State-dependent altered connectivity in late-life depression: a functional near-infrared spectroscopy study.

There is a large body of evidence showing a substantial relationship between depression and deficits in cognitive functioning. Especially in late-life depression, cognitive impairments are associated with worse treatment progress and are considered a risk factor for neurodegenerative disorders. However, little is known about the differences in neural processing and coupling during rest and cognitive functions in patients with late-life depression compared to healthy elderly individuals. The study at hand aims to investigate the cognitive control network in late-life depression during a cognitive task and at rest by means of functional near-infrared spectroscopy. Hemodynamic responses were measured at rest and during the Trail Making Test using functional near-infrared spectroscopy in a matched sample of 49 depressed and 51 nondepressed elderly subjects (age range: 51-83 years; 64.1 ± 6.58 [mean ± standard deviation]). Functional connectivity (FC) and network metrics were derived from the data and analyzed with respect to differences between the subject groups. Depressed and nondepressed subjects showed significant differences in FC both at rest and during task performance. Depressed subjects showed reduced FC in a left frontopolar cortical network during task performance and increased FC in a left frontoparietal cortical network at rest. Depressed elderly subjects showed altered FC and network organization during different mental states. Higher FC at rest may be an indicator of self-referential processes such as rumination that may reduce FC during task performance due to an overtaxed executive control system.

Effects of cholinesterase inhibitor on brain activation in Alzheimer's patients measured with functional near-infrared spectroscopy.

RATIONALE: Neurobiological effects of neuropsychiatric medication can contribute to the understanding of mechanisms of action and to the evaluation of target medication effects. Cholinesterase inhibitors (ChEI) have been used in patients with Alzheimer's disease (AD) for years with only small knowledge about the underlying neurobiological effects. The measurement of brain activation links neurobiological and functional aspects but is challenging in the group of demented patients; here, an alternative method, functional near-infrared spectroscopy (fNIRS), is introduced to measure those medication effects. OBJECTIVES: The current study investigated the influence of ChEI on cortical activation of patients with AD measured using fNIRS during a verbal fluency task (VFT). METHODS: In this study, 24 probable AD patients were investigated three times using fNIRS: before medication with rivastigmine was given (t0), when the medication was at the target dose after 4 weeks (t1), and after the target dose was kept constant for a further 8 weeks (t2). RESULTS: The results show a concentration increase of oxygenated hemoglobin as measured with fNIRS from t0 to t2 in speech relevant areas and a general decrease in prefrontal areas. Behaviorally, an improvement was found for the VFT used to measure cortical activation during fNIRS. In the neuropsychological test battery, no significant changes were found, yet high effect sizes for the mini mental status examination, immediate and delayed word list recall were found. CONCLUSIONS: The results indicate a positive effect of ChEI on cognitive function. The underlying cortical changes can be imaged using fNIRS.

The relation of SMI and the VSEP in a risk sample for neurodegenerative disorders.

Vagus somatosensory evoked potentials (VSEP) have been shown to have higher latencies with aging, which are even more increased in patients with Alzheimer's disease and subjects with mild cognitive impairment compared to age-matched healthy controls. In this study, the association of VSEP with subjective memory impairment (SMI), a potential risk or prodromal marker for Alzheimer's disease, was examined. The association of VSEP latencies and SMI was studied in a healthy risk cohort, including 358 elderly subjects, who are in a longitudinal study of risk factors for neurodegenerative disorders. The results show increased VSEP latencies for peak P2 at Fz-F4 in subjects who report SMI and are worried about it as compared to subjects who report memory impairment, but are not concerned and subjects without complaints. The results support a potential role of VSEP for the detection of very early neurodegenerative processes which may precede Alzheimer's disease.

Influence of different stimulation parameters on the somatosensory evoked potentials of the nervus vagus--how varied stimulation parameters affect VSEP.

