Apparatus and methods for use in diagnosis and treatment of attention deficit hyperactivity disorder

Abstract

The present invention relates to apparatus and methods for use in diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) and alleviation of symptoms of ADHD. We describe an apparatus having a housing for positioning the apparatus on the head of the wearer and comprising: a virtual or augmented visual display for viewing by the wearer for presenting images to the wearer; a pupillometric analysis module for evaluation of pupil responses; an eye-tracking module; a cerebral oxygen saturation sensor; an electroencephalography (EEG) sensor; an electrodermal sensor; and a neuromodulation module. We also describe a method for diagnosis and treatment of attention deficit hyperactivity disorder, the method comprising providing the apparatus; receiving inputs from the modules; determining a distraction score based on the inputs; comparing the distraction score with a predetermined value; and causing the neuromodulation module to generate an output when the distraction score exceeds a predetermined value.

Description

[0001] APPARATUS AND METHODS FOR USE IN DIAGNOSIS AND TREATMENT OF ATTENTION DEFICIT HYPERACTIVITY DISORDER

[0002] Technical Field

[0003] The present invention relates to apparatus and methods for use in diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) and alleviation of symptoms of ADHD.

[0004] Background

[0005] ADHD is a neurodevelopmental disorder characterized by attention problems, excessive physical activity and impulsivity. ADHD affects 4-12% of school-aged children world wide.

[0006] ADHD is classified into three categories: i) Combined ADHD (highest prevalence); ii) Impulsive / hyperactive ADHD; and iii) Inattentive / distractible ADHD.

[0007] Patients with ADHD are at increased risk of anxiety, personality disorder, substance dependence, and psychiatric disorder.

[0008] The primary management and treatment options for ADHD are medication and Cognitive behavioral therapy (CBT).

[0009] Medications such as methylphenidate, are not always effective and may have serious side effects. Methylphenidate and atomoxetine are commonly cause side effects affecting sleep and eating, which can exacerbate behavioral aspects of ADHD; and can impact child development and growth.

[0010] Low adherence to medication regimens is also common problem associated with medicating children with ADHD. In CBT, patients must attend several sessions with therapist which, for school children with substantial time limitations, is problematic.

[0011] Accordingly, there is an urgent need to develop further routes to the diagnosis and treatment of ADHD and alleviation of symptoms of ADHD.

[0012] Summary of the invention

[0013] In a first aspect, in its broadest sense, the present invention provides a head-wearable display apparatus for use in the diagnosis and treatment of attention deficit hyperactivity disorder of a wearer of the apparatus. The apparatus comprises a housing for positioning the apparatus on the head of the wearer and comprises: i) a virtual or augmented visual display for viewing by the wearer for presenting images to the wearer; ii) a pupillometric analysis module for evaluation of pupil responses; iii) an eye-tracking module; iv) a cerebral oxygen saturation sensor; v) an electroencephalography (EEG) sensor; vi) an electrodermal sensor; and vi) a neuromodulation module.

[0014] Accordingly, the present invention provides a wearable and portable measurement system suitable for use in diagnosis and treatment of ADHD and in alleviation of symptoms of ADHD. The apparatus is convenient and the system is suitable for physiological monitoring in clinical environments and in home and out-of-hospital environments.

[0015] In one embodiment, the neuromodulation module comprises an ultrasound module or a pair of ultrasound modules positioned in the housing substantially equally from a sagittal plane of the head of the wearer, optionally in the area of the temples of the wearer.

[0016] In certain examples, the ultrasound module is a low intensity focused ultrasound module.

[0017] The ultrasound module may comprise a single element transducer.

[0018] In some examples, the ultrasound module generates pulses of ultrasound signals. Optionally, the pulses of ultrasound signals comprises pulses of ultrasound signals having a duration of from about 5 seconds to about 90 seconds; about 10 seconds, about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, about 35 seconds, about 40 seconds, about 45 seconds, about 50 seconds, about 55 seconds or about 60 seconds.

[0019] In some examples, the pulses are generated in blocks of from about 3 pulses to about 20 pulses; or about 10 pulses.

[0020] In certain embodiments, the pulses have a duration of about 30 seconds and are generated in blocks of about 10 pulses.

[0021] Suitably, the neuromodulation module is positioned within the housing such that, in use, the neuromodulation module is positioned substantially adjacent at least one temple of the wearer.

[0022] In certain embodiments, the cerebral oxygen saturation sensor comprises at least one near-infrared spectrometry module.

