Analyzing fractal dimension in electroconvulsive therapy: Unraveling complexity in structural and functional neuroimaging.

BACKGROUND: Numerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This study aims to investigate ECT-induced plasticity of anterior and posterior hippocampi using mathematical complexity measures in neuroimaging, namely Higuchi's fractal dimension (HFD) for fMRI time series and the fractal dimension of cortical morphology (FD-CM). Furthermore, we explore the potential of these complexity measures to predict ECT treatment response. METHODS: Twenty patients with a current depressive episode (16 with major depressive disorder and 4 with bipolar disorder) underwent MRI-scans before and after an ECT-series. Twenty healthy controls matched for age and sex were also scanned twice for comparison purposes. Resting-state fMRI data were processed, and HFD was computed for anterior and posterior hippocampi. Group-by-time effects for HFD in anterior and posterior hippocampi were calculated and correlations between HFD changes and improvement in depression severity were examined. For FD-CM analyses, we preprocessed structural MRI with CAT12's surface-based methods. We explored group-by-time effects for FD-CM and the predictive value of baseline HFD and FD-CM for treatment outcome. RESULTS: Patients exhibited a significant increase in bilateral hippocampal HFD from baseline to follow-up scans. Right anterior hippocampal HFD increase was associated with reductions in depression severity. We found no group differences and group-by-time effects in FD-CM. After applying a whole-brain regression analysis, we found that baseline FD-CM in the left temporal pole predicted reduction of overall depression severity after ECT. Baseline hippocampal HFD did not predict treatment outcome. CONCLUSION: This study suggests that HFD and FD-CM are promising imaging markers to investigate ECT-induced neuroplasticity associated with treatment response.

Cerebral blood flow and structural connectivity after working memory or physical training in paediatric cancer survivors - Exploratory findings.

Paediatric cancer survivors often suffer from cognitive long-term difficulties. Consequently, strengthening cognition is of major clinical relevance. This study investigated cerebral changes in relation to cognition in non-brain tumour paediatric cancer survivors after working memory or physical training compared to a control group. Thirty-four children (≥one-year post-treatment) either underwent eight weeks of working memory training (n = 10), physical training (n = 11), or a waiting period (n = 13). Cognition and MRI, including arterial spin labelling and diffusion tensor imaging, were assessed at three time points (baseline, post-training, and three-month follow-up). Results show lower cerebral blood flow immediately after working memory training (z = -2.073, p = .038) and higher structural connectivity at the three-month follow-up (z = -2.240, p = .025). No cerebral changes occurred after physical training. Short-term changes in cerebral blood flow correlated with short-term changes in cognitive flexibility (r = -.667, p = .049), while long-term changes in structural connectivity correlated with long-term changes in working memory (r = .786, p = .021). Despite the caution given when interpreting data from small samples, this study suggests a link between working memory training and neurophysiological changes. Further research is needed to validate these findings.

Submillimeter T1 atlas for subject-specific abnormality detection at 7T.

PURPOSE: Studies at 3T have shown that T1 relaxometry enables characterization of brain tissues at the single-subject level by comparing individual physical properties to a normative atlas. In this work, an atlas of normative T1 values at 7T is introduced with 0.6 mm isotropic resolution and its clinical potential is explored in comparison to 3T. METHODS: T1 maps were acquired in two separate healthy cohorts scanned at 3T and 7T. Using transfer learning, a template-based brain segmentation algorithm was adapted to ultra-high field imaging data. After segmenting brain tissues, volumes were normalized into a common space, and an atlas of normative T1 values was established by modeling the T1 inter-subject variability. A method for single-subject comparisons restricted to white matter and subcortical structures was developed by computing Z-scores. The comparison was applied to eight patients scanned at both field strengths for proof of concept. RESULTS: The proposed method for morphometry delivered segmentation masks without statistically significant differences from those derived with the original pipeline at 3T and achieved accurate segmentation at 7T. The established normative atlas allowed characterizing tissue alterations in single-subject comparisons at 7T, and showed greater anatomical details compared with 3T results. CONCLUSION: A high-resolution quantitative atlas with an adapted pipeline was introduced and validated. Several case studies on different clinical conditions showed the feasibility, potential and limitations of high-resolution single-subject comparisons based on quantitative MRI atlases. This method in conjunction with 7T higher resolution broadens the range of potential applications of quantitative MRI in clinical practice.

