[Show abstract][Hide abstract] ABSTRACT: Objectives. Seasonal affective disorder (SAD) is a subtype of recurrent unipolar or bipolar depressive disorder with a higher prevalence in winter than in summer. The biological underpinnings of SAD are so far poorly understood. Studies examining SAD have found disturbances between the molecular and connectivity scales. The aim of the study was to explore changes in functional connectivity typical for SAD. Methods. We investigated unmedicated, untreated SAD patients and healthy controls using resting-state functional magnetic resonance imaging (rs-fMRI) utilizing graph theory, a data driven and hypothesis free approach, to model functional networks of the brain. Results. Comparing whole brain network properties using graph theory we observed globally affected network topologies with increasing pathlength in SAD. Nodal changes, however, were highly restricted to bilateral inferior occipital cortex. Interestingly, we found a lateralization where hyper-connectedness was restricted to right inferior occipital cortex and hyper-efficiency was found in the left inferior occipital cortex. Furthermore, we found these nodes became more "hub like" in patients, suggesting a greater functional role. Conclusions. Our work stresses the importance of abnormal intrinsic processing during rest, primarily affecting visual areas and subsequently changing whole brain networks, and thus providing an important hint towards potential future therapeutic approaches.
Full-text · Article · Nov 2014 · The World Journal of Biological Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Background
Bright light treatment is effective for seasonal affective disorder (SAD), although the mechanisms of action are still unknown. We investigated whether transcranial bright light via the ear canals has an antidepressant effect in the treatment of SAD.Methods
During the four-week study period, 89 patients (67 females; 22 males, aged 22-65, mean¿±¿SD age: 43.2¿±¿10.9 years) suffering from SAD were randomized to receive a 12-min daily dose of photic energy of one of three intensities (1 lumen/0.72 mW/cm2; 4 lumens/2.881 mW/cm2; 9 lumens/6.482 mW/cm2) via the ear canals. The light was produced using light-emitting diodes. The severity of depressive symptoms was assessed with the Hamilton Depression Rating Scale ¿ Seasonal Affective Disorder (SIGH-SAD), the Hamilton Anxiety Rating Scale (HAMA), and the Beck Depression Inventory (BDI). Cognitive performance was measured by the Trail Making Test (TMT). The within-group and between-group changes in these variables throughout the study were analysed with a repeated measures analysis of variance (ANOVA), whereas gender differences at baseline within the light groups were analysed using Student¿s t-tests.ResultsPatients in all three groups showed significant decreases in their BDI, HAMA, and SIGH-SAD scores. Response rates, i.e., an at least 50% decrease of symptoms as measured by the BDI, were 74%-79% in the three treatment groups. Corresponding variations for the SIGH-SAD and the HAMA were 35-45% and 47-62%, respectively. No intensity-based dose-response relationships in the improvement of anxiety and depressive symptoms or cognitive performance between treatment groups were observed. Approximately one in four patients experienced mild adverse effects, of which the most common were headache, insomnia, and nausea.Conclusions
These results suggests that transcranial bright light treatment may have antidepressant and anxiolytic effect in SAD patients, as both self- and psychiatrist-rated depressive and anxiety symptoms decreased in all treatment groups. These improvements are comparable to findings of earlier bright light studies that used conventional devices. The lack of dose response may be due to a saturation effect above a certain light intensity threshold. Further studies on the effects of transcranial bright light with an adequate placebo condition are needed.Trial registration NCT01293409, ClinicalTrials.gov.
[Show abstract][Hide abstract] ABSTRACT: We investigated whether transcranial bright light (TBL) affects nocturnal melatonin and cortisol secretion in sham-controlled crossover trial. Young healthy adults were exposed in random order to 24 minutes of TBL or sham exposure via ear canals at 01:10 h. Saliva and urine samples were collected hourly between 21 h-03 h and 06 h-09 h. There were no significant differences in melatonin or cortisol concentrations between TBL and sham exposures at any sampling point indicating that TBL via ear canals does not suppress nocturnal melatonin secretion. Thus, non-visual effects of TBL are mediated via a pathway not involving melatonin suppression.
Full-text · Article · May 2014 · Chronobiology International
[Show abstract][Hide abstract] ABSTRACT: Purpose: A recent study suggests that transcranial brain targeted light treatment via ear canals may have physiological effects on brain function studied by functional magnetic resonance imaging (fMRI) techniques in humans. We tested the hypothesis that bright light treatment could improve psychomotor speed in professional ice hockey players.
