Osmo Tervonen

Persistent default-mode network connectivity during light sedation

The default‐mode network (DMN) is a set of specific brain regions whose activity, predominant in the resting‐state, is attenuated during cognitively demanding, externally‐cued tasks. The cognitive correlates of this network have proven difficult to interrogate, but one hypothesis is that regions in the network process episodic memories and semantic knowledge integral to internally‐generated mental activity. Here, we compare default‐mode functional connectivity in the same group of subjects during rest and conscious sedation with midazolam, a state characterized by anterograde amnesia and a reduced level of consciousness. Although the DMN showed functional connectivity during both rest and conscious sedation, a direct comparison found that there was significantly reduced functional connectivity in the posterior cingulate cortex during conscious sedation. These results confirm that low‐frequency oscillations in the DMN persist and remain highly correlated even at reduced levels of consciousness. We hypothesize that focal reductions in DMN connectivity, as shown here in the posterior cingulate cortex, may represent a stable correlate of reduced consciousness. Hum Brain Mapp, 2008.

Periradicular infiltration for sciatica: a randomized controlled trial.

Study Design. A randomized, double-blind trial was conducted. Objectives. To test the efficacy of periradicular corticosteroid injection for sciatica. Summary of Background Data. The efficacy of epidural corticosteroids for sciatica is controversial. Periradicular infiltration is a targeted technique, but there are no randomized controlled trials of its efficacy. Methods. In this study 160 consecutive, eligible patients with sciatica who had unilateral symptoms of 1 to 6 months duration, and who never underwent surgery were randomized for double-blind injection with methylprednisolone bupivacaine combination or saline. Objective and self-reported outcome parameters and costs were recorded at baseline, at 2 and 4 weeks, at 3 and 6 months, and at 1 year. Results. Recovery was better in the steroid group at 2 weeks for leg pain (P = 0.02), straight leg raising (P = 0.03), lumbar flexion (P = 0.05), and patient satisfaction (P = 0.03). Back pain was significantly lower in the saline group at 3 and 6 months (P = 0.03 and 0.002, respectively), and leg pain at 6 months (13.5, P = 0.02). Sick leaves and medical costs were similar for both treatments, except for cost of therapy visits and drugs at 4 weeks, which were in favor of the steroid injection (P = 0.05 and 0.005, respectively). By 1 year, 18 patients in the steroid group and 15 in the saline group underwent surgery. Conclusions. Improvement during the follow-up period was found in both the methylprednisolone and saline groups. The combination of methylprednisolone and bupivacaine seems to have a short-term effect, but at 3 and 6 months, the steroid group seems to experience a “rebound” phenomenon.

Independent component analysis of nondeterministic fMRI signal sources

Neuronal activation can be separated from other signal sources of functional magnetic resonance imaging (fMRI) data by using independent component analysis (ICA). Without deliberate neuronal activity of the brain cortex, the fMRI signal is a stochastic sum of various physiological and artifact related signal sources. The ability of spatial-domain ICA to separate spontaneous physiological signal sources was evaluated in 15 anesthetized children known to present prominent vasomotor fluctuations in the functional cortices. ICA separated multiple clustered signal sources in the primary sensory areas in all of the subjects. The spatial distribution and frequency spectra of the signal sources correspond to the known properties of 0.03-Hz very-low-frequency vasomotor waves in fMRI data. In addition, ICA was able to separate major artery and sagittal sinus related signal sources in each subject. The characteristics of the blood vessel related signal sources were different from the parenchyma sources. ICA analysis of fMRI can be used for both assessing the statistical independence of brain signals and segmenting nondeterministic signal sources for further analysis.

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.

Alterations in regional homogeneity of resting-state brain activity in autism spectrum disorders

Measures assessing resting-state brain activity with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) can reveal cognitive disorders at an early stage. Analysis of regional homogeneity (ReHo) measures the local synchronization of spontaneous fMRI signals and has been successfully utilized in detecting alterations in subjects with attention-deficit hyperactivity disorder (ADHD), depression, schizophrenia, Parkinsons disease and Alzheimers dementia. Resting-state brain activity was investigated in 28 adolescents with autism spectrum disorders (ASD) and 27 typically developing controls being imaged with BOLD fMRI and analyzed with the ReHo method. The hypothesis was that ReHo of resting-state brain activity would be different between ASD subjects and controls in brain areas previously shown to display functional alterations in stimulus or task based fMRI studies. Compared with the controls, the subjects with ASD had significantly decreased ReHo in right superior temporal sulcus region, right inferior and middle frontal gyri, bilateral cerebellar crus I, right insula and right postcentral gyrus. Significantly increased ReHo was discovered in right thalamus, left inferior frontal and anterior subcallosal gyrus and bilateral cerebellar lobule VIII. We conclude that subjects with ASD have right dominant ReHo alterations of resting-state brain activity, i.e., areas known to exhibit abnormal stimulus or task related functionality. Our results demonstrate that there is potential in utilizing the ReHo method in fMRI analyses of ASD.

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.

Slow vasomotor fluctuation in fMRI of anesthetized child brain.

Signal intensity changes in fMRI during rest caused by vasomotor fluctuations were investigated in this work. Resting‐state baseline fluctuations were evaluated in 12 children anesthetized with thiopental. Five subjects had fluctuations related to subvoxel motion. In seven subjects without significant motion, slow signal fluctuation at 0.025–0.041 Hz near one or more primary sensory cortices was observed. In each subject the amplitude and frequency of the fluctuations were stable. It is hypothesized that thiopental, which reduces blood pressure and flow in the cortex, alters the feedback in neurovascular coupling leading to an increase in the magnitude and a reduction in the frequency of these fluctuations. The use of anesthesia in fMRI may provide new insight into neural connectivity and the coupling of blood flow and neural metabolism. Magn Reson Med 44:373–378, 2000.

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 Sliding Time-Window ICA Reveals Spatial Variability of the Default Mode Network in Time

Recent evidence on resting-state networks in functional (connectivity) magnetic resonance imaging (fcMRI) suggests that there may be significant spatial variability of activity foci over time. This study used a sliding time window approach with the spatial domain-independent component analysis (SliTICA) to detect spatial maps of resting-state networks over time. The study hypothesis was that the spatial distribution of a functionally connected network would present marked variability over time. The spatial stability of successive sliding-window maps of the default mode network (DMN) from fcMRI data of 12 participants imaged in the resting state was analyzed. Control measures support previous findings on the stability of independent component analysis in measuring sliding-window sources accurately. The spatial similarity of successive DMN maps varied over time at low frequencies and presented a 1/f power spectral pattern. SliTICA maps show marked temporal variation within the DMN; a single voxel was detected inside a group DMN map in maximally 82% of time windows. Mapping of incidental connectivity reveals centrifugally increasing connectivity to the brain cortex outside the DMN core areas. In conclusion, SliTICA shows marked spatial variance of DMN activity in time, which may offer a more comprehensive measurement of the overall functional activity of a network.

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.