{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:07:36Z","timestamp":1789726056473,"version":"4.0.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2004,4,14]],"date-time":"2004-04-14T00:00:00Z","timestamp":1081900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI51951"],"award-info":[{"award-number":["AI51951"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ES10844"],"award-info":[{"award-number":["ES10844"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS37483"],"award-info":[{"award-number":["NS37483"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["MH60450"],"award-info":[{"award-number":["MH60450"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,5,1]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>Pharmacological experiments in brain microscopy study patterns of cellular activ- ation in response to psychotropic drugs for connected neuroanatomic regions. A typical ex- perimental design produces replicated point patterns having highly complex spatial variability. Modelling this variability hierarchically can enhance the inference for comparing treatments. We propose a semiparametric formulation that combines the robustness of a nonparametric kernel method with the efficiency of likelihood-based parameter estimation. In the convenient framework of a generalized linear mixed model, we decompose pattern variation by kriging the intensities of a hierarchically heterogeneous spatial point process. This approximation entails discretizing the inhomogeneous Poisson likelihood by Voronoi tiling of augmented point patterns. The resulting intensity-weighted log-linear model accommodates spatial smoothing through a reduced rank penalized linear spline. To correct for anatomic distortion between subjects, we interpolate point locations via an isomorphic mapping so that smoothing occurs relative to common neuroanatomical atlas co-ordinates. We propose a criterion for choosing the degree and spatial locale of smoothing based on truncating the ordered set of smoothing covariates to minimize residual extra-dispersion. Additional spatial covariates, experimental design factors, hierarchical random effects and intensity functions are readily accommodated in the linear predictor, enabling comprehensive analyses of the salient properties underlying replicated point patterns. We illustrate our method through application to data from a novel study of drug effects on neuronal activation patterns in the brain of rats.<\/jats:p>","DOI":"10.1046\/j.1369-7412.2003.05285.x","type":"journal-article","created":{"date-parts":[[2004,12,28]],"date-time":"2004-12-28T14:41:00Z","timestamp":1104244860000},"page":"429-446","source":"Crossref","is-referenced-by-count":23,"title":["Modelling Spatial Intensity for Replicated Inhomogeneous Point Patterns in Brain Imaging"],"prefix":"10.1093","volume":"66","author":[{"given":"C. G.","family":"Wager","sequence":"first","affiliation":[{"name":"Harvard School of Public Health , Boston , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. A.","family":"Coull","sequence":"additional","affiliation":[{"name":"Harvard School of Public Health , Boston , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Lange","sequence":"additional","affiliation":[{"name":"Harvard Medical School and Harvard School of Public Health , Boston"},{"name":"McLean Hospital , Belmont , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,4,14]]},"reference":[{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"641","DOI":"10.2307\/2986181","article-title":"Analysis of a three-dimensional point pattern with replication","volume":"42","author":"Baddeley","year":"1993","journal-title":"Appl. Statist."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/1467-842X.00128","article-title":"Practical maximum pseudolikelihood for spatial point patterns","volume":"3","author":"Baddeley","year":"2000","journal-title":"Aust. New Zeal. J. Statist."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.2517-6161.1989.tb01750.x","article-title":"Estimating weighted integrals of the second-order intensity of a spatial point process","volume":"51","author":"Berman","year":"1989","journal-title":"J. R. Statist. Soc."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2307\/2347614","article-title":"Approximating point process likelihoods with GLIM","volume":"41","author":"Berman","year":"1992","journal-title":"Appl. Statist."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2307\/2987782","article-title":"Statistical analysis of non-lattice data","volume":"24","author":"Besag","year":"1975","journal-title":"Statistician"},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1080\/01621459.1993.10594284","article-title":"Approximate inference in generalized linear mixed models","volume":"88","author":"Breslow","year":"1993","journal-title":"J. Am. Statist. Ass."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/biomet\/82.1.81","article-title":"Bias correction in generalised linear mixed models with a single component of dispersion","volume":"82","author":"Breslow","year":"1995","journal-title":"Biometrika"},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s00213-003-1423-0","article-title":"Cells in midline thalamus, central amygdala and nucleus accumbens responding specifically to antipsychotic drugs","volume":"167","author":"Cohen","year":"2003","journal-title":"Psychopharmacology"},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/j.0006-341X.2001.00539.x","article-title":"Simple incorporation of interactions into additive models","volume":"57","author":"Coull","year":"2001","journal-title":"Biometrics"},{"key":"2023040304312776100_","volume-title":"Introduction to Geometry","author":"Coxeter","year":"1969","edition":"2nd"},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"138","DOI":"10.2307\/2347366","article-title":"A kernel method for smoothing point process data","volume":"34","author":"Diggle","year":"1985","journal-title":"Appl. Statist."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1080\/01621459.1991.10475087","article-title":"Analysis of variance for replicated spatial point patterns in clinical neuroanatomy","volume":"86","author":"Diggle","year":"1991","journal-title":"J. Am. Statist. Ass."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1239\/aap\/1013540166","article-title":"A comparison between parametric and non-parametric approaches to the analysis of replicated spatial point patterns","volume":"32","author":"Diggle","year":"2000","journal-title":"Adv. Appl. Probab."