[0023] In some examples, the cerebral oxygen saturation sensor is positioned within the housing such that, in use, the sensor is positioned adjacent the forehead of the wearer.

[0024] Suitably, the cerebral oxygen saturation sensor monitors brain oxyhemoglobin and deoxyhemoglobin concentration.

[0025] In certain examples, the electroencephalography (EEG) sensor comprises a plurality of EEG electrodes. Optionally, the plurality of electrodes comprises a pair of electrodes located in the housing to obtain EEG signals from a front portion of the head of the wearer and / or a pair of electrodes located in the housing to obtain EEG signals from a back portion of the head of the wearer. Further optionally, each electrode of a pair of electrodes is positioned substantially equally distanced from a sagittal plane of the head of the wearer.

[0026] In certain embodiments, the pupillometric analysis module comprises a stimulus light emitter, a light sensor responsive to the stimulus light, and a beam splitter arranged to direct stimulus light to an eye of the wearer and to direct light reflected from an eye of the wearer to the light sensor. Optionally, the stimulus light emitter emits infra-red light. In certain embodiments, the apparatus comprising a left eye pupillometric analysis module and a right eye pupillometric module.

[0027] In certain embodiments, the apparatus further comprises at least one of an inertial measurement unit and a microphone.

[0028] In certain examples, the apparatus further comprises a control module; wherein the control module receives inputs from the pupillometric analysis module, the eye-tracking module, the cerebral oxygen saturation sensor, the electroencephalography (EEG) sensor and the electrodermal sensor; and determines a distraction score for the wearer; wherein the control module causes the neuromodulation module to generate an output when the distraction score exceeds a predetermined value.

[0029] In a second aspect, the present invention provides a method for diagnosis and treatment of attention deficit hyperactivity disorder. The method comprises i) providing an apparatus as claimed in any preceding claim; ii) receiving inputs from the pupillometric analysis module, the eye-tracking module, the cerebral oxygen saturation sensor, the electroencephalography (EEG) sensor and the electrodermal sensor; iii) determining a distraction score based on the inputs; iv) comparing the distraction score with a predetermined value; and v) causing the neuromodulation module to generate an output when the distraction score exceeds a predetermined value.

[0030] In some embodiments, the neuromodulation module generates an output comprising pulses of signals, optionally ultrasound signals.

[0031] In certain examples, the pulses are pulses having a duration of from about 5 seconds to about 90 seconds; about 10 seconds, about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, about 35 seconds, about 40 seconds, about 45 seconds, about 50 seconds, about 55 seconds or about 60 seconds.

[0032] In some embodiments, the pulses are generated in blocks of from about 3 pulses to about 20 pulses; or about 10 pulses. In certain embodiments, the pulses have a duration of about 30 seconds and are generated in blocks of about 10 pulses.

[0033] Brief description of the drawings

[0034] The above and other aspects of the present invention will now be described in further detail, by way of example only, with reference to the accompanying figures, in which:

[0035] Figure 1 is a rear-perspective view of an embodiment of an apparatus in accordance with the present invention;

[0036] Figure 2 is a schematic view illustrating components of a pupilometer module of an embodiment of an apparatus in accordance with the present invention;

[0037] Figure 3 is a schematic view illustrating components of a near infra-red module of an embodiment of an apparatus in accordance with the present invention;

[0038] Figure 4 is a schematic representation of a typical system architecture for an embodiment of an apparatus in accordance with the present invention;

[0039] Figure 5 is a chart showing normalized power, as an index, in respect of stress alpha and stress beta conditions in a subject having ADHD against a control subject; and

[0040] Figure 6 is a plot showing skin temperature and electrodermal activity outputs for a subject having ADHD and having symptoms of sleep apnea.

[0041] Detailed description

[0042] Example embodiments are described below in sufficient detail to enable those of ordinary skill in the art to embody and implement the systems and processes herein described. It is important to understand that embodiments can be provided in many alternate forms and should not be construed as limited to the examples set forth herein. Accordingly, while embodiments can be modified in various ways and take on various alternative forms, specific embodiments thereof are shown in the drawings and described in detail below as examples. There is no intent to limit to the particular forms disclosed. On the contrary, all modifications, equivalents, and alternatives falling within the scope of the appended claims should be included. Elements of the example embodiments are consistently denoted by the same reference numerals throughout the drawings and detailed description where appropriate.

