Integrative role of attention networks in frequency-dependent modular organization of human brain.

Despite converging evidence of hierarchical organization in the cerebral cortex, with sensory-motor and association regions at opposite ends, the mechanism of such hierarchical interactions remains elusive. This organization was primarily investigated regarding the spatiotemporal dynamics of intrinsic connectivity networks (ICNs). However, more effort is needed to investigate network dynamics in the frequency domain. We aimed to examine the integrative role of brain regions in the frequency domain with graph metrics. Phase-based connectivity estimation was performed in three frequency bands (0.011-0.038, 0.043-0.071, and 0.076-0.103 Hz) in the BOLD signal during rest. We applied modularity analysis to connectivity matrices and investigated those areas, which we called integrative regions, that showed frequency-domain flexibility. Integrative regions, mostly belonging to attention networks, were densely connected to higher-order cognitive ICNs in lower frequency bands but to sensory-motor ICNs in higher frequency bands. We compared the normalized participation coefficient (Pnorm) values of integrative and core regions with respect to their relation to higher-order cognition using a permutation-based t-test for multiple linear regression. Regression parameters of integrative regions in relation to three cognitive scores in executive functions, and working memory were significantly larger than those of core regions (Pfdr < 0.05) for salience ventral attention network. Parameters of integrative regions in relation to intelligence scores were significantly larger than those with core regions (Pfdr < 0.05) in dorsal attention network. Larger parameters of neuropsychological test scores in relation to these flexible parcels further indicate their essential role at an intermediate level in behavior. Results emphasize the importance of frequency-band analysis of brain networks.

Volumetric and functional connectivity changes of the thalamic nuclei in different stages of Alzheimer's disease.

OBJECTIVE: Memory processes known to be impaired in Alzheimer's disease (AD) are maintained by a large-scale neurocognitive network with subcortical components, including the thalamus. Therefore, we aimed to examine the volumetric and functional changes of the thalamic nuclei at different scales across AD stages. METHODS: MRI data of patients diagnosed with 20 AD dementia (ADD), 30 amnestic mild cognitive impairment (MCI), and 30 subjective cognitive impairment (SCI) were used. Volumetric and functional connectivity analyzes were performed by dividing the thalamus into anterior, medial, posterior, lateral and intralaminar nucleus groups and their specific subnuclei. RESULTS: In the course of AD, the volume of the medial group nuclei, especially the mediodorsal medial magnocellular (MDm) nucleus, decreases. Medial group nuclei and MDm functional connectivity with frontal areas were decreased both in ADD and MCI compared to SCI group, while both of them increased their functional connectivity with visual areas in the ADD group compared to the MCI group. CONCLUSIONS: Our study suggests that the medial group of the thalamus, and specifically the MDm, may be affected in AD. SIGNIFICANCE: Specific thalamic nuclei may be a critical anatomical region for investigating structural and functional changes in AD.

Functional and structural connectivity in the Papez circuit in different stages of Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is a progressive neurodegenerative continuum with memory impairment. We aimed to examine the detailed functional (FC) and structural connectivity (SC) pattern of the Papez circuit, known as the memory circuit, along the AD. METHODS: MRI data of 15 patients diagnosed with AD dementia (ADD), 15 patients with the amnestic mild cognitive impairment (MCI), and 15 patients with subjective cognitive impairment were analyzed. The FC analyses were performed between main nodes of the Papez circuit, and the SC was quantified as fractional anisotropy (FA) of the main white matter pathways of the Papez circuit. RESULTS: The FC between the retrosplenial (RSC) and parahippocampal cortices (PHC) was the earliest affected FC, while a manifest SC change in the ventral cingulum and fornix was observed in the later ADD stage. The RSC-PHC FC and the ventral cingulum FA efficiently predicted the memory performance of the non-demented participants. CONCLUSIONS: Our findings revealed the importance of the Papez circuit as target regions along the AD. SIGNIFICANCE: The ventral cingulum connecting the RSC and PHC, a critical overlap area between the Papez circuit and the default mode network, seems to be a target region associated with the earliest objective memory findings in AD.

Morphometric analysis of medial temporal lobe subregions in Alzheimer's disease using high-resolution MRI.