Vagus somatosensory evoked potentials are a method for assessing the function of the vagus nerve, which were shown to be altered in neurodegenerative diseases like Alzheimer's and Parkinson's disease. Various parameters of the stimulation such as the electrode position and the stimulus intensity have already been investigated. In this study, the focus is on the systematic examination of the other parameters of the stimulation of the vagus somatosensory evoked potentials: stimulus duration, interstimulus interval, and, again, the stimulation intensity. Thirty young and healthy subjects were examined using five different sets of stimulation parameters, and 24 were included in the further analysis. The results show that a reduction of the stimulus duration and a decrease in stimulus intensity have a significant effect on the amplitudes. A shortening of the interstimulus interval does not seem to have such an effect, but this stimulation is rated more painful and unpleasant than the standard stimulation. Overall, the standard stimulation used so far seems to be the most preferable condition.

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 Alzheimer's disease or Parkinson's 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 Broca's 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.

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

While progressive neurocognitive impairments are associated with aging and Alzheimer's 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.

Vagus somatosensory evoked potentials--a possibility for diagnostic improvement in patients with mild cognitive impairment?.

OBJECTIVE: Vagus somatosensory evoked potentials (VSEP) are far-field potentials probably generated in nuclei of then. vagus in the lower brainstem. They represent a putative, easily applicable method for discrimination between patients with Alzheimer's disease (AD), patients with mild cognitive impairment (MCI), and healthy controls (HC). METHODS: Thirteen patients with AD, 12 with MCI, and 27 age- and gender-matched HC were investigated by stimulating the cutaneous branch of the n. vagus; 8, 6, and 20, respectively, were included in the main part of the analysis. RESULTS: In fronto-central recordings (electrode positions Fz-F4) a grading from HC over MCI to AD could be found, with a significant linear trend over the three groups and significantly increased latencies of the cognitively impaired patients but no significant difference between MCI and AD. CONCLUSION: The results indicate that the method of VSEP is able to discriminate between cognitively declined patients and HC, whereas no clear-cut differences were detected between MCI and AD.

Decreased α-synuclein serum levels in patients with Lewy body dementia compared to Alzheimer's disease patients and control subjects.

BACKGROUND/AIMS: Detection and differentiation of neurodegenerative dementias, such as dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), with blood-based biomarkers would facilitate diagnosis and treatment. METHODS: By use of a commercially available ELISA kit, we measured α-synuclein levels in the serum of 40 DLB patients and controls, and of 80 AD patients. RESULTS: We found significantly reduced α-synuclein serum levels in DLB compared to both AD (p = 0.006) and control subjects (p = 0.001), reaching an area under the curve of >0.70. CONCLUSION: Although these results do not justify a definition of serum α-synuclein as a potential single biomarker, results may contribute to a multimarker strategy in DLB diagnosis.

Stem cell factor plasma levels are decreased in Alzheimer's disease patients with fast cognitive decline after one-year follow-up period: the Pythia-study.

Alzheimer's disease (AD) is the most common cause of cognitive decline in the elderly and is characterized by massive neuronal loss in the brain. Stem cell factor (SCF) is a hematopoietic growth factor that promotes neuroprotective effects and supports neurogenesis in the brain. Decreased SCF plasma levels have been described in AD patients. Whether SCF plasma levels are also associated with the rate of cognitive decline in AD patients has not been reported so far. In the present study, we demonstrate that SCF plasma levels are significantly decreased in AD patients with fast cognitive decline (decrease of Mini-Mental State Examination [MMSE] score > 4 after one year; n = 12) compared to AD patients with slow cognitive decline (decrease of MMSE score ≤ 4 after one year; n = 28) (fast versus slow cognitive decline: mean ± SD: 1051.1 ± 178.7 versus 1237.9 ± 274.2 pg/ml; p = 0.037). Moreover, SCF plasma levels correlated with the rate of cognitive decline after one year follow-up period (r = 0.315; p = 0.048). In a multiple linear regression analysis, independent predictors of the rate of cognitive decline in our study cohort were age, MMSE scores at baseline, SCF plasma levels, as well as brain-derived neurotrophic factor and activated glycoprotein (GP) IIb/IIIa. These results suggest that lower SCF plasma levels are associated with a higher rate of cognitive decline in AD patients. Thus, treatment strategies increasing SCF plasma levels could be useful for delaying the progression of AD. Further prospective studies are needed to elucidate the value of plasma SCF in a multimarker approach determining AD prognosis.

