Florian B. Haeussinger

Simulation of Near-Infrared Light Absorption Considering Individual Head and Prefrontal Cortex Anatomy: Implications for Optical Neuroimaging

Functional near-infrared spectroscopy (fNIRS) is an established optical neuroimaging method for measuring functional hemodynamic responses to infer neural activation. However, the impact of individual anatomy on the sensitivity of fNIRS measuring hemodynamics within cortical gray matter is still unknown. By means of Monte Carlo simulations and structural MRI of 23 healthy subjects (mean age: years), we characterized the individual distribution of tissue-specific NIR-light absorption underneath 24 prefrontal fNIRS channels. We, thereby, investigated the impact of scalp-cortex distance (SCD), frontal sinus volume as well as sulcal morphology on gray matter volumes () traversed by NIR-light, i.e. anatomy-dependent fNIRS sensitivity. The NIR-light absorption between optodes was distributed describing a rotational ellipsoid with a mean penetration depth of considering the deepest of light. Of the detected photon packages scalp and bone absorbed and absorbed of the energy. The mean volume was negatively correlated () with the SCD and frontal sinus volume () and was reduced by in subjects with relatively large compared to small frontal sinus. Head circumference was significantly positively correlated with the mean SCD () and the traversed frontal sinus volume (). Sulcal morphology had no significant impact on . Our findings suggest to consider individual SCD and frontal sinus volume as anatomical factors impacting fNIRS sensitivity. Head circumference may represent a practical measure to partly control for these sources of error variance.

Aging-related cortical reorganization of verbal fluency processing: a functional near-infrared spectroscopy study

While progressive neurocognitive impairments are associated with aging and Alzheimers disease (AD), cortical reorganization might delay difficulties in effortful word retrieval, which represent one of the earliest cognitive signs of AD. Using functional near-infrared spectroscopy (fNIRS), we investigated cortical hemodynamic responses elicited by phonological and semantic verbal fluency in non-demented, healthy subjects (n = 325; age: 51-82 years). Age predicted bilaterally reduced inferior frontal junction (IFJ) and increased middle frontal and supramarginal gyri activity in both task conditions using multiple regressions. Compared with age the years of education as well as sex (IFJ activation in females > males) partly predicted opposite effects on activation, while task performance was not significant predictor. All predictors showed small effect sizes. IFJ activation was more pronounced during phonological compared with semantic fluency, and higher in the left hemisphere. Age only marginally predicted relative lateralization. Middle frontal and supramarginal gyri activity may compensate for an aging-related decrease in IFJ recruitment during verbal fluency. Longitudinal observations will further investigate these neural changes regarding an early AD prediction, while individuals are still cognitively healthy.

Reconstructing functional near-infrared spectroscopy (fNIRS) signals impaired by extra-cranial confounds: an easy-to-use filter method.

Functional near-infrared spectroscopy (fNIRS) is an optical neuroimaging method that detects temporal concentration changes of oxygenated and deoxygenated hemoglobin within the cortex, so that neural activation can be inferred. However, even though fNIRS is a very practical and well-tolerated method with several advantages particularly in methodically challenging measurement situations (e.g., during tasks involving movement or open speech), it has been shown to be confounded by systemic compounds of non-cerebral, extra-cranial origin (e.g. changes in blood pressure, heart rate). Especially event-related signal patterns induced by dilation or constriction of superficial forehead and temple veins impair the detection of frontal brain activation elicited by cognitive tasks. To further investigate this phenomenon, we conducted a simultaneous fNIRS-fMRI study applying a working memory paradigm (n-back). Extra-cranial signals were obtained by extracting the BOLD signal from fMRI voxels within the skin. To develop a filter method that corrects for extra-cranial skin blood flow, particularly intended for fNIRS data sets recorded by widely used continuous wave systems with fixed optode distances, we identified channels over the forehead with probable major extra-cranial signal contributions. The averaged signal from these channels was then subtracted from all fNIRS channels of the probe set. Additionally, the data were corrected for motion and non-evoked systemic artifacts. Applying these filters, we can show that measuring brain activation in frontal brain areas with fNIRS was substantially improved. The resulting signal resembled the fMRI parameters more closely than before the correction. Future fNIRS studies measuring functional brain activation in the forehead region need to consider the use of different filter options to correct for interfering extra-cranial signals.

Activation during the Trail Making Test measured with functional near-infrared spectroscopy in healthy elderly subjects

Cognitive decline is very common in age and particularly in subjects with neurodegenerative conditions. Besides memory and language, executive functions are very often affected in elderly and patients with Alzheimers disease or Parkinsons disease. However, the neural alterations associated with these executive deficits are still not fully understood. Therefore, we measured cortical activation using functional near-infrared spectroscopy (fNIRS) in 16 healthy elderly subjects (50-75 years) performing the Trail Making Test (TMT), a widely used neuropsychological instrument measuring executive function. In line with previous studies focusing on younger subjects, the results showed frontal activation during the TMT A and the TMT B in the dorsolateral prefrontal cortex, the frontopolar area and also Brocas area. Furthermore, significant activation in the left motor, somatosensory cortices and somatosensory association cortices was demonstrated. Additionally, after a median split the differences between younger (<58 years) and older (>58 years) subjects were analyzed with the older subjects showing a less focused prefrontal activation. Altogether, fNIRS was found to be suitable to detect cortical activation in elderly subjects during performance of the TMT as well as aging-related differences in prefrontal activation topography. These neural correlates of executive functions should be further investigated as a potential prodromal neural marker of executive deficits and neurodegenerative processes.

Task-dependent and polarity-specific effects of prefrontal transcranial direct current stimulation on cortical activation during word fluency.