Methods: Psychomotor speed tests with audio and visual warning signals were administered to a Finnish National Ice Hockey League team before and after 24 days of transcranial bright light or sham treatment. The treatments were given during seasonal darkness in the Oulu region (latitude 65 degrees north) when the strain on the players was also very high (10 matches during 24 days). A daily 12-min dose of bright light or sham (n = 11 for both) treatment was given every morning between 8 and 12 am at home with a transcranial bright light device. Mean reaction time and motor time were analyzed separately for both psychomotor tests. Analysis of variance for repeated measures adjusted for age was performed.
Results: Time × group interaction for motor time with a visual warning signal was p = 0.024 after adjustment for age. In Bonferroni post-hoc analysis, motor time with a visual warning signal decreased in the bright light treatment group from 127 ± 43 to 94 ± 26 ms (p = 0.024) but did not change significantly in the sham group 121 ± 23 vs. 110 ± 32 ms (p = 0.308). Reaction time with a visual signal did not change in either group. Reaction or motor time with an audio warning signal did not change in either the treatment or sham group.
Conclusion: Psychomotor speed, particularly motor time with a visual warning signal, improves after transcranial bright light treatment in professional ice-hockey players during the competition season in the dark time of the year.
Full-text · Article · May 2014 · Frontiers in Physiology
[Show abstract][Hide abstract] ABSTRACT: OPN4 (Melanopsin) is extravisual opsinreceptor sensing light outside of visual system. Earlier literature has described OPN4 in entraining circadian rhythms via retinohypothalamic track in human brain.Objectives
To investigate whether OPN4 protein is present also outside the retinohypothalamic track.AimsTo study the distribution on OPN4 protein in functionally central areas of human brain.Methods
The localization of OPN4 protein in human brain and peripheral tissues was assessed by immunohistochemical staining using polyclonal antibody against OPN4. OPN4 protein content was measured using Western blotting and SDS-PAGE. The samples from altogether nine cadavers were assessed during forensic examination and their tissues prepared. Samples were cut into sections and stained with fluorescent dye labeled antibody before confocal laser scanning microscopy. The specificity of labeling and immununoreaction was verified by primary antibody omitting and immunizing peptide blocking.ResultsWe found OPN4 protein abundant in Human brain, but not in periphery or in negative controls. Neuronal OPN4 was present in granular pattern intracellularly altogether in all eighteen examined sites, including numerous cerebral cortical areas, cerebellar cortex and several nuclei in phylogenetically old regions. Immunoreaction expressed mostly in neuronal soma, but not in nuclei.Conclusions
Previously OPN4 has been known to be present only in non-image forming visual system mediating circadian timing properties of light to the pacemaker (Zeitgeber). However, our findings of abundant presense of OPN4 protein in neurons of human brain call further studies of effects on direct photic stimuli to brain.
No preview · Article · Dec 2012 · European Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Encephalopsin belongs to the family of extraretinal opsins having a putative role in CNS tissue photosensitivity. Encephalopsin mRNA has earlier been localized in rodent brains, but expression and localization of the protein has not yet been reported. In this study, we aimed to define encephalopsin protein abundance and localization in the rodent brain. The distribution and localization of encephalopsin protein in a mouse brain and selected peripheral tissues were analysed in ten mice, using Western blotting and immunohistochemistry. The specificity of immunoreaction was validated by primary antibody omitting and immunizing peptide blocking experiment. We found encephalopsin protein abundant in the mouse brain, but not in the periphery. Encephalopsin protein was present in neurons of the mouse cerebral cortex, paraventricular area, and cerebellar cells. Our results show that encephalopsin is expressed at the protein level in different brain areas of the mouse. Therefore, the suggested idea that encephalopsin plays a role in non-visual photic processes seems to be applicable. Evidently, further investigations are needed to find out the signalling mechanisms, and the potential physiological role of encephalopsin in phototransduction due to the changes in ambient light.
