Visual Alcohol Cue-Reactivity and Cognitive Control in Non-Dependent Heavy Alcohol Drinkers Assessed by Simultaneous fNIRS-EEG.

OBJECTIVE: Addictive behavior is characterized by fast automatic responses to drug-related cues (termed cue reactivity) and deficient cognitive control. The ability to detect errors is a prerequisite for an adaptive increase of cognitive control to prevent further errors. In the current study, cue-reactivity effects on cognitive control were assessed via hemodynamic activity within the dorsolateral prefrontal cortex (dlPFC) using functional near-infrared spectroscopy (fNIRS) and simultaneous electroencephalography (EEG), assessing error monitoring (error-related negativity/error negativity, ERN/Ne) and error adaption in subsequent trials (N2). Nondependent social drinkers were the focus in this multimodal approach. METHOD: Effects of alcohol consumption patterns and the personality trait of impulsivity were assessed in n = 55 social drinkers. Hemodynamic activity within the dlPFC (cognitive control), error monitoring (ERN/Ne), post-error conflict monitoring (N2), error rates, and post-error slowing (PES) were measured during a modified Eriksen flanker task cued by beverage pictures. RESULTS: ERN/Ne amplitudes were reduced during alcohol-cued trials. Post-error adaption was reflected in increased dlPFC activity after errors, whereas N2 amplitudes were reduced. There was a correlation of impulsivity and alcohol-cued ERN/Ne amplitude that was mediated by alcohol consumption pattern. CONCLUSIONS: Impulsivity-related decreases in error monitoring during cue reactivity were mediated by alcohol consumption pattern. However, cognitive control was not affected by cue reactivity, suggesting more complex interactions than previously assumed.

Monitoring Processes and Their Neuronal Correlates as the Basis of Auditory Verbal Hallucinations in a Non-clinical Sample.

Auditory verbal hallucinations (AVH) are a characteristic symptom of psychosis. An influential cognitive model accounting for the mechanisms in the generation of AVHs describes a defective monitoring of inner speech, leading to the misidentification of internally generated thoughts as externally generated events. In this study, we utilized an inner speech paradigm during a simultaneous measurement with functional near-infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI), in order to replicate the findings of neural correlates of inner speech and auditory verbal imagery (AVI) in healthy subjects, reported in earlier studies, and to provide the first validation of the paradigm for fNIRS measurements. To this end, 20 healthy subjects were required to generate and silently recite first and second person sentences in their own voice (inner speech) and imagine the same sentences in a different, alien voice (AVI). Furthermore, questionnaires were deployed to assess the predisposition to acoustic hallucinations and schizotypal traits to investigate their connection to activation patterns associated with inner speech and monitoring processes. The results showed that both methods, fNIRS and fMRI, exhibited congruent activations in key brain areas, claimed to be associated with monitoring processes, indicating that the paradigm seems to be applicable using fNIRS alone. Furthermore, the results showed similar brain areas activated during inner speech and monitoring processes to those from earlier studies. However, our results indicate that the activations were dependent more on the sentence form and less on the imaging condition, showing more active brain areas associated with second person sentences. Integration of the sentence construction into the model of inner speech and deficient monitoring processes as the basis for the formation of AVHs should be considered in further studies. Furthermore, negative correlations between questionnaires' scores and activations in precentral gyrus and premotor cortex indicate a relationship of schizotypal characteristics and a deficient activation pattern.

