James Giordano

Georgetown University | GU · Office of the Senior Vice President for Research

The present paper identifies a critical factor that leads to false negative results (i.e., failing to indicate efficacy when beneficial results did occur) in randomized human drug trials. The paper demonstrates that human performance can only be enhanced by a maximum of 30-60% as described by the hormetic dose response which defines the limits of b...

The lack of reliable therapies for regeneration or repair of the injured central nervous system, coupled with the promise of iPSC-derived neurons in basic and preclinical studies, has led to rapid expansion of research and development into this area (Boer, 2010; Meloni, Mallet, Faucon-Biguet, 2011). Alongside the promise of iPSC-derived treatments...

This paper reexamines the technical report (∼ one page) of Uphoff and Stern (1949) in Science that was highly relied upon by the US National Academy of Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) I Genetics Panel to support a linearity dose response for radiation risk assessment. The present paper demonstrates that research of Upho...

Deep brain stimulation is an effective treatment for obsessive–compulsive disorder but is rarely used. Action is needed by psychologists, psychiatrists and insurers so that patients with otherwise intractable cases can receive this therapy to improve their mental health.

This paper illustrates how the acceptance of the linear non-threshold (LNT) dose response model was unethically advocated and advanced both by key scientists within the radiation genetics community, and by editorial practices in Science, a leading international scientific journal. Four key papers became the cornerstones in the acceptance of the LNT...

At present, there are two hypotheses about the emergence of SARS-CoV-2; the first is that it was due to a naturally occurring zoonotic jump, and the second contends that it spread due to an accidental dispersion of a laboratory-acquired infection in Wuhan, China. While the pandemic's actual origins remain occluded, it is useful to examine the latte...

This paper provides a detailed identification and assessment of hormetic dose responses in neural stem cells (NSCs) as identified in a number of animal models and human tissues, with particular emphasis on cell proliferation and differentiation. Hormetic dose responses were commonly observed following administration of a number of agents, including...

There is growing interest in finding ways to enhance longevity and the quality of life. This paper summarizes a vast scientific literature over the past two decades that has suggested approaches to enhancing biological resilience – and particularly neurological function - via hormetic and preconditioning processes. The employment of hormesis and pr...

[This corrects the article DOI: 10.3389/fnhum.2021.644593.].

This paper describes evidence establishing that ultra-low doses of diverse chemical agents at concentrations from 10⁻¹⁸ to 10⁻²⁴ M (e.g., approaching and/or less than 1 atom or molecule of a substance/cell based on Avogadro’s constant - 6.022 ×10²³/mole) are capable of engaging receptor and intracellular signaling systems to elicit reproducible eff...

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was fou...

Novel mechanistic insights are discussed herein that link a single, nontoxic, low-dose radiotherapy (LDRT) treatment (0.5-1.0 Gy) to (1) beneficial subcellular effects mediated by the activation of nuclear factor erythroid 2-related transcription factor (Nrf2) and to (2) favorable clinical outcomes for COVID-19 pneumonia patients displaying symptom...

This paper provides evidence to support that riluzole, an FDA-approved treatment for amyotrophic lateral sclerosis (ALS), like many neuroprotective agents, displays and exerts hormetic biphasic dose responses. These findings have important implications for the experimental study and clinical treatment of ALS.

This paper addresses a novel putative mechanism by which atypical antipsychotic agents induce clinically significant neuroprotective effects that may be viable in the treatment of schizophrenia – and perhaps other neuropsychiatric disorders. Based upon experimental studies with multiple in vitro models (i.e., PC 12 cells, NSC-34 hybrid cells, SH-SY...

Low-dose radiation therapy (LD-RT) has historically been a successful treatment for pneumonia and is clinically established as an immunomodulating therapy for inflammatory diseases. The ongoing COVID-19 pandemic has elicited renewed scientific interest in LD-RT and multiple small clinical trials have recently corroborated the historical LD-RT findi...

This review describes neuroprotective effects mediated by pre- and post-conditioning-induced processes that act via the quantitative features of the hormetic dose response. These lead to the development of acquired resilience that can protect neuronal systems from endogenous and exogenous stresses and insult. Particular attention is directed to iss...

