Decreased Brain Structural Network Connectivity in Patients with Mild Cognitive Impairment: A Novel Fractal Dimension Analysis.

Mild cognitive impairment (MCI) is widely regarded to be the intermediate stage to Alzheimer's disease. Cerebral morphological alteration in cortical subregions can provide an accurate predictor for early recognition of MCI. Thirty patients with MCI and thirty healthy control subjects participated in this study. The Desikan-Killiany cortical atlas was applied to segment participants' cerebral cortex into 68 subregions. A complexity measure termed fractal dimension (FD) was applied to assess morphological changes in cortical subregions of participants. The MCI group revealed significantly decreased FD values in the bilateral temporal lobes, right parietal lobe including the medial temporal, fusiform, para hippocampal, and also the orbitofrontal lobes. We further proposed a novel FD-based brain structural network to compare network parameters, including intra- and inter-lobular connectivity between groups. The control group had five modules, and the MCI group had six modules in their brain networks. The MCI group demonstrated shrinkage of modular sizes with fewer components integrated, and significantly decreased global modularity in the brain network. The MCI group had lower intra- and inter-lobular connectivity in all lobes. Between cerebral lobes, the MCI patients may maintain nodal connections between both hemispheres to reduce connectivity loss in the lateral hemispheres. The method and results presented in this study could be a suitable tool for early detection of MCI.

Differences in Physiological Signals Due to Age and Exercise Habits of Subjects during Cycling Exercise.

Numerous studies indicated the physical benefits of regular exercise, but the neurophysiological mechanisms of regular exercise in elders were less investigated. We aimed to compare changes in brain activity during exercise in elderly people and in young adults with and without regular exercise habits. A total of 36 healthy young adults (M/F:18/18) and 35 healthy elderly adults (M/F:20/15) participated in this study. According to exercise habits, each age group were classified into regular and occasional exerciser groups. ECG, EEG, and EMG signals were recorded using V-AMP with a 1-kHz sampling rate. The participants were instructed to perform three 5-min bicycle rides with different exercise loads. The EEG spectral power of elders who exercised regularly revealed the strongest positive correlation with their exercise intensity by using Pearson correlation analysis. The results demonstrate that exercise-induced significant cortical activation in the elderly participants who exercised regularly, and most of the p-values are less than 0.001. No significant correlation was observed between spectral power and exercise intensity in the elders who exercised occasionally. The young participants who exercised regularly had greater cardiac and neurobiological efficiency. Our results may provide a new exercise therapy reference for adult groups with different exercise habits, especially for the elders.

Classification of Prefrontal Cortex Activity Based on Functional Near-Infrared Spectroscopy Data upon Olfactory Stimulation.

The sense of smell is one of the most important organs in humans, and olfactory imaging can detect signals in the anterior orbital frontal lobe. This study assessed olfactory stimuli using support vector machines (SVMs) with signals from functional near-infrared spectroscopy (fNIRS) data obtained from the prefrontal cortex. These data included odor stimuli and air state, which triggered the hemodynamic response function (HRF), determined from variations in oxyhemoglobin (oxyHb) and deoxyhemoglobin (deoxyHb) levels; photoplethysmography (PPG) of two wavelengths (raw optical red and near-infrared data); and the ratios of data from two optical datasets. We adopted three SVM kernel functions (i.e., linear, quadratic, and cubic) to analyze signals and compare their performance with the HRF and PPG signals. The results revealed that oxyHb yielded the most efficient single-signal data with a quadratic kernel function, and a combination of HRF and PPG signals yielded the most efficient multi-signal data with the cubic function. Our results revealed superior SVM analysis of HRFs for classifying odor and air status using fNIRS data during olfaction in humans. Furthermore, the olfactory stimulation can be accurately classified by using quadratic and cubic kernel functions in SVM, even for an individual participant data set.

Using Fractal Dimension Analysis with the Desikan-Killiany Atlas to Assess the Effects of Normal Aging on Subregional Cortex Alterations in Adulthood.

Normal aging is associated with functional and structural alterations in the human brain. The effects of normal aging and gender on morphological changes in specific regions of the brain are unknown. The fractal dimension (FD) can be a quantitative measure of cerebral folding. In this study, we used 3D-FD analysis with the Desikan-Killiany (DK) atlas to assess subregional morphological changes in adulthood. A total of 258 participants (112 women and 146 men) aged 30-85 years participated in this study. Participants in the middle-age group exhibited a decreased FD in the lateral frontal lobes, which then spread to the temporal and parietal lobes. Men exhibited an earlier and more significant decrease in FD values, mainly in the right frontal and left parietal lobes. Men exhibited more of a decrease in FD values in the subregions on the left than those in the right, whereas women exhibited more of a decrease in the lateral subregions. Older men were at a higher risk of developing mild cognitive impairment (MCI) and exhibited age-related memory decline earlier than women. Our FD analysis using the DK atlas-based prediagnosis may provide a suitable tool for assessing normal aging and neurodegeneration between groups or in individual patients.