Targeted modulation of cortical functions by non-invasive brain stimulation is widely used for the investigation of the neurophysiological signatures of executive functions and put forward as a potential specific treatment for its disorders. To further investigate the underlying mechanisms, we performed two experiments involving 46 subjects that performed a semantic and a phonological verbal fluency task (VFT) as well as a simple speech-production task after application of 1mA anodal or cathodal transcranial direct current stimulation (tDCS) to the left inferior frontal gyrus (IFG). Brain activation was measured by functional near-infrared spectroscopy (fNIRS) during task performance. Neither preceding anodal nor cathodal tDCS was found to modulate VFT performance of either difficulty. However, preconditioning with anodal tDCS increased brain activity during the VFT whereas a trendwise decrease of activation was found after cathodal stimulation. Notably, this difference was not found with simple speech production. These findings support the notion of a polarity-specific malleability of neuronal network activity underlying speech production by tDCS. Most importantly, the task-specificity of the modulatory effect observed after the end of stimulation demonstrates lasting neurophysiological effects of tDCS that are reflected in modifications of cortical excitability by challenging cognitive tasks.

Haemodynamic and electrophysiological markers of pragmatic language comprehension in schizophrenia

Abstract Objectives. The present study aimed at investigating neurophysiological markers of language perception in schizophrenia using simultaneous near-infrared spectroscopy (NIRS) and event-related potentials (ERPs), which have been proven to be useful for studying language processing abilities in psychiatric patients. The study shall help to integrate previous findings from ERP and fMRI studies on figurative language comprehension in schizophrenia and elucidate how electrophysiological and haemodynamic markers of language processing are related. Methods. Twenty-two healthy subjects and 22 schizophrenia patients judged 120 sentences regarding their meaningfulness. Phrases were literal, metaphoric, or meaningless. EEG-fNIRS signals were recorded throughout the entire experiment. Results. Schizophrenia patients showed deficient and delayed sentence comprehension. Both the early N400 and left-hemispheric activation during language comprehension were altered in patients. Correlation analyses showed that metaphor-related ERPs were strongly linked to haemodynamic cortical activity in healthy subjects, but not in patients. Conclusions. Our results indicate group differences in cortical electrophysiological and haemodynamic activation that represent rather general impairments in the processing of complex language. Simultaneous EEG/NIRS applications are useful to depict these neural markers and to investigate their relationship. Future studies are needed to clarify the nature of respective anomalies and their potential as putative neural markers in schizophrenia research.

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.

Age and Vascular Burden Determinants of Cortical Hemodynamics Underlying Verbal Fluency.

Background Aging processes and several vascular burden factors have been shown to increase the risk of dementia including Alzheimers disease. While pathological alterations in dementia precede diagnosis by many years, reorganization of brain processing might temporarily delay cognitive decline. We hypothesized that in healthy elderly individuals both age-related neural and vascular factors known to be related to the development of dementia impact functional cortical hemodynamics during increased cognitive demands. Methods Vascular burden factors and cortical functional hemodynamics during verbal fluency were assessed in 1052 non-demented elderly individuals (51 to 83 years; cross-sectional data of the longitudinal TREND study) using functional near-infrared spectroscopy (fNIRS). The prediction of functional hemodynamic responses by age in multiple regressions and the impact of single and cumulative vascular burden factors including hypertension, diabetes, obesity, smoking and atherosclerosis were investigated. Results Replicating and extending previous findings we could show that increasing age predicted functional hemodynamics to be increased in right prefrontal and bilateral parietal cortex, and decreased in bilateral inferior frontal junction during phonological fluency. Cumulative vascular burden factors, with hypertension in particular, decreased left inferior frontal junction hemodynamic responses during phonological fluency. However, age and vascular burden factors showed no statistical interaction on functional hemodynamics. Conclusion Based on these findings, one might hypothesize that increased fronto-parietal processing may represent age-related compensatory reorganization during increased cognitive demands. Vascular burden factors, such as hypertension, may contribute to regional cerebral hypoperfusion. These neural and vascular hemodynamic determinants should be investigated longitudinally and combined with other markers to advance the prediction of future cognitive decline and dementia.

Does rTMS Alter Neurocognitive Functioning in Patients with Panic Disorder/Agoraphobia? An fNIRS-Based Investigation of Prefrontal Activation during a Cognitive Task and Its Modulation via Sham-Controlled rTMS

Objectives. Neurobiologically, panic disorder (PD) is supposed to be characterised by cerebral hypofrontality. Via functional near-infrared spectroscopy (fNIRS), we investigated whether prefrontal hypoactivity during cognitive tasks in PD-patients compared to healthy controls (HC) could be replicated. As intermittent theta burst stimulation (iTBS) modulates cortical activity, we furthermore investigated its ability to normalise prefrontal activation. Methods. Forty-four PD-patients, randomised to sham or verum group, received 15 iTBS-sessions above the left dorsolateral prefrontal cortex (DLPFC) in addition to psychoeducation. Before first and after last iTBS-treatment, cortical activity during a verbal fluency task was assessed via fNIRS and compared to the results of 23 HC. Results. At baseline, PD-patients showed hypofrontality including the DLPFC, which differed significantly from activation patterns of HC. However, verum iTBS did not augment prefrontal fNIRS activation. Solely after sham iTBS, a significant increase of measured fNIRS activation in the left inferior frontal gyrus (IFG) during the phonological task was found. Conclusion. Our results support findings that PD is characterised by prefrontal hypoactivation during cognitive performance. However, verum iTBS as an “add-on” to psychoeducation did not augment prefrontal activity. Instead we only found increased fNIRS activation in the left IFG after sham iTBS application. Possible reasons including task-related psychophysiological arousal are discussed.

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.