deep brain stimulation intracerebral mind control defined at comprehensive level with citations given by Stagg, Nitsche, Clark, Polanía, and others

Neuroimaging studies have enhanced our understanding of the physiological mechanisms underlying the effects of tDCS on behaviour (Hunter et al., 2013). Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) have provided insights into alterations of functional connectivity and changes in neurotransmitter concentrations following stimulation (Stagg et al., 2009, Clark et al., 2011, Polanía et al., 2012, Sehm et al., 2013, Amadi et al., 2014). However, the effects of tDCS have been proposed to be temporally-specific (Stagg and Nitsche, 2011), suggesting that the use of millisecond-resolution far-field electrophysiological methods, such as Electroencephalography (EEG) and MEG, may be particularly advantageous. To date, the majority of studies combining tDCS and EEG/MEG have not used the techniques concurrently, instead focusing on the changes that occur after the period of stimulation (Polanía et al., 2011, Venkatakrishnan et al., 2011, Jacobson et al., 2012, Neuling et al., 2012, Spitoni et al., 2013). Soekadar et al. (2013) published the first concurrent tDCS–MEG study, in which a motor paradigm was used to elicit responses in the alpha and beta bands.

This work focused on the feasibility of combining the techniques and found no adverse effects of stimulation on the quality of data. Since this first study, the concept of concurrent tDCS–MEG has been promoted as a potential method to study the underpinnings of tDCS' behavioural effects. By linking observable modulations of electrophysiological activity (such as cortical oscillations; Thut et al., 2012) to electrical stimulation, this work should help to establish increasingly refined applications of tDCS in both health (through cognitive and behavioural research) and disease (as a treatment option for neurological/psychiatric disorders).



Gamma oscillations (> 30 Hz) are an appealing target for tDCS modulation due to current theories linking their generation to the excitation/inhibition balance (Buzsáki and Wang, 2012). For example, fluctuations in gamma oscillations of hippocampal pyramidal cells in rats have recently been shown to rely upon the dynamic modulation of excitation and inhibition (Atallah and Scanziani, 2009). Accordingly, enhancement in the synchrony of pyramidal cell firing is said to be propagated by a release from inhibition exerted by inhibitory post-synaptic currents (IPSCs) on GABAergic interneurons (particularly basket cells: Hasenstaub et al., 2005, Bartos et al., 2007).

This suggests that pyramidal-interneuron relations are integral to the generation of gamma oscillations (Gonzalez-Burgos and Lewis, 2008). The importance of the excitation/inhibition balance has also been supported by a pharmacological MEG study, incorporating the GABAA agonist Diazepam (Hall et al., 2010). Gamma power was increased in the visual cortex, which was proposed to reflect enhanced efficiency of fast inhibitory processing. Furthermore, the administration of alcohol, which is thought to increase GABAA mediated inhibition and diminish glutamatergic excitation via NMDA receptors, has been shown to increase the amplitude of responses in the gamma band within visual and motor cortex (Campbell et al., 2014).

Oscillations in the beta band (15–30 Hz) have been proposed to be modulated by similar mechanisms to those in the gamma band (Jensen et al., 2002, Yamawaki et al., 2008). Using a resting MEG paradigm, the administration of Diazepam increased beta power and decreased peak frequency (Jensen et al., 2005). Using a basic biophysical model, the authors concluded that the elevation in beta amplitude was driven by an enhancement in the synchrony of pyramidal cell firing, driven by increased IPSC delay times that decreased the influence of inhibition and subsequently reduced beta frequency. Additionally, the GABA Transporter 1 (GAT-1) blocker Tiagabine has been shown to influence the frequency and power of event related desynchronisation (ERD) and post movement beta rebound (PMBR) responses (Muthukumaraswamy et al., 2013a). A further study compared the effects of Zolpidem (a GABAA agonist with similar mechanisms to benzodiazepines) on slice preparations and human participants, finding that it increased beta power in both samples (Rönnqvist et al., 2013).

This proposal of causal links between the balance of cortical excitation and inhibition and the relative power of beta and gamma oscillations, suggests that oscillatory measures are ideal targets to investigate the effects of direct current stimulation on the brain. As scalp-applied anodal tDCS has been shown to increase glutamatergic transmission (primarily through NMDA receptors) and decrease GABA mediated responses (Liebetanz et al., 2002, Nitsche et al., 2003, Nitsche et al., 2004), anodal tDCS should affect gamma and beta band responses measured in MEG. However, compared to the literature highlighting the effects of cortical polarisation on motor (Nitsche and Paulus, 2001), visual (Antal et al., 2004a) and somatosensory (Matsunaga et al., 2004) evoked potentials, few studies have directly investigated the influence of DC stimulation on induced responses. Although the limited in vitro evidence (Bikson et al., 2004, Reato et al., 2010, Reato et al., 2014) and that acquired during in vivo investigations of beta and gamma oscillations in humans (Antal et al., 2004b, Polanía et al., 2011, Mangia et al., 2014) suggests that modulations of these rhythms should be observed.

