Search

Significance: Cancer therapy treatments produce extensive changes in the physiological and morphological properties of tissues, which are also individual dependent. Currently, a key challenge involves developing more tailored cancer therapy, and consequently, individual biological response measurement during therapy, such as tumor hypoxia, is of high interest. This is the first time human cerebral haemodynamics and cerebral tissue oxygenation index (TOI) changes were measured during the irradiation in clinical radiotherapy and functional near-infrared spectroscopy (fNIRS) technique was demonstrated as a feasible technique for clinical use in radiotherapy, based on 34 online patient measurements. Aim: Our aim is to develop predictive biomarkers and noninvasive real-time methods to establish the effect of radiotherapy during treatment as well as to optimize radiotherapy dose planning for individual patients. In particular, fNIRS-based technique could offer an effective and clinically feasible online technique for continuous monitoring of brain tissue hypoxia and responses to chemo- and radiotherapy, which involves modulating tumor oxygenation to increase or decrease tumor hypoxia. We aim to show that fNIRS is feasible for repeatability measuring in patient radiotherapy, the temporal alterations of tissue oxygenation induced by radiation. Approach: Fiber optics setup using multiwavelength fNIRS was built and combined with a medical linear accelerator to measure cerebral tissue oxygenation changes during the whole-brain radiotherapy treatment, where the radiation dose is given in whole brain area only preventing dosage to eyes. Correlation of temporal alterations in cerebral haemodynamics and TOI response to brain irradiation was quantified. Results: Online fNIRS patient measurement of cerebral haemodynamics during clinical brain radiotherapy is feasible in clinical environment, and results based on 34 patient measurements show strong temporal alterations in ce

Respiratory brain pulsations pertaining to intra-axial hydrodynamic solute transport are markedly altered in focal epilepsy. We used optical flow analysis of ultra-fast functional magnetic resonance imaging (fMRI) data to investigate the velocity characteristics of respiratory brain impulse propagation in patients with focal epilepsy treated with antiseizure medication (ASM) (medicated patients with focal epilepsy; ME, n = 23), drug-naïve patients with at least one seizure (DN, n = 19) and matched healthy control subjects (HC, n = 75). We detected in the two patient groups (ME and DN) several significant alterations in the respiratory brain pulsation propagation velocity, which showed a bidirectional change dominated by a reduction in speed. Furthermore, the respiratory impulses moved more in reversed or incoherent directions in both patient groups vs. the HC group. The speed reductions and directionality changes occurred in specific phases of the respiratory cycle. In conclusion, irrespective of medication status, both patient groups showed incoherent and slower respiratory brain impulses, which may contribute to epileptic brain pathology by hindering brain hydrodynamics.

Functional magnetic resonance imaging (fMRI) is a common medical device to diagnose Alzheimer’s disease (AD), but it is not for all subjects due to its cost and other issues. We investigated the potential of functional near-infrared spectroscopy (fNIRS) to separate AD patients from controls as a pre-screening prior to more thorough examination using fMRI. For this purpose, two-channel fNIRS device with 690 nm and 830 nm, sampled at 10 Hz, was placed on the forehead with 3 cm distance between light source and detector to provide resting state fNIRS signals from both sides of pre-frontal cortex. We applied fractional amplitude of physiological fluctuation (fAPF), modified from fractional amplitude of low frequency fluctuation (fALFF), to oxy-, deoxy-, and total-hemoglobin in very low frequency (0.008‐0.1 Hz), respiratory (0.1‐0.6 Hz), and cardiac (0.6‐5 Hz) bands. A t-test at 0.05 significance level was used to evaluate if the fAPF score from AD patients and healthy controls is significantly different. We found that fAPF score of total hemoglobin from both side at cardiac band showed its potential to distinguish AD patients from healthy controls. This finding was in-line with the recent finding that heart failure may co-occur in AD patients with the prevalence of one third of cases.

