Marianne Haapea

Functional segmentation of the brain cortex using high model order group PICA

Baseline activity of resting state brain networks (RSN) in a resting subject has become one of the fastest growing research topics in neuroimaging. It has been shown that up to 12 RSNs can be differentiated using an independent component analysis (ICA) of the blood oxygen level dependent (BOLD) resting state data. In this study, we investigate how many RSN signal sources can be separated from the entire brain cortex using high dimension ICA analysis from a group dataset. Group data from 55 subjects was analyzed using temporal concatenation and a probabilistic independent component analysis algorithm. ICA repeatability testing verified that 60 of the 70 computed components were robustly detectable. Forty‐two independent signal sources were identifiable as RSN, and 28 were related to artifacts or other noninterest sources (non‐RSN). The depicted RSNs bore a closer match to functional neuroanatomy than the previously reported RSN components. The non‐RSN sources have significantly lower temporal intersource connectivity than the RSN (P < 0.0003). We conclude that the high model order ICA of the group BOLD data enables functional segmentation of the brain cortex. The method enables new approaches to causality and connectivity analysis with more specific anatomical details. Hum Brain Mapp, 2009.

Modic changes in endplates of lumbar vertebral bodies: prevalence and association with low back and sciatic pain among middle-aged male workers.

Study Design. Cross-sectional comparison of self-reported low back pain (LBP) symptoms and Modic findings on magnetic resonance imaging (MRI). Objectives. To investigate associations of frequency and intensity of LBP and sciatic pain with Modic changes in a sample of middle-aged male workers with or without whole-body vibration exposure. Summary of Background Data. Vertebral endplate changes are bone marrow lesions visible on MRI and are assumed to be associated with degenerative intervertebral disc disease. Associations of these so-called Modic changes with clinical symptoms are controversial. Furthermore, most of these studies have been performed in selected series of patients. Methods. A total of 228 middle-aged male workers (159 train engineers and 69 sedentary controls) from northern Finland underwent sagittal T1 and T2-weighted MRI. Both endplates of 1140 lumbar interspaces were graded for type and extent of Modic changes. Logistic regression was used to analyze associations of pain variables with Modic changes. Results. Train engineers had on the average higher sciatic pain scores than the sedentary controls, but the prevalence of Modic changes was similar in both occupational groups. Altogether, 178 Modic changes in 128 subjects were recorded: 30% were type I, 66% type II, and 4% both types I and II. Eighty percent of changes occurred at L4–L5 or L5–S1. Modic changes at L5–S1 showed significant association with pain symptoms with increased frequency of LBP (odds ratio [OR] 2.28; 95% confidence interval [CI] 1.44–3.15) and sciatica episodes (OR 1.44; 95% CI 1.01–1.89), and with higher LBP visual analog scores during the past week (OR 1.36; 95% CI 1.06–1.70). Type I lesions and extensive lesions in particular were closely associated with pain. Conclusions. Modic changes at L5–S1 and Modic type I lesions are more likely to be associated with pain symptoms than other types of Modic changes or changes located at other lumbar levels.

The Treatment of Disc Herniation-induced Sciatica With Infliximab: One-year Follow-up Results of First Ii, a Randomized Controlled Trial

Study Design. A randomized controlled trial. Objectives. To evaluate the long-term efficacy of infliximab, a monoclonal antibody against tumor necrosis factor alpha (TNF-α), in patients with acute/subacute sciatica secondary to herniated disc. Summary of Background Data. The results of experimental studies and our open-label trial support the use of infliximab in sciatica. Here we report the 1-year results of a randomized controlled trial (FIRST II, Finnish Infliximab Related STudy) evaluating the efficacy and safety of a single infusion of infliximab for sciatic pain. Methods. Inclusion criteria were unilateral sciatic pain with a disc herniation concordant with the symptoms and signs of radicular pain. Patients had to be candidates for discectomy. Criteria for discectomy included (in addition to a symptomatic disc herniation on MRI) neural entrapment (straight leg raising [SLR] ≤60°) with either a short-term (2–4 weeks) severe or long-term (4–12 weeks) moderate leg pain. Forty patients were allocated to a single intravenous infusion of either infliximab 5 mg/kg or placebo. Differences in the clinical examination parameters (straight leg raise [SLR], muscle strength, sensory defects, tendon reflexes), patient-reported symptoms (leg and back pain using a visual analog scale [VAS], Oswestry disability, quality-of-life [RAND-36]), sick leaves, number of discectomies, and adverse effects between the two treatment groups over the 1-year follow-up were compared using Mann-Whitney U test or Students t test, repeated-measures analysis, or Cox proportional hazards model. Logistic regression was used to assess the predictors of good response. Results. Sixty-seven percent of patients in the infliximab group reported no pain at 52 weeks compared with 63% in the control group (P = 0.72). Similar efficacy was observed between treatment groups for other outcomes. Eight patients in each group required surgery. Three nonserious adverse reactions were encountered in the infliximab group. The response (irrespective of the treatment) was significantly better with shorter symptom duration and less SLR restriction at baseline. Patients in the infliximab group appeared to especially benefit in cases of a L4–L5 (or L3–L4) herniation and if a Modic change was colocalized at the symptomatic level. Conclusions. Although the long-term results of this randomized trial do not support the use of infliximab compared with placebo for lumbar radicular pain in patients with disc herniation-induced sciatica, further study in a subgroup of patients with L4–L5 or L3–L4 herniations, especially in the presence of Modic changes, appears to be warranted.

