1. Field of the Invention
The present invention relates to devices and methods for communication achieved by neuromodulation via transcranial ultrasound. In various embodiments, messages are sent between one or more individuals, computerized devices, or animals to communicate instructions, words, concepts, cognitive states, emotions, experiences, sensory stimuli, or other forms of conscious or sub-conscious experience.
Communication is a fundamental feature of human and animal behavior. Information exchanged between two or more individuals underlies a wide range of human experience. Spoken, written, and signed language plays a central role in many aspects of communication—from education to storytelling to political speeches and love letters. Other important forms of communication are non-verbal: a hand signal, tap on the shoulder, emotive posture, or facial expression.
In recent years, technological advances have permitted new forms of communication that leverage computers, mobile devices, the Internet, and other digital media known in the art. For the most part, these forms of communication provide new means to use similar verbal, visual, and auditory communication modalities as have been used for millennia.
Other technological advances permit forms of communication that were not previously possible. Brain machine interfaces enable a paralyzed individual to enter text into a computer or move a mouse cursor via a system that decodes patterns of brain activity. Refreshable Braille terminals communicate language via haptic signals to the blind. A belt with an array of vibrating components has been developed that instructs an individual which direction to move or is coupled to a compass to indicate magnetic North by haptic signals. Other simple forms of communication between a device and its operator are tactile feedback such as through video game controllers, keyboards, or touch screens. Communication based on automated transmissions from computerized systems to an individual have become commonplace. An example of an automated communication from a computerized system is a text message alert that a passenger's airline flight is delayed. Further technologies to enhance or supplement existing forms of communication—and create new forms of communication—are desired.
The present invention relates to devices and methods for communication wherein the message is transmitted to the recipient via non-invasive brain neuromodulation (also known in the field as non-invasive neuromodulation).
Various techniques for invasive and non-invasive neuromodulation have been demonstrated in human beings. A non-exhaustive list of these neuromodulation techniques includes transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), targeted electrical stimulation (TES) (as described in patent application 61/663,409 from some of the named inventors of this patent titled “DEVICE AND METHODS FOR NONINVASIVE NEUROMODULATION USING TARGETED TRANSCRANIAL ELECTRICAL STIMULATION”), deep brain stimulation (DBS), and one electrode or an array of electrodes implanted on the surface of the brain or dura (electrocorticography (ECoG) arrays).
Ultrasound (US) has been used for many medical applications, and is generally known as cyclic sound pressure with a frequency greater than the upper limit of human hearing. The production of ultrasound is used in many different fields, typically to penetrate a medium and measure the reflection signature or to supply focused energy. For example, the reflection signature can reveal details about the inner structure of the medium. A well-known application of this technique is its use in sonography to produce a picture of a fetus in a womb. There are other applications which may provide therapeutic effects, such as lithotripsy for ablation of kidney stones or high-intensity focused ultrasound for thermal ablation of brain tumors. An important benefit of ultrasound therapy is its non-invasive nature. US waveforms can be defined by their acoustic frequency, intensity, waveform duration, and other parameters that vary the timecourse of acoustic waves in a target tissue. US waveforms based on pulses less than about 1 second are generally referred to as pulsed ultrasound and are repeated at a rate equivalent to the pulse repetition frequency. Tone bursts that extend for about 1 second or longer—though, strictly speaking, also pulses—are often referred to as continuous wave (CW).
Neurons are mechanically sensitive and can act as a piezoelectric material by converting a mechanical displacement into electrical currents or membrane polarization. Several potential mechanisms for the conversion of mechanical energy into neuronal activity have been proposed. Stretch-induced activation or inactivation of ion channels is one mechanism for converting mechanical force into currents that modulate neuronal activity. Mechanosensitive ion channels convert mechanical force into an electrical signal and contribute to transduction of hearing and touch. Ion channels and receptors that mediate their primary physiological effect through non-mechanical means are also sensitive to mechanical forces. Reversible activation and inactivation responses to stretch have been observed in recombinant systems for voltage-gated Na+, Ca2+ (L-type and N-type), and K+ ion channels, as well as for the hyperpolarization-activated channel, HCN. The linear spring properties endowed by the structure of ion channels is one putative mechanism for stretch-induced effects. An additional or alternative mechanism of stretch-induced effects in ion channels may relate to mechanical effects on cytoskeletal proteins such as actin or tubulin that could then be transduced to membrane-bound ion channels through the cytoskeletal structure.