[0043] The terminology used herein to describe embodiments is not intended to limit the scope. The articles “a,” “an,” and “the” are singular in that they have a single referent, however the use of the singular form in the present document should not preclude the presence of more than one referent. In other words, elements referred to in the singular can number one or more, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises,” “comprising,” “includes,” and / or “including,” when used herein, specify the presence of stated features, items, steps, operations, elements, and / or components, but do not preclude the presence or addition of one or more other features, items, steps, operations, elements, components, and / or groups thereof.

[0044] Unless otherwise defined, all terms (including technical and scientific terms) used herein are to be interpreted as is customary in the art. It will be further understood that terms in common usage should also be interpreted as is customary in the relevant art and not in an idealized or overly formal sense unless expressly so defined herein.

[0045] Figure 1 illustrates, figuratively, an embodiment of an apparatus in accordance with the present invention in the form of a head-wearable apparatus 10. The apparatus is based around a band 11 adapted to fit the head of a wearer. In the embodiment shown, the band 11 is a continuous band and may be formed of any material suitable for retaining the apparatus on the head of a wearer. Suitable materials will be readily apparent to the skilled person, for example from the field of virtual reality headsets.

[0046] Band 11 provides a support for the sensors of the apparatus of the present invention. In the exemplary embodiment shown, the apparatus includes an electroencephalography (EEG) sensor system 12; pupilometer modules 13; at least one electrodermal activity sensor 14; a microphone 15; a near infra-red module 16; and an inertial measurement unit 17. The apparatus further includes an ultrasound transducer system 18.

[0047] The apparatus further includes, omitted for clarity in the figures, a control system and architecture, including a processor and associated hardware and firmware, and a power source for each component of the apparatus; and including a data fusion module 60 as described below. Each component will now be described in further detail.

[0048] The electroencephalography (EEG) sensor system 12 includes four electroencephalography (EEG) sensors, arranged in pairs. A frontal EEG pair is positioned to be adjacent the wearer’s frontal lobe, with each sensor of the frontal EEG sensor pair being equidistant from the sagittal plane of the wearer’s skull and consisting of a left frontal EEG sensor 12a and a right frontal EEG sensor 12b. A corresponding anterior EEG pair is positioned anteriorally with respect to the wearer’s head, with a left anterior EEG sensor 12c and a right anterior EEG sensor 12d. It will be appreciated that left frontal EEG sensor 12a and left anterior EEG sensor 12c also form an EEG sensor pair, as do right frontal EEG sensor 12b and right anterior EEG sensor 12d.

[0049] Each EEG sensor may be of conventional construction and will not be described in further details.

[0050] By determining the 0 / p ratio, EEG can differentiate with 81% accuracy between treated and untreated (unmedicated) ADHD. 0-y coupling is able to differentiate with 71.7% accuracy between ADHD and healthy controls. Absolute 6 and 0 power is able to differentiate with a sensitivity of 83.3% and a specificity of 83.3% between an unmedicated youth with ADHD and a control subject who does not have ADHD.

[0051] In the exemplary embodiment shown, the apparatus 10 includes a pair of pupilometer modules 13, a left pupilometer module 13a associated with the left eye of the wearer of the apparatus and a right pupilometer module 13b associated with the right eye. Each pupilometer module stimulates the subject’s pupils with light and records the effect of the light on the pupils.

[0052] The configuration of each pupilometer module 13 is illustrated schematically in more detail in Figure 2. Each module includes a stimulus light source 20, typically a light emitting diode (LED) light source, which may emit light across a range of wavelengths. Light from light source 20 is reflected by a beam splitter 21 to a respective eye 22 of the subject, to stimulate the pupil of the eye. The eye is imaged through the beam splitter 21 by an infra-red camera 23. Image data is output to an image processor unit 24 and processed image data is output to a data processor or data fusion system 25, as will be described further below.

[0053] In preferred embodiments of the invention, an infra-red camera is provided adjacent both the left and right sides of each eye. In the embodiment of Figure 1, the left pupilometer module 13a includes a left infra-red camera 23al and a right infra-red camera 23a2. Similarly, the right pupilometer module 13b includes a left infra-red camera 23b 1 and a right infra-red camera 23b2.

[0054] The pupilometer module 13 further includes control system to control operation of the stimulus light source 20. In the embodiment illustrated, the control system includes a host controller 26 and micro-controller unit 27. The practical details of the host controller and micro-controller unit will be apparent to the skilled person and will not be described in further detail.