[Show abstract][Hide abstract] ABSTRACT: Bright light therapy (BLT) is widely accepted as first-line treatment of seasonal affective disorder (SAD). However, the mechanism of action of BLT is still widely unknown. On the other hand, in mammals, light penetrates the skull bone and reaches the brain, and extra ocular transcranial phototransduction has physiological influences such as changed reproductive cycles and increased brain serotonin levels. Therefore, we challenged the existing conceptual framework that light therapy would only be mediated through the eyes. Consequently, we run a pilot study on the putative effect of transcranial bright light in the treatment of SAD. The light was produced using light-emitting diodes (LEDs), which were attached to earplugs. The amount of photic energy was 6.0-8.5 lumens in both ear canals, and the length of treatment was 8 or 12 min five times a week during a four-week study period. Subjects were recruited through advertisements in the city of Oulu, Finland (latitude 65°01'N) during 14 January 2009-03 February 2009. The final patient series consisted of 13 (aged 37.1 ± 7.2 years) physically healthy indoor workers suffering from SAD according to DSM-IV-TR criteria. Severity of depressive symptoms was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) and Beck Depression Inventory (BDI)-21. Furthermore, severity of anxiety symptoms was measured by the 14-item Hamilton Anxiety Rating Scale (HAMA). The HAMD-17 mean sum score at screening was 23.1 ± 1.6. Ten out of 13 SAD patients (76.9%) achieved full remission (i.e., HAMD-17 sum score ≤ 7), and 92.3% (12/13) at least 50% reduction in HAMD-17 sum scores at "Week 4". By using a mixed regression model of repeated measures (AR-1) controlling for age, gender, and HAMD-17 mean sum score at screening, significant differences were found comparing the HAMD-17 mean sum scores of "Week 0" with the corresponding scores at the "Week 3" (t=-2.05, p=0.045) and "Week 4" visit (t=-2.77, p=0.008). Correspondingly, significant differences were found comparing the BDI-21 mean sum scores (15.2 ± 6.7) of "Week 0" with the corresponding scores at the "Week 3" (t=-2.37, p=0.021) and "Week 4" visit (t=-3.65, p<0.001). The HAMA mean sum score at screening was 20.5 ± 5.4. During the study period, 12 out of 13 (92.3%) patients achieved at least 50% reduction in their HAMA sum scores, and in 10 out of 13 patients (76.9%), the HAMA sum score was <7. In conclusion, it is hard to believe that our findings could be explained solely by placebo effect. Consequently, the basic assumptions underlying extraocular photoreception in humans deserve to be reconsidered. Given that a proper placebo treatment can be implemented via ear canals, further investigations with randomized placebo-controlled and/or dose-finding study designs regarding the extraocular transcranial bright light in the treatment of SAD are called for.
Full-text · Article · Jan 2012 · Medical Hypotheses
[Show abstract][Hide abstract] ABSTRACT: Resting-state networks (RSNs) can be reliably and reproducibly detected using independent component analysis (ICA) at both individual subject and group levels. Altering ICA dimensionality (model order) estimation can have a significant impact on the spatial characteristics of the RSNs as well as their parcellation into sub-networks. Recent evidence from several neuroimaging studies suggests that the human brain has a modular hierarchical organization which resembles the hierarchy depicted by different ICA model orders. We hypothesized that functional connectivity between-group differences measured with ICA might be affected by model order selection. We investigated differences in functional connectivity using so-called dual regression as a function of ICA model order in a group of unmedicated seasonal affective disorder (SAD) patients compared to normal healthy controls. The results showed that the detected disease-related differences in functional connectivity alter as a function of ICA model order. The volume of between-group differences altered significantly as a function of ICA model order reaching maximum at model order 70 (which seems to be an optimal point that conveys the largest between-group difference) then stabilized afterwards. Our results show that fine-grained RSNs enable better detection of detailed disease-related functional connectivity changes. However, high model orders show an increased risk of false positives that needs to be overcome. Our findings suggest that multilevel ICA exploration of functional connectivity enables optimization of sensitivity to brain disorders.