},{"key":"2023040304312776100_","first-page":"299","article-title":"Model-based geostatistics (with discussion)","volume":"47","author":"Diggle","year":"1998","journal-title":"Appl. Statist."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1137\/S0036144599352836","article-title":"Centroidal Voronoi tessellations: applications and algorithms","volume":"41","author":"Du","year":"1999","journal-title":"SIAM Rev."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","DOI":"10.1007\/b98818","volume-title":"Matrix Algebra from a Statistician's Perspective","author":"Harville","year":"1997"},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.2517-6161.1996.tb02088.x","article-title":"Pseudosplines","volume":"58","author":"Hastie","year":"1996","journal-title":"J. R. Statist. Soc. B"},{"key":"2023040304312776100_","volume-title":"Generalized Additive Models","author":"Hastie","year":"1990"},{"key":"2023040304312776100_","volume-title":"Technical Report","author":"Hobert","year":"2000"},{"key":"2023040304312776100_","first-page":"1","article-title":"Geoadditive models","volume":"52","author":"Kammann","year":"2003","journal-title":"Appl. Statist."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1191\/0962280203sm342ra","article-title":"What can modern statistics offer imaging neuro-science?","volume":"12","author":"Lange","year":"2003","journal-title":"Statist. Meth. Med. Res."},{"key":"2023040304312776100_","article-title":"Two macroscopic and microscopic brain imaging studies of human hippocampus in early Alzheimer's disease and schizophrenia research","author":"Lange","year":"2003","journal-title":"Statist. Med."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0167-9473(92)90140-B","article-title":"GLIM and normalising constant models in spatial and directional data analysis","volume":"13","author":"Lawson","year":"1992","journal-title":"Comput. Statist. Data Anal."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/biomet\/73.1.13","article-title":"Longitudinal data analysis using generalized linear models","volume":"73","author":"Liang","year":"1986","journal-title":"Biometrika"},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/S0306-4522(03)00397-X","article-title":"Dynorphinergic and gabaergic neurons co-localize for neuroleptic antipsychotic drugs in rat forebrain, thalamus and amygdala","volume":"121","author":"Ma","year":"2003","journal-title":"Neuroscience"},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/1521-4036(200106)43:3<375::AID-BIMJ375>3.0.CO;2-Q","article-title":"Parametric procedures in the analysis of replicated pairwise interaction point patterns","volume":"43","author":"Mateu","year":"2001","journal-title":"Biometr. J."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4899-3242-6","volume-title":"Generalized Linear Models","author":"McCullagh","year":"1989","edition":"2nd"},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1080\/01621459.1997.10473613","article-title":"Maximum likelihood algorithms for generalized linear mixed models","volume":"92","author":"McCulloch","year":"1997","journal-title":"J. Am. Statist. Ass."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/1467-9469.00115","article-title":"Log Gaussian Cox processes","volume":"25","author":"M\u00f8ller","year":"1998","journal-title":"Scand. J. Statist."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"4270","DOI":"10.1073\/pnas.89.10.4270","article-title":"Differential expression of c-fos and zif268 in rat striatum after Haloperidol, Clozapine, and Amphetamine","volume":"89","author":"Nguyen","year":"1992","journal-title":"Proc. Natn. Acad. Sci. USA"},{"key":"2023040304312776100_","doi-asserted-by":"crossref","DOI":"10.1002\/9780470317013","volume-title":"Spatial Tessellations: Concepts and Applications of Voronoi Diagrams","author":"Okabe","year":"2000","edition":"2nd"},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1145\/225545.225546","article-title":"Algorithm 751: TRIPACK: a constrained two-dimensional Delaunay triangulation package","volume":"22","author":"Renka","year":"1996","journal-title":"ACM Trans. Math. Softwr."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/0098-3004(93)90099-Q","article-title":"Splancs: spatial point pattern analysis code in S-plus (stma V34 4780)","volume":"19","author":"Rowlingson","year":"1993","journal-title":"Comput. Geosci."},{"key":"2023040304312776100_","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511755453","volume-title":"Semiparametric Regression","author":"Ruppert","year":"2003"},{"key":"2023040304312776100_","volume-title":"Cluster priors in the Bayesian modelling of FMRI data","author":"Taskinen","year":"2001"},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/00949659308811554","article-title":"Generalized linear mixed models: a pseudo-likelihood approach","volume":"48","author":"Wolfinger","year":"1993","journal-title":"J. Statist. Computn Simuln"},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/biomet\/85.2.251","article-title":"Poisson\/gamma random field models for spatial statistics","volume":"85","author":"Wolpert","year":"1998","journal-title":"Biometrika"},{"key":"2023040304312776100_","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1093\/biostatistics\/2.3.351","article-title":"Automated identification of Fos expression","volume":"2","author":"Young","year":"2001","journal-title":"Biostatistics"}],"container-title":["Journal of the Royal Statistical Society Series B: Statistical Methodology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1369-7412.2003.05285.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jrsssb\/article-pdf\/66\/2\/429\/49727534\/jrsssb_66_2_429.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jrsssb\/article-pdf\/66\/2\/429\/49727534\/jrsssb_66_2_429.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T16:14:14Z","timestamp":1734797654000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jrsssb\/article\/66\/2\/429\/7098407"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,4,14]]},"references-count":38,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2004,4,14]]},"published-print":{"date-parts":[[2004,5,1]]}},"URL":"https:\/\/doi.org\/10.1046\/j.1369-7412.2003.05285.x","relation":{},"ISSN":["1369-7412","1467-9868"],"issn-type":[{"value":"1369-7412","type":"print"},{"value":"1467-9868","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2004,5]]},"published":{"date-parts":[[2004,4,14]]}}}