Flexoelectric effects are a second mechanism for converting mechanical energy into changes in neuronal activity. Flexoelectricity was first discovered in the study of liquid crystals. Petrov described flexoelectricity in the context of biological membranes as “a phenomenon of curvature-induced electric polarization of a liquid crystal membrane, in which the molecules of the membrane are uniaxially orientated. Curvature of a membrane bilayer splays the uniaxial orientation of the molecules (lipids, proteins) that it contains and imposes a polar symmetry, such that on one side of the membrane the molecules are moved apart whereas on the other side they are moved closer together. Flexoelectricity results from the resultant electrical polarization of the membrane” (Petrov et al., 1993). Alternatively, flexoelectric effects can operate in the reverse direction in which mechanical energy is converted into membrane polarization. Thermodynamic investigations of lipid-phase transitions have shown that mechanical waves can be adiabatically propagated through lipid monolayers and bilayers, as well as neuronal membranes to influence fluidity and excitability. Notably, such sound wave propagation in pure lipid membranes has been estimated to produce depolarizing potentials ranging from 1 to 50 mV with negligible heat generation (˜0.01 K) (Griesbauer et al., 2009), potentially via a flexoelectric effect. In this manner, mechanical energy delivered by an acoustic wave can cause membrane polarization and affect voltage-gated channels and thus neuronal activity.
Another potential mechanism for neuromodulation by ultrasound is by causing changes in blood flow through mechanical and/or thermal effects.
Neuromodulation of the brain, spinal cord, and peripheral nervous system by ultrasound has been shown in animals using transcranial ultrasound for neuromodulation (bioTU). Other transcranial ultrasound based techniques use a combination of parameters to disrupt, damage, destroy, or otherwise affect neuronal cell populations so that they do not function properly and/or cause heating to damage or ablate tissue. Transcranial ultrasound techniques that cause these effects may include high intensities (greater than about 1 W/cm2 at the target tissue) and/or high acoustic frequencies (greater than about 1 MHz) bioTU employs a combination of parameters that transmits mechanical energy through the skull to its target in the brain without causing significant thermal or mechanical damage and induces neuromodulation primarily through mechanical means.
Recent research and disclosures have described the use of bioTU to activate, inhibit, or modulate neuronal activity ((Bystritsky et al., 2011; Tufail et al., 2010; Tufail et al., 2011; Tyler et al., 2008; Yoo et al., 2011; Zaghi et al., 2010), the full disclosures of which are incorporated herein by reference. Also see U.S. Pat. No. 7,283,861 and US patent applications 20070299370, 20110092800 titled “Methods for modifying currents in neuronal circuits” by inventor Alexander Bystritsky; U.S. patent application Ser. No. 12/940,052 (US patent application publication US 2011/0112394) titled “Neuromodulation of deep-brain targets using focused ultrasound” by inventor David J. Mishelevich; and patent applications by one of the named inventors of this submission, William J Tyler: PCT application number US2009/050560 and patent Ser. No. 61/175,413 titled “Methods and Devices for Modulating Cellular Activity using Ultrasound” and PCT application number US2010/055527 titled “Devices and Methods for Modulating Brain Activity”, the full disclosures of which are incorporated herein by reference.) The actual mechanisms underlying bioTU have not been fully elucidated. However, one confirmed mechanism for bioTU stimulation of electrical activity in neurons is by activating voltage-gated sodium channels and voltage-gated calcium channels (Tyler et al., 2008). bioTU can induce SNARE-mediated vesicle release and synaptic transmission (Tyler et al., 2008). In contrast to US waves with higher intensities, bioTU does not lead to significant tissue heating in the targeted brain region (Tufail et al., 2010). bioTU activates c-fos and does not disrupt the blood brain barrier (Tufail et al., 2010).
