Patent Description:
<CIT> describes a method that includes delivering, via one or more stimulation generators of a medical device implanted in a patient, electrical stimulation to the patient. In this example, the method also includes disturbing, by one or more components of the medical device, an image of the patient generated by a magnetic resonance image (MRI) scanner.

<CIT> relates to an electronic system of an implantable medical device, comprising at least one first circuit, at least one tracking means, which is configured such that radio frequency bursts and/or a gradient magnetic field of a magnetic resonance imaging apparatus can be tracked, and at least one synchronizing means, whereby the synchronizing means is configured such that based on the tracked radio frequency bursts and/or the gradient magnetic field the at least one first circuit and/or the electronic system as a whole is synchronized with the radio frequency bursts and/or the gradient magnetic field.

<CIT> is directed to structure and methods for coordinating the operation of an implantable medical device (IMD) with magnetic resonance imaging (MRI) techniques. For example, the IMD can be made to activate a blanking period during the time when the electromagnetic radiation bursts occur. Blanking an IMD at times when MRI electromagnetic radiation bursts occur can prevent an undesirable action or incorrect sensing by the IMD while under the influence of the electromagnetic radiation bursts.

Post-stroke depression (PSD) is a common effect of a stroke, occurring in <NUM>-<NUM>% of stroke survivors, and has a negative impact on the functional recovery, cognition and rehabilitation of stroke patients. In particular, PSD is associated with a higher risk of suboptimal recovery, recurrent vascular events, poor quality of life, and mortality.

Pharmacological (e.g. antidepressant medication) and psychotherapy (e.g. Cognitive Behavioral Therapy) approaches have both been used to treat PSD. While these approaches have proven to be beneficial for treating depression in general, they have limited efficacy in the case of PSD. This is, in part, due to problems caused by timing of intervention and/or side effects of medication, but also because these approaches do not take into account clinical and functional differences between patients, nor do they account for the physiological, rather than psychological, cause of PSD.

There is therefore a need for improved treatment for PSD.

According to examples in accordance with an aspect of the invention, there is proposed a system for providing stimulation to a subject with post-stroke depression during an MRI scan, the system comprising: the control unit as described below; and an MRI scanner, in communication with the control unit and configured to obtain a sequence of images representative of brain activity of the subject.

In some examples, the MRI scanner is further configured to provide the rhythmic stimulation signal based on an instruction from the control unit.

The system may further comprise a sensory stimulation system configured to provide the rhythmic stimulation signal based on an instruction from the control unit.

The control unit is configured for controlling stimulation provided to a subject with post-stroke depression during a magnetic resonance imaging, MRI, scan.

The control unit is configured to control a rhythmic stimulation signal provided to the subject during the MRI scan, wherein the rhythmic stimulation signal is controlled to be synchronized with a scanning frequency of the MRI scanner performing the MRI scan.

The invention is based on the recognition that post-stroke depression, PSD, is physiological, rather than psychological, in origin, and may therefore be more effectively treated by repairing neuronal functions.

There is growing evidence to support the idea that functional neuronal repair may be beneficial in treating PSD. In particular, <NPL> describes the beneficial effect of neurogenesis in repairing mood-related areas after stroke. The inventors propose that neurogenesis for perception-related brain areas may also be effective in treating PSD.

It is known that multisensory stimulation aids the brain in controlling attentional focus, particularly when applied rhythmically synchronously in at least two perceptual modalities (e.g., visual, auditory, tactile) simultaneously (see, for example, <NPL>). Attentional focus is an important factor in engaging neurons in a particular task; the inventors therefore propose the use of attentional focus, controlled by the application of multisensory stimulation, to repair neural function.

A stimulation signal that is synchronized with the scanning frequency of the MRI signal provides (e.g. a change of) stimulations at a same or similar frequency (e.g. with peak amplitudes aligned or near-aligned) as the scanning frequency of the MRI. A rhythmic stimulation signal is one that provides a stimulation or a change of stimulation at predetermined time intervals (e.g. the beat of an audio signal). Since an MRI scanner automatically provides rhythmic sensory stimulation in the form of scanner noise, providing an additional rhythmic sensory stimulation signal during the MRI scan means that the subject is provided with rhythmic stimulation in two perceptual modalities simultaneously.