A three-year follow-up of lumbar spine endplate (modic) changes

Study Design. A longitudinal follow-up of Modic changes on magnetic resonance imaging (MRI). Objectives. To assess the prevalence and natural course Modic changes over a 3-year follow-up period. Summary of Background Data. Modic changes are bone marrow and endplate lesions visible on MRI. To the authors’ knowledge, no follow-up studies on their natural course have been published. Methods. The study population consisted of 60 unoperated sciatica patients 23 to 76 years of age. Baseline and 3-year lumbar MR images from L1–L2 through L5–S1 were analyzed independently by 2 radiologists and a consensus reading was performed. Results. At baseline, the prevalence of Modic changes was 23%. Seven discs had mixed Type I/II, and 63 Type II change. Changes typically occurred at L4–L5 and L5–S1, and associated positively with age (P = 0.009). Ten of 70 discs (14%) with Modic changes at baseline displayed another type at 3 years. Furthermore, the nonconverted changes increased significantly in size. The incidence of new Modic changes during the follow-up was 6% (13 of 230). Conclusions. Modic changes are common MRI findings in patients with degenerative lumbar disc disease. We found evidence that Modic Type II changes may be less stable than previously assumed.

Fronto-cerebellar systems are associated with infant motor and adult executive functions in healthy adults but not in schizophrenia

Delineating longitudinal relationships between early developmental markers, adult cognitive function, and adult brain structure could clarify the pathogenesis of neurodevelopmental disorders such as schizophrenia. We aimed to identify brain structural correlates of infant motor development (IMD) and adult executive function in nonpsychotic adults and to test for abnormal associations between these measures in people with schizophrenia. Representative samples of nonpsychotic adults (n = 93) and people with schizophrenia (n = 49) were drawn from the Northern Finland 1966 general population birth cohort. IMD was prospectively assessed at age 1 year; executive function testing and MRI were completed at age 33–35 years. We found that earlier motor development in infancy was correlated with superior executive function in nonpsychotic subjects. Earlier motor development was also normally associated with increased gray matter density in adult premotor cortex, striatum, and cerebellum and increased white matter density in frontal and parietal lobes. Adult executive function was normally associated with increased gray matter density in a fronto-cerebellar system that partially overlapped, but was not identical to, the gray matter regions normally associated with IMD. People with schizophrenia had relatively delayed IMD and impaired adult executive function in adulthood. Furthermore, they demonstrated no normative associations between fronto-cerebellar structure, IMD, or executive function. We conclude that frontal cortico-cerebellar systems correlated with adult executive function are anatomically related to systems associated with normal infant motor development. Disruption of this anatomical system may underlie both the early developmental and adult cognitive abnormalities in schizophrenia.

Determinants of spontaneous resorption of intervertebral disc herniations

Study Design. A follow-up of disc herniation (herniated nucleus pulposus [HNP]) resorption on magnetic resonance imaging (MRI). Objective. To assess the determinants of resorption of HNP. Summary of Background Data. Neovascularization in the outermost areas of HNP, presenting as an enhancing rim in gadolinium diethylenetriamine pentaacetic acid MR images, is thought to be a major determinant of spontaneous resorption of HNP. Methods. Patients with HNP-induced sciatica at baseline were rescanned at 2 months (N = 74) and after 12 months (N = 53). The volume of HNP (mm3), thickness (mm) and extent (%) of enhancement, and the degree of HNP migration (Komori classification) were analyzed. Repeated measures analysis of covariance was used in statistical analysis. Results. Significant resorption of HNP occurred from baseline to 2 months, although the resorption rate was more pronounced over the whole 1-year follow-up. Higher baseline scores of rim enhancement thickness, higher degree of HNP displacement in the Komori classification, and age category 41–50 years were associated with a higher resorption rate. Thickness of rim enhancement was a stronger determinant of spontaneous resorption than extent of rim enhancement. Clinical symptom alleviation occurs concordantly with a faster resorption rate. Conclusions. MRI is a useful prognostic tool for identifying patients with HNP-induced sciatica with a benign natural course.

Preoperative localization of the sensorimotor area using independent component analysis of resting-state fMRI

Analysis of resting-state functional magnetic resonance imaging (fMRI) data is based on detecting low-frequency signal fluctuations in functionally connected brain areas. These synchronous fluctuations in resting-state networks have been observed in several studies with healthy subjects. In this study, we explored if independent component analysis (ICA) can be used to localize the sensorimotor area from resting-state fMRI data in patients with brain tumors. Finger-tapping activation task and resting-state blood-oxygenation-level-dependent fMRI data were acquired from 8 patients with brain tumors and 10 healthy volunteers. Sensorimotor task independent components (IC(task)) were used to verify resting-state independent components (IC(rest)) individually. In addition, sensorimotor IC(rest)s were compared between the groups and no significant differences were detected in volume, spatial correlation or temporal correlation. These results show that it is possible to localize a sensorimotor area from resting-state data using ICA in patients with brain tumors. This offers a complementary method for assessing the sensorimotor area in subjects with brain tumors who have difficulties in performing motor paradigms.