The spread pattern of progressive degeneration seen in Alzheimer's disease (AD) to small-scale medial temporal lobe subregions is critical for early diagnosis. In this context, it was aimed to examine the morphometric changes of the hippocampal subfields, amygdala nuclei, entorhinal cortex (ERC), and parahippocampal cortex (PHC) using MRI. MRI data of patients diagnosed with 20 Alzheimer's disease dementia (ADD), 30 amnestic mild cognitive impairment (aMCI), and 30 subjective cognitive impairment (SCI) without demographic differences were used. Segmentation and parcellation were performed using FreeSurfer. The segmentation process obtained volume values of 12 hippocampal subfields and 9 amygdala nuclei. Thickness values of ERC and PHC were calculated with the parcellation process. ANCOVA was performed using age, education and gender as covariates to evaluate the intergroup differences. Linear discriminant analysis was used to investigate whether atrophy predicted groups at an early stage. ERC and PHC thickness decreased significantly throughout the disease continuum, while only ERC was affected in the early stage. When the hippocampal and amygdala subfields were compared volumetrically, significant differences were found in the amygdala between the SCI and aMCI groups. In the early period, only volume reduction in the anterior amygdaloid area of the amygdala nuclei exceeded the significance threshold. Research on AD primarily focuses on original hippocampocentric structures and their main function which is episodic memory. Our results emphasized the significance of so far relatively neglected olfactocentric structures and their functions, such as smell and social cognition in the pre-dementia stages of the AD process.

Volumetric changes within hippocampal subfields in Alzheimer's disease continuum.

Neurodegeneration in Alzheimer's disease continuum (ADC) starts from the transentorhinal cortex and progresses within hippocampal circuitry following the connectivity of its subfields transsynaptically. We aimed to track volumetric changes of the hippocampal subfields by comparing three stages of the ADC. MRI data of 15 patients diagnosed with Alzheimer's disease dementia (ADD), 15 patients with amnestic mild cognitive impairment (MCI), and 15 individuals with subjective cognitive impairment (SCI) were analyzed. The hippocampal formation was subdivided into CA1, CA3, subiculum (SUB), and dentate gyrus (DG) using FreeSurfer and volumetric values were obtained. The volumetric values were analyzed with ANCOVA and intracranial volume was selected as a covariate. ANCOVA results of the hippocampal subfields displayed statistically significant differences among the three groups in bilateral CA1, SUB, and DG volumes (Right CA1: F = 7.316, p = 0.002; left CA1: F = 6.768, p = 0.003; right SUB: F = 9.390, p < 0.001; left SUB: F = 5.925, p = 0.005; right DG: F = 9.469, p < 0.001; left DG: F = 9.354, p < 0.001), while CA3 volumes were not significantly different among the groups. Post hoc comparisons revealed that volume reductions in bilateral CA1, DG, and SUB were present in ADD compared to both MCI and SCI groups. No significant volumetric changes were found between the SCI and MCI groups. While our results are generally consistent with the literature in terms of the CA1 and SUB findings, they additionally point to the importance of the significant volume loss in DG and the resilience of the CA3 sector.

Functional connectivity disturbances of ascending reticular activating system and posterior thalamus in juvenile myoclonic epilepsy in relation with photosensitivity: A resting-state fMRI study.

OBJECTIVE: Juvenile myoclonic epilepsy (JME) is typified by the occurrence of myoclonic seizures after awakening, though another common trait is myoclonic seizures triggered by photic stimulation. We aimed to investigate the functional connectivity (FC) of nuclei in the ascending reticular activating system (ARAS), thalamus and visual cortex in JME with and without photosensitivity. METHODS: We examined 29 patients with JME (16 photosensitive (PS), 13 non- photosensitive-(NPS)) and 28 healthy controls (HCs) using resting-state functional magnetic resonance imaging (rs-fMRI). Seed-to-voxel FC analyses were performed using 25 seeds, including the thalamus, visual cortex, and ARAS nuclei. RESULTS: Mesencephalic reticular formation seed revealed significant hyperconnectivity between the bilateral paracingulate gyrus and anterior cingulate cortex in JME group, and in both JME-PS and JME-NPS subgroups compared to HCs (pFWE-corr < 0.001; pFWE-corr < 0.001; pFWE-corr = 0.002, respectively). Locus coeruleus seed displayed significant hyperconnectivity with the bilateral lingual gyri, intracalcarine cortices, occipital poles and left occipital fusiform gyrus in JME-PS group compared to HCs (pFWE-corr <0.001). Additionally, locus coeruleus seed showed significant hyperconnectivity in JME-PS group compared to JME-NPS group with a cluster corresponding to the bilateral lingual gyri and right intracalcarine cortex (pFWE-corr < 0.001). Lastly, the right posterior nuclei of thalamus revealed significant hyperconnectivity with the right superior lateral occipital cortex in JME-PS group compared to HCs (pFWE-corr < 0.002). CONCLUSIONS: In JME, altered functional connectivity of the arousal networks might contribute to the understanding of myoclonia after awakening, whereas increased connectivity of posterior thalamus might explain photosensitivity.