An understanding of the functional repertoire of neural circuits and their plasticity requires knowledge of neural connectivity diagrams and their dynamical evolution. However, one must additionally take into account the fast and reversible functional effects induced by neuromodulatory mechanisms which do not alter neural circuit diagrams. Neuromodulators contribute crucially to determine the performativity of a neural circuit, that is, its ability to change behavior, and especially behavioral changes occurring under temporal constraints that are incompatible with the longer time scales of (...) Hebbian learning and other forms of neural learning. This paper focuses on two properties of neuromodulatory action that have been relatively neglected so far. These properties are the functional soundness of neuromodulated circuits and the robustness of neuromodulatory action. Both properties are analyzed here as sources of functional specifications for the computational modeling of neural circuit performativity. In particular, taking dynamical systems that are based on CTRNNs as an exemplary class of computational models, it is argued that robustness is suitably modeled there by means of a hysteresis process, and functional soundness by means of a multiplicity of stable fixed points. (shrink)

Background: Mild traumatic brain injury results from an external force to the head or body causing neurophysiological changes within the brain. The number and severity of symptoms can vary, with some individuals experiencing rapid recovery, and others having persistent symptoms for months to years, impacting their quality of life. Current rehabilitation is limited in its ability to treat persistent symptoms and novel approaches are being sought to improve outcomes following mTBI. Neuromodulation is one technique used to encourage adaptive neuroplasticity within (...) the brain.Objective: To systematically review the literature on the efficacy of neuromodulation in the mTBI population.Method: A systematic review was conducted using Medline, Embase, PsycINFO, PsycARTICLES and EBM Review. Preferred Reporting Items for Systematic Reviews and the Synthesis Without Meta-analysis reporting guidelines were used and a narrative review of the selected studies was completed. Fourteen articles fulfilled the inclusion criteria which were published in English, investigating an adult sample and using a pre- and post-intervention design. Studies were excluded if they included non-mild TBI severities, pediatric or older adult populations.Results: Thirteen of fourteen studies reported positive reductions in mTBI symptomatology following neuromodulation. Specifically, improvements were reported in post-concussion symptom ratings, headaches, dizziness, depression, anxiety, sleep disturbance, general disability, cognition, return to work and quality of life. Normalization of working memory activation patterns, vestibular field potentials, hemodynamics of the dorsolateral prefrontal cortex and excessive delta wave activity were also seen. The studies reviewed had several methodological limitations including small, heterogenous samples and varied intervention protocols, limiting generalisability. Further research is required to understand the context in which neuromodulation may be beneficial.Conclusions: While these positive effects are observed, limitations included unequal representation of neuromodulation modalities in the literature, and lack of literature describing the efficacy of neuromodulation on the development or duration of persistent mTBI symptoms. Better clarity regarding neuromodulation efficacy could have a significant impact on mTBI patients, researchers, clinicians, and policy makers, facilitating a more productive post-mTBI population. Despite the limitations, the literature indicates that neuromodulation warrants further investigation. PROSPERO registration number: CRD42020161279. (shrink)

Clinical and experimental evidence suggests that hippocampal damage causes more severe disruption of episodic memories if those memories were encoded in the recent rather than the more distant past. This decrease in sensitivity to damage over time might reflect the formation of multiple traces within the hippocampus itself, or the formation of additional associative links in entorhinal and association cortices. Physiological evidence also supports a two-stage model of the encoding process in which the initial encoding occurs during active waking and (...) deeper consolidation occurs via the formation of additional memory traces during quiet waking or slow-wave sleep. In this article I will describe the changes in cholinergic tone within the hippocampus in different stages of the sleep-wake cycle and will propose that these changes modulate different stages of memory formation. In particular, I will suggest that the high levels of acetylcholine that are present during active waking might set the appropriate dynamics for encoding new information in the hippocampus, by partially suppressing excitatory feedback connections and so facilitating encoding without interference from previously stored information. By contrast, the lower levels of acetylcholine that are present during quiet waking and slow-wave sleep might release this suppression and thereby allow a stronger spread of activity within the hippocampus itself and from the hippocampus to the entorhinal cortex, thus facilitating the process of consolidation of separate memory traces. (shrink)