The physiological underpinnings of the necessity of sleep remain uncertain. Recent evidence suggests that sleep increases the convection of cerebrospinal fluid (CSF) and promotes the export of interstitial solutes, thus providing a framework to explain why all vertebrate species require sleep. Cardiovascular, respiratory and vasomotor brain pulsations have each been shown to drive CSF flow along perivascular spaces, yet it is unknown how such pulsations may change during sleep in humans. To investigate these pulsation phenomena in relation to sleep, we simultaneously recorded fast fMRI, magnetic resonance encephalography (MREG), and electroencephalography (EEG) signals in a group of healthy volunteers. We quantified sleep-related changes in the signal frequency distributions by spectral entropy analysis and calculated the strength of the physiological (vasomotor, respiratory, and cardiac) brain pulsations by power sum analysis in 15 subjects (age 26.5 ± 4.2 years, 6 females). Finally, we identified spatial similarities between EEG slow oscillation (0.2–2 Hz) power and MREG pulsations. Compared with wakefulness, nonrapid eye movement (NREM) sleep was characterized by reduced spectral entropy and increased brain pulsation intensity. These effects were most pronounced in posterior brain areas for very low-frequency (≤0.1 Hz) vasomotor pulsations but were also evident brain-wide for respiratory pulsations, and to a lesser extent for cardiac brain pulsations. There was increased EEG slow oscillation power in brain regions spatially overlapping with those showing sleep-related MREG pulsation changes. We suggest that reduced spectral entropy and enhanced pulsation intensity are characteristic of NREM sleep. With our findings of increased power of slow oscillation, the present results support the proposition that sleep promotes fluid transport in human brain.

Respiratory brain pulsations have recently been shown to drive electrophysiological brain activity in patients with epilepsy. Furthermore, functional neuroimaging indicates that respiratory brain pulsations have increased variability and amplitude in patients with epilepsy compared to healthy individuals. To determine whether the respiratory drive is altered in epilepsy, we compared respiratory brain pulsation synchronicity between healthy controls and patients. Whole brain fast functional magnetic resonance imaging was performed on 40 medicated patients with focal epilepsy, 20 drug-naïve patients and 102 healthy controls. Cerebrospinal fluid associated respiratory pulsations were used to generate individual whole brain respiratory synchronization maps, which were compared between groups. Finally, we analyzed the seizure frequency effect and diagnostic accuracy of the respiratory synchronization defect in epilepsy. Respiratory brain pulsations related to the verified fourth ventricle pulsations were significantly more synchronous in patients in frontal, periventricular and mid-temporal regions, while the seizure frequency correlated positively with synchronicity. The respiratory brain synchronicity had a good diagnostic accuracy (ROCAUC = 0.75) in discriminating controls from medicated patients. The elevated respiratory brain synchronicity in focal epilepsy suggests altered physiological effect of cerebrospinal fluid pulsations possibly linked to regional brain water dynamics involved with interictal brain physiology.

Background: Narcolepsy is a chronic neurological disease characterized by daytime sleep attacks, cataplexy, and fragmented sleep. The disease is hypothesized to arise from destruction or dysfunction of hypothalamic hypocretin-producing cells that innervate wake-promoting systems including the ascending arousal network (AAN), which regulates arousal via release of neurotransmitters like noradrenalin. Brain pulsations are thought to drive intracranial cerebrospinal fluid flow linked to brain metabolite transfer that sustains homeostasis. This flow increases in sleep and is suppressed by noradrenalin in the awake state. Here we tested the hypothesis that narcolepsy is associated with altered brain pulsations, and if these pulsations can differentiate narcolepsy type 1 from healthy controls. Methods: In this case-control study, 23 patients with narcolepsy type 1 (NT1) were imaged with ultrafast fMRI (MREG) along with 23 age- and sex-matched healthy controls (HC). The physiological brain pulsations were quantified as the frequency-wise signal variance. Clinical relevance of the pulsations was investigated with correlation and receiving operating characteristic analysis. Results: We find that variance and fractional variance in the very low frequency (MREGvlf) band are greater in NT1 compared to HC, while cardiac (MREGcard) and respiratory band variances are lower. Interestingly, these pulsations differences are prominent in the AAN region. We further find that fractional variance in MREGvlf shows promise as an effective bi-classification metric (AUC = 81.4%/78.5%), and that disease severity measured with narcolepsy severity score correlates with MREGcard variance (R = −0.48, p = 0.0249). Conclusions: We suggest that our novel results reflect impaired CSF dynamics that may be linked to altered glymphatic circulation in narcolepsy type 1.