In other words, the present disclosure proposes a mechanism by which at least two rhythmic stimulations are provided to the subject being scanned, including at least one rhythmic stimulation being a noise naturally generated by the MRI device.

A perceptual modality is a user-perceptible output, such that different forms of perceptual modalities provide different user-perceptible outputs. In some examples, the two perceptual modalities of the rhythmic stimulation may be the same (i.e., both are audio stimulation). For instance, the rhythmic stimulation signal may be music synchronized with the scanner's noise. In other examples, the rhythmic stimulation signal may provide stimulation in a different perceptual modality to the scanner noise. For instance, the rhythmic stimulation signal may be a visual or tactile signal. Any form of perceptual modality that can be rhythmically controlled is envisaged, including visual, audio and tactile outputs.

A rhythmic stimulation signal is any user-perceptible signal (a visual, audio and/or tactile signal) that has a controllable rhythm or "beat". Examples include music (which has a beat or rhythm), a moving image (which can move according to a beat or rhythm) and so on.

Providing the stimulation during an MRI scan allows the effect of the stimulation on affected brain regions and functional neuronal networks to be monitored. The stimulation may then be adjusted to improve the effectiveness of the stimulation.

The synchronization of the provided stimulation with the MRI scanning frequency ensures that interfering rhythms are not present while the stimulation is being provided, and means that the MRI images taken during the scan are all from the same section of the stimulation cycle, allowing a better comparison of brain activity between the images.

The stimulation may, for example, be provided to the subject during a resting state MRI scan or while the subject is engaged in a cognitive or perceptual task such as a memory task or visual detection task.

In some examples, the use of multisensory stimulation to treat PSD may be combined with pharmacological therapy and/or behavioral therapy. This may be more effective than any single approach used alone.

In some examples, the rhythmic stimulation signal is provided by the MRI scanner. This makes use of the fact that the MRI scanner may provide further sensory stimulation as a side effect of performing an MRI scan. For example, the MRI scanner may be used to provide a tactile stimulation signal, by intentionally inducing peripheral nerve stimulation (PNS) in the subject with a modulation according to the desired stimulation frequency. PNS occurs when the strong currents applied to the scanner's gradient coils excite sensorial and motor nerves in the subject, causing them to feel a tickling sensation or slight muscle contraction, and is generally considered an undesirable side effect of MRI scanning.

The rhythmic stimulation signal may be provided by a sensory stimulation system, e.g. a sensory stimulation system that is separate to the functionality of the MRI scanner.

The use of a separate sensory stimulation enables a greater flexibility in the type of stimulation offered to the patient, for example, visual stimulation, allowing the provision of more engaging stimulation than the MRI scanner is capable of providing.

The control unit may be further configured to: receive, from the MRI scanner, a sequence of images representative of brain activity of the subject taken during the MRI scan; and analyze an effect of the rhythmic stimulation signal based on the received sequence of images. This allows the stimulation to be adjusted in cases where the stimulation does not achieve a desired effect.

The control unit may be further configured to: determine an effectiveness of the rhythmic stimulation signal based on the analysis of the effect; and adjust the rhythmic stimulation signal in response to a determination that the effectiveness is below a predefined threshold. The stimulation signal may be adjusted, for example, by changing a type of stimulation, or by adjusting the stimulation rhythm.

The control unit may be further configured to control the scanning frequency of the MRI scanner. In this way, the control unit may adjust the frequency of the stimulation signal (for example, in order to improve an effectiveness of the provided stimulation) while keeping the stimulation signal and the MRI scanning frequency synchronized.

The rhythmic stimulation signal may be based on a personal preference of the subject. For example, the stimulation may be designed to take into account particular features or information that the subject finds engaging, such as images and/or recordings of the subject's family members/loved ones or images of preferred nature scenes.

In some examples, the control unit is further configured to provide the subject with reward-based interaction. In this way, dopamine release may be induced in the subject, further contributing towards neuronal repair.

There is also proposed a computer program product comprising computer program code which, when executed on the system in accordance with any of the above embodiments, cause the system to perform a computer-implemented method for controlling stimulation provided to a subject with post-stroke depression during an MRI scan. The computer-implemented method comprises controlling a rhythmic stimulation signal provided to the subject during the MRI scan, wherein the rhythmic stimulation signal is controlled to be synchronized with a scanning frequency of an MRI scanner performing the MRI scan.