Effect of Acoustic fMRI-Scanner Noise on the Human Resting State.

Our knowledge about the human resting state is predominantly based on either electroencephalographic (EEG) or functional magnetic resonance imaging (fMRI) methods. While EEG recordings can be performed in seated posture in quiet conditions, the fMRI environment presents a substantial contrast with supine and restricted posture in a narrow tube that is filled with acoustic scanner noise (ASN) at a chainsaw-like volume level. However, the influence of these diverging conditions on resting-state brain activation is neither well studied nor broadly discussed. In order to promote data as a source of sharper hypotheses for future studies, we investigated alterations in EEG-frequency-band power (delta, theta, alpha, beta, gamma) and spatial power distribution as well as cortical vigilance measures in different postures and ASN surroundings over the course of time. Participants (N = 18) underwent three consecutive resting-state EEG recordings with a fixed posture and ASN setting sequence; seated, supine, and supine with ASN (supnoise) using an MRI simulator. The results showed that compared to seated, supnoise, the last instance within the posture sequence, was characterized by lower power and altered spatial power distribution in all assessed frequency bands. This might also have been an effect of time alone. In delta, theta, alpha, and beta, the power of supnoise was also reduced compared to supine, as well as the corresponding distribution maps. The vigilance analysis revealed that in supine and supnoise, the highest and lowest vigilance stages were more dominant compared to the seated and earliest posture condition within the sequence. Hence, our results demonstrate that the differences in recording settings and progress of time are related to changes in cortical arousal and vigilance regulation, findings that should be taken into account more profoundly for hypothesis generation as well as analytic strategies in future resting-state studies.

Reduced structural connectivity of the amygdala is associated with childhood trauma in adult patients with alcohol use disorder.

Childhood trauma (CT) is frequent in patients with alcohol use disorder (AUD) and may impact on adult drinking behaviour and treatment outcome. This study aimed to investigate the structural correlates of CT in AUD, focusing on the amygdala, which plays a crucial role in the neurobiology of trauma. We hypothesized reduced amygdala volume and reduced structural connectivity as quantified by fractional anisotropy (FA) and by number of streamlines in those AUD patients with a history of moderate to severe CT (AUD-CT). T1-weighted MP2RAGE and diffusion-weighted imaging (DWI) 3-Tesla MRI-scans were acquired in 41 recently abstinent patients with AUD. We compared bilateral amygdala volume and structural connectivity (FA and number of streamlines) of pathways emanating from the amygdala between AUD-CT (n = 20) and AUD without CT (AUD-NT, n = 21) using a mixed model multivariate analysis of variance (MANCOVA) controlling for age and gender. AUD-CT displayed reduced FA and reduced number of streamlines of amygdalar tracts. There were no differences regarding amygdala volume. The severity of physical abuse, a subscale of the childhood trauma questionnaire, was negatively correlated with FA and with number of streamlines. AUD-CT and AUD-NT differ regarding structural connectivity of pathways projecting to and from the amygdala, but not regarding amygdala volume. Those alterations of structural connectivity in AUD-CT may represent a distinguishable neurobiological subtype of AUD, which might be associated with the complex clinical picture and poorer outcome that patients with CT and AUD often present.

A tutorial on data-driven methods for statistically assessing ERP topographies.