A randomized-controlled neurofeedback trial in adult attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a childhood onset disorder persisting into adulthood for a large proportion of cases. Neurofeedback (NF) has shown promising results in children with ADHD, but randomized controlled trials in adults with ADHD are scarce. We aimed to compare slow cortical potential (SCP)- and functional near-infrared spectroscopy (fNIRS) NF to a semi-active electromyography biofeedback (EMG-BF) control condition regarding changes in symptoms and the impact of learning success, as well as changes in neurophysiological parameters in an adult ADHD population. Patients were randomly assigned to SCP-NF (n = 26), fNIRS-NF (n = 21) or EMG-BF (n = 20). Outcome parameters were assessed over 30 training sessions (pre, intermediate, post) and at 6-months follow-up (FU) including 3 booster sessions. EEG was recorded during two auditory Go/NoGo paradigms assessing the P300 and contingent negative variation (CNV). fNIRS measurements were conducted during an n-back- as well as a Go/NoGo task. All three groups showed equally significant symptom improvements suggesting placebo- or non-specific effects on the primary outcome measure. Only when differentiating between learners and non-learners, fNIRS learners displayed stronger reduction of ADHD global scores compared to SCP non-learners at FU, and fNIRS learners showed specifically low impulsivity ratings. 30.8% in the SCP-NF and 61.9% of participants in the fNIRS-NF learned to regulate the respective NF target parameter. We conclude that some adults with ADHD learn to regulate SCP amplitudes and especially prefrontal hemodynamic activity during NF. We did not find any significant differences in outcome between groups when looking at the whole sample. When evaluating learners only, they demonstrate superior effects as compared to non-learners, which suggests specific effects in addition to non-specific effects of NF when learning occurs.

Reduced spontaneous low frequency oscillations as measured with functional near-infrared spectroscopy in mild cognitive impairment.

Spontaneous low frequency oscillations (LFO) in functional imaging data have gained increased interest in the study of cognitive decline. Persons diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD) display alterations in their amount of LFO in various brain regions. This is commonly interpreted as disruptions in the autoregulation of the cerebral microvascular system. In the present study LFO (0,07-0,11 Hz) were measured with 52-channel near-infrared spectroscopy (NIRS) in 61 healthy elderly persons (70-76 years), 54 MCI subjects (70-76 years) and 25 healthy young controls (21-48 years) during rest over the frontal and the parietal cortex. Both MCI and healthy elderly controls showed less LFO in the frontal cortex as compared to young subjects. For the parietal cortex a decrease in LFO could be observed for the MCI group in comparison to healthy elderly subjects. Correlations of more LFO with worse performance in neuropsychological tests point to compensatory processes. LFO measured with NIRS might be especially suited for longitudinal studies aiming at predicting cognitive decline.

Feasibility of NIRS-based neurofeedback training in social anxiety disorder: behavioral and neural correlates.

Attention biases towards threat signals have been linked to the etiology and symptomatology of social anxiety disorder (SAD). Dysfunction of the dorsolateral prefrontal cortex (dlPFC) may contribute to attention biases in anxious individuals. The aim of this study was to investigate the feasibility of near-infrared spectroscopy (NIRS) neurofeedback (NF) training-targeting the dlPFC-and its effects on threat-related attention biases of individuals with SAD. 12 individuals with SAD participated in the NIRS-NF training lasting 6-8 weeks and including a total of 15 sessions. NF performance increased significantly, while the attention bias towards threat-related stimuli and SAD symptom severity decreased after the training. The individual increase in neurofeedback performance as well as the individual decrease in SAD symptom severity was correlated with decreased responses to social threat signals in the cerebral attention system. Thus, this pilot study does not only demonstrate that NIRS-based NF is feasible in SAD patients, but also may be a promising method to investigate the causal role of the dlPFC in attention biases in SAD. Its effectiveness as a treatment tool might be examined in future studies.

Disrupted prefrontal functional connectivity during post-stress adaption in high ruminators.