[0055] In the exemplary embodiment, the subject’s eyes are isolated from external influences and artefacts such that the data obtained is indicative of the subject’s response only to the stimulus light source.

[0056] ADHD represents a primary biological dysfunction of the central nervous system. The autonomic nervous system has two primary branches - the sympathetic and the parasympathetic nervous systems. The two systems are normally in dynamic balance and play an essential role in the regulation of body functions. Autonomic regulation is impaired in subjects having ADHD.

[0057] It is considered that observation of pupillary light reflex (PLR) can be indicative of changes of autonomic balance in subjects having ADHD. Pupillometric evaluation can therefore be used for the assessment of functioning of both autonomic nervous system branches and parameters of pupil responsivity can be helpful as a tool for medical diagnostic and treatment.

[0058] The image captured by the infra-red camera 23 includes part of the pupil and some unnecessary areas. To eliminate the unnecessary areas. Infra-red LEDs are used to increase the contrast and the image processing routine yields a threshold to determine the edge of the pupil and exclude surrounding areas. Accordingly, the pupilometer module is able to derive, as a biomarker, a pupillary light reflex.

[0059] The pupilometer module is able to measure several parameters, including: diameter of the pupil before the application of light stimulus and after illumination at the peak of the constriction, a change of the pupil diameter, conveniently as a percentage, during constriction, average constriction velocity, maximum constriction velocity and average dilation velocity; all of which parameters are useful parameters in the diagnosis of ADHD of the subject.

[0060] The exemplary apparatus 10 further includes an electrodermal activity sensor 14 located in or on band 11 to contact the forehead of the wearer of the apparatus. The electrodermal sensor measures skin temperature variation. Skin temperature spectral characteristics have been shown to indicate stress-related changes of peripheral vasomotor activity in non-ADHD subjects and analysis of variations in skin temperature response is considered to be useful in diagnosis of ADHD.

[0061] Microphone 15 is positioned, in the embodiment shown, in a nasal recess formed in band 11, to pick up sounds from the mouth and nose of the subject wearer of the apparatus, in particular to monitor breathing rate and depth.

[0062] The near infra-red (NIR) module 16 is positioned adjacent the forehead of the subject and detects changes in brain oxyhemoglobin and deoxyhemoglobin concentration, in particular in the adjacent prefrontal cortex, which is responsible for complex thinking and decision making as well as emotional regulation. It is known that sleep disorders such as sleep apnea significantly deteriorate cerebral oxygen supply to the brain. By using behavioral tasks requiring attentiveness and concentration, functional NIR spectroscopy imaging has demonstrated that ADHD-related symptoms are associated with low cerebral cortical activity in a number of regions, including the PFC (prefrontal cortex). Activation of the parietal cortex was also decreased in ADHD patients during a verbal n-back task [Gu, Y., Miao, S., Han, J., Zeng, K., Ouyang, G., Yang, J., & Li, X. (2017). Complexity analysis of fNIRS signals in ADHD children during working memory task. Scientific Reports, 7(1), 1-11. https: / / doi.org / 10.1038 / s41598-017-00965-4]. During NoGo block, ADHD children had a weaker increase in HbO over prefrontal cortex compared to controls, which indicated that children with ADHD were not activating the prefrontal cortex. In the embodiment shown, the NIR module includes a left NIR module 16a associated with the left eye of the subject and a right NIR module 16b associated with the right eye of the subject. As shown in Figure 3, the NIR module includes an infra-red emission module 30 which emits infra-red radiation to the prefrontal cortex of the brain 31; and a sampling module 32 which receives and processes near infra-red signals received by a photodiode module 33. In convenient embodiments, photodiode module 33 typically includes a 2 x 2 spaced array of near infra-red photodiodes. Suitably, the photodiodes are arranged in a square configuration with each diode at the corner of the square and having a spacing of about 40 mm from an adjacent photodiode.

[0063] Inertial measurement unit 17 is conveniently positioned in an anterior location of the apparatus. The skilled person will be well aware of numerous practical implementations of inertial measurement units suitable for inclusion in the apparatus of the present invention, typically including accelerometer and gyroscopic devices.

[0064] The apparatus of the present invention further includes an eye tracking module 40 which tracks eye movement of the subject when undertaking specific tasks assigned for the purposes of diagnosis, or during normal, everyday, activities. Eye tracking can assist clinicians in monitoring where the subject focuses attention and can prompt adaption of exercises or treatment. Eye-movement impairments are common in subjects with ADHD and are at least partially reflective of a disrupted attentional system.