Green tea, and its principal constituent (–)-epigallocatechin-3-gallate (EGCG), are commonly shown to induce biphasic concentration/dose responses in a broad range of cell types, including non-tumor cells, and tumor cell lines. The most active area of research dealt with an assessment of neural cells with application to neurodegenerative diseases s...

The Seventh Annual Deep Brain Stimulation (DBS) Think Tank held on September 8th of 2019 addressed the most current: (1) use and utility of complex neurophysiological signals for development of adaptive neurostimulation to improve clinical outcomes; (2) Advancements in recent neuromodulation techniques to treat neuropsychiatric disorders; (3) New d...

The annual deep brain stimulation (DBS) Think Tank aims to create an opportunity for a multidisciplinary discussion in the field of neuromodulation to examine developments, opportunities and challenges in the field. The proceedings of the Sixth Annual Think Tank recapitulate progress in applications of neurotechnology, neurophysiology, and emerging...

This paper assesses in vivo cytotoxicity models of Huntington's disease (HD). Nearly 150 agents were found to be moderately to highly effective in mitigating the pathological sequelae of cytotoxic induction of HD features in multiple rodent models. Typically, rodents are treated with a prospective HD-protective agent before, during, or after the ap...

If It Only Had a Brain: What “Neuro” Means for Science and Ethics - Volume 27 Special Issue - THOMASINE KUSHNER, JAMES GIORDANO

Central neurotrauma, such as spinal cord injury or traumatic brain injury, can damage critical axonal pathways and neurons and lead to partial to complete loss of neural function that is difficult to address in the mature central nervous system. Improvement and innovation in the development, manufacture, and delivery of stem-cell based therapies, a...

Age‐related changes in the brain reflect a dynamic interaction of genetic, epigenetic, phenotypic, and environmental factors that can be temporally restricted or more longitudinally present throughout the lifespan. Fundamental to these mechanisms is the capacity for physiological adaptation through modulation of diverse molecular and biochemical si...

Recent research indicates that transcranial electrical stimulation (tES) of specific brain regions can successfully improve various forms of creative cognition. Although the endeavor to increase human creative capacity is intriguing from a neuroscientific perspective, and of interest to the general public, it raises numerous neuroethico-legal and s...

This paper assessed approximately 30 studies, mostly involving occupationally exposed subjects, concerning the extent to which those who developed elemental mercury (Hg)-induced central and/or peripheral neurotoxicities from chronic or acute exposures recover functionality and/or performance. While some recovery occurred in the vast majority of cas...

A persistent debate about moral capacity - and neuroethics - focuses upon the internalism-externalism controversy. Internalism holds that moral judgments necessarily motivate an agent's actions; externalism views moral judgments as not inherently motivating an agent to perform moral actions. Neuroethical discussions of the putative cognitive basis...

Advances in neuroscientific techniques have found increasingly broader applications, including in legal neuroscience (or “neurolaw”), where experts in the brain sciences are called to testify in the courtroom. But does the incursion of neuroscience into the legal sphere constitute a threat to individual liberties? And what legal protections are the...

In order to better understand the pathogenesis of Parkinson's Disease (PD) it is important to consider possible contributory factors inherent to the aging process, as age-related changes in a number of physiological systems (perhaps incurred within particular environments) appear to influence the onset and progression of neurodegenerative disorders...

Neuroethics - Volume 26 Special Issue - THOMASINE KUSHNER, JAMES GIORDANO

We present device standards for low-power non-invasive electrical brain stimulation devices classified as limited output transcranial electrical stimulation (tES). Emerging applications of limited output tES to modulate brain function span techniques to stimulate brain or nerve structures, including transcranial direct current stimulation (tDCS), t...

After the publication of this article [1] it has come to our attention that the following quote from the article by Lombera and Illes [2] ".must have the power - defined by quality of knowledge and ease of access - to help shape that future.". was missing a reference citation in the introduction. The omission of the reference citation for this quot...

After a decade of growth and development, neuroethics as a defined discipline is establishing domains of inquiry and action, a defined canon, and set(s) of practices. Neuroethical address and discourse must engage the realities forged and fostered by brain science no matter where they emerge and deliberate upon neurotechnological applications on th...