Rumination is a perseverative thinking style that is associated with adverse mental and physical health. Stressful situations have been considered as a trigger for this kind of thinking. Until today, there are mixed findings with respect to the relations of functional connectivity (FC) and rumination. The study at hand aimed to investigate, in how far high and low ruminators would show elevated levels of state rumination after a stress induction and if these changes would show corresponding changes in FC in the cognitive control network (CCN) and dorsal attention network (DAN). 23 high and 22 low trait ruminators underwent resting-state measurements before and after a stress induction with the Trier Social Stress Test (TSST). Changes in rsFC through the TSST were measured with functional near-infrared spectroscopy within and between regions of the CCN. Stress successfully induced state rumination in both groups but stronger in the high trait ruminators. High trait ruminators showed elevated FC within the CCN at baseline, but attenuated increase in FC following the TSST. Increases in FC correlated negatively with state rumination. A lack of FC reactivity within the CCN in high ruminators might reflect reduced network integration between brain regions necessary for emotion regulation and cognitive control.

Stress-related dysfunction of the right inferior frontal cortex in high ruminators: An fNIRS study.

Repetitive thinking styles such as rumination are considered to be a key factor in the development and maintenance of mental disorders. Different situational triggers (e.g., social stressors) have been shown to elicit rumination in subjects exhibiting such habitual thinking styles. At the same time, the process of rumination influences the adaption to stressful situations. The study at hand aims to investigate the effect of trait rumination on neuronal activation patterns during the Trier Social Stress Test (TSST) as well as the physiological and affective adaptation to this high-stress situation. Methods: A sample of 23 high and 22 low ruminators underwent the TSST and two control conditions while their cortical hemodynamic reactions were measured with functional near-infrared spectroscopy (fNIRS). Additional behavioral, physiological and endocrinological measures of the stress response were assessed. Results: Subjects showed a linear increase from non-stressful control conditions to the TSST in cortical activity of the cognitive control network (CCN) and dorsal attention network (DAN), comprising the bilateral dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus (IFG) and superior parietal cortex/somatosensory association cortex (SAC). During stress, high ruminators showed attenuated cortical activity in the right IFG, whereby deficits in IFG activation mediated group differences in post-stress state rumination and negative affect. Conclusions: Aberrant activation of the CCN and DAN during social stress likely reflects deficits in inhibition and attention with corresponding negative emotional and cognitive consequences. The results shed light on possible neuronal underpinnings by which high trait rumination may act as a risk factor for the development of clinical syndromes.

Cortical hemodynamic changes during the Trier Social Stress Test: An fNIRS study.

The study of the stress response has been of great interest in the last decades due to its relationship to physical and mental health. Along with the technological progress in the neurosciences, different methods of stress induction have been developed for the special requirements regarding the acquisition of neuroimaging data. However, these paradigms often differ from ecologically valid stress inductions such as the Trier Social Stress Test (TSST) in substantial ways. In the study at hand, we used the rather robust optical imaging method of functional Near-infrared Spectroscopy (fNIRS) to assess brain activation during the TSST and two non-stressful control conditions. Additionally, we measured other stress parameters including the cortisol response and subjective stress ratings. As expected we found significant increases in subjective and physiological stress measures during the TSST in comparison to the baseline and control conditions. We found higher activation in parts of the cognitive control network (CCN) and dorsal attention network (DAN) - comprising the dorsolateral prefrontal cortex, the inferior frontal gyrus and superior parietal cortex - during the performance of the TSST in comparison to the control conditions. Further, calculation errors during the TSST as well as subjective and physiological stress parameters correlated significantly with the activation in the CCN. Our study confirms the validity of previous neuroimaging data obtained from adapted stress procedures by providing cortical activation data during a classical stress induction paradigm (i.e., the TSST) for the first time.

Cue Reactivity Essentials: Event-Related Potentials During Identification of Visual Alcoholic Stimuli in Social Drinkers.