[0065] In the embodiment of Figure 1, outputs from the infra-red cameras 23, or each of a pair of infrared cameras, of the pupilometer module 13 are shared with the eye tracking module 40 to track eye movement of the subject. In other embodiments, eye tracking module 40 may be provided as separate component of the apparatus.

[0066] Eye movement patterns associated with ADHD include: poor fixation and increased saccades. Eye movements are linked with performances in brain regions affected by ADHD, e.g. prefrontal cortex, striatal structures, posterior parietal cortex. Individuals diagnosed with ADHD typically exhibit increased micro-saccades and fixated for longer durations on non- relevant regions (regions unrelated to target stimuli during task performance) in comparison with typically-developing individuals without ADHD. The neural mechanisms of saccadic eye- movements are closely linked to that of attentional control and eye-movements have a long history of being used as a proxy for the locus of attention.

[0067] For the purposes of treatment and / or rehabilitation and alleviation of the symptoms of ADHD, the apparatus of the present invention also includes an ultrasound module 18. In the embodiment shown, the ultrasound module includes a left ultrasound module (obscured in Figure 1) and a right ultrasound module 18. Each ultrasound module is positioned to be adjacent a respective temple of the subject. Each ultrasound comprises a transducer using an array of piezoelectric crystals. Each piezoelectric crystal vibrates ultrasonically upon application of an electric current, producing high frequency sound pressure waves. Equally, each piezoelectric crystal is able to convert received high frequency sound pressure waves into an electric current, which can be measured. The transducer is typically a conventional medical transducer, comprising a large array of piezoelectric crystals, allowing the creation of a series of images that together form a complete image frame (sonogram).

[0068] As the transducer send waves into the body, they pass through the skin and enter the internal anatomy. As the waves encounter different tissues with different characteristics and densities, they produce echoes that reflect back to piezo electrode crystals in the ultrasound module. The frequency of such transmission of signals and reception of echoes occurs more than one thousand times a second.

[0069] The returning echoes are converted by a processor to generate an image (sonogram) with points of brightness corresponding with the anatomic position of the reflected echoes and their strength.

[0070] Ultrasound waves are able reach a volume inside human organ, or biological tissue noninvasively. The depth of the penetration depends on the frequency and power of the emitted signal. Attenuation and absorption of the medium in which the ultrasound propagates depends on the position the dimension of the transducer.

[0071] The near field distance N, calculated according to the formula: where D is the transducer diameter F is the frequency

[0072] C is the speed of sound in the medium

[0073] The field depth of focal zone, which defines the -6 dB signal amplitude drop from the maximum amplitude, is calculated as: where F, the focal distance, is the distance between the transducer and the focal point that is the target zone of the waves.

[0074] A typical system architecture for the apparatus of the present invention is shown in Figure 4. As discussed above, EEG sensor system 12 allows the determination of 9 / p ratio 40, 0-y coupling 41 and absolute 6 and 9 power (42). NIR module 16 provides hemoglobin oxygen concentration 43 and reduced hemoglobin concentration 44. The pupilometer module may generate pupil light reflex values 45, pupil diameter values 46, dilation velocity values 47 and contraction velocity values 48. The eye tracking module 40 generates values for fast relocation 49, saccades 50 and fixation 51. These values are output, together with the outputs from microphone 15, inertial movement unit 17 and electrodermal activity sensor 14 to a data fusion module 60 which applies an analysis to the data to determine a classification of ADHD and determine a treatment. The treatment may be behavioral 61 or involve the application 62 of ultrasound waves from the ultrasound module or modules 18.

[0075] In combination, data obtained from the apparatus may also be used to determine a reaction time 52 for tasks performed by the subject, which is also output to the data fusion module.

[0076] Treatment

[0077] 1 - ADHD Rehabilitation: Behavioral

[0078] Using a customized application, the ADHD subject wear the apparatus of the present invention and is instructed to perform a task. Distractions are added -such as the sound of a bird nearby- to assess what types of distractions prevent the subject from completing the task or interfere with completion of the task. Biomarkers collected from the sensors are all collected, including head movement from the inertial movement unit and determined reaction time 52, and a distraction score determined and compared with a predetermined target value . When there is an indication of a distraction from the sum of the biomarkers and responses, a notification / vibration is transmitted to the patient to remind the patient to focus on the task.