This year marks the Eighth Review Conference (RevCon) of the Biological Toxins and Weapons Convention (BWC). At the same time, ongoing international efforts to further and more deeply investigate the brain's complex neuronal circuitry are creating unprecedented capabilities to both understand and control neurological processes of thought, emotion,...

Background As a discipline, neuroethics addresses a range of questions and issues generated by basic neuroscientific research (inclusive of studies of putative neurobiological processes involved in moral and ethical cognition and behavior), and its use and meanings in the clinical and social spheres. Here, we present Part 4 of a four-part bibliogra...

This paper addresses how hormesis, a biphasic dose response, can protect and affect performance of neural systems. Particular attention is directed to the potential role of hormesis in mitigating age-related neurodegenerative diseases, genetically based neurological diseases, as well as stroke, traumatic brain injury, seizure, and stress-related co...

Deep brain stimulation (DBS) is currently approved by the US Food and Drug Administration to treat Parkinson disease, essential tremor, and dystonia. However, so-called off-label use of DBS may be permissible under research-based or compassionate use guidelines to treat severe, medication-refractory cases of other neurological and psychiatric disor...

Abnormal redox homeostasis and oxidative stress have been proposed to play a role in the etiology of several neuropsychiatric spectrum disorders. Emerging interest has recently focused on markers of oxidative stress and neuroinflammation in schizophrenic spectrum disorders, at least in particular subgroups of patients. Altered expression of genes r...

Here we have a case in which (1) the outcome(s) for the patient do not comport with the projected—or initially defined—outcomes of the research study, and (2) these outcomes represent cognitive and behavioral effects that are positively interpreted by the patient, but not by the patient’s immediate family. The 6Cs approach, which frames the techniq...

Ongoing developments in neuroscientific techniques and technologies—such as neuroimaging—offer potential for greater insight into human behavior and have fostered temptation to use these approaches in legal contexts. Neuroscientists are increasingly called on to provide expert testimony, interpret brain images, and thereby inform judges and juries...

From the Editors - Volume 25 Issue 4 - THOMASINE KUSHNER, JAMES GIORDANO

Background: Neuroethics describes several interdisciplinary topics exploring the application and implications of engaging neuroscience in societal contexts. To explore this topic, we present Part 3 of a four-part bibliography of neuroethics' literature focusing on the "ethics of neuroscience." Methods: To complete a systematic survey of the neur...

In the United States, 1.1–1.5% of children have been diagnosed with autism spectrum disorders (ASD), corresponding to a 30% increase in incidence and prevalence. Social and communication impairments are the main signs and symptoms of ASD, and currently available medications have been ineffective in reducing these core deficits. Observational studie...

Vascular dementia (VaD), considered the second most common cause of cognitive impairment after Alzheimer disease in the elderly, involves the impairment of memory and cognitive function as a consequence of cerebrovascular disease. Chronic cerebral hypoperfusion is a common pathophysiological condition frequently occurring in VaD. It is generally as...

Research in neuroscience and neurotechnology (neuroS/T) is progressing at a rapid pace with translational applications both in medicine, and more widely in the social milieu. Current and projected neuroS/T research and its applications evoke a number of neuroethicolegal and social issues (NELSI). This paper defines inherent and derivative NELSI of...

In this chapter, we address if and how big data computational capability could enable the establishment of a common, accessible database for neuroscientific research and its translation that provides a resource for 1) (raw) data harvesting; 2) data fusion; 3) data integration, functional formulation, and exchange; and 4) broad data access and use....

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisc...

The possibility of a human head transplant poses unprecedented philosophical and neuroethical questions. Principal among them are the personal identity of the resultant individual, her metaphysical and social status: Who will she be and how should the “new” person be treated - morally, legally and socially - given that she incorporates characterist...

An integrated and principled neuroethics offers ethical guidelines able to transcend conventional and medical reliance on normality standards. Elsewhere we have proposed four principles for wise guidance on human transformations. Principles like these are already urgently needed, as bio- and cyberenhancements are rapidly emerging. Context matters....