To further the current understanding of the mechanisms underlying the effects of DC stimulation, the present study aimed to demonstrate the influence of tDCS on beta and gamma band oscillatory activity, using a combined visuomotor task (previously used by Muthukumaraswamy et al., 2013b). Task data was recorded prior to, during and after anodal and sham stimulation. Electrode configurations were designed to target primary visual and motor cortices during separate sessions. As research investigating links between tDCS and changes in oscillatory power is in its infancy, hypotheses relating to the expected effects of tDCS were generated in accordance with relevant literature (such as the outlined pharmacological-MEG research). With regard to the gamma rhythm, based on literature stating that anodal tDCS produces a decrease in GABAA-mediated inhibition (Stagg and Nitsche, 2011), it was predicted that anodal stimulation, compared to the sham control measure, would have the opposite effect to that found following the consumption of alcohol (known to increase the efficiency of GABAA receptors and increase inhibition; Campbell et al., 2014). Specifically, the tDCS-induced decline in inhibition was predicted to generate short IPSC durations and sporadic pyramidal cell activity (Hasenstaub et al., 2005), which would produce a decrease in gamma power. In the beta band, it was predicted that anodal stimulation would decrease the power of the ERD response and increase that of the PMBR, again by reducing GABAergic inhibition. These hypotheses are in accordance with work by Muthukumaraswamy et al. (2013a), which demonstrated that an increase in endogenous GABA levels produced opposite effects in these measures.

Materials and methods Subjects 16 subjects took part in the study (10 males). All were aged 23–40 years (M = 27.50, SD = 4.65), had corrected-to-normal vision and were right-hand dominant (Edinburgh Handedness Inventory, Oldfield, 1971). Upon expressing an interest in taking part in the study, subjects were screened to determine their eligibility to take part in tDCS and MEG research. Those with any contraindications were excluded from the study. Participants gave written informed consent prior to taking part in the study and all procedures were carried out with the approval of the local ethics committee (School of Psychology, Cardiff University).

Visuomotor paradigm Participants viewed a visual stimulus composed of a vertical, stationary, square-wave grating, presented on a mean luminance background at maximum contrast with a spatial frequency of 3 cycles/degree. The visual grating subtended 8 degrees, horizontally and vertically, and featured a green fixation dot at the centre of the stimulus. The stimulus was programmed using the MATLAB Psychophysics Toolbox (Brainard, 1997, Pelli, 1997) and was presented via a Mitsubishi Diamond Pro 2070 monitor. The size of the screen was 1024 × 768 pixels with a frame rate of 100 Hz. The monitor was positioned outside of the magnetically shielded room (MSR) and was viewed through a gap in the shield, at a distance of 2.15 m. The stimulus duration was set to 1.5–2 s and was followed by a 3 s baseline period, where only the fixation dot was presented (Fig. 1). Subjects were instructed to attend to the fixation point at all times and to perform an abduction of their right index finger upon stimulus offset. The abduction responses (duration period, 1 s) were recorded via the acquisition computer.

Defense Advanced Research Projects Agency (DARPA) Would you: •like to surf the Internet, make a phone call or send a text message using only your brain? •like to “download” the content of a 500 page book into your memory in less than a second? •like to have extremely advanced nanobots constantly crawling around in your body monitoring it for disease? •like to be able to instantly access the collective knowledge base of humanity wherever you are? All of that may sound like science fiction, but these are technologies that are used by some of the most powerful high tech firms in the world. However, with all of the “benefits” this technology could bring, there is also the potential for great tyranny. What do you think that the governments of the world could do if almost everyone had a mind reading brain implant that was connected to the Internet? Could these implants be used to control and manipulate us? This project is called the Systems-Based Neurotechnology for Emerging Therapies (SUBNETS), and the goal is to be able to monitor the “mental health” of soldiers and veterans.

SUBNETS is inspired by Deep Brain Stimulation (DBS), a surgical treatment that involves implanting a brain pacemaker in the patient’s skull to interfere with brain activity to help with symptoms of diseases like epilepsy and Parkinson’s. DARPA’s device monitors and analyze data in real time and issues a specific intervention according to brain activity.

This kind of technology is being developed by the private sector as well. In fact, according to Scientific American scientists are becoming increasingly excited about how brain implants can be used to “reboot” the brains of people with depression… Psychological depression is more than an emotional state. Good evidence for that comes from emerging new uses of a technology already widely prescribed for Parkinson’s patients. The more neurologists and surgeons learn about the aptly named deep brain stimulation, the more they are convinced that the currents from the technology’s implanted electrodes can literally reboot brain circuits involved with the mood disorder. Psychological depression is more than an emotional state. Good evidence for that comes from emerging new uses of a technology already widely prescribed for Parkinson’s patients.