[0079] Possible assessment tools include: composite score (overall performance) simple reaction time code substitution (learning) procedural reaction time mathematical processing (working memory 1) matching to sample (spatial working memory) code substitution - delayed (delayed memory) simple reaction time (SRT 2) Go / no-go (inhibition) logical relations (reasoning) spatial processing tower puzzle (problem solving), tapping R hand (motor speed), tapping L hand (motor speed), two-choice reaction time (attention / processing speed), and running memory (working memory 2).

[0080] 2 - ADHD Treatment: Neuromodulation

[0081] Low Intensity Focused Ultrasound (LIFU) provided by the ultrasound module or modules 18 for neuromodulation is novel for treatment of ADHD and can be used to stimulate areas of the brain with greater resolution and depth than other methodologies. This technology applies non- invasive acoustic energy to reversibly modulate cortical and subcortical structures with millimeter precision and higher depth penetration.

[0082] In preferred methodologies, the apparatus of the present invention administers LIFU in short pulses, which reduces energy deposition. In some examples, the pulses are pulses of ultrasound signals having a duration of from about 5 seconds to about 90 seconds; about 10 seconds, about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, about 35 seconds, about 40 seconds, about 45 seconds, about 50 seconds, about 55 seconds or about 60 seconds.

[0083] The pulses may be provided as blocks of multiple pulses. In some examples, the pulses are generated in blocks of from about 3 pulses to about 20 pulses; or about 10 pulses.

[0084] In a particular embodiment, a single element ultrasound transducer (71.5mm 650 HZ) having an output of 720 mW / cm3has been determined to be particularly suitable with pulses having a duration of about 30 seconds and generated in blocks of about 10 pulses.

[0085] The apparatus of the present invention may particularly be used to address or alleviate the following common symptoms and / or conditions of ADHD:

[0086] Major depressive disorder'. EEG monitoring of alpha asymmetry (see Figure 5);

[0087] Sleep staging'. Enhancement of sleep staging by adding EDA and temperature sensor;

[0088] Mental stress'. EEG - alpha rhythm reduced with stress, beta rhythms correlated with stress in temporal lobe, ECG and NIRS (see Figure 5);

[0089] Mental fatigue - sleep deprived and rested, or fatigue due to drug effects;

[0090] Cognitive decline,'

[0091] Schizophrenia diagnosis,' and

[0092] Sleep apnea (see the effect of sleep apnea on skin temperature and electrodermal activity shown in Figure 6).

[0093] In certain embodiments, the apparatus includes a visual display screen or a visual display screen associated with each eye. In these embodiments, specific images may be displayed to the subject under assessment and the responses monitored. In other embodiments, the apparatus allows the subject to view their surroundings in a normal manner such that their responses, eye movement, blood oxygen concentration and so on, may be monitored whilst performing day- to-day activities.

[0094] In the above description, the term ‘associated with’ is intended to indicate a sufficient proximity to the relevant part of the wearer’s anatomy for the component to achieve its intended function or operation. For example, those sensors which require contact with the skin of the wearer, such as EEG sensors 12 and electrodermal activity sensor 14 are mounted on or in band 11 such that the sensor contacts the skin at the appropriate location. Sensors which detect movement of the eye, for example, are positioned at a location in band 11 that the sensor has a view of the relevant anatomy of the subject.

[0095] Accordingly, the present invention provides a wearable and portable measurement system design for diagnosis and treatment of ADHD. The system is designed for physiological monitoring and can be deployed for home and out of hospital environment.

[0096] The invention provides two methods for improvement / treatment depending on the severity of ADHD degree: i) neuropsychological training tools, with a feedback for helping participants to learn concentration techniques; ii) neuromodulation, with neurofeedback, using low intensity focused ultrasound; and iii) treatment using low intensity focused ultrasound and neurofeedback system to quantify the effect - where the beams converge, focused ultrasound produces neuromodulated therapeutic effects.

[0097] As regards control of the apparatus of the present invention and its components, examples can be provided as methods, systems or machine-readable instructions, such as any combination of software, hardware, firmware or the like. Such machine-readable instructions may be included on a computer readable storage medium (including but not limited to disc storage, CD-ROM, optical storage, etc.) having computer readable program codes therein or thereon.