Primary central nervous system lymphoma (PCNSL) is an aggressive brain disease where lymphocytes invade along perivascular spaces of arteries and veins. The invasion markedly changes (peri)vascular structures but its effect on physiological brain pulsations has not been previously studied. Using physiological magnetic resonance encephalography (MREGBOLD) scanning, this study aims to quantify the extent to which (peri)vascular PCNSL involvement alters the stability of physiological brain pulsations mediated by cerebral vasculature. Clinical implications and relevance were explored. In this study, 21 PCNSL patients (median 67y; 38% females) and 30 healthy age-matched controls (median 63y; 73% females) were scanned for MREGBOLD signal during 2018–2021. Motion effects were removed. Voxel-by-voxel Coefficient of Variation (CV) maps of MREGBOLD signal was calculated to examine the stability of physiological brain pulsations. Group-level differences in CV were examined using nonparametric covariate-adjusted tests. Subject-level CV alterations were examined against control population Z-score maps wherein clusters of increased CV values were detected. Spatial distributions of clusters and findings from routine clinical neuroimaging were compared [contrast-enhanced, diffusion-weighted, fluid-attenuated inversion recovery (FLAIR) data]. Whole-brain mean CV was linked to short-term mortality with 100% sensitivity and 100% specificity, as all deceased patients revealed higher values (n = 5, median 0.055) than surviving patients (n = 16, median 0.028) (p < .0001). After adjusting for medication, head motion, and age, patients revealed higher CV values (group median 0.035) than healthy controls (group median 0.024) around arterial territories (p ≤ .001). Abnormal clusters (median 1.10 × 10₅mm₃) extended spatially beyond FLAIR lesions (median 0.62 × 10₅mm₃) with differences in volumes (p = .0055).

The physiological pulsations that drive tissue fluid homeostasis are not well characterized during brain activation. Therefore, we used fast magnetic resonance encephalography (MREG) fMRI to measure full band (0–5 Hz) blood oxygen level-dependent (BOLDFB) signals during a dynamic visual task in 23 subjects. This revealed brain activity in the very low frequency (BOLDVLF) as well as in cardiac and respiratory bands. The cardiovascular hemodynamic envelope (CHe) signal correlated significantly with the visual BOLDVLF response, considered as an independent signal source in the V1-V2 visual cortices. The CHe preceded the canonical BOLDVLF response by an average of 1.3 (± 2.2) s. Physiologically, the observed CHe signal could mark increased regional cardiovascular pulsatility following vasodilation.

Accumulation of amyloid-β is a key neuropathological feature in brain of Alzheimer’s disease patients. Alterations in cerebral haemodynamics, such as arterial impulse propagation driving the (peri)vascular CSF flux, predict future Alzheimer’s disease progression. We now present a non-invasive method to quantify the three-dimensional propagation of cardiovascular impulses in human brain using ultrafast 10 Hz magnetic resonance encephalography. This technique revealed spatio-temporal abnormalities in impulse propagation in Alzheimer’s disease. The arrival latency and propagation speed both differed in patients with Alzheimer’s disease. Our mapping of arterial territories revealed Alzheimer’s disease-specific modifications, including reversed impulse propagation around the hippocampi and in parietal cortical areas. The findings imply that pervasive abnormality in (peri)vascular CSF impulse propagation compromises vascular impulse propagation and subsequently glymphatic brain clearance of amyloid-β in Alzheimer’s disease.

Near-infrared spectroscopy (fNIRS) measures concentrations of oxygenated (HbO) and deoxygenated (HbR) hemoglobin in the brain. Recently, we demonstrated its potential also for measuring concentrations of cerebral water (cH₂O). We performed fNIRS measurements during rest to study fluctuations in concentrations of cH₂O, HbO and HbR in 33 well-rested healthy control subjects (HC) and 18 acutely sleep-deprived HC. Resting-state fNIRS signal was filtered in full-band, cardiac, respiratory, low-, and very-low-frequency bands. The sum of HbO and HbR constitutes the regional cerebral blood volume (CBV). CBV and cH₂O concentrations were analyzed via temporal correlation and phase synchrony. Fluctuation in concentrations of cH₂O and CBV was strongly anti-correlated across all frequency bands in both frontal and parietal cortices. Fluctuation in concentrations of cH₂O and CBV showed neither a completely synchronous nor a random phase relationship in both frontal and parietal cortices. Acutely sleep-deprived subjects did not show significant differences in temporal correlation or phase synchrony between fluctuations in cH₂O and CBV concentrations compared with well-rested HC. The reciprocal interrelation between fluctuations in CBV and cH₂O concentrations is consistent with the Munro–Kellie doctrine of constant intracranial volume. This coupling may constitute a functional mechanism underlying glymphatic circulation, which persists despite acutely disturbed sleep patterns.