Alteration of the Intra- and Inter-Lobe Connectivity of the Brain Structural Network in Normal Aging.

The morphological changes in cortical parcellated regions during aging and whether these atrophies may cause brain structural network intra- and inter-lobe connectivity alterations are subjects that have been minimally explored. In this study, a novel fractal dimension-based structural network was proposed to measure atrophy of 68 parcellated cortical regions. Alterations of structural network parameters, including intra- and inter-lobe connectivity, were detected in a middle-aged group (30-45 years old) and an elderly group (50-65 years old). The elderly group exhibited significant lateralized atrophy in the left hemisphere, and most of these fractal dimension atrophied regions were included in the regions of the "last-in, first-out" model. Globally, the elderly group had lower modularity values, smaller component size modules, and fewer bilateral association fibers. They had lower intra-lobe connectivity in the frontal and parietal lobes, but higher intra-lobe connectivity in the temporal and occipital lobes. Both groups exhibited similar inter-lobe connecting pattern. The elderly group revealed separations, sparser long association fibers, commissural fibers, and lateral inter-lobe connectivity lost effect, mainly in the right hemisphere. New wiring and reconfiguring modules may have occurred within the brain structural network to compensate for connectivity, decreasing and preventing functional loss in cerebral intra- and inter-lobe connectivity.

Supratentorial and Infratentorial Lesions in Spinocerebellar Ataxia Type 3.

Background: Spinocerebellar ataxia type 3 (SCA) is a cerebellum-dominant degenerative disorder that is characterized primarily by infratentorial damage, although less severe supratentorial involvement may contribute to the clinical manifestation. These impairments may result from the efferent loss of the cerebellar cortex and degeneration of the cerebral cortex. Method: We used the three-dimensional fractal dimension (3D-FD) method to quantify the morphological changes in the supratentorial regions and assessed atrophy in the relatively focal regions in patients with SCA3. A total of 48 patients with SCA3 and 50 sex- and age-matched healthy individuals, as the control group, participated in this study. The 3D-FD method was proposed to distinguish 97 automatic anatomical label regions of gray matter (left cerebrum: 45, right cerebrum: 45, cerebellum: 7) between healthy individuals and patients with SCA3. Results: Patients with SCA3 exhibited reduced brain complexity within both the traditional olivopontocerebellar atrophy (OPCA) pattern and specific supratentorial regions. The study results confirmed the extensive involvement of extracerebellar regions in SCA3. The atrophied regions of SCA3 in infratentorial and supratentorial cortex showed a wide range of overlapped areas as in two functional cortexes, namely cerebellum-related cortex and basal ganglia-related cortex. Conclusions: Our results found that the atrophy of the SCA3 are not only limited in the infratentorial regions. Both cerebellar related cortex and basal ganglia related cortex were affected in the disease process of SCA3. Our findings might correlate to the common symptoms of SCA3, such as ataxia, Parkinsonism, dysarthria, and dysmetria. SCA3 should no longer be considered a disease limited to the cerebellum and its connections; rather, it should be considered a pathology affecting the whole brain.

Diffusion Tensor Magnetic Resonance Imaging for Differentiating Multiple System Atrophy Cerebellar Type and Spinocerebellar Ataxia Type 3.

Multiple system atrophy cerebellar type (MSA-C) and spinocerebellar ataxia type 3 (SCA3) demonstrate similar manifestations, including ataxia, pyramidal and extrapyramidal signs, as well as atrophy and signal intensity changes in the cerebellum and brainstem. MSA-C and SCA3 cannot be clinically differentiated through T1-weighted magnetic resonance imaging (MRI) alone; therefore, clinical consensus criteria and genetic testing are also required. Here, we used diffusion tensor imaging (DTI) to measure water molecular diffusion of white matter and investigate the difference between MSA-C and SCA3. Four measurements were calculated from DTI images, including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). Fifteen patients with MSA-C, 15 patients with SCA3, and 30 healthy individuals participated in this study. Both patient groups demonstrated a significantly decreased FA but a significantly increased AD, RD, and MD in the cerebello-ponto-cerebral tracts. Moreover, patients with SCA3 demonstrated a significant decrease in FA but more significant increases in AD, RD, and MD in the cerebello-cerebral tracts than patients with MSAC. Our results may suggest that FA and MD can be effectively used for differentiating SCA3 and MSA-C, both of which are cerebellar ataxias and have many common atrophied regions in the cerebral and cerebellar cortex.