Global mental health is a relatively new field that has focused on disparities in mental health services across different settings, and on innovative ways to provide feasible, acceptable, and effective services in poorly-resourced settings. Neuroethics, too, is a relatively new field, lying at the intersection of bioethics and neuroscience; it has...

Moral philosophy and psychology have sought to define the nature of right and wrong, and good and evil. The industrial turn of the twentieth century fostered increasingly technological approaches that conjoined philosophy to psychology, and psychology to the natural sciences. Thus, moral philosophy and psychology became ever more vested to investig...

The techniques and tools of neurosciences have developed at ever increasing pace and sophistication. Calls for increased clinical translation of the European Union's Human Brain Project, ongoing activities of the United States' Brain Research through Advancing Innovative Neurotechnologies' (BRAIN) initiative, and a number of other international eff...

Patients with acute brain injury that are comatose, persistently vegetative (PVS), and/or otherwise severely neurologically compromised are often considered candidates for withholding or withdrawal of life sustaining treatment on grounds of futility because of the debilitating and irreversible nature of their injuries. Medical interventions are fut...

This chapter focuses on the engagement of real-time functional magnetic resonance imaging-brain-computer interfacing (rtfMRI-BCI) in the treatment of psychopathy and some of the more pertinent ethico-legal and social issues fostered by such use of this neurotechnological approach. To this end, we first provide an overview of the nature of psychopat...

The unknowns of the brain-mind relationship and the novelty of neurologic techniques and technologies give rise to ethical questions that can be described, analyzed, and answered using a preparatory neuroethical framework to mitigate potential problems.

The Presidential Commission for the Study of Bioethical Issues (PCSBI) released the second volume of its Gray Matters report in March 2015 to address neuroethical, legal, and social issues arising in and from efforts of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. In concert with recommendations made in the...

Abstract The proceedings of the 2(nd) Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsyc...

Neuroethics has greater responsibilities than merely noting potential human enhancements ascribed to brain science, and tracking their implications for ethics and civic life. Neuroethics must utilize current neuroscientific knowledge to shape incisive discussions about what could count as enhancement in the first place, and what should count as gen...

Background Neuroethics entails investigations of neurocognitive mechanisms of morality and ethics; and studies and address of the ethical issues spawned by the use of neuroscience and its technologies to investigate cognition, emotion and actions. These two principal emphases, or what have been called “traditions” of neuroethics both mirror traditi...

There appears to be an inconsistency in experimental paradigms used in fMRI research on moral judgments. As stimuli, moral dilemmas or moral statements/ pictures that induce emotional reactions are usually employed; a main difference between these stimuli is the perspective of the participants reflecting first-person (moral dilemmas) or third-perso...

Background: There appears to be an inconsistency in experimental paradigms used in fMRI research on moral judgments. As stimuli, moral dilemmas or moral statements/ pictures that induce emotional reactions are usually employed; a main difference between these stimuli is the perspective of the participants reflecting first-person (moral dilemmas) or...

Neuroscience: Addressing Perdurable Questions of Humanity Research in, and applications of neuroscience and neurotechnology are increasingly becoming an international enterprise. The past 10 years reveal the accelerated pace of both neuroscientific advancement, and investment of non-Western nations, corporate and venture capital companies, and acto...

Neuroscience affords knowledge that can be leveraged in the ontological valuation of individuals, groups, and species. Sociocultural sentiments, norms, and mores may impede embracing such knowledge to revise moral attitudes, ethics, and policies. We argue that the practices of neuroethics will be valuable in that they ground ethico-legal discourse...

In light of the recent events of terrorism and publicized cases of mass slayings and serial killings, there have been calls from the public and policy-makers alike for neuroscience and neurotechnology (neuroS/T) to be employed to intervene in ways that define and assess, if not prevent, such wanton acts of aggression and violence. Ongoing advanceme...

Neuroethics applies cognitive neuroscience for prescribing alterations to conceptions of self and society, and for prescriptively judging the ethical applications of neurotechnologies. Plentiful normative premises are available to ground such prescriptivity, however prescriptive neuroethics may remain fragmented by social conventions, cultural ideo...