This video-based study examines the pragmatic non-verbal comprehension skills and corresponding neural-level findings in young Finnish autistic adults, and controls. Items from the Assessment Battery of Communication (ABaCo) were chosen to evaluate the comprehension of non-verbal communication. Inter-subject correlation (ISC) analysis of the functional magnetic resonance imaging data was used to reveal the synchrony of brain activation across participants during the viewing of pragmatically complex scenes of ABaCo videos. The results showed a significant difference between the ISC maps of the autistic and control groups in tasks involving the comprehension of non-verbal communication, thereby revealing several brain regions where correlation of brain activity was greater within the control group. The results suggest a possible weaker modulation of brain states in response to the pragmatic non-verbal communicative situations in autistic participants. Although there was no difference between the groups in behavioural responses to ABaCo items, there was more variability in the accuracy of the responses in the autistic group. Furthermore, mean answering and reaction times correlated with the severity of autistic traits. The results indicate that even if young autistic adults may have learned to use compensatory resources in their communicative-pragmatic comprehension, pragmatic processing in naturalistic situations still requires additional effort.

An amazing amount of activity is continuously occurring in the brain in multiple temporal and spatial scales even in the absence of explicit environmental outputs or inputs; this is called the resting-state, or spontaneous brain activity. It is now widely known that spontaneous brain activity, measured using resting state functional magnetic resonance imaging (fMRI) of the blood oxygen level dependent (BOLD) signal, is dominated by very low frequencies (VLFs; less than 0.1 Hz). Spatial correlations within VLF spontaneous brain activity result in what is widely referred to as functional connectivity, and the associated functionally connected regions are known as resting-state networks (RSNs). Conventional functional connectivity analyses such as seed-based analysis and independent component analysis (ICA), have revealed that spontaneous activity vary in different tasks and in some diseases, but also in a resting state in healthy subjects. However, conventional functional connectivity analyses have not addressed the temporal dimension of brain communication, that is, the propagation of information flow between brain regions. By studying temporal lags in the brain, it has recently been established that spontaneous BOLD fluctuations consist of reproducible patterns of whole brain activity propagation and these patterns are markedly altered as a function of brain state, whether pathological or physiological. In this thesis, we utilised fast magnetic resonance encephalography (MREG) imaging data and provided a comprehensive analysis approach, dynamic lag analysis (DLA), to study probabilistic patterns of information flow between brain regions. Our temporal analyses revealed new patterns in the way slow signals propagate between functional brain regions, and suggested that information flow is aberrant in autism spectrum disorder (ASD) and type 1 narcolepsy with cataplexy compared with neurotypical individuals. Our findings offer a glimpse into the principles that, Tiivistelmä Aivot ovat monimutkainen järjestelmä, jossa on käynnissä jatkuvasti valtava määrä aktiivisuutta monissa avaruudellisissa ja ajallisissa ulottuvuuksissa. Tätä toimintaa kutsutaan aivojen spontaaniksi tai lepotila-aktiivisuudeksi. Toiminnallisen magneettikuvauksen (TMK) tutkimusten kautta tiedämme nykyään, että aivotoiminnan spontaania aktiivisuutta dominoivat erittäin hitaat vaihtelut. Spontaanin aivotoiminnan erittäin hitaiden vaihteluiden avaruudellisia korrelaatioita kutsutaan yleisesti toiminnalliseksi liittyvyydeksi, ja näitä toiminnallisesti liittyneitä alueita aivojen lepotilahermoverkostoiksi. Perinteiset toiminnallisen liitettävyyden analyysien kautta tiedämme nykyään, että spontaani aivotoiminta huojuu tietyissä tehtävissä, jossain sairauksissa, mutta myös terveillä koehenkilöillä. Perinteiset analyysit eivät kuitenkaan ole keskittyneet aivotoiminnan ajallisiin vaihteluihin eli kuinka informaatio aivoalueiden välillä ajallisesti etenee. Aivan hiljattain on aivotoiminnan ajallisen kytkeytymisen tutkimuksista saatu selville, että veren happipitoisuudesta riippuvan (engl. blood oxygen level dependent, BOLD) signaalin spontaaneissa vaihteluissa on tunnistettavissa toistettavia ajallisia kytkeytymisiä. Ne vaihtelevat riippuen aivotoiminnan fysiologisesta tilasta tai patologisista prosesseista. Tässä väitöskirjatutkimuksessa kehitimme uuden analyysimenetelmän, dynaamisen viiveanalyysin (engl. dynamic lag analysis, DLA), ja hyödynsimme nopeaa magneettiresonanssienkefalogrammi (MREG) kuvantamista tutkiaksemme informaation kulkua ihmisillä eri toiminnallisten aivoalueiden välillä. Ajallisen analyysimenetelmän avulla löysimme uusia mekanismeja aivotoiminnan hitaiden vaihteluiden ajallisessa välittymisessä aivoalueiden välillä. Havaitsimme lisäksi, että aivotoiminnan ajallinen kytkeytyminen on poikkeava autismin kirjon oireyhtymässä ja tyypin 1 narkolepsiassa verrattuna terveisiin koehenkilöihin. Tuloksemme tarjoavat pilkahduksen mielenkiintoista uutta tie