OBJECTIVE: Cue reactivity is an automatic reaction to alcohol-related cues, contributing to the maintenance of drinking behavior and relapse in alcohol dependency. The identification of valid cue-reactivity features is a prerequisite for its clinical application. We were interested in the effects of visual features of alcohol cues (e.g., color) on cue reactivity. Assuming its development at a pre-pathological stage, we analyzed cue reactivity in heavy social drinkers, with light social drinkers as controls. We investigated whether cue reactivity was independent of visual features at an attentional (P100) and a motivational level (late positive potential, LPP). METHOD: Event-related potentials (ERPs; P100, LPP) were analyzed during a visual beverage classification task in heavy social drinkers and light social drinkers (N = 34 university students). Photographs of beverages were classified as alcoholic or nonalcoholic. Two additional stimulus sets depicted unrecognizable scrambled visual information and recognizable black silhouettes of the original beverages. Analysis of contrast waves inferred content (unrecognized scrambled trials subtracted from original) and color information (recognized shape trials subtracted from original) during visual processing. Linear regression was used to predict Alcohol Use Disorders Identification Test (AUDIT) scores from ERPs. RESULTS: In heavy social drinkers, alcoholic-content LPP was increased and P100 latency was shorter compared with nonalcoholic cues. Linear regression for alcohol content condition in the overall sample revealed shorter P100 latency and increased LPP amplitude predicting AUDIT scores. None of those effects were significant in the visual-feature control condition. CONCLUSIONS: Alcohol cue reactivity in heavy social drinkers was related to faster early attentional processes and motivational salience. The effect occurred independently of visual features in the pictures.

Meditation and the brain - Neuronal correlates of mindfulness as assessed with near-infrared spectroscopy.

Mindfulness meditation as a therapeutic intervention has been shown to have positive effects on psychological problems such as depression, pain or anxiety disorders. In this study, we used functional near-infrared spectroscopy (fNIRS) to detect differences in hemodynamic responses of meditation experts (14 participants) and a control group (16 participants) in a resting and a mindfulness condition. In both conditions, the sound of a meditation bowl was used to find group differences in the auditory system and adjacent cortical areas. Different lateralization patterns of the brain were found in expert meditators while being in a resting state (amplified left hemisphere) or being in mindfulness state (amplified right hemisphere). Compared to the control group, meditation experts had a more widespread pattern of activation in the auditory cortex, while resting. In the mindfulness condition, the control group showed a decrease of activation in higher auditory areas (BA 1, 6 and 40), whereas the meditation experts had a significant increase in those areas. In addition, meditation expert had highly activated brain areas (BA 39, 40, 44 and 45) beyond the meditative task itself, indicating possible long-term changes in the brain and their positive effects on empathy, meta cognitive skills and health.

Neurobiological and clinical effects of fNIRS-controlled rTMS in patients with panic disorder/agoraphobia during cognitive-behavioural therapy.

BACKGROUND: A relevant proportion of patients with panic disorder (PD) does not improve even though they receive state of the art treatment for anxiety disorders such as cognitive-behavioural therapy (CBT). At the same time, it is known, that from a neurobiological point of view, PD patients are often characterised by prefrontal hypoactivation. Intermittent Theta Burst Stimulation (iTBS) is a non-invasive type of neurostimulation which can modulate cortical activity and thus has the potential to normalise prefrontal hypoactivity found in PD. We therefore aimed at investigating the effects of iTBS as an innovative add-on to CBT in the treatment for PD. METHODS: In this double-blind, bicentric study, 44 PD patients, randomised to sham or verum stimulation, received 15 sessions of iTBS over the left prefrontal cortex (PFC) in addition to 9 weeks of group CBT. Cortical activity during a cognitive as well as an emotional (Emotional Stroop) paradigm was assessed both at baseline and post-iTBS treatment using functional near-infrared spectroscopy (fNIRS) and compared to healthy controls. RESULTS: In this manuscript we only report the results of the emotional paradigm; for the results of the cognitive paradigm please refer to Deppermann et al. (2014). During the Emotional Stroop test, PD patients showed significantly reduced activation to panic-related compared to neutral stimuli for the left PFC at baseline. Bilateral prefrontal activation for panic-related stimuli significantly increased after verum iTBS only. Clinical ratings significantly improved during CBT and remained stable at follow-up. However, no clinical differences between the verum- and sham-stimulated group were identified, except for a more stable reduction of agoraphobic avoidance during follow-up in the verum iTBS group. LIMITATIONS: Limitations include insufficient blinding, the missing control for possible state-dependent iTBS effects, and the timing of iTBS application during CBT. CONCLUSION: Prefrontal hypoactivity in PD patients was normalised by add-on iTBS. Clinical improvement of anxiety symptoms was not affected by iTBS.