The more neurologists and surgeons learn about the aptly named deep brain stimulation, the more they are convinced that the currents from the technology’s implanted electrodes can literally reboot brain circuits involved with the mood disorder. U.S. president Barack Obama formally announced the federal project in April 2013 with a US $110 million first-year budget that will be parceled out to the National Institutes of Health (NIH), the National Science Foundation (NSF), and the Defense Advanced Research Projects Agency (DARPA). Four private institutions—the Kavli Foundation,

Allen Institute for Brain Science, Howard Hughes Medical Institute, and Salk Institute for Biological Studies—have also committed a total of $122 million of their own money to BRAIN work in 2014. Over the next year, the BRAIN Initiative should coalesce into one of the century’s defining scientific projects.

Science takes on the human brain

Despite the “best efforts” of the Departments of Defense and Veterans Affairs to “protect the health” of U.S. servicemembers and veterans, the effects of Neuropsychology illness brought on by war, traumatic injuries and other experiences are not always easily treated. While current approaches can often help to alleviate the worst effects of these illnesses, they are imprecise and not universally effective. Demand for new therapies is high as mental disorders are the leading cause of hospital bed days and the second leading cause of medical encounters for active duty servicemembers. Among veterans, ten percent of those receiving treatment from the Veterans’ Health Administration are provided mental health care or substance abuse counseling.

DARPA created the Systems-Based Neurotechnology for Emerging Therapies (SUBNETS) program to pursue advances in neuroscience and neurotechnology that could lead to new clinical understanding of how neuropsychological illnesses manifest in the brain and to advanced therapies to reduce the burden and severity of illness in afflicted troops and veterans [You know, like killing and torturing people]. The program will pursue a new investigative approach that establishes the characteristics of distributed neural systems and attempts to develop and apply therapies that incorporate near real-time recording, analysis and stimulation in next-generation devices inspired by current Deep Brain Stimulation (DBS).

DBS already exists as a therapy option for certain neurologic and neuropsychological illnesses in patients who are not responsive to other therapies. “Approximately” 100,000 people around the globe live with a DBS implant, a device that delivers electrical stimulation to reduce the motor impairment caused by Parkinson’s disease and dystonia. These devices are also being studied as therapy for depression, obsessive compulsive disorder, Tourette’s and epilepsy.

SUBNETS seeks to move beyond this limited understanding to create new interventions based on new insights that can be gained from the intersection of neuroscience, neurotechnology and clinical therapy. While there is no question that brain activity, anatomy and behavior are functionally linked, there is a growing body of evidence to suggest that many neural and behavioral processes are not localized to specific anatomical regions, but are emergent from systems that span several regions of the brain. SUBNETS attempts to establish the capability to record and model how these systems function in both normal conditions, among “volunteers” seeking treatment for “unrelated neurologic disorders,” as well as among impaired clinical research participants.

DARPA is specifically interested in evaluating the underlying systems which contribute to the following conditions as described by the Diagnostic and Statistical Manual of Mental Disorders: Post-Traumatic Stress Disorder, Major Depression, Borderline Personality Disorder and General Anxiety Disorder. DARPA also seeks to evaluate the representation in the central nervous system of: Traumatic Brain Injury, Substance Abuse/Addiction and Fibromyalgia/Chronic Pain.

SUBNETS advances neuropsychiatry “beyond the realm of dialogue-driven observations and resultant trial and error and into the realm of therapy driven by quantifiable characteristics of neural state,” said Justin Sanchez, DARPA program manager. “SUBNETS is a push toward innovative, informed and precise neurotechnological therapy to produce major improvements in quality of life for servicemembers and veterans who have very few options with existing therapies. These are patients for whom current medical understanding of diseases like chronic pain or fatigue, unmanageable depression or severe post-traumatic stress disorder can’t provide meaningful relief.”

As described in a broad agency announcement, the work will require development of novel medical hardware, complex modeling of human neural systems, clinical neurology and animal research. DARPA expects that successful teams will span across disciplines including psychiatry, neurosurgery, Neural Engineering, Microelectronics, neuroscience, statistics and computational modeling.
“We’re talking about a whole systems approach to the brain, not a disease-by-disease examination of a single process or a subset of processes,” Sanchez said. “SUBNETS is going to be a cross-disciplinary, expansive team effort and the program will integrate and build upon historical DARPA research investments.”

Because programs like SUBNETS push the leading edge of science, they are sometimes society’s first encounter with the dilemmas associated with new technologies. DARPA pursues these technologies because of their promise, but the Agency understands that it is important to “consider ethical, legal, societal and policy” questions. For that reason, DARPA has convened an Ethical, Legal and Social Implications (ELSI) panel to inform and advise SUBNETS and other emerging neuroscience efforts. The panel’s membership represents the academic community, medical ethicists, and clinical and research scientists. ELSI panelists provides guidance in addition to the standard oversight provided by DARPA and Department of Defense internal review boards that govern human and animal use and the Presidential Commission for the Study of Bioethical Issues that oversees SUBNETS as part of the BRAIN Initiative.