Dynamic changes in ERP topographies can be conveniently analyzed by means of microstates, the so-called "atoms of thoughts", that represent brief periods of quasi-stable synchronized network activation. Comparing temporal microstate features such as on- and offset or duration between groups and conditions therefore allows a precise assessment of the timing of cognitive processes. So far, this has been achieved by assigning the individual time-varying ERP maps to spatially defined microstate templates obtained from clustering the grand mean data into predetermined numbers of topographies (microstate prototypes). Features obtained from these individual assignments were then statistically compared. This has the problem that the individual noise dilutes the match between individual topographies and templates leading to lower statistical power. We therefore propose a randomization-based procedure that works without assigning grand-mean microstate prototypes to individual data. In addition, we propose a new criterion to select the optimal number of microstate prototypes based on cross-validation across subjects. After a formal introduction, the method is applied to a sample data set of an N400 experiment and to simulated data with varying signal-to-noise ratios, and the results are compared to existing methods. In a first comparison with previously employed statistical procedures, the new method showed an increased robustness to noise, and a higher sensitivity for more subtle effects of microstate timing. We conclude that the proposed method is well-suited for the assessment of timing differences in cognitive processes. The increased statistical power allows identifying more subtle effects, which is particularly important in small and scarce patient populations.

Altered Functional Coupling of the Bed Nucleus of the Stria Terminalis and Amygdala in Spider Phobic Fear.

Background: Individuals with spider phobic (SP) fear show hypervigilance and amygdala hyperactivity toward fear-associated stimuli, which may promote the development of other anxiety disorders. The amygdala is a key region within the fear network, which is connected to the anxiety system, where the bed nucleus of the stria terminalis (BNST) plays a crucial role. However, the BNST's involvement in phobic fear is unknown. Therefore, this study investigated the association of phobic fear and anxiety on these regions' functional connectivity (FC) in SP compared to healthy controls (HC). Methods: 7T-functional MRI resting-state FC of 30 individuals with SP and 45 HC was assessed to detect network differences between these groups. The association of phobic fear severity, trait anxiety, and social anxiety on FC was explored using linear regressions combined with seed-to-voxel analyses with amygdala and BNST as primary seeds, corrected for age and sex. Results: In SP, phobic fear was associated with reduced FC between the left amygdala and the right supramarginal gyrus. In contrast, anxiety severity was related to increased FC between the right BNST and the left inferior frontal gyrus. Moreover, social anxiety was related to decreased FC between bilateral BNST and left precuneus. Conclusions: These findings show changes in FC in SP, connecting fear with altered activity in the BNST and amygdala. The results suggest that persistent anxiety in phobic fear is associated with abnormal brain function in these regions, potentially explaining susceptibility to anxiety disorders and processes involved in phobic fear, such as threat perception, avoidance, and salience. Impact statement This is the first study to report altered FC mechanisms of BNST and amygdala in individuals with SP using 7T ultra-high field resting-state data. So far, only distinct characterization of brain regions, especially of BNST and amygdala, involved in those disorders exists. Our results contribute to closing this knowledge gap by providing the first evidence that deviant BNST and amygdala function in SP might elucidate the susceptibility to other anxiety disorders.

Associations of thalamocortical networks with reduced mindfulness in alcohol use disorder.

Background: Increased mindfulness is associated with reduced alcohol consumption in patients with alcohol use disorder (AUD) after residential treatment. However, the underlying neurobiological mechanism of mindfulness in AUD is unclear. Therefore, we investigate the structural and functional alterations of the thalamocortical system with a focus on the mediodorsal thalamic nucleus (MD-TN), the default mode and the salience network (DMN/SN) which has previously been associated with mindfulness in healthy subjects. We hypothesized lower mindfulness and reduced structural and functional connectivity (FC) of the thalamocortical system, particularly in the DMN/SN in AUD. We assumed that identified neurobiological alterations in AUD are associated with impairments of mindfulness. Methods: Forty-five abstinent patients with AUD during residential treatment and 20 healthy controls (HC) were recruited. Structural and resting-state functional MRI-scans were acquired. We analysed levels of mindfulness, thalamic volumes and network centrality degree of the MD-TN using multivariate statistics. Using seed-based whole brain analyses we investigated functional connectivity (FC) of the MD-TN. We performed exploratory correlational analyses of structural and functional DMN/SN measurements with levels of mindfulness. Results: In AUD we found significantly lower levels of mindfulness, lower bilateral thalamic and left MD-TN volumes, reduced FC between MD-TN and anterior cingulum/insula and lower network centrality degree of the left MD-TN as compared to HC. In AUD, lower mindfulness was associated with various reductions of structural and functional aspects of the MD-TN. Conclusion: Our results suggest that structural and functional alterations of a network including the MD-TN and the DMN/SN underlies disturbed mindfulness in AUD.