Since many aspects of human cognition relate to communication with others, application of bioTU for communication between individuals or groups would be beneficial. Due to the capacity for US to be delivered non-invasively through the skull in a targeted and focused manner, bioTU can be used to affect brain function in many cognitive domains and in so doing achieve communication to the recipient of bioTU.
The inventions described herein relate primarily to methods and systems that use bioTU as a form of communication.
2. Background Art
The following publications are relevant to the present application.    Arroyo, S., Lesser, R. P., Gordon, B., Uematsu, S., Hart, J., Schwerdt, P., Andreasson, K., and Fisher, R. S. (1993). Mirth, laughter and gelastic seizures. Brain 116 (Pt 4), 757-780.    Bystritsky, A., Korb, A. S., Douglas, P. K., Cohen, M. S., Melega, W. P., Mulgaonkar, A. P., DeSalles, A., Min, B.-K., and Yoo, S.-S. (2011). A review of low-intensity focused ultrasound pulsation. Brain Stimul 4, 125-136.    Farrell, D. F., Leeman, S., and Ojemann, G. A. (2007). Study of the human visual cortex: direct cortical evoked potentials and stimulation. J Clin Neurophysiol 24, 1-10.    Feurra, M., Paulus, W., Walsh, V., and Kanai, R. (2011). Frequency specific modulation of human somatosensory cortex. Front Psychol 2, 13.    Griesbauer, J., Wixforth, A., and Schneider, M. F. (2009). Wave Propagation in Lipid Monolayers. Biophys J 97, 2710-2716.    Petrov, A. G., Miller, B. A., Hristova, K., and Usherwood, P. N. (1993). Flexoelectric effects in model and native membranes containing ion channels. Eur Biophys J 22, 289-300.    Satow, T., Usui, K., Matsuhashi, M., Yamamoto, J., Begum, T., Shibasaki, H., Ikeda, A., Mikuni, N., Miyamoto, S., and Hashimoto, N. (2003). Mirth and laughter arising from human temporal cortex. J Neurol Neurosurg Psychiatr 74, 1004-1005.    Sperli, F., Spinelli, L., Pollo, C., and Seeck, M. (2006). Contralateral smile and laughter, but no mirth, induced by electrical stimulation of the cingulate cortex. Epilepsia 47, 440-443.    Tufail, Y., Matyushov, A., Baldwin, N., Tauchmann, M. L., Georges, J., Yoshihiro, A., Tillery, S. I. H., and Tyler, W. J. (2010). Transcranial pulsed ultrasound stimulates intact brain circuits. Neuron 66, 681-694.    Tufail, Y., Yoshihiro, A., Pati, S., Li, M. M., and Tyler, W. J. (2011). Ultrasonic neuromodulation by brain stimulation with transcranial ultrasound. Nat Protoc 6, 1453-1470.    Tyler, W. J., Tufail, Y., Finsterwald, M., Tauchmann, M. L., Olson, E. J., and Majestic, C. (2008). Remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound. PLoS ONE 3, e3511.    Yoo, S.-S., Bystritsky, A., Lee, J.-H., Zhang, Y., Fischer, K., Min, B.-K., McDannold, N. J., Pascual-Leone, A., and Jolesz, F. A. (2011). Focused ultrasound modulates region-specific brain activity. Neuroimage 56, 1267-1275.    Zaehle, T., Rach, S., and Herrmann, C. S. (2010). Transcranial Alternating Current Stimulation Enhances Individual Alpha Activity in Human EEG. PLoS ONE 5, e13766.    Zaghi, S., Acar, M., Hultgren, B., Boggio, P. S., and Fregni, F. (2010). Noninvasive brain stimulation with low-intensity electrical currents: putative mechanisms of action for direct and alternating current stimulation. Neuroscientist 16, 285-307.    See also WO 2011/057028, WO 2011/009141; and U.S. Pat. No. 7,350,522.
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