[0098] The present disclosure is described with reference to flow charts and / or block diagrams of the method, devices and systems according to examples of the present disclosure. Although the flow diagrams described above show a specific order of execution, the order of execution may differ from that which is depicted. Blocks described in relation to one flow chart may be combined with those of another flow chart. In some examples, some blocks of the flow diagrams may not be necessary and / or additional blocks may be added. It shall be understood that each flow and / or block in the flow charts and / or block diagrams, as well as combinations of the flows and / or diagrams in the flow charts and / or block diagrams can be realized by machine readable instructions. The machine-readable instructions may, for example, be executed by a machine such as a general-purpose computer, a platform comprising user equipment such as a smart device, e.g., a smart phone, a special purpose computer, an embedded processor or processors of other programmable data processing devices to realize the functions described in the description and diagrams. For example, machine-readable instructions may, for example, be executed by a machine such as an event signal processor configured to generate event data representing asynchronous changes in intensity of a scene or object to be imaged.

[0099] A processor or processing modules or apparatus may execute the machine-readable instructions. Thus, modules of apparatus (for example, an encoder or decoder as described above) may be implemented by a processor executing machine readable instructions stored in a memory, or a processor operating in accordance with instructions embedded in logic circuitry. The term 'processor' is to be interpreted broadly to include a CPU, processing unit, ASIC, logic unit, programmable gate set, or event signal processor etc. The methods and modules may all be performed by a single processor or divided amongst several processors.

[0100] Such machine-readable instructions may also be stored in a computer readable storage that can guide the computer or other programmable data processing devices to operate in a specific mode. For example, the instructions may be provided on a non-transitory computer readable storage medium encoded with instructions, executable by a processor.

[0101] Such machine-readable instructions may also be loaded onto a computer or other programmable data processing devices, so that the computer or other programmable data processing devices perform a series of operations to produce computer-implemented processing, thus the instructions executed on the computer or other programmable devices provide an operation for realizing functions specified by flow(s) in the flow charts and / or block(s) in the block diagrams.

[0102] Further, the teachings herein may be implemented in the form of a computer or software product, such as a non-transitory machine-readable storage medium, the computer software or product being stored in a storage medium and comprising a plurality of instructions, e.g., machine readable instructions, for making a computer device implement the methods recited in the examples of the present disclosure. In some examples, some methods can be performed in a cloud-computing or network-based environment. Cloud-computing environments may provide various services and applications via the Internet. These cloud-based services (e.g., software as a service, platform as a service, infrastructure as a service, etc.) may be accessible through a web browser or other remote interface of the user equipment for example. Various functions described herein may be provided through a remote desktop environment or any other cloud-based computing environment.

[0103] While various embodiments have been described and / or illustrated herein in the context of fully functional computing systems, one or more of these exemplary embodiments may be distributed as a program product in a variety of forms, regardless of the particular type of computer- readable-storage media used to actually carry out the distribution. The embodiments disclosed herein may also be implemented using software modules that perform certain tasks. These software modules may include script, batch, or other executable files that may be stored on a computer-readable storage medium or in a computing system. In some embodiments, these software modules may configure a computing system to perform one or more of the exemplary embodiments disclosed herein. In addition, one or more of the modules described herein may transform data, physical devices, and / or representations of physical devices from one form to another.

[0104] The preceding description has been provided to enable others skilled in the art to best utilize various aspects of the exemplary embodiments disclosed herein. This exemplary description is not intended to be exhaustive or to be limited to any precise form disclosed. Many modifications and variations are possible without departing from the spirit and scope of the instant disclosure. The embodiments disclosed herein should be considered in all respects illustrative and not restrictive. Reference should be made to the appended claims and their equivalents in determining the scope of the instant disclosure.

Claims

CLAIMS1. A head-wearable display apparatus for use in the diagnosis and treatment of attention deficit hyperactivity disorder of a wearer of the apparatus, the apparatus having a housing for positioning the apparatus on the head of the wearer and comprising: i) a virtual or augmented visual display for viewing by the wearer for presenting images to the wearer; ii) a pupillometric analysis module for evaluation of pupil responses; iii) an eye-tracking module; iv) a cerebral oxygen saturation sensor; v) an electroencephalography (EEG) sensor; vi) an electrodermal sensor; and vi) a neuromodulation module.

2. An apparatus as claimed in claim 1 wherein the neuromodulation module comprises an ultrasound module or a pair of ultrasound modules positioned in the housing substantially equally from a sagittal plane of the head of the wearer, optionally in the area of the temples of the wearer.

