Method and systems for analyzing functional imaging data

Patent metadata

Field	Value
Publication number	US-11564615-B2
Application number	US-201716072476-A
Country	US
Kind code	B2
Filing date	Jan 30, 2017
Priority date	Feb 1, 2016
Publication date	Jan 31, 2023
Grant date	Jan 31, 2023

Abstract

Methods and systems for analyzing brain functional activity data are provided. Also provided are systems that find use in performing the present methods.

First claim

What is claimed is:

1. A method comprising:
obtaining functional activity data for a region of a brain of a first individual, wherein the functional activity data represent a collective activity of a plurality of neurons in the region; and
estimating relative activities of neural pathways regulated by each of a plurality of neuronal subtypes by computationally processing the functional activity data, wherein the computational processing comprises:
i) generating a connectivity model from the functional activity data based on a network model of functional connections among interconnected nodes representing the region, wherein the interconnected nodes comprise a node corresponding to each of the plurality of neuronal subtypes; and
ii) deriving a set of coefficients from a linear regression between a) the connectivity model; and b) neuronal subtype-specific connectivity estimates among the interconnected nodes,

wherein the set of coefficients of the regression represent the contribution to the functional activity data of a neural pathway regulated by each of the plurality of distinct neuronal subtypes, wherein each of the neuronal subtypes comprise neurons categorized by neuronal identity and the neuronal identity comprises expression of neuronal subtype-specific marker and/or neuronal subtype-specific spatial location.

2. The method of claim 1 , wherein the functional activity data is resting-state functional activity data.

3. The method of claim 1 , wherein the functional activity data is obtained by functional magnetic resonance imaging (fMRI), magentoencephalography (MEG), and/or electroencephalography (EEG).

4. The method of claim 1 , wherein the obtaining comprises measuring functional activity of the region using fMRI, MEG, and/or EEG, to obtain the functional activity data.

5. The method of claim 1 , wherein the region of the brain comprises the thalamus, cortex, ventral tegmental area (VTA), prefontal cortex (PFC), nucleus accumbens (NAc), amygdala (BLA), substantia nigra (SN), ventral pallidum, globus pallidus, dorsal striatum, ventral striatum, subthalamic nucleus (STN), anterior caudate putamen (CPu), globus pallidus external (GPe), globus pallidus internal (GPi), hippocampus, dentate gyrus, cingulate gyrus, entorhinal cortex, olfactory cortex, motor cortex, or cerebellum, or combinations thereof.

6. The method of claim 1 , wherein the neuronal subtypes comprise dopaminergic, cholinergic, gamma-aminobutyric acid-(GABA)ergic, glutamatergic, or peptidergic neurons.

7. The method of claim 1 , wherein the neuronal subtype-specific connectivity estimate is derived from a different species of organism than the species of organism to which the first individual belongs.

8. The method of claim 1 , wherein the first individual is a human individual.

9. The method of claim 1 , wherein the first individual is a healthy individual.

10. The method of claim 1 , wherein the first individual has a neurological disorder.

11. The method of claim 10 , wherein the neurological disorder is a neurological disease, or an age-related neurological disorder.

12. The method of claim 11 , wherein the neurological disease is Parkinson's disease, Alzheimer's disease, dementia, epilepsy, autism, bipolar disorder, schizophrenia, Tourette's syndrome, obsessive compulsive disorder, attention deficit hyperactivity disorder, Huntington's disease, multiple sclerosis, or migraine.

13. A method of identifying a neural circuit-level biomarker associated with a neurological disorder, comprising:
i) estimating relative activities of neural pathways regulated by each of a plurality of neuronal subtypes by performing the method of claim 1 in each first individual of a plurality of groups of first individuals, the plurality of groups comprising:
a case group of first individuals having the neurological disorder; and a control group of first individuals, thereby generating a plurality of sets of regression coefficients comprising:
a case set of regression coefficients representing the contribution to a case functional activity data of the neural pathway regulated by each of the plurality of distinct neuronal subtypes in the case group; and
a control set of regression coefficients representing the contribution to a control functional activity data of the neural pathway regulated by each of the plurality of distinct neuronal subtypes in the control group;

ii) calculating a difference measurement between the case set and the control set of regression coefficients; and
iii) determining that the case set of regression coefficients is a neural circuit-level biomarker associated with the neurological disorder when the difference measurement for one or more regression coefficients meets a threshold criterion, or determining that the case set of regression coefficients is not a neural circuit-level biomarker associated with the neurological disorder when the difference measurement for one or more regression coefficients does not meet the threshold criterion.

14. The method of claim 13 , wherein the control group comprises individuals not having the neurological disorder.

15. The method of claim 13 , wherein the case group comprises individuals having a neurological disorder and to whom a treatment for the neurological disorder has been administered, and the control group comprises individuals having a neurological disorder and to whom a treatment for the neurological disorder has not been administered.

16. The method of claim 13 , wherein the neurological disorder is a neurological disease, or an age-related neurological disorder.

17. The method of claim 16 , wherein the neurological disease is Parkinson's disease, Alzheimer's disease, dementia, epilepsy, autism, bipolar disorder, schizophrenia, Tourette's syndrome, obsessive compulsive disorder, attention deficit hyperactivity disorder, Huntington's disease, multiple sclerosis, or migraine.

18. A method of treating an individual for a neurological disease, the method comprising:
i) estimating relative activities of neural pathways regulated by each of a plurality of neuronal subtypes in a brain of a first individual by performing the method of claim 1 , wherein the first individual has a neurological disorder;
ii) stimulating a region of the brain in a manner sufficient to modulate the activity of neurons of one or more of the plurality of neuronal subtypes based on the estimated relative activities.

19. A system, comprising:
a magnetic resonance imaging (MRI) device,
a processor; and
a non-transient computer-readable medium comprising instructions that, when executed by the processor, cause:
the MRI device to record a functional activity of a brain of an individual, thereby generating functional activity data for a region of the brain; and
the processor to perform the method of claim 1 using the generated functional activity data.

20. The system of claim 19 , further comprising a deep brain stimulation device, or a transcranial magnetic stimulation device.

21. The system of claim 19 , further comprising a user interface and a data connector that transmits data from the processor to the user interface.

22. A method comprising:
obtaining functional activity data for a region of a brain of a first individual, wherein the functional activity data represent a collective activity of a plurality of neurons in the region; and
estimating relative activities of neural pathways regulated by each of a plurality of neuronal subtypes by computationally processing

Assignees

• Univ Leland Stanford Junior
• The Board of Trastees of the Leland
• Stanford Junior Univ

Inventors

• Lee Jin Hyung
• Bernal-Casas David

Classifications

• G06T7/0012

  Biomedical image inspection · CPC title

• G16H50/20

  for computer-aided diagnosis, e.g. based on medical expert systems · CPC title

• A61B5/245

  specially adapted for magnetoencephalographic [MEG] signals · CPC title

• G16Z99/00

  Subject matter not provided for in other main groups of this subclass · CPC title

• A61B5/246

  using evoked responses · CPC title