Augmented cognitive training

Abstract

The present invention provides methods of therapy of cognitive deficits associated with a central nervous system disorder or condition, methods of enhancing cognitive performance and methods for repeated stimulation of neuronal activity or a pattern of neuronal activity, such as that underlying a specific neuronal circuit(s). The methods comprise combining cognitive training protocols and a general administration of CREB pathway-enhancing agents.

What is claimed is: 
     
         1 . A method of treating a cognitive deficit associated with a central nervous system disorder or condition in an animal in need of said treatment comprising the steps of:
 (a) administering to said animal an augmenting agent which enhances CREB pathway function; and   (b) training said animal under conditions sufficient to produce an improvement in performance by said animal of a cognitive task whose deficit is associated with said central nervous system disorder or condition,   whereby said cognitive deficit is treated.   
     
     
         2 . The method of  claim 1  wherein said animal has undergone neuronal stem cell manipulation. 
     
     
         3 . The method of  claim 1  wherein a performance gain is achieved relative to the performance of said cognitive task achieved by training alone. 
     
     
         4 . The method of  claim 1  wherein in step b), training comprises multiple training sessions. 
     
     
         5 . The method of  claim 4  wherein said augmenting agent is administered before and during each training session. 
     
     
         6 . The method of  claim 1  wherein said animal is a mammal. 
     
     
         7 . The method of  claim 6  wherein said mammal is a human. 
     
     
         8 . The method of  claim 1  wherein said augmenting agent induces CREB-dependent gene expression. 
     
     
         9 . The method of  claim 8  wherein said augmenting agent up-regulates a positive effector of CREB pathway function. 
     
     
         10 . The method of  claim 9  wherein said positive effector of CREB pathway function is a CREB activator. 
     
     
         11 . The method of  claim 8  wherein said augmenting agent down-regulates a negative effector of CREB pathway function. 
     
     
         12 . The method of  claim 11  wherein said negative effector of CREB pathway function is a CREB repressor. 
     
     
         13 . The method of  claim 1  wherein said augmenting agent is a CREB functional modulator. 
     
     
         14 . A method of enhancing a specific aspect of cognitive performance in an animal in need thereof comprising the steps of:
 (a) administering to said animal an augmenting agent which enhances CREB pathway function; and   (b) training said animal under conditions sufficient to produce an improvement in performance of a specified cognitive task by said animal,   whereby said specific aspect of cognitive performance is enhanced.   
     
     
         15 . The method of  claim 14  wherein a performance gain is achieved relative to the performance of said specified cognitive task achieved by training alone. 
     
     
         16 . The method of  claim 14  wherein in step b), training comprises multiple training sessions. 
     
     
         17 . The method of  claim 16  wherein said augmenting agent is administered before and during each training session. 
     
     
         18 . The method of  claim 14  wherein said animal is a mammal. 
     
     
         19 . The method of  claim 18  wherein said mammal is a human. 
     
     
         20 . The method of  claim 14  wherein said augmenting agent induces CREB-dependent gene expression. 
     
     
         21 . The method of  claim 20  wherein said augmenting agent up-regulates a positive effector of CREB pathway function. 
     
     
         22 . The method of  claim 21  wherein said positive effector of CREB pathway function is a CREB activator. 
     
     
         23 . The method of  claim 20  wherein said augmenting agent down-regulates a negative effector of CREB pathway function. 
     
     
         24 . The method of  claim 23  wherein said negative effector of CREB pathway function is a CREB repressor. 
     
     
         25 . The method of  claim 14  wherein said augmenting agent is a CREB functional modulator. 
     
     
         26 . A method of treating a cognitive deficit associated with age-associated memory impairment in an animal in need of said treatment comprising the steps of:
 (a) administering to said animal an augmenting agent which enhances CREB pathway function; and   (b) training said animal under conditions sufficient to produce an improvement in performance by said animal of a cognitive task whose deficit is associated with age-associated memory impairment,   whereby said cognitive deficit is treated.   
     
     
         27 . The method of  claim 26  wherein a performance gain is achieved relative to the performance of said cognitive task achieved by training alone. 
     
     
         28 . The method of  claim 26  wherein in step b), training comprises multiple training sessions. 
     
     
         29 . The method of  claim 28  wherein said augmenting agent is administered before and during each training session. 
     
     
         30 . The method of  claim 26  wherein said animal is a mammal. 
     