Full-text · Article · Jun 2011 · Frontiers in Systems Neuroscience
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to compare hormonal, neuromuscular, and aerobic performance changes between a constant 2-minute interset recovery time and an interset recovery time based on individual heart rate (HR) responses during a 7-week (3 sessions per week, 3 × 10 repetition maximum [RM]) hypertrophic strength training period. The HR-dependent recovery time was determined with a Polar FT80 HR monitor, whereas the control groups used constant 2-minute periods between sets. From 24 male subjects who were divided in 2 equal groups, 21 completed the study (FT80, n = 12; CONTROL, n = 9). Serum blood samples analyzed for testosterone (TES) and cortisol (COR) were taken before and after the 7-week training period at rest. Concentric knee extension 1RM was measured before, after 4 weeks, and at the end of the training period. Concentric knee extension and knee flexion 10RM, central activation ratio (CAR), and maxVO2 were measured before and after the training. Serum TES concentrations were significantly higher after the training period in FT80 (p < 0.001), whereas no significant changes were observed in the CONTROL. Serum COR and maxVO2 were unchanged in both groups. In FT80 (p < 0.001), the increase in 10RM was higher (p < 0.05) than in CONTROL (p < 0.001). Central activation ratio increased in both groups, with the significant increase observed in FT80 (p < 0.05). The higher TES responses, 10RM, and CAR development in FT80 suggest that an HR-based recovery period system of the FT80 may be more efficient in this type of hypertrophic strength training (3 × 10RM). The protocol in this study may be considered as a metabolic training cycle that coaches and trainers can use within a longer periodized training program.
No preview · Article · May 2011 · The Journal of Strength and Conditioning Research
[Show abstract][Hide abstract] ABSTRACT: The purpose was (a) to study the effect of an 8-week Finnish military basic training period (BT) on physical fitness, body composition, mood state, and serum biochemical parameters among new conscripts; (b) to determine the incidence of overreaching (OR); and (c) to evaluate whether initial levels or training responses differ between OR and noOR subjects. Fifty-seven males (19.7 ± 0.3 years) were evaluated before and during BT. Overreaching subjects had to fulfill 3 of 5 criteria: decreased aerobic physical fitness (VO2max), increased rating of perceived exertion (RPE) in 45-minute submaximal test at 70% of VO2max or sick absence from these tests, increased somatic or emotional symptoms of OR, and high incidence of sick absence from daily service. VO2max improved during the first 4 weeks of BT. During the second half of BT, a stagnation of increase in VO2max was observed, basal serum sex hormone-binding globulin (SHBG) increased, and insulin-like growth factor-1 and cortisol decreased. Furthermore, submaximal exercise-induced increases in cortisol, maximum heart rate, and postexercise increase in blood lactate were blunted. Of 57 subjects, 33% were classified as OR. They had higher basal SHBG before and after 4 and 7 weeks of training and higher basal serum cortisol at the end of BT than noOR subjects. In addition, in contrast to noOR, OR subjects exhibited no increase in basal testosterone/cortisol ratio but a decrease in maximal La/RPE ratio during BT. As one-third of the conscripts were overreached, training after BT should involve recovery training to prevent overtraining syndrome from developing. The results confirm that serum SHBG, cortisol, and testosterone/cortisol and maximal La/RPE ratios could be useful tools to indicate whether training is too strenuous.
Full-text · Article · Mar 2011 · The Journal of Strength and Conditioning Research
[Show abstract][Hide abstract] ABSTRACT: To test the utility of HR variability (HRV) in daily exercise prescription in moderately active (approximately two exercises per week) men and women.
A total of 21 men and 32 women were divided into standard training (ST: males = 7 and females = 7), HRV-guided training (HRV-I: males = 7 and females = 7; HRV-II: females = 10), and control (males = 7 and females = 8) groups. The 8-wk aerobic training period included 40-min exercises at moderate and vigorous intensities (70% and 85% of maximal HR). The ST group was instructed to perform two or more sessions at moderate and three or more sessions at vigorous intensity weekly. HRV-I and HRV-II groups trained on the basis of changes in HRV, measured every morning. In the HRV-I group, an increase or no change in HRV resulted in vigorous-intensity training on that day. Moderate-intensity exercise or rest was prescribed if HRV had decreased. The HRV-II group performed a vigorous-intensity exercise only when HRV had increased. Peak oxygen consumption (VO2peak) and maximal workload (Loadmax) were measured by a maximal bicycle ergometer test before and after the intervention.
The changes in VO2peak did not differ between the training groups either in men or in women. In men, the change in Loadmax was higher in the HRV-I group than in the ST group (30 +/- 8 vs 18 +/- 10 W, P = 0.033). In women, no differences were found in the changes in Loadmax between the training groups (18 +/- 10, 15 +/- 11, and 18 +/- 5 W for ST, HRV-I, and HRV-II, respectively). The HRV-II group performed fewer vigorous-intensity exercises than the ST and HRV-I groups (1.8 +/- 0.3 vs 2.8 +/- 0.6 and 3.3 +/- 0.2 times per week, respectively, P < 0.01 for both).
HRV measurements are beneficial in exercise training prescription in moderately active men and women. Women benefit from HRV guidance by achieving significant improvement in fitness with a lower training load.