The Temporal Muscle of the Head Can Cause Artifacts in Optical Imaging Studies with Functional Near-Infrared Spectroscopy.

Background: Extracranial signals are the main source of noise in functional near-infrared spectroscopy (fNIRS) as light is penetrating the cortex but also skin and muscles of the head. Aim: Here we performed three experiments to investigate the contamination of fNIRS measurements by temporal muscle activity. Material and methods: For experiment 1, we provoked temporal muscle activity by instructing 31 healthy subjects to clench their teeth three times. We measured fNIRS signals over left temporal and frontal channels with an interoptode distance of 3 cm, in one short optode distance (SOD) channel (1 cm) and electromyography (EMG) over the edge of the temporal muscle. In experiment 2, we screened resting state fNIRS-fMRI (functional magnetic resonance imaging) data of one healthy subject for temporal muscle artifacts. In experiment 3, we screened a dataset of sound-evoked activity (n = 33) using bi-temporal probe-sets and systematically contrasted subjects presenting vs. not presenting artifacts and blocks/events contaminated or not contaminated with artifacts. Results: In experiment 1, we could demonstrate a hemodynamic-response-like increase in oxygenated (O2Hb) and decrease in deoxygenated (HHb) hemoglobin with a large amplitude and large spatial extent highly exceeding normal cortical activity. Correlations between EMG, SOD, and fNIRS artifact activity showed only limited evidence for associations on a group level with rather clear associations in a sub-group of subjects. The fNIRS-fMRI experiment showed that during the temporal muscle artifact, fNIRS is completely saturated by muscle oxygenation. Experiment 3 showed hints for contamination of sound-evoked oxygenation by the temporal muscle artifact. This was of low relevance in analyzing the whole sample. Discussion: Temporal muscle activity e.g., by clenching the teeth induces a large hemodynamic-like artifact in fNIRS measurements which should be avoided by specific subject instructions. Data should be screened for this artifact might be corrected by exclusion of contaminated blocks/events. The usefulness of established artifact correction methods should be evaluated in future studies. Conclusion: Temporal muscle activity, e.g., by clenching the teeth is one major source of noise in fNIRS measurements.

Near-Infrared Spectroscopy-Based Frontal Lobe Neurofeedback Integrated in Virtual Reality Modulates Brain and Behavior in Highly Impulsive Adults.

Based on neurofeedback (NF) training as a neurocognitive treatment in attention-deficit/hyperactivity disorder (ADHD), we designed a randomized, controlled functional near-infrared spectroscopy (fNIRS) NF intervention embedded in an immersive virtual reality classroom in which participants learned to control overhead lighting with their dorsolateral prefrontal brain activation. We tested the efficacy of the intervention on healthy adults displaying high impulsivity as a sub-clinical population sharing common features with ADHD. Twenty participants, 10 in an experimental and 10 in a shoulder muscle-based electromyography control group, underwent eight training sessions across 2 weeks. Training was bookended by a pre- and post-test including go/no-go, n-back, and stop-signal tasks (SST). Results indicated a significant reduction in commission errors on the no-go task with a simultaneous increase in prefrontal oxygenated hemoglobin concentration for the experimental group, but not for the control group. Furthermore, the ability of the subjects to gain control over the feedback parameter correlated strongly with the reduction in commission errors for the experimental, but not for the control group, indicating the potential importance of learning feedback control in moderating behavioral outcomes. In addition, participants of the fNIRS group showed a reduction in reaction time variability on the SST. Results indicate a clear effect of our NF intervention in reducing impulsive behavior possibly via a strengthening of frontal lobe functioning. Virtual reality additions to conventional NF may be one way to improve the ecological validity and symptom-relevance of the training situation, hence positively affecting transfer of acquired skills to real life.