Morphometric Brain Abnormalities in Schizophrenia in a Population-Based Sample: Relationship to Duration of Illness

Biased recruitment and sample selection may cause variability in neuroimaging studies. Epidemiologically principled population-based magnetic resonance imaging (MRI) studies of schizophrenia are very rare. We gathered structural MRI data on 154 subjects from the Northern Finland 1966 Birth Cohort, aged 33-35 (100 controls, 54 schizophrenia patients). Regional differences in density of gray matter, white matter, and cerebrospinal fluid (CSF) were identified between groups using nonparametric statistical analysis, and the relationship of the regional differences to duration of illness was explored. Gray matter reductions were found bilaterally in the cerebellum, thalamus, basal ganglia, middle frontal gyrus, inferior frontal gyrus, precentral gyrus, insula, superior temporal gyrus, fusiform gyrus, parahippocampal gyrus, cuneus, and lingual gyrus; in the left posterior cingulate, superior frontal gyrus, transverse temporal gyrus, and precuneus; and in the right postcentral gyrus. Gray matter excesses were observed bilaterally in the basal ganglia, anterior cingulate, and medial orbitofrontal cortices. There were white matter deficits in an extensive network including inter- and intrahemispheric tracts bilaterally in the frontal, temporal, parietal, and occipital lobes, subcortical structures, cerebellum, and brain stem. CSF excesses were found bilaterally in the lateral ventricles, third ventricle, interhemispheric, and left Sylvian fissure. We replicated the previous findings of structural brain abnormalities in schizophrenia on a general population level. Gray and white matter deficits were associated with duration of illness suggesting either that developmental brain deficits relate to an earlier age of onset or that brain abnormalities in schizophrenia are progressive in nature.

Hippocampus and amygdala volumes in schizophrenia and other psychoses in the Northern Finland 1966 birth cohort

Structural brain differences have been reported in many studies with schizophrenia, but few have involved a general population birth cohort. We investigated differences in volume, shape and laterality of hippocampus and amygdala in patients with schizophrenia, all psychoses and comparison subjects within a large general birth cohort sample, and explored effects of family history of psychosis, perinatal risk and age-at-onset of illness. All subjects with psychosis from the Northern Finland 1966 birth cohort were invited to a survey including MRI scan of the brain, conducted in 1999-2001. Comparison subjects not known to have psychosis were randomly selected from the same cohort. Volumes of hippocampus and amygdala were measured in 56 subjects with DSM-III-R schizophrenia, 26 patients with other psychoses and 104 comparison subjects. Small hippocampal volume reductions in schizophrenia (2%) and all psychoses (3%) were not significant when adjusted for total brain volume. The shape of hippocampus in schizophrenia did not differ significantly from comparison subjects. Right hippocampus and amygdala were significantly larger than the left in all groups. Mean amygdala volume in schizophrenia or all psychoses did not differ from comparison subjects. Patients with family history of psychosis had larger hippocampus than patients without. Neither perinatal risk nor age-at-onset of illness had any effect on hippocampal or amygdala volumes. Small hippocampal volume reduction in schizophrenia and all psychoses was not disproportionate to reduced whole brain volume in this population-based sample. Perinatal events that have been suggested as of etiological importance in structural pathology of psychosis had no effect.

Non-participation in a field survey with respect to psychiatric disorders.

Aims: Higher rates of psychiatric morbidity among non-participants may lead to biased estimates of prevalence and incidence in epidemiological studies of psychiatric disorders. We had a unique opportunity to explore psychiatric morbidity and non-participation in a large epidemiological survey including questionnaires and a clinical examination. Methods: Members of the Northern Finland 1966 Birth Cohort were included in the study. In phase I, a postal questionnaire was mailed to all those with a known address in 1997 (N=11,540). In phase II, all subjects living in northern Finland or the Helsinki area (N=8463) were invited to a clinical examination. In phase III, clinical examination participants were given a questionnaire with psychological subscales to be filled in at home and returned by mail. The data on hospital-treated psychiatric disorders were obtained from the Finnish Hospital Discharge Register. Educational level was obtained from Statistics Finland. Results: The participation rates were 76%, 71% and 61% in phases I, II and III, respectively. Subjects with any psychiatric disorder participated less actively than those without any psychiatric disorder in all phases, in both genders and at all educational levels. Participation was not found to vary across specific disorders. Gender or education did not explain the association of psychiatric disorders with participation. Conclusions: Owing to non-participation, the true prevalence of psychiatric disorders may be higher than the prevalence estimated from epidemiological field surveys.