     
         31 . The method of  claim 30  wherein said mammal is a human. 
     
     
         32 . The method of  claim 26  wherein said augmenting agent induces CREB-dependent gene expression. 
     
     
         33 . A method of treating a cognitive deficit associated with a neurodegenerative disease in an animal in need of said treatment comprising the steps of:
 (a) administering to said animal an augmenting agent which enhances CREB pathway function; and   (b) training said animal under conditions sufficient to produce an improvement in performance by said animal of a cognitive task whose deficit is associated with said neurodegenerative disease,   whereby said cognitive deficit is treated.   
     
     
         34 . The method of  claim 33  wherein a performance gain is achieved relative to the performance of said cognitive task achieved by training alone. 
     
     
         35 . The method of  claim 33  wherein said neurodegenerative disease is selected from the group consisting of: delirium, dementia, Alzheimer's disease, Parkinson's disease and Huntington's disease. 
     
     
         36 . The method of  claim 33  wherein in step b), training comprises multiple training sessions. 
     
     
         37 . The method of  claim 36  wherein said augmenting agent is administered before and during each training session. 
     
     
         38 . The method of  claim 33  wherein said animal is a mammal. 
     
     
         39 . The method of  claim 38  wherein said mammal is a human. 
     
     
         40 . The method of  claim 33  wherein said augmenting agent induces CREB-dependent gene expression. 
     
     
         41 . A method of treating a cognitive deficit associated with a psychiatric disease in an animal in need of said treatment comprising the steps of:
 (a) administering to said animal an augmenting agent which enhances CREB pathway function; and   (b) training said animal under conditions sufficient to produce an improvement in performance by said animal of a cognitive task whose deficit is associated with said psychiatric disease,   whereby said cognitive deficit is treated.   
     
     
         42 . The method of  claim 41  wherein a performance gain is achieved relative to the performance of said cognitive task achieved by training alone. 
     
     
         43 . The method of  claim 41  wherein said psychiatric disease is selected from the group consisting of: depression, schizophrenia, autism and attention deficit disorder. 
     
     
         44 . The method of  claim 41  wherein in step b), training comprises multiple training sessions. 
     
     
         45 . The method of  claim 44  wherein said augmenting agent is administered before and during each training session. 
     
     
         46 . The method of  claim 41  wherein said animal is a mammal. 
     
     
         47 . The method of  claim 46  wherein said mammal is a human. 
     
     
         48 . The method of  claim 41  wherein said augmenting agent induces CREB-dependent gene expression. 
     
     
         49 . A method of treating a cognitive deficit associated with cerebrovascular disease in an animal in need of said treatment comprising the steps of:
 (a) administering to said animal an augmenting agent which enhances CREB pathway function; and   (b) training said animal under conditions sufficient to produce an improvement in performance by said animal of a cognitive task whose deficit is associated with said cerebrovascular disease,   whereby said cognitive deficit is treated.   
     
     
         50 . The method of  claim 49  wherein a performance gain is achieved relative to the performance of said cognitive task achieved by training alone. 
     
     
         51 . The method of  claim 49  wherein said cerebrovascular disease is selected from the group consisting of stroke and ischemia. 
     
     
         52 . The method of  claim 49  wherein in step b), training comprises multiple training sessions. 
     
     
         53 . The method of  claim 49  wherein said augmenting agent is administered before and during each training session. 
     
     
         54 . The method of  claim 49  wherein said animal is a mammal. 
     
     
         55 . The method of  claim 54  wherein said mammal is a human. 
     
     
         56 . The method of  claim 49  wherein said augmenting agent induces CREB-dependent gene expression. 
     
     
         57 . A method of treating a cognitive deficit associated with a trauma dependent loss of cognitive function in an animal in need of said treatment comprising the steps of:
 (a) administering to said animal an augmenting agent which enhances CREB pathway function; and   (b) training said animal under conditions sufficient to produce an improvement in performance by said animal of a cognitive task whose deficit is associated with said trauma dependent loss of cognitive function,   whereby said cognitive deficit is treated.   
     
     
         58 . The method of  claim 57  wherein a performance gain is achieved relative to the performance of said cognitive task achieved by training alone. 
     
     
         59 . The method of  claim 57  wherein said trauma dependent loss of function is selected from the group consisting of: head trauma and brain trauma. 
     