3. An apparatus as claimed in claim 2 wherein the ultrasound module is a low intensity focused ultrasound module.

4. An apparatus as claimed in claim 2 or claim 3 wherein the ultrasound module comprises a single element transducer.

5. An apparatus as claimed in any one of claims 2 to 4 wherein the ultrasound module generates pulses of ultrasound signals.

6. An apparatus as claimed in claim 5 wherein the pulses comprises pulses of ultrasound signals having a duration of from about 5 seconds to about 90 seconds; about 10 seconds, about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, about 35 seconds, about 40 seconds, about 45 seconds, about 50 seconds, about 55 seconds or about 60 seconds.

7. An apparatus as claimed in claim 5 or claim 6 wherein the pulses are generated in blocks of from about 3 pulses to about 20 pulses; or about 10 pulses.

8. An apparatus as claimed in claim 7 wherein the pulses have a duration of about 30 seconds and are generated in blocks of about 10 pulses.

9. An apparatus as claimed in any preceding claim wherein the neuromodulation module is positioned within the housing such that, in use, the neuromodulation module is positioned substantially adjacent at least one temple of the wearer10. An apparatus as claimed in any preceding claim wherein the cerebral oxygen saturation sensor comprises at least one near-infra-red spectrometry module.11 An apparatus as claimed in any preceding claim wherein the cerebral oxygen saturation sensor is positioned within the housing such that, in use, the sensor is positioned adjacent the forehead of the wearer.

12. An apparatus as claimed in any preceding claim wherein the cerebral oxygen saturation sensor monitors brain oxyhemoglobin and deoxyhemoglobin concentration.

13. An apparatus as claimed in any preceding claim wherein the electroencephalography (EEG) sensor comprises a plurality of EEG electrodes.

14. An apparatus as claimed in claim 13 wherein the plurality of electrodes comprises a pair of electrodes located in the housing to obtain EEG signals from a front portion of the head of the wearer and / or a pair of electrodes located in the housing to obtain EEG signals from a back portion of the head of the wearer.

15. An apparatus as claimed in claim 14 wherein each electrode of a pair of electrodes is positioned substantially equally from a sagittal plane of the head of the wearer.

16. An apparatus as claimed in any preceding claim wherein the pupillometric analysis module comprises a stimulus light emitter, a light sensor responsive to the stimulus light, and abeam splitter arranged to direct stimulus light to an eye of the wearer and to direct light reflected from an eye of the wearer to the light sensor.

17. An apparatus as claimed in claim 16 wherein the stimulus light emitter emits infra-red light.

18. An apparatus as claimed in any preceding claim comprising a left eye pupillometric analysis module and a right eye pupillometric module.

19. An apparatus as claimed in any preceding claim further comprising at least one of an inertial measurement unit and a microphone.

20. An apparatus as claimed in any preceding claim further comprising a control module; wherein the control module receives inputs from the pupillometric analysis module, the eyetracking module, the cerebral oxygen saturation sensor, the electroencephalography (EEG) sensor and the electrodermal sensor; and determines a distraction score for the wearer; wherein the control module causes the neuromodulation module to generate an output when the distraction score exceeds a predetermined value.

21. A method for diagnosis and treatment of attention deficit hyperactivity disorder, the method comprising i) providing an apparatus as claimed in any preceding claim; ii) receiving inputs from the pupillometric analysis module, the eye-tracking module, the cerebral oxygen saturation sensor, the electroencephalography (EEG) sensor and the electrodermal sensor; iii) determining a distraction score based on the inputs; iv) comparing the distraction score with a predetermined value; and v) causing the neuromodulation module to generate an output when the distraction score exceeds a predetermined value.

22. A method as claimed in claim 21 wherein the neuromodulation module generates an output comprising pulses of signals, optionally ultrasound signals.

23. A method as claimed in claim 22 wherein the pulses are pulses having a duration of from about 5 seconds to about 90 seconds; about 10 seconds, about 15 seconds, about 20 seconds, about 25 seconds, about 30 seconds, about 35 seconds, about 40 seconds, about 45 seconds, about 50 seconds, about 55 seconds or about 60 seconds.

24. A method as claimed in claim 22 or claim 23 wherein the pulses are generated in blocks of from about 3 pulses to about 20 pulses; or about 10 pulses.

25. A method as claimed in claim 22 wherein the pulses have a duration of about 30 seconds and are generated in blocks of about 10 pulses.

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