All Hands Meeting 2004 Ontologies for Data Mediation Christine Fennema-Notestine, Ph.D.

Neuropsychological Ontologies  GOAL: To present examples of needed structure based on assessments common to clinical research.  Resource sampled for this discussion: American Psychological Association (APA) Thesaurus  On-line PsychInfo site  Other useful sources used as basis for neuroanatomical ontology Unified Medical Language System (UMLS; National Library of Medicine) NeuroNames codes KnowMe UMLS neighborhood

Query Questions  Does hippocampal atrophy contribute to impairment in recognition memory performance in Alzheimer’s disease? Is there volume loss in AD relative to normal controls? Are AD individuals impaired on recognition memory relative to controls? Is the relationship modulated by dementia severity?

Existing neuroanatomical ontology Next, need to create related function- based ontology Brain Cerebellum Cerebrum Cerebral white matter … Frontal cortex Temporal cortex Superior temporal Mesial temporal AmygdalaHippocampus … Cerebral cortex … … … Memory

 Bottom-up: ?When reviewing data, user questions what a given assessment measures and what the score measures.  Must include assessment name as a term that will link to clinical data provenance information (task description and score interpretation)  Must provide link to term for assessed function(s) (cognitive, behavioral, psychiatric domain)  Must provide link to potentially related brain regions  User could then simply enter assessment name to find description and related clinical and anatomical terms Clinical research questions define structure

 Top-down: ? User investigates brain-behavior relationships, e.g., between the hippocampus and memory performance  Must include cognitive terms such as: cognitive assessment, memory, recognition, recall  Link terms to existing assessment terms  Link as appropriate to “hippocampus” in neuroanatomical ontology  User could then search via specific cognitive domain or through “hippocampus” to reach relevant assessments

#1 Basic clinical assessment:  Mini-mental State Examination (MMSE; Folstein et al., 1975 ) Brief standardized measure of cognitive status  to monitor progression/stabilization in medical setting  to screen research participants Often used in cognitive disorders and dementia (e.g., Alzheimer’s) or other illnesses; not disease specific Relatively non-specific relationship to general brain changes Usually reflected as a single score  Based on brief assessment of orientation, attention, immediate recall, short term recall, language, ability to follow simple verbal commands

Bottom-up search: User’s resultant dataset contains the MMSE – what does it measure?  Search for MMSE  no results in APA thesaurus  Search for Mini-mental State Exam  Mini-mental State Examination found in APA thesaurus  APA result, however, leads you only to a BROADER term of “Neuropsychological Assessment.” This doesn’t answer the user’s question. What is needed to answer the search question?  Existing definition of assessment and interpretation guide  Link to function assessed by MMSE  general cognitive ability, cognitive impairment, dementia severity, brain damage …  Link to anatomical regions reflected in change of performance on this measure, although a relatively non-specific measure  brain

Top-down search: What variables exist that would provide a measure of general cognitive function and dementia severity?  Search for (general) cognitive function  in APA thesaurus eventually reach cognitive and neuropsychological assessment, which lists MMSE as a heading  APA result relatively non-specific as to exactly what listed measure provides. This doesn’t answer the user’s question. What is needed to answer the search question?  Existing definition of assessment and interpretation guide  Link to specific function of MMSE  general cognitive ability, cognitive impairment, dementia severity, …  Link to anatomical regions related to performance change on this measure, although a relatively non-specific measure  brain

Brain Cerebrum Temporal cortex Mesial temporal Hippocampus Cerebral cortex MMSE Cognitive impairment Dementia severity Cognition Assessment Neuropsychology Alzheimer’s Task and score description

#2: Moderately complex assessment  Trail Making Test (TMT; Parts A & B) “Connect the dots” - Trails A simple numbers; Trails B alternating numbers and letters (1-A-2-B-3-C…) Standardized measure most commonly described as a measure of executive function or attention  Executive function = concentration, problem solving, impulse control and perseveration, flexibility, shifting skills  But other task components include visual search, motor coordination, motor and psychomotor speed, motivation Measure often related to frontal lobe dysfunction, e.g., Pick’s disease