The computer-implemented method may further comprise receiving, from the MRI scanner, a sequence of images representative of brain activity of the subject taken during the MRI scan; and analyzing an effect of the rhythmic stimulation signal based on the received sequence of images.

The computer-implemented method may further comprise steps of determining an effectiveness of the rhythmic stimulation signal based on the analysis of the effect; and adjusting the rhythmic stimulation signal in response to a determination that the effectiveness is below a predefined threshold. There is also proposed a (non-transitory) computer readable medium comprising the computer program product.

According to a concept of the invention, there is proposed a system and method for controlling rhythmic sensory stimulation provided to a subject with post-stroke depression, PSD, during an MRI scan. A control unit is configured to control a rhythmic sensory stimulation signal such that the signal is rhythmically synchronous to a scanning rhythm of an MRI scanner performing the MRI scan.

Embodiments are at least partly based on the realizations that multisensory stimulation is effective in improving attentional focus, that attentional focus may play an important role in repairing neuronal function, and that functional neuronal repair may be effective in treating PSD.

The inventors propose that, since failure of neuronal functions is at least partly responsible for the occurrence of PSD in a subject, PSD may be treated by repairing the relevant neuronal functions. Repairing neuronal function is considered distinct from repairing a particular damaged "brain area": for example, a cognitive function such as memory may be repaired (e.g. by performing exercises) without necessarily repairing the damaged memory neurons. The inventors propose that the use of attentional focus may aid the repair of neuronal function, since attentional focus is an important factor in engaging neurons in a particular task.

Research has shown that immersive multisensory stimulation aids the brain in controlling attentional focus, particularly when the stimulation is applied rhythmically synchronously in at least two perceptual modalities simultaneously, as heteromodal congruency allows the brain to identify signal relevance in a bombardment of sensory signals.

The inventors have recognized that an MRI scanner produces a rhythmic noise while performing a scan, and that this may be considered a first form of rhythmic sensory stimulation of a rhythmic multisensory stimulation provided to the subject if the subject is also provided with a second form of rhythmic sensory stimulation synchronized to the scanner noise. In other words, the invention makes use of the noise produced by the scanner during an MRI scan by combining the noise with a rhythmic sensory stimulation signal synchronized to the scanning rhythm to provide an immersive multisensory stimulation therapy for treating PSD.

Illustrative embodiments may, for example, be employed in MRI scanning systems.

<FIG> illustrates a system <NUM> for providing rhythmic multisensory stimulation to a subject <NUM> with post-stroke depression during an MRI scan, according to an embodiment of the invention. The system comprises an MRI scanner <NUM> and a control unit <NUM>. In some embodiments, the system further comprises a sensory stimulation system <NUM>.

The MRI scanner <NUM> performs an MRI scan on the subject <NUM> to obtain a sequence of images <NUM> representative of brain activity of the subject. As the MRI scanner performs the scan, the scanner automatically produces a rhythmic noise, with the rhythm dependent on the scanning parameters of the MRI scan. This noise is caused by vibrations of the gradient coils in the MRI scanner.

The control unit <NUM> is configured to control rhythmic sensory stimulation provided to the subject <NUM> (e.g. via the sensory stimulation system <NUM>), by controlling a (first) rhythmic stimulation signal <NUM> such that the signal is synchronized with a scanning frequency of the MRI scanner <NUM> and, therefore, with the rhythmic noise produced by the MRI scanner <NUM>. In this way, the subject is provided with two types of rhythmic and synchronous stimulation simultaneously: the rhythmic noise of the scanner, and the rhythmic stimulation signal controlled by the control unit.

The rhythmic stimulation signal <NUM> may be independent of the effectiveness and/or operation of the MRI scan itself. In particular, the rhythmic stimulation signal may control a stimulation that does not result from a conventional or intended operation of a conventional MRI scan.

The rhythmic stimulation signal <NUM> may be provided in any suitable perceptual modality. For example, the rhythmic stimulation signal may be an audio signal, in which case the subject <NUM> is provided with two types of audio stimulation (the scanner noise and the audio stimulation via the rhythmic stimulation signal). The rhythmic stimulation signal may therefore control, for example, the operation of a speaker or speakers (e.g. in headphones or a headset).