Tiivistelmä Tässä tutkimuksessa selvitetään, millaisia kriittisiä tapahtumia voidaan havaita perheyritysten omistajajohtajien kokemuksellisessa oppimisessa. Perheyritysten merkitys maamme taloudelle on suuri, sillä Suomessa työllistävistä yrityksistä 70 % on perheyrityksiä. Omistajajohtajien osaaminen ja valinnat ovat ratkaisevia perheyritysten uudistamiselle. Tämän tutkimuksen aineisto koostuu kymmenen suomalaisen omistajajohtajan haastatteluista, jotka kerättiin kolmesta menestyneestä, sukupolvenvaihdoksen läpikäyneestä perheyrityksestä. Merkittävistä tapahtumista kertovat narratiivit tunnistettiin kriittisten tapahtumien menetelmällä. Narratiiveissa esiintyvien teemojen avulla muodostettiin kuusi kriittisistä tapahtumista kertovaa tapahtumatyyppiä. Ne kertoivat haetusta ja saadusta tuesta, johtajan sisäistä motivaatiota vahvistavista tapahtumista, ristiriita-, muutos- ja valintatilanteista, sitouttavasta kasvuympäristöstä ja omistajuudesta, perheen ja yrittäjyyden välisestä tasapainoilusta sekä yrityksen ulkoisen toimintaympäristön haastavista ja auttavista tapahtumista. Huolimatta siitä, olivatko tapahtumat positiivisia vai negatiivisia, tapahtumat edistivät johtajana kasvamista kokemuksellisuuden kautta. Tutkimustulokset vahvistavat aiempaa tutkimusta siitä, että yrittäjien tehtävässä kasvaminen tapahtuu enemmän kokemuksellisena oppimisena kuin muodollisen koulutuksen kautta. Omistajajohtajat myös kokivat työn kautta oppimisen sisäisenä motivaatiotekijänä. Tämä tutkimus tuottaa empiiristä tietoa kokemukselliseen oppimiseen liittyvään teoreettiseen keskusteluun, aikuis- ja johtamiskoulutuksiin sekä perheyrityskeskusteluun., The critical incidents behind the experiential learning of family business owner-managers This study examines the critical incidents behind the experiential learning of family business owner-managers. In Finland, 70 % of employing companies are family businesses, forming the bulk of the Finnish economy. The skills and choices of owner-managers are crucial to the renewal of family businesses. The data of this study consists of ten Finnish owner-managers’ interviews, gathered from three successful family businesses that have undergone business succession. The narratives of significant incidents were identified by using the critical incident technique. Through themes in the narratives, six types of critical incidents were identified related to the support sought and received, internal motivation, conflicts, changes and choices, the engagement of the growth environment and ownership, the balance between family and entrepreneurship, and to the company’s external operating environment as a challenger and helper. Even though events were positive or negative, they contributed to the growth of managers through experience. This study confirms previous research indicating, that the growth of entrepreneurs occurs more through experiential learning than through formal education. Owner-managers also saw learning through work as an internal motivating factor. This study provides empirical insight into the theory of experiential learning, leader- and adult education, and debate on family businesses.