Full-text · Article · Jul 2010 · Medicine and science in sports and exercise
[Show abstract][Hide abstract] ABSTRACT: Purpose: To test the utility of HR variability (HRV) in daily exercise prescription in moderately active (approximately two exercises per week) men and women.
Methods: A total of 21 men and 32 women were divided into standard training (ST: males = 7 and females = 7), HRV-guided training (HRV-I: males = 7 and females = 7; HRV-II: females = 10), and control (males = 7 and females = 8) groups. The 8-wk aerobic training period included 40-min exercises at moderate and vigorous intensities (70% and 85% of maximal HR). The ST group was instructed to perform two or more sessions at moderate and three or more sessions at vigorous intensity weekly. HRV-I and HRV-II groups trained on the basis of changes in HRV, measured every morning. In the HRV-I group, an increase or no change in HRV resulted in vigorous-intensity training on that day. Moderate-intensity exercise or rest was prescribed if HRV had decreased. The HRV-II group performed a vigorous-intensity exercise only when HRV had increased. Peak oxygen consumption (V˙O2peak) and maximal workload (Loadmax) were measured by a maximal bicycle ergometer test before and after the intervention.
Results: The changes in V˙O2peak did not differ between the training groups either in men or in women. In men, the change in Loadmax was higher in the HRV-I group than in the ST group (30 ± 8 vs 18 ± 10 W, P = 0.033). In women, no differences were found in the changes in Loadmax between the training groups (18 ± 10, 15 ± 11, and 18 ± 5 W for ST, HRV-I, and HRV-II, respectively). The HRV-II group performed fewer vigorous-intensity exercises than the ST and HRV-I groups (1.8 ± 0.3 vs 2.8 ± 0.6 and 3.3 ± 0.2 times per week, respectively, P < 0.01 for both).
Conclusions: HRV measurements are beneficial in exercise training prescription in moderately active men and women. Women benefit from HRV guidance by achieving significant improvement in fitness with a lower training load.
Full-text · Article · Jun 2010 · Medicine & Science in Sports & Exercise
[Show abstract][Hide abstract] ABSTRACT: The autonomic nervous system and circulating hormones control a stress reaction through a complex interaction. We tested the hypothesis that changes in cardiac vagal regulation may be positively associated with the serum testosterone-to-cortisol ratio during the first week of military service in 24 conscripts aged 19.0±0.3 years. Cardiac autonomic function was assessed by measuring high-frequency (HF: 0.15–0.4 Hz) and low-frequency (LF: 0.04–0.15 Hz) power spectral indices of R-R intervals during supine rest and during a controlled standing condition (5 min for both) from the second to the seventh mornings at the beginning of military service. Blood samples were collected to analyse the basal serum testosterone-to-cortisol ratio on the seventh morning. Changes in heart rate and high-frequency power measured in the standing condition were positively correlated with the serum testosterone-to-cortisol ratio at day 7 (r= − 0.42 and r=0.45, respectively; P
Full-text · Article · Sep 2009 · European Journal of Sport Science
[Show abstract][Hide abstract] ABSTRACT: The present study examined whether activity energy expenditure related to body mass (AEE/kg) is associated with maximal aerobic fitness (VO(2max)), energy balance, and body mass index (BMI) during the 2 hardest weeks of the military basic training season (BT). An additional purpose was to study the accuracy of the pre-filled food diary energy intake. Energy expenditure (EE) with doubly labeled water, energy intake (EI), energy balance, and mis-recording was measured from 24 male conscripts with varying VO(2max). AEE/kg was calculated as (EE x 0.9-measured basal metabolic rate)/body mass. The reported EI was lower (P<0.001) than EE (15.48 MJ/day) and mis-recording of the pre-filled diary was -20%. The negative energy balance (-6+/-26%) was non-significant; however, the variation was high. The subjects with a low VO(2max), a high BMI, and a negative energy balance were vulnerable to low AEE/kg. However, in the multivariate regression analysis only BMI remained in the model, explaining 33% of the variation in AEE/kg. During wintertime BT, AEE/kg is affected by energy balance, VO(2max), and BMI. From these three factors, overweight limits high-level training the most. Furthermore, an optimal energy balance facilitates physical performance and enables high training loads to be sustained during the BT season.
No preview · Article · Oct 2008 · Scandinavian Journal of Medicine and Science in Sports