Background: Newer “closed-loop” neurostimulation devices in development could, in theory, induce changes to patients’ personalities and self-perceptions. Empirically, however, only limited data of patient and family experiences exist. Responsive neurostimulation (RNS) as a treatment for refractory epilepsy is the first approved and commercially available closed-loop brain stimulation system in clinical practice, presenting an opportunity to observe how conceptual neuroethical concerns manifest in clinical treatment. Methods: We conducted ethnographic research at a single academic medical center with an active RNS treatment program (...) and collected data via direct observation of clinic visits and in-depth interviews with 12 patients and their caregivers. We used deductive and inductive analyses to identify the relationship between these devices and patient changes in personality and self-perception. Results: Participants generally did not attribute changes in patients’ personalities or self-perception to implantation of or stimulation using RNS. They did report that RNS affected patients’ experiences and conceptions of illness. In particular, the capacity to store and display electrophysiological data produced a common frame of reference and a shared vocabulary among patients and clinicians .Discussion: Empirical experiences of a clinical population being treated with closed-loop neuromodulation do not corroborate theoretical concerns about RNS devices described by neuroethicists and technology developers. However, closed-loop devices demonstrated an ability to change illness experiences. Even without altering identify and self-perception, they provided new cultural tools and metaphors for conceiving of epilepsy as an illness and of the process of diagnosis and treatment. These findings call attention to the need to situate neuroethical concerns in the broader contexts of patients’ illness experiences and social circumstances. (shrink)

We present simulation results of an olfactory cortex model complementing the results presented in Wright & Liley's target article. We show how the cortical dynamics as expressed in EEG can be regulated by neuromodulation and discuss how the system can attain global stability without cortical-subcortical interaction, as presumed necessary by Wright & Liley. Network structure is shown to be crucial.

Powerful ultrastructural tools are providing new insights into neuronal circuits, revealing a wealth of anatomically‐defined synaptic connections. These wiring diagrams are incomplete, however, because functional connectivity is actively shaped by neuromodulators that modify neuronal dynamics, excitability, and synaptic function. Studies of defined neural circuits in crustaceans, C. elegans, Drosophila, and the vertebrate retina have revealed the ability of modulators and sensory context to reconfigure information processing by changing the composition and activity of functional circuits. Each ultrastructural connectivity map encodes multiple (...) circuits, some of which are active and some of which are latent at any given time. (shrink)

Idiopathic generalized epilepsy is a common type of epilepsy and despite an increase in the number of available anti-seizure medications, approximately 20–30% of people with IGE continue to experience seizures despite adequate medication trials. Unlike focal epilepsy, resective surgery is not a viable treatment option for IGE; however, neuromodulation may be an effective surgical treatment for people with IGE. Thalamic stimulation through deep brain stimulation and responsive neurostimulation have been explored for the treatment of generalized and focal epilepsies. Although the (...) data regarding DBS and RNS in IGE is limited to case reports and case series, the results of the published studies have been promising. The current manuscript will review the published literature of DBS and RNS within the centromedian nucleus of the thalamus for the treatment of IGE, as well as highlight an illustrative case. (shrink)

Racial and ethnic disparities exist for many nervous system disorders that are intervention targets for neuromodulation investigators. Yet, to date, there has been both a lack of racial and ethnic diversity and a lack of emphasis on diversity in neuromodulation research. In this paper, we suggest three potential reasons for the lack of racial and ethnic diversity in neuromodulation research: 1) the lack of diversity in the neuromodulation workforce, 2) incompatibility between the technologies employed and phenotypic traits (e.g., hair texture) (...) commonly present in minoritized populations, and 3) minoritized populations’ reluctance to participate in clinical trials. We argue that increasing diversity in the neuromodulation workforce, in conjunction with mutual collaboration between current neuromodulation researchers and underrepresented communities in neuromodulation, can aid in removing barriers to diversity, equity, and inclusion in neuromodulation research. This is important, because greater diversity, equity, and inclusion in neuromodulation research brings with it the development of novel, yet safe and effective, treatment approaches for brain disorders and enhances the rigor and generalizability of discoveries in the field. (shrink)