It is recognized that the effectiveness of the stimulation in improving attentional focus in the subject may be improved by providing the rhythmic stimulation signal to provide a stimulation in a different perceptual modality to the scanner noise (i.e. a perceptual modality other than audio). For example, the rhythmic stimulation signal may be a signal that controls a visual or tactile output (e.g. to provide visual or tactile stimulation).

In some examples, the control unit <NUM> may control a plurality of different rhythmic stimulation signals provided to the subject <NUM>, each controlled to provide a rhythmic stimulation that is synchronized with the scanning frequency of an MRI scanner. Provision of multiple rhythmic stimulation is considered to increase an effectiveness of cognitive function repair. The plurality of rhythmic stimulation signals may have different perceptual modalities. This approach will increase the likelihood of success.

In some examples, the control unit <NUM> may obtain the scanning frequency of the MRI scanner <NUM> from the MRI scanner or based on an input from an operator of the MRI scanner, and determine a desired rhythm of the rhythmic stimulation signal based on the obtained scanning frequency. In other examples, the control unit may control the scanning frequency of the MRI scanner as well as the rhythmic stimulation signal, e.g. the control unit may form part of a control system for the MRI scanner.

In some examples, both kinds of rhythmic sensory stimulation are provided by the MRI scanner <NUM>. In other words, the MRI scanner may provide the (rhythmic simulation provided by the) rhythmic stimulation signal in addition to producing the rhythmic scanner noise. For instance, the MRI scanner may provide a rhythmic tactile stimulation signal in the form of peripheral nerve stimulation (PNS). PNS is a side-effect of MRI scanning that occurs when the strong currents applied to the gradient coils of the MRI scanner excite sensorial and motor nerves in the subject. The subject typically feels this as a ticking sensation or spontaneous slight muscle contraction at their arms or back. This effect occurs particularly in newer MRI scanners with higher magnetic strengths, such as <NUM> tesla scanners.

PNS is generally considered an undesirable side-effect, and the scanning parameters of the MRI scan are set to avoid or reduce PNS. Here, the control unit <NUM> may cause PNS to be intentionally induced in the subject <NUM> by providing an additional modulation of the gradient coil signals with a desired periodicity.

In other examples, such as the system <NUM> shown in <FIG>, the rhythmic stimulation signal is provided by a sensory stimulation system <NUM>, which receives instructions from the control unit <NUM> and is separate and/or distinct to the MRI scanner (i.e. does not contribute to the generation of MRI images).

In <FIG>, the sensory stimulation system comprises a pair of headphones for providing an audio signal (e.g. music), but the sensory stimulation system may comprise any device(s) suitable for providing rhythmic sensory stimulation in one or more perceptual modalities (e.g. audio, visual and/or tactile). In some examples, the sensory stimulation system may be configured to provide a variety of different stimulation signals to a subject. This allows the provision of multiple rhythmic sensory stimulation signals simultaneously and allows a type of stimulation to be changed if a particular stimulation signal does not produce a desired effect in the subject.

For example, the sensory stimulation system may comprise a wearable device that may be worn by the subject <NUM> during the MRI scan, such as headphones, a virtual reality headset and/or a wearable patch for providing haptic feedback, or a device fitted to the MRI scanner <NUM>, such as a speaker within the scanner bore, a display unit disposed on the inside of the scanner bore, and/or a light emitting device within the scanner bore. Further examples of suitable means for providing rhythmic sensory stimulation to a subject during an MRI scan will be apparent to the skilled person.

An example of a suitable audio stimulation is music, speech (e.g. poetry) or other rhythmic sounds. An example of a suitable visual stimulation comprises images (e.g. a slideshow of images) or a rhythmic visualization (e.g. a pulsating or moving image or rendering). An example of a suitable tactile stimulation includes a vibration (e.g. of a vibration element in contact with the subject) or a massaging effect. Other suitable examples will be readily apparent to the skilled person.

The sequence of images <NUM> obtained by the MRI scanner <NUM> during the scan may be used to analyze and evaluate an efficacy of the rhythmic sensory stimulation on the subject, and the rhythmic sensory stimulation may be adjusted as required depending on the efficacy. For example, by employing real-time fMRI, brain activity in brain regions and/or functional neuronal networks affected by the stroke may be monitored as the stimulation is provided to the subject <NUM>.