Increased arithmetic complexity is associated with domain-general but not domain-specific magnitude processing in children: A simultaneous fNIRS-EEG study.

The investigation of the neural underpinnings of increased arithmetic complexity in children is essential for developing educational and therapeutic approaches and might provide novel measures to assess the effects of interventions. Although a few studies in adults and children have revealed the activation of bilateral brain regions during more complex calculations, little is known about children. We investigated 24 children undergoing one-digit and two-digit multiplication tasks while simultaneously recording functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) data. FNIRS data indicated that one-digit multiplication was associated with brain activity in the left superior parietal lobule (SPL) and intraparietal sulcus (IPS) extending to the left motor area, and two-digit multiplication was associated with activity in bilateral SPL, IPS, middle frontal gyrus (MFG), left inferior parietal lobule (IPL), and motor areas. Oscillatory EEG data indicated theta increase and alpha decrease in parieto-occipital sites for both one-digit and two-digit multiplication. The contrast of two-digit versus one-digit multiplication yielded greater activity in right MFG and greater theta increase in frontocentral sites. Activation in frontal areas and theta band data jointly indicate additional domain-general cognitive control and working memory demands for heightened arithmetic complexity in children. The similarity in parietal activation between conditions suggests that children rely on domain-specific magnitude processing not only for two-digit but-in contrast to adults-also for one-digit multiplication problem solving. We conclude that in children, increased arithmetic complexity tested in an ecologically valid setting is associated with domain-general processes but not with alteration of domain-specific magnitude processing.

Aberrant functional connectivity in depression as an index of state and trait rumination.

Depression has been shown to be related to a variety of aberrant brain functions and structures. Particularly the investigation of alterations in functional connectivity (FC) in major depressive disorder (MDD) has been a promising endeavor, since a better understanding of pathological brain networks may foster our understanding of the disease. However, the underling mechanisms of aberrant FC in MDD are largely unclear. Using functional near-infrared spectroscopy (fNIRS) we investigated FC in the cortical parts of the default mode network (DMN) during resting-state in patients with current MDD. Additionally, we used qualitative and quantitative measures of psychological processes (e.g., state/trait rumination, mind-wandering) to investigate their contribution to differences in FC between depressed and non-depressed subjects. Our results indicate that 40% of the patients report spontaneous rumination during resting-state. Depressed subjects showed reduced FC in parts of the DMN compared to healthy controls. This finding was linked to the process of state/trait rumination. While rumination was negatively correlated with FC in the cortical parts of the DMN, mind-wandering showed positive associations.

Functional brain imaging of walking while talking - An fNIRS study.

Since functional imaging of whole body movements is not feasible with functional magnetic resonance imaging (fMRI), the present study presents in vivo functional near-infrared spectroscopy (fNIRS) as a suitable technique to measure body movement effects on fronto-temporo-parietal cortical activation in single- and dual-task paradigms. Previous fNIRS applications in studies addressing whole body movements were typically limited to the assessment of prefrontal brain areas. The current study investigated brain activation in the frontal, temporal and parietal cortex of both hemispheres using functional near-infrared spectroscopy (fNIRS) with two large 4×4 probe-sets with 24 channels each during single and dual gait tasks. 12 young healthy adults were measured using fNIRS walking on a treadmill: the participants performed two single-task (ST) paradigms (walking at different speeds, i.e. 3 and 5km/h) and a dual task (DT) paradigm where a verbal fluency task (VFT) had to be executed while walking at 3km/h. The results show an increase of activation in Broca's area during the more advanced conditions (ST 5km/h vs. ST 3km/h, DT vs. ST 3km/h, DT vs. 5km/h), while the corresponding area on the right hemisphere was also activated. DT paradigms including a cognitive task in conjunction with whole body movements elicit wide-spread cortical activation patterns across fronto-temporo-parietal areas. An elaborate assessment of these activation patterns requires more extensive fNIRS assessments than the traditional prefrontal investigations, e.g. as performed with portable fNIRS devices.