Several investigations have shown language impairments following electrode implantation surgery for Deep Brain Stimulation (DBS) in movement disorders. The impact of the actual stimulation, however, differs between DBS targets with further deterioration in formal language tests induced by thalamic DBS in contrast to subtle improvement observed in subthalamic DBS. Here, we studied speech samples from interviews with participants treated with DBS of the thalamic ventral intermediate nucleus (VIM) for essential tremor (ET), or the subthalamic nucleus (STN) for Parkinson’s disease (PD), (...) and healthy volunteers (eachn= 13). We analyzed word frequency and the use of open and closed class words. Active DBS increased word frequency in case of VIM, but not STN stimulation. Further, relative to controls, both DBS groups produced fewer open class words. Whereas VIM DBS further decreased the proportion of open class words, it was increased by STN DBS. Thus, VIM DBS favors the use of relatively common words in spontaneous language, compatible with the idea of lexical simplification under thalamic stimulation. The absence or even partial reversal of these effects in patients receiving STN DBS is of interest with respect to biolinguistic concepts suggesting dichotomous thalamic vs. basal ganglia roles in language processing. (shrink)

IntroductionConcussion is a growing public health concern. No uniformly established therapy exists; neurofeedback studies report treatment value. We use infralow frequency neuromodulation to remediate disabling neurological symptoms caused by traumatic brain injury and noted improved outcomes with a novel concussion protocol. Postconcussion symptoms and persistent postconcussion symptoms are designated timelines for protracted neurological complaints following TBI. We performed a retrospective study to explore effectiveness of ILF in PCS/PPCS and investigated the value of using this concussion protocol.MethodPatients with PCS/PPCS seen for (...) their first neurology office visit or received their first neurofeedback session between 1 August 2018 and 31 January 2021 were entered. Outcomes were compared following treatment as usual vs. TAU with ILF neurotherapy. The study cohort was limited to PPCS patients; the TAU+ILF group was restricted further to PPCS patients receiving at least 10 neurotherapy sessions. Within the TAU+ILF group, comparisons were made between those who trained at least 10 sessions using concussion protocol and those who trained for at least 10 sessions of ILF regardless of protocol.ResultsAmong our resultant PPCS cohort leading persistent neurological complaints were headache, memory impairment, and brain fog. PPCS patients in TAU+ILF+CP demonstrated greater net and percent improvement of symptoms compared to PPCS subjects in TAU. PPCS patients in TAU+ILF-CP trended toward significant symptom improvements compared to TAU, and TAU+ILF+CP trended toward greater efficacy than TAU+ILF-CP.ConclusionPPCS patients who received TAU+ILF+CP demonstrated significantly greater improvement as a group when compared to TAU. When used as an integrative modality to treatment as usual in managing patients with PPCS, ILF neuromodulation with use of concussion protocol provided significant symptom improvements. (shrink)

‘Neuroeconomics’ can be broadly defined as the research of how the brain interacts with the environment to make decisions that are functional given individual and contextual constraints. Deciphering such brain-environment transactions requires mechanistic understandings of the neurobiological processes that implement value-dependent decision making. To this end, a common empirical approach is to investigate neural mechanisms of reward-based decision making. Flexible updating of choices and associated expected outcomes in ways that are adaptive for a given task (or a given set of (...) tasks) at hand relies on dynamic neurochemical tuning of the brain’s functional circuitries involved in the representation of tasks, goals and reward prediction. Empirical evidence as well as computational theories indicate that various neurotransmitter systems (e.g., dopamine, norepinephrine, and serotonin) play important roles in reward-based decision making. In light of the apparent aging-related decline in various aspects of the dopaminergic system as well as the effects of neuromodulation on reward-related processes, this article focuses selectively on the literature that highlights the triadic relations between dopaminergic modulation, reward-based decision making, and aging. Directions for future research on aging and neuroeconomoics are discussed. (shrink)

Stereotactic neurosurgery emerged in the mid-20th century following the development of a stereotactic frame by Spiegel and Wycis. Historically women were underrepresented in clinical and academic neurosurgery. There is still a significant deficit of female scientists in this field. This article aims to demonstrate the career and scientific work of some of the most important women who contributed to the development of stereotactic and functional neurosurgery. Exceptional women from all over the world, represented in this review, assisted the evolution of (...) modern stereotactic and functional neurosurgery as neurosurgeons, neuropathologists, neurologists, neurophysiologists and occupational therapists. Fortunately, we could conclude that in the last two decades the number of female researchers has increased significantly. (shrink)