The subject may simply lie still in the scanner bore during the MRI scan (i.e., the MRI scan may be a resting state MRI scan). Alternatively, the subject may be engaged in one or more cognitive or perceptual tasks during the MRI scan. This may allow the effect of the stimulation to be more accurately determined by tailoring the task to the affected brain regions and/or functional neuronal networks. For example, a subject who has suffered a stroke that has affected brain regions associated with memory may be asked to perform a memory task during the MRI scan, while a subject who has suffered a stroke that has affected brain regions associated with visual perception may be given a visual detection task.

The effect of the stimulation may be determined by a medical specialist, e.g. an operator of the MRI scan, based on a display of the obtained sequence of images <NUM>, and the stimulation provided to the subject may be adjusted based on an input from the medical specialist.

Alternatively, the control unit <NUM> may be configured to receive the sequence of images <NUM> from the MRI scanner <NUM> and analyze an effect of the stimulation based on the received sequence of images. The control unit may analyze the effect of the stimulation by, for example, comparing one or more images obtained before the stimulation was provided to the subject with one or more images obtained while the stimulation was being applied, in order to determine a change in the subject's brain activity. Computer-implemented methods for analyzing MRI images are well known, and any suitable method for detecting a change in brain activity may be used by the control unit. In some examples, the control unit may analyze the effect based on whether a change in brain activity is determined in one or more particular brain regions and/or functional neuronal networks.

The control unit <NUM> may be configured to provide an indication of the effect of the stimulation to an operator of the MRI scan, for example, via a display unit (not shown), to allow the operator to determine whether an adjustment to the stimulation is required. Alternatively, the control unit may be configured to determine whether an adjustment to the stimulation is required and to adjust the stimulation accordingly.

For example, the control unit <NUM> may be configured to determine an effectiveness of the rhythmic stimulation provided to the subject <NUM> based on the analysis of the effect of the stimulation. An effectiveness may, for instance, comprise a measure or indicator of effectiveness or success of providing the rhythmic stimulation to the subject. In some examples, an effectiveness may be generated by comparing MRI image data obtained before the rhythmic stimulation signal to MRI image data obtained whilst the rhythmic stimulation signal is provided to the subject.

An effectiveness may, for example, comprise a measure of a difference between brain activity (e.g. in a predetermined portion of the brain) before the rhythmic stimulation signal is provided and while the rhythmic stimulation signal is being provided. Brain activity is measurable and identifiable from MRI data, e.g. from functional MRI data (fMRI data). For example, the effectiveness may comprise a percentage change in the number of active voxels in the fMRI data.

Methods for measuring a change in brain activity based on fMRI data, and in particular measuring a brain response to stimuli, are well known. See, for example, <NPL>, and <NPL>.

In some examples, the effectiveness may comprise a measure of attentional focus. For instance, the effectiveness may comprise a measure of a difference in brain activity before the rhythmic stimulation signal is provided and while the rhythmic stimulation signal is being provided in brain regions and/or neuronal networks associated with attentional focus.

The effect of attentional focus on brain activity, and the brain regions and networks in which the effect is observed are well known: see, for example, <NPL>, <NPL>, <NPL>, <NPL>, and <NPL>.

The control unit may determine that an adjustment to the stimulation is required if the effectiveness is determined to be below a predefined threshold. In other words, the control unit may adjust the rhythmic stimulation signal based on a determination that the effectiveness of the rhythmic stimulation is below the threshold.

An adjustment to the stimulation may comprise a change in the type of stimulation provided (e.g. a change in perceptual modality) and/or a change in the rhythm of the stimulation. If the rhythm of the stimulation is adjusted, the scanning frequency of the MRI scan may also be adjusted so that the rhythmic stimulation remains synchronized with the scanner noise. This may be achieved by instructing an operator of the MRI scanner <NUM> to adjust the scanning parameters, or by configuring the control unit <NUM> to control the scanning frequency of the MRI scanner.

In this way, the system <NUM> may effectively operate as a closed loop (feedback) system configured to tailor the rhythmic stimulation to the subject <NUM>, by monitoring the effect of the rhythmic stimulation as the rhythmic stimulation is adjusted, until a desired effect of the rhythmic stimulation is detected in the brain activity of the subject.

