiveness does not determine which ethical issues are prioritized for a given type of neurotechnology. Overall, this study affirms the importance of understanding the meaning and use of the concept of invasiveness in ethical discussion of neurotechnology while also suggesting the need for further work in the area and consideration for rethinking what forms of technology we consider to be invasive. (shrink)

Research into the neural correlates of consciousness (NCCs) has blossomed, due to the advent of new and increasingly sophisticated brain research tools. Neuroimaging has uncovered a variety of brain processes that relate to conscious perception, obtained in a range of experimental paradigms. But methods such as functional magnetic resonance imaging or electroencephalography do not always afford inference on the functional role these brain processes play in conscious vision. Such empirical NCCs could reflect neural prerequisites, neural consequences, or (...) neural substrates of a conscious experience. Here, we take a closer look at the use of non-invasive brain stimulation (NIBS) techniques in this context. We discuss and review how NIBS methodology can enlighten our understanding of brain mechanisms underlying conscious vision by disentangling the empirical NCCs. (shrink)