Bottom-up search: User’s dataset contains the TMT – what does it measure?  Search for term  no results in APA thesaurus What is needed to answer the search question?  Existing definition of assessment and interpretation guide  Link to functions assessed by TMT  executive function and attention ? Question: proposed expansiveness of ontology? -Addition of terms covered under executive function and attention such as concentration, problem solving, impulse control and perseveration, flexibility, shifting skills -Addition of other related functions including visual search, motor coordination, motor and psychomotor speed, motivation  Link to frontal lobe in neuroanatomical ontology

Top-down search: What variables exist that would provide a measure of executive function and/or frontal lobe function?  Search for executive function  only link to cognitive ability, or level of functioning in intellectual tasks  Search frontal lobe  provides only neuroanatomical links What is needed to answer the search question?  Existing links to information specific to the term, only broader links to cognitive ability  provide additional narrower terms including relevant assessments  Link to anatomical regions related to the measure  frontal lobe

Brain Cerebrum Temporal Mesial temporal Hippocampus Cerebral cortex TMT Task and score description Frontal Cognitive impairment Cognition Assessment Neuropsychology Pick’s disease Executive function Attention

 California Verbal Learning Test (CVLT) Comprehensive assessment of memory and learning Widely used, often in head injury including frontal lobe damage, amnesia, dementia (e.g., Alzheimer’s), depression, learning disorders, etc. Provides numerous measures including:  Recognition discriminability  memory disorders, hippocampus, …  Measurement of retention across time  amnesia, Alzheimer’s, …  Free recall of information  retrieval, frontal lobe, Huntington’s,…  Cued recall of information  memory disorders, Alzheimer’s, …  Response bias  malingering, depression, motivation, …  Serial position effects  short term memory, primacy & recency effects, …  Single trial learning  learning disorders, attention, frontal lobe, …  Learning over several trials  retention, frontal lobe, hippocampus, …  Semantic organization  association cortex, superior temporal lobe, …  and more… #3: Highly complex assessment

Bottom-up search: User’s dataset contains the CVLT – what does it measure?  Search for term  no results in APA thesaurus What is needed to answer the search question?  Existing definition of assessment and interpretation guide  Link to functions assessed by CVLT  memory and learning ? Question: proposed expansiveness of ontology? -Addition of terms covered under memory and learning such as recognition, recall, attention, motivation, serial position effects, episodic memory, semantic memory, …  Link to neuroanatomical ontology ? Question: Link by subscore and/or by overall measure E.g., CVLT can assess recognition memory, usually linked to hippocampus, but also retrieval of information, often linked to frontal lobe function.

Top-down search: What variables exist that would provide a measure of memory and learning and/or hippocampal function?  First search for memory  abundant links, including free recall, which is a subtest on the CVLT

What variables exist that would provide a measure of memory and learning and/or hippocampal function?  Search for memory  abundant links, including free recall, which is a subtest on the CVLT  Search hippocampus  provides only neuroanatomical links

What variables exist that would provide a measure of memory and learning and/or hippocampal function?  Search for memory  abundant links, including free recall, which is a subtest on the CVLT  Search hippocampus  provides only neuroanatomical links What is needed to answer the search question?  Specific test names, such as the CVLT, although some basic test labels are included (e.g., Free Recall)  Linked to Amnesia, although need links to other disorders and to anatomical regions related to the measures  e.g., Alzheimer’s, hippocampus

Brain Cerebrum Temporal Mesial temporal Hippocampus Cerebral cortex CVLT Task and score description Frontal Cognitive impairment Cognition Assessment Neuropsychology Amnesia Memory Learning

Memory Recognition Recall Free recall Cued Recall CVLT Retrieval Hippocampus Frontal lobe

Summary of proposed steps towards an ontology  Entry of assessments into ontology base system  Full name and common acronym  Description and score interpretation guide  Employ base ontology to start with if at all possible (e.g., UMLS plus APA) and add terms  Link assessments to relevant cognitive, neuropsychological, neuropsychiatric terms  Create links between these terms and relevant neuroanatomical regions May need to reference books such as Lezak’s Neuropsychological Assessment