Biomarkers sensitive to prodromal or early pathophysiological changes in Alzheimer’s disease (AD) symptoms could improve disease detection and enable timely interventions. Changes in brain hemodynamics may be associated with the main clinical AD symptoms. To test this possibility, we measured the variability of blood oxygen level-dependent (BOLD) signal in individuals from three independent datasets (totaling 80 AD patients and 90 controls). We detected a replicable increase in brain BOLD signal variability in the AD populations, which constituted a robust biomarker for clearly differentiating AD cases from controls. Fast BOLD scans showed that the elevated BOLD signal variability in AD arises mainly from cardiovascular brain pulsations. Manifesting in abnormal cerebral perfusion and cerebrospinal fluid convection, present observation presents a mechanism explaining earlier observations of impaired glymphatic clearance associated with AD in humans.

Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 μV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery.

In brain studies, the function of the cerebrospinal fluid (CSF) awakes growing interest, particularly related to studies of the glymphatic system in the brain, which is connected with the complex system of lymphatic vessels responsible for cleaning the tissues. The CSF is a clear, colourless liquid including water (H2O) approximately with a concentration of 99 %. In addition, it contains electrolytes, amino acids, glucose, and other small molecules found in plasma. The CSF acts as a cushion behind the skull, providing basic mechanical as well as immunological protection to the brain. Disturbances of the CSF circulation have been linked to several brain related medical disorders, such as dementia. Our goal is to develop an in vivo method for the non-invasive measurement of cerebral blood flow and CSF circulation by exploiting optical and capacitive sensing techniques simultaneously. We introduce a prototype of a wearable probe that is aimed to be used for long-term brain monitoring purposes, especially focusing on studies of the glymphatic system. In this method, changes in cerebral blood flow, particularly oxy- and deoxyhaemoglobin, are measured simultaneously and analysed with the response gathered by the capacitive sensor in order to distinct the dynamics of the CSF circulation behind the skull. Presented prototype probe is tested by measuring liquid flows inside phantoms mimicking the CSF circulation.

Noninvasive techniques, surface electromyography (sEMG) in particular, are being increasingly employed for assessing muscle activity. In these studies, local oxygen consumption and muscle metabolism are of great interest. Measurements can be performed noninvasively using optics-based methods such as near-infrared spectroscopy (NIRS). By combining energy consumption data provided by NIRS with muscle level activation data from sEMG, we may gain an insight into the metabolic and functional characteristics of muscle tissue. However, muscle motion may induce artifacts into EMG and NIRS. Thus, the inclusion of simultaneous motion measurements using accelerometers (ACMs) enhances possibilities to perceive the effects of motion on NIRS and EMG signals. This paper reviews the current state of noninvasive EMG and NIRS-based methods used to study muscle function. In addition, we built a combined sEMG/NIRS/ACM sensor to perform simultaneous measurements for static and dynamic exercises of a biceps brachii muscle. Further, we discuss the effect of muscle motion in response of NIRS and EMG when measured noninvasively. Based on our preliminary studies, both NIRS and EMG supply specific information on muscle activation, but their signal responses also showed similarities with acceleration signals which, in this case, were supposed to be solely sensitive to motions.

Studies with magnetoencephalography (MEG) are still quite rarely combined simultaneously with methods that can provide a metabolic dimension to MEG investigations. In addition, continuous blood pressure measurements which comply with MEG compatibility requirements are lacking. For instance, by combining methods reflecting neurovascular status one could obtain more information on low frequency fluctuations that have recently gained increasing interest as a mediator of functional connectivity within brain networks. This paper presents a multimodal brain imaging setup, capable to non-invasively and continuously measure cerebral hemodynamic, cardiorespiratory and blood pressure oscillations simultaneously with MEG. In the setup, all methods apart from MEG rely on the use of fibre optics. In particular, we present a method for measuring of blood pressure and cardiorespiratory oscillations continuously with MEG. The potential of this type of multimodal setup for brain research is demonstrated by our preliminary studies on human, showing effects of mild hypercapnia, gathered simultaneously with the presented modalities.