For example, a subject whose visual perception has been affected by a stroke may complete a visual detection task during the MRI scan. The control unit <NUM> may then determine, based on MRI images obtained during the scan, whether the rhythmic stimulation provided to the subject produces a desired increase in brain activity in the functional neuronal networks involved in the successful detection of a visual object in a particular part of the visual field. If the desired increase is not observed, the control unit may adjust the rhythmic stimulation signal, and optionally the scanning frequency of the MRI scanner, until the desired increase is detected in the subject's brain activity.

In some examples, the rhythmic stimulation signal may be based on a personal preference of the subject <NUM>. For instance, the subject may be provided with images/pictures and/or voices of family members/loved ones or with images/pictures of preferred nature scenes. Where the stimulation comprises images, a change or transition between different images (e.g. the frequency of changing an image) may be rhythmically synchronous with the MRI scanning frequency. This may improve the subject's engagement with the rhythmic stimulation signal, improving its efficacy.

In some examples, gamification techniques may be used to provide the subject <NUM> with additional pleasure while the rhythmic stimulation is applied, leading to dopaminergic facilitation of neuronal repair. For instance, the control unit <NUM> may be configured to provide reward-based interaction in addition to, or as part of, the rhythmic stimulation. The reward-based interaction may be provided by the sensory stimulation system <NUM>, e.g. by providing user-preferred stimulation, or by a separate interactive system. In some examples, the sensory stimulation system may include a user-input device.

The reward-based interaction may be tailored to the subject <NUM>. For example, a subject who has difficulty in moving their left arm following a stroke may be presented with targets that the subject should point at with their left arm, and rewarded with points when they succeed in pointing at the target. The interaction may further be designed to increase in difficulty as the subject's performance improves.

In some examples, the system <NUM> may be used in combination with existing therapies for PSD (i.e. pharmacological and/or psychotherapy treatments) to improve an effectiveness of the treatment. The inventors have recognized that, in some cases, PSD may be caused by a complex combination of many factors in addition to the failure of neuronal function. This may particularly be the case when the depression has existed for a prolonged period of time.

<FIG> illustrates a computer-implemented method <NUM> for controlling multisensory stimulation provided to a subject with post-stroke depression during an MRI scan, according to an embodiment of the invention.

The method comprises step <NUM>, in which a rhythmic stimulation signal provided to the subject is controlled such that the rhythmic stimulation signal is synchronized with a scanning frequency of an MRI scanner performing the MRI scan.

In some examples, the method further comprises steps <NUM> and <NUM>. At step <NUM>, a sequence of images representative of brain activity of the subject taken during the MRI scan is received from the MRI scanner. At step <NUM>, an effect of the rhythmic stimulation on the subject is analyzed based on the received sequence of images.

In some examples, the method further comprises step <NUM>, in which an effectiveness of the rhythmic stimulation is determined based on the analysis of the effect. If the effectiveness is found to be below a predefined threshold, the method may proceed to step <NUM>, in which the rhythmic stimulation signal is adjusted. Otherwise, a current rhythmic stimulation signal may continue to be provided to the subject.

In some examples, steps <NUM> to <NUM> may be repeated until it is determined that a current rhythmic stimulation signal has a desired effect (i.e. the effectiveness is no longer below the predefined threshold).

By way of further example, <FIG> illustrates an example of a control unit <NUM> (e.g. a computer) within which one or more parts of an embodiment may be employed. Various operations discussed above may utilize the capabilities of the control unit <NUM>. For example, one or more parts of a system for controlling stimulation to a subject may be incorporated in any element, module, application, and/or component discussed herein. In this regard, it is to be understood that system functional blocks can run on a single control unit or may be distributed over several control units and locations (e.g. connected via internet).

The control unit <NUM> includes, but is not limited to, PCs, workstations, laptops, PDAs, palm devices, servers, storages, and the like. Generally, in terms of hardware architecture, the control unit <NUM> may include one or more processors <NUM>, memory <NUM>, and one or more I/O devices <NUM> that are communicatively coupled via a local interface (not shown). The local interface can be, for example but not limited to, one or more buses or other wired or wireless connections, as is known in the art. The local interface may have additional elements, such as controllers, buffers (caches), drivers, repeaters, and receivers, to enable communications. Further, the local interface may include address, control, and/or data connections to enable appropriate communications among the aforementioned components.