The myoseptal system in Chimaera monstrosa: collagenous fiber architecture and its evolution in the gnathostome stem lineage.

Recent studies have revealed the 3D morphology and collagen fiber architecture of myosepta in teleostome fishes. Here we present the first data set on the myoseptal structure of a representative of the chondrichthyan clade. We investigate the series of myosepta in the ratfish Chimaera monstrosa (Holocephali) from the anterior to the posterior body using microdissections of cleared and stained specimens, polarized light microscopy of excised myosepta, and histology. The features of the myoseptal system of Chimaera are compared to data from closely related vertebrate groups and are mapped onto a phylogenetic tree to further clarify the characteristics of the myoseptal series in the gnathostome ancestor. The 3D morphology and collagen fiber architecture of the myoseptal series in C. monstrosa resembles that of Teleostomi (Actinopterygii+Sarcopterygii) with regard to several features. Our comparative analysis reveals that some of them have evolved in the gnathostome stem lineage. (1) A series of epineural and epaxial lateral tendons (LTs) along the whole body, and a series of epipleural and hypaxial LTs in the postanal region evolved in the gnathostome stem lineage. (2) The LTs increase in length towards the posterior body (three-fold in Chimaera). Data on Chimaera and some comparative data on actinopterygian fishes indicate that LTs also increase in thickness towards the posterior body, but further data are necessary to test whether this holds true generally. (3) Another conspicuous apomorphic gnathostome feature is represented by multi-layer structures of myosepta. These are formed along the vertebral column by converging medial regions of successive sloping parts of myosepta. (4) The dorsalmost and ventralmost flanking parts of myosepta bear a set of mediolaterally oriented collagen fibers that are present in all gnathostomes but are lacking in outgroups. Preanal hypaxial myosepta are clearly different from epaxial myosepta and postanal hypaxial myosepta in terms of their collagen fiber architecture. In Chimaera, preanal hypaxial myosepta consist of an array of mediolaterally oriented collagen fibers closely resembling the condition in other gnathostome groups and in petromyzontids. Only one series of tendons, the myorhabdoid tendons of the flanking parts of myosepta, have evolved in the stem lineage of Myopterygii (Gnathostomata+Petromyzontida). Similar to LTs, the tendons of this series also increase in length towards the posterior body. In combination with other studies, the present study provides a framework for the design of morphologically based experiments and modeling to further address the function of myosepta and myoseptal tendons in gnathostomes.

Evolutionary transformations of myoseptal tendons in gnathostomes.

Axial undulations in fishes are powered by a series of three-dimensionally folded myomeres separated by sheets of connective tissue, the myosepta. Myosepta have been hypothesized to function as transmitters of muscular forces to axial structures during swimming, but the difficulty of studying these delicate complex structures has precluded a more complete understanding of myoseptal mechanics. We have developed a new combination of techniques for visualizing the three-dimensional morphology of myosepta, and here we present their collagen-fibre architecture based on examination of 62 species representing all of the major clades of notochordates. In all gnathostome fishes, each myoseptum bears a set of six specifically arranged tendons. Because these tendons are not present outside the gnathostomes (i.e. they are absent from lampreys, hagfishes and lancelets), they represent evolutionary novelties of the gnathostome ancestor. This arrangement has remained unchanged throughout 400 Myr of gnathostome evolution, changing only on the transition to land. The high uniformity of myoseptal architecture in gnathostome fishes indicates functional significance and may be a key to understanding general principles of fish swimming mechanics. In the design of future experiments or biomechanical models, myosepta have to be regarded as tendons that can distribute forces in specific directions.