     
         60 . The method of  claim 57  wherein in step b), training comprises multiple training sessions. 
     
     
         61 . The method of  claim 60  wherein said augmenting agent is administered before and during each training session. 
     
     
         62 . The method of  claim 57  wherein said animal is a mammal. 
     
     
         63 . The method of  claim 62  wherein said mammal is a human. 
     
     
         64 . The method of  claim 57  wherein said augmenting agent induces CREB-dependent gene expression. 
     
     
         65 . A method of treating a cognitive deficit associated with a genetic defect in an animal in need of said treatment comprising the steps of:
 (a) administering to said animal an augmenting agent which enhances CREB pathway function; and   (b) training said animal under conditions sufficient to produce an improvement in performance by said animal of a cognitive task associated with said genetic defect,   whereby said cognitive deficit is treated.   
     
     
         66 . The method of  claim 65  wherein a performance gain is achieved relative to the performance of said cognitive task achieved by training alone. 
     
     
         67 . The method of  claim 65  wherein said genetic defect is selected from the group consisting of: Rubinstein-Taybi syndrome and down syndrome. 
     
     
         68 . The method of  claim 65  wherein in step b), training comprises multiple training sessions. 
     
     
         69 . The method of  claim 68  wherein said augmenting agent is administered before and during each training session. 
     
     
         70 . The method of  claim 65  wherein said animal is a mammal. 
     
     
         71 . The method of  claim 70  wherein said mammal is a human. 
     
     
         72 . The method of  claim 65  wherein said augmenting agent induces CREB-dependent gene expression. 
     
     
         73 . A method of improving learning in an animal with a learning disability comprising the steps of:
 (a) administering to said animal an augmenting agent which enhances CREB pathway function; and   (b) training said animal under conditions sufficient to produce an improvement in performance by said animal of a cognitive task whose deficit is associated with said learning disability,   whereby learning is improved.   
     
     
         74 . The method of  claim 73  wherein a performance gain is achieved relative to the performance of said cognitive task achieved by training alone. 
     
     
         75 . The method of  claim 73  wherein in step b), training comprises multiple training sessions. 
     
     
         76 . The method of  claim 75  wherein said augmenting agent is administered before and during each training session. 
     
     
         77 . The method of  claim 73  wherein said animal is a mammal. 
     
     
         78 . The method of  claim 77  wherein said mammal is a human. 
     
     
         79 . The method of  claim 73  wherein said augmenting agent induces CREB-dependent gene expression. 
     
     
         80 . A method for repeated stimulation of neuronal activity or a pattern of neuronal activity in an animal comprising the steps of:
 (a) administering to said animal an augmenting agent which enhances CREB pathway function; and   (b) training said animal under conditions sufficient to stimulate neuronal activity or a pattern of neuronal activity in said animal.   
     
     
         81 . The method of  claim 80  wherein in step b), training comprises multiple training sessions. 
     
     
         82 . The method of  claim 81  wherein said augmenting agent is administered before and during each training session. 
     
     
         83 . The method of  claim 80  wherein said animal is a mammal. 
     
     
         84 . The method of  claim 83  wherein said mammal is a human. 
     
     
         85 . The method of  claim 80  wherein said augmenting agent induces CREB-dependent gene expression. 
     
     
         86 . A method of therapy of a cognitive deficit associated with a central nervous system disorder or condition in an animal having undergone neuronal stem cell manipulation comprising the steps of:
 (a) administering to said animal an augmenting agent which enhances CREB pathway function; and   (b) training said animal under conditions sufficient to stimulate neuronal activity or a pattern of neuronal activity in said animal.   
     
     
         87 . The method of  claim 86  wherein training in step b) further produces an improvement in performance by said animal of a cognitive task whose deficit is associated with said central nervous system disorder or condition. 
     
     
         88 . The method of  claim 87  wherein a performance gain is achieved relative to the performance of said cognitive task achieved by training alone. 
     
     
         89 . The method of  claim 86  wherein in step b), training comprises multiple training sessions. 
     
     
         90 . The method of  claim 89  wherein said augmenting agent is administered before and during each training session. 
     
     
         91 . The method of  claim 86  wherein said animal is a mammal. 
     
     
         92 . The method of  claim 91  wherein said animal is a human. 
     
     
         93 . The method of  claim 86  wherein said augmenting agent induces CREB-dependent gene expression.