Prefrontal functional connectivity measured with near-infrared spectroscopy during smoking cue exposure.

Cue reactivity (CR) is an important concept for relapse in substance use disorders (SUD). Although cue exposure (CE) therapy is discussed as relapse prevention, current approaches still need improvement considering its efficacy. From a neurobiological perspective, CR is related to an over-activation in sensitized subcortical structures, their projections to motivationally relevant cortical structures (e.g. orbitofrontal cortex, OFC) and deficient prefrontal inhibitory control. Therefore, we analyzed prefrontal cortical activation and its relation to craving during smoking CE. We focused on the OFC-as a projection area of sensitized subcortical structures-due its importance in the processing of reinforcement value and the dorsolateral prefrontal cortex (dlPFC) based on its importance for behavioral inhibition. Functional near-infrared spectroscopy (fNIRS) was used to assess hemodynamics in prefrontal regions during smoking CE in 24 subjects (n = 12 occasional smokers, n = 12 controls). Subjective craving intensity (minimum craving as marker of baseline inhibition, range as marker of inhibition time course) was additionally assessed. Craving ratings indicated that CR was elicited solely in smokers, not controls. Those subjective ratings correlated with hemodynamic activity in OFC (craving range) and dlPFC (minimum craving). OFC activation was found earlier throughout the CE in smokers compared to controls. Connectivity (seed-based correlation) between OFC and dlPFC was increased in smokers. fNIRS can capture prefrontal hemodynamic activity involved in CR elicited during CE and is therefore a promising method to investigate CR and its implications for relapse prevention in SUD.

Brain activation in frontotemporal and Alzheimer's dementia: a functional near-infrared spectroscopy study.

BACKGROUND: Frontotemporal dementia is an increasingly studied disease, the underlying functional impairments on a neurobiological level of which have not been fully understood. Patients with the behavioral-subtype frontotemporal dementia (bvFTD) are particularly challenging for clinical measurements such as functional imaging due to their behavioral symptoms. Here, an alternative imaging method, functional near-infrared spectroscopy (fNIRS), is introduced to measure task-related cortical brain activation based on blood oxygenation. The current study investigated differences in cortical activation patterns of patients with bvFTD, Alzheimer's dementia (AD), and healthy elderly subjects measured by fNIRS. METHOD: Eight probable bvFTD patients completed the semantic, phonological, and control conditions of a verbal fluency task. Eight AD patients and eight healthy controls were compared on the same task. Simultaneously, an fNIRS measurement was conducted and analyzed using a correction method based on the expected negative correlation between oxygenated and deoxygenated hemoglobin. RESULTS: Healthy controls show an increase in cortical activation measured in frontoparietal areas such as the dorsolateral prefrontal cortex. The activation pattern of patients with AD is similar, but weaker. In contrast, bvFTD patients show a more frontopolar pattern, with activation of Broca's area, instead of the dorsolateral prefrontal cortex and the superior temporal gyrus. The frontoparietal compensation mechanisms, seen in the healthy elderly, were missing in bvFTD patients. CONCLUSION: Different frontoparietal cortical activation patterns may indicate a correlate of diverse pathophysiological mechanisms of AD and bvFTD during verbal fluency processing. The AD pattern is weaker and more similar to the healthy pattern, whereas the bvFTD pattern is qualitatively different, namely more frontopolar and without frontoparietal compensation activation. It adheres to a change of cortical activation during the course of the disease.