The processor <NUM> is a hardware device for executing software that can be stored in the memory <NUM>. The processor <NUM> can be virtually any custom made or commercially available processor, a central processing unit (CPU), a digital signal processor (DSP), or an auxiliary processor among several processors associated with the control unit <NUM>, and the processor <NUM> may be a semiconductor-based microprocessor (in the form of a microchip) or a microprocessor.

The software in the memory <NUM> may include one or more separate programs, each of which comprises an ordered listing of executable instructions for implementing logical functions. The software in the memory <NUM> includes a suitable operating system (O/S) <NUM>, compiler <NUM>, source code <NUM>, and one or more applications <NUM> in accordance with exemplary embodiments. As illustrated, the application <NUM> comprises numerous functional components for implementing the features and operations of the exemplary embodiments. The application <NUM> of the control unit <NUM> may represent various applications, computational units, logic, functional units, processes, operations, virtual entities, and/or modules in accordance with exemplary embodiments, but the application <NUM> is not meant to be a limitation.

If the control unit <NUM> is a PC, workstation, intelligent device or the like, the software in the memory <NUM> may further include a basic input output system (BIOS) (omitted for simplicity). The BIOS is a set of essential software routines that initialize and test hardware at startup, start the O/S <NUM>, and support the transfer of data among the hardware devices. The BIOS is stored in some type of read-only-memory, such as ROM, PROM, EPROM, EEPROM or the like, so that the BIOS can be executed when the control unit <NUM> is activated.

When the control unit <NUM> is in operation, the processor <NUM> is configured to execute software stored within the memory <NUM>, to communicate data to and from the memory <NUM>, and to generally control operations of the control unit <NUM> pursuant to the software. The application <NUM> and the O/S <NUM> are read, in whole or in part, by the processor <NUM>, perhaps buffered within the processor <NUM>, and then executed.

It will be understood that the disclosed methods are computer-implemented methods. As such, there is also proposed a concept of a computer program product comprising code for implementing any described method when said program is run on a processing system.

As discussed above, embodiments make use of a control unit. The control unit can be implemented in numerous ways, with software and/or hardware, to perform the various functions required. A processor is one example of a control unit which employs one or more microprocessors that may be programmed using software (e.g. microcode) to perform the required functions. A control unit may however be implemented with or without employing a processor, and also may be implemented as a combination of dedicated hardware to perform some of the functions and a processor (e.g. one or more programmed microprocessors and associated circuitry) to perform other functions.

Examples of control unit components that may be employed in various embodiments of the present disclosure include, but are not limited to, conventional microprocessors, application specific integrated circuits (ASICs), and field-programmable gate arrays (FPGAs).

In various implementations, a processor or control unit may be associated with one or more storage media such as volatile and non-volatile control unit memory such as RAM, PROM, EPROM, and EEPROM. The storage media may be encoded with one or more programs that, when executed on one or more processors and/or control units, perform the required functions. Various storage media may be fixed within a processor or control unit or may be transportable, such that the one or more programs stored thereon can be loaded into a processor or control unit.

Claim 1:
A system (<NUM>) for providing stimulation to a subject (<NUM>) with post-stroke depression during an MRI scan, the system comprising:
a control unit (<NUM>) configured to control a rhythmic stimulation signal (<NUM>) provided to the subject during the MRI scan; and
an MRI scanner (<NUM>), in communication with the control unit and configured to obtain a sequence of images (<NUM>) representative of brain activity of the subject, wherein
▪ the MRI scanner (<NUM>) is further configured to provide the rhythmic stimulation signal based on an instruction from the control unit (<NUM>), and/or
▪ the system (<NUM>) further comprises a sensory stimulation system (<NUM>) configured to provide the rhythmic stimulation signal based on an instruction from the control unit (<NUM>),
and characterized in that
the rhythmic stimulation signal is controlled to be synchronized with a scanning frequency of the MRI scanner (<NUM>) performing the MRI scan, wherein the rhythmic stimulation signal is a user-perceptible visual, audio and/or tactile signal.