DBS Think Tank IX was held on August 25–27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers can freely discuss current and emerging deep brain stimulation technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in (...) its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year’s meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury. (shrink)

Cranial electrotherapy stimulation is a neuromodulation tool used for treating several clinical disorders, including insomnia, anxiety, and depression. More recently, a limited number of studies have examined CES for altering affect, physiology, and behavior in healthy, non-clinical samples. The physiological, neurochemical, and metabolic mechanisms underlying CES effects are currently unknown. Computational modeling suggests that electrical current administered with CES at the earlobes can reach cortical and subcortical regions at very low intensities associated with subthreshold neuromodulatory effects, and studies using electroencephalography (...) and functional magnetic resonance imaging show some effects on alpha band EEG activity, and modulation of the default mode network during CES administration. One theory suggests that CES modulates brain stem, limbic, and cortical regions and increases relative parasympathetic to sympathetic drive in the autonomic nervous system. There is no direct evidence supporting this theory, but one of its assumptions is that CES may induce its effects by stimulating afferent projections of the vagus nerve, which provides parasympathetic signals to the cardiorespiratory and digestive systems. In our critical review of studies using CES in clinical and non-clinical populations, we found severe methodological concerns, including potential conflicts of interest, risk of methodological and analytic biases, issues with sham credibility, lack of blinding, and a severe heterogeneity of CES parameters selected and employed across scientists, laboratories, institutions, and studies. These limitations make it difficult to derive consistent or compelling insights from the extant literature, tempering enthusiasm for CES and its potential to alter nervous system activity or behavior in meaningful or reliable ways. The lack of compelling evidence also motivates well-designed and relatively high-powered experiments to assess how CES might modulate the physiological, affective, and cognitive responses to stress. Establishing reliable empirical links between CES administration and human performance is critical for supporting its prospective use during occupational training, operations, or recovery, ensuring reliability and robustness of effects, characterizing if, when, and in whom such effects might arise, and ensuring that any benefits of CES outweigh the risks of adverse events. (shrink)

Both the therapeutic effects and the complications associated with neuromodulation of the brain can result in experiences that are neither reliably predictable nor easily describable. For this reason, protocols for informed consent must be carefully tailored to the procedure, the indication, and the patient, and satisfy very strict, often subjective patient standards of disclosure. These three elements can be combined to categorize procedures for neuromodulation (and as well as others) and optimize the protection of the patient.

Growing interest in psychiatric neurosurgery, and in deep brain stimulation (DBS) in particular, requires that the field be placed in the appropriate historical and scientific context. Current methods of neuromodulation for refractory psychiatric conditions are premised on assumptions similar to those proposed in earlier attempts, namely, the number of resistant patients and the absence of any other effective treatments. As a result, a discussion of the current and future prospects, as well as the limits, of neuromodulation is required to avoid (...) a replay of earlier transgressions, and to place its current chapter in the appropriate historical and ethical context. (shrink)

Using a longitudinal case study design, we have tracked the recovery of motor function following severe traumatic brain injury (TBI) through a multimodal neuroimaging approach. In 2006, Canadian Soldier Captain (retired) Trevor Greene (TG) was attacked with an axe to the head while on tour in Afghanistan. TG continues intensive daily rehabilitation, which recently included the integration of physical therapy (PT) with neuromodulation using translingual neurostimulation (TLNS) to facilitate neuroplasticity. Recent findings with PT+TLNS demonstrated that recovery of motor function occurred (...) beyond conventional time limits, currently extending past 14-years post-injury. To investigate whether PT+TLNS similarly resulted in associated cognitive function improvements, we examined event-related potentials (ERPs) with the brain vital signs framework. In parallel with motor function improvements, brain vital signs detected significant increases in basic attention (as measured by P300 response amplitude) and cognitive processing (as measured by contextual N400 response amplitude). These objective cognitive improvements corresponded with TG’s self-reported improvements, including a noteworthy and consistent reduction in ongoing symptoms of post-traumatic stress disorder (PTSD). The findings provide valuable insight into the potential importance of non-invasive neuromodulation in cognitive rehabilitation, in addition to initial indications for physical rehabilitation. (shrink)

Major depression is among the most common, challenging and disabling conditions. It is highly heterogeneous, affects patients throughout the lifespan and, in up to one-third of people affected, res...