Genetic Predisposition and Disease Expression of Bipolar Disorder Reflected in Shape Changes of the Anterior Limbic Network.

Bipolar disorder (BD) is a genetically and phenotypically complex psychiatric disease. Although previous studies have suggested that the relatives of BD patients have an increased risk of experiencing affective disturbances, most relatives who have similar genotypes may not manifest the disorder. We aim to identify the neuroimaging alterations-specifically, the cortical folding structures of the anterior limbic network (ALN)-in BD patients and their siblings, compared to healthy controls. The shared alterations in patients and their siblings may indicate the hereditary predisposition of BD, and the altered cortical structures unique to BD patients may be a probe of BD expression. High-resolution, T1-weighted magnetic resonance images for 17 euthymic patients with BD, 17 unaffected siblings of BD patients, and 22 healthy controls were acquired. We categorized the cortical regions within the ALN into sulcal and gyral areas, based on the shape index, followed by the measurement of the folding degree, using the curvedness. Our results revealed that the changes in cortical folding in the orbitofrontal and temporal regions were associated with a hereditary predisposition to BD. Cortical folding structures in multiple regions of the ALN, particularly in the striatal-thalamic circuit and anterior cingulate cortex, could be used to differentiate BD patients from healthy controls and unaffected siblings. We concluded that the cortical folding structures of ALN can provide potential biomarkers for clinical diagnosis of BD and differentiation from the unaffected siblings.

Intra- and Inter-Modular Connectivity Alterations in the Brain Structural Network of Spinocerebellar Ataxia Type 3.

In addition to cerebellar degeneration symptoms, patients with spinocerebellar ataxia type 3 (SCA3) exhibit extensive involvements with damage in the prefrontal cortex. A network model has been proposed for investigating the structural organization and functional mechanisms of clinical brain disorders. For neural degenerative diseases, a cortical feature-based structural connectivity network can locate cortical atrophied regions and indicate how their connectivity and functions may change. The brain network of SCA3 has been minimally explored. In this study, we investigated this network by enrolling 48 patients with SCA3 and 48 healthy subjects. A novel three-dimensional fractal dimension-based network was proposed to detect differences in network parameters between the groups. Copula correlations and modular analysis were then employed to categorize and construct the structural networks. Patients with SCA3 exhibited significant lateralized atrophy in the left supratentorial regions and significantly lower modularity values. Their cerebellar regions were dissociated from higher-level brain networks, and demonstrated decreased intra-modular connectivity in all lobes, but increased inter-modular connectivity in the frontal and parietal lobes. Our results suggest that the brain networks of patients with SCA3 may be reorganized in these regions, with the introduction of certain compensatory mechanisms in the cerebral cortex to minimize their cognitive impairment syndrome.

Impaired Efficiency and Resilience of Structural Network in Spinocerebellar Ataxia Type 3.

Background: Recent studies have shown that the patients with spinocerebellar ataxia type 3 (SCA3) may not only have disease involvement in the cerebellum and brainstem but also in the cerebral regions. However, the relations between the widespread degenerated brain regions remains incompletely explored. Methods: In the present study, we investigate the topological properties of the brain networks of SCA3 patients (n = 40) constructed based on the correlation of three-dimensional fractal dimension values. Random and targeted attacks were applied to measure the network resilience of normal and SCA3 groups. Results: The SCA3 networks had significantly smaller clustering coefficients (P < 0.05) and global efficiency (P < 0.05) but larger characteristic path length (P < 0.05) than the normal controls networks, implying loss of small-world features. Furthermore, the SCA3 patients were associated with reduced nodal betweenness (P < 0.001) in the left supplementary motor area, bilateral paracentral lobules, and right thalamus, indicating that the motor control circuit might be compromised. Conclusions: The SCA3 networks were more vulnerable to targeted attacks than the normal controls networks because of the effects of pathological topological organization. The SCA3 revealed a more sparsity and disrupted structural network with decreased values in the largest component size, mean degree, mean density, clustering coefficient, and global efficiency and increased value in characteristic path length. The cortico-cerebral circuits in SCA3 were disrupted and segregated into occipital-parietal (visual-spatial cognition) and frontal-pre-frontal (motor control) clusters. The cerebellum of SCA3 were segregated from cerebellum-temporal-frontal circuits and clustered into a frontal-temporal cluster (cognitive control). Therefore, the disrupted structural network presented in this study might reflect the clinical characteristics of SCA3.