Brain disorders such as epilepsy, dementia and other mental illnesses induce increasing costs on health care systems with aging populations. The most effective treatment of these disorders would be either prevention or intervention of the disorder before irreversible damage develops. However, despite the increased interest in different brain diseases, many of them are still detected too late. One reason for this is the lack of appropriate functional imaging modality that can critically sample the targeted physiological phenomenon. Furthermore, it has been shown that one imaging modality is not enough to cover brain functionality properly; a multimodal approach is required. The main goal of this thesis was to validate near-infrared spectroscopy (NIRS) for brain measurement and to integrate it into a multimodal neuroimaging setup that can critically sample basic human physiological phenomena. A novel key element was the combined use of NIRS with ultra-fast magnetic resonance encephalography (MREG), electroencephalography (EEG), continuous non-invasive blood pressure and anesthesia monitoring as a synchronous system. This unique multimodal neuroimaging set-up with a new functional magnetic resonance imaging sequence, MREG, can sample human brain physiology at 10 Hz sampling rate without cardiorespiratory aliasing. The implemented setup was successfully used in scanning multiple patient and control populations. With the help of critical sampling rate, non-stationarity between the measured signals reflecting brain pulsations could be detected. Combined NIRS and EEG showed the capability to monitor therapeutic opening of the blood-brain barrier during treatment of central nervous system lymphoma for the first time in humans. Furthermore, our multimodal neuroimaging setup enabled the mapping of the recently described brain avalanches and glymphatic pulsation mechanisms of the brain. In conclusion, the ultra-fast multimodal laboratory with integrated NIRS offers no, Tiivistelmä Aivosairaudet kuten epilepsia, dementia ja muut mielenterveyden häiriöt aiheuttavat kasvavissa määrin kuluja ikääntyvien ihmisten terveydenhuollossa. Näiden tautien tehokkain hoitokeino olisi joko ennaltaehkäisy tai varhainen havaitseminen ennen peruuttamattomien kudosvaurioiden kehittymistä. Lisääntyneestä kiinnostuksesta huolimatta monet aivosairaudet havaitaan edelleen liian myöhään. Osasyy tähän on sopivan toiminnallisen kuvausmenetelmän puuttuminen, jolla voitaisiin kuvata haluttu fysiologinen ilmiö riittävän nopeasti. Onkin osoitettu, ettei yksittäinen kuvausmenetelmä riitä aivojen toiminnan riittävän tarkkaan ymmärtämiseen, vaan siihen tarvitaan eri menetelmien yhdistämistä. Tämän väitöskirjatutkimuksen päätarkoituksena oli arvioida lähi-infrapunaspektroskopian (NIRS) soveltuvuutta aivojen toiminnan mittaamisessa sekä integroida se osaksi multimodaalista neurokuvantamisjärjestelmää. Uutena elementtinä NIRS:iä käytettiin yhdessä ultranopean magneettiresonanssienkefalogrammin (MREG), aivosähkökäyrän (EEG), jatkuva-aikaisen kajoamattoman verenpaineen mittauksen ja anestesiamonitoroinnin kanssa samanaikaisesti, ajallisesti synkronoituna. Yhdessä uuden toiminnallisen magneettikuvaussekvenssin, MREG:n, kanssa tällä ainutlaatuisella multimodaalisella neurokuvantamisjärjestelmällä voidaan kuvata ihmisen aivojen perusfysiologiaa 10 Hz näytteistysnopeudella ilman sydämen sykkeen ja hengityksen laskostumista. Toteutetulla multimodaalisella mittausjärjestelmällä tehtiin useita onnistuneita kuvauksia eri potilasryhmillä ja terveillä koehenkilöillä. Kriittisen näytteistämisen ansiosta voitiin havaita epästationaarisuutta aivojen pulsaatioita heijastelevien signaalien välillä. NIRS:n ja EEG:n samanaikainen mittaaminen mahdollisti ensimmäistä kertaa ihmisen veriaivoesteen aukeamisen monitoroinnin keskushermostolymfoomapotilaiden hoidossa. Lisäksi multimodaalinen neurokuvantamisjärjestelmä mahdollisti hiljattain havaittujen aivojen vyöryjen (engl. avalanches) ja g