How is Cerebral Perfusion Associated with Functional Outcome in Pediatric Cancer Survivors?

Pediatric cancer survivors (PCS) experience functional difficulties and brain alterations. However, little is known about cerebral perfusion and its relationship to functional outcome (cognitive and motor performance) in PCS. We examined cerebral blood flow (CBF) in non-brain tumor PCS and the associations between CBF and age, as well as functional outcome. Forty PCS and 40 age-comparable controls were included. CBF did not differ between PCS and controls. CBF decreased with age only in controls. In PCS, CBF was associated with functional outcome. Our data indicate an altered relationship between age and CBF in survivors, with stronger brain-behavior mechanisms after cancer.

Right Inferior Frontal Activation During Alcohol-Specific Inhibition Increases With Craving and Predicts Drinking Outcome in Alcohol Use Disorder.

Alcohol use disorder (AUD) is characterized by enhanced cue-reactivity and the opposing control processes being insufficient. The ability to inhibit reactions to alcohol-related cues, alcohol-specific inhibition, is thus crucial to AUD; and trainings strengthening this ability might increase treatment outcome. The present study investigated whether neurophysiological correlates of alcohol-specific inhibition (I) vary with craving, (II) predict drinking outcome in AUD and (III) are modulated by alcohol-specific inhibition training. A total of 45 recently abstinent patients with AUD and 25 controls participated in this study. All participants underwent functional magnetic resonance imaging (fMRI) during a Go-NoGo task with alcohol-related as well as neutral conditions. Patients with AUD additionally participated in a double-blind RCT, where they were randomized to either an alcohol-specific inhibition training or an active control condition (non-specific inhibition training). After the training, patients participated in a second fMRI measurement where the Go-NoGo task was repeated. Percentage of days abstinent was assessed as drinking outcome 3 months after discharge from residential treatment. Whole brain analyses indicated that in the right inferior frontal gyrus (rIFG), activation related to alcohol-specific inhibition varied with craving and predicted drinking outcome at 3-months follow-up. This neurophysiological correlate of alcohol-specific inhibition was however not modulated by the training version. Our results suggest that enhanced rIFG activation during alcohol-specific (compared to neutral) inhibition (I) is needed to inhibit responses when craving is high and (II) fosters sustained abstinence in patients with AUD. As alcohol-specific rIFG activation was not affected by the training, future research might investigate whether potential training effects on neurophysiology are better detectable with other methodological approaches.

The role of the orbitofrontal cortex and the nucleus accumbens for craving in alcohol use disorder.

This study aimed to investigate structural and functional alterations of the reward system and the neurobiology of craving in alcohol use disorder (AUD). We hypothesized reduced volume of the nucleus accumbens (NAcc), reduced structural connectivity of the segment of the supero-lateral medial forebrain bundle connecting the orbitofrontal cortex (OFC) with the NAcc (OFC-NAcc), and reduced resting-state OFC-NAcc functional connectivity (FC). Furthermore, we hypothesized that craving is related to an increase of OFC-NAcc FC. Thirty-nine recently abstinent patients with AUD and 18 healthy controls (HC) underwent structural (T1w-MP2RAGE, diffusion-weighted imaging (DWI)) and functional (resting-state fMRI) MRI-scans. Gray matter volume of the NAcc, white matter microstructure (fractional anisotropy (FA)) and macrostructure (tract length) of the OFC-NAcc connection and OFC-NAcc FC were compared between AUD and HC using a mixed model MANCOVA controlling for age and gender. Craving was assessed using the thoughts subscale of the obsessive-compulsive drinking scale (OCDS) scale and was correlated with OFC-NAcc FC. There was a significant main effect of group. Results were driven by a volume reduction of bilateral NAcc, reduced FA in the left hemisphere, and reduced tract length of bilateral OFC-NAcc connections in AUD patients. OFC-NAcc FC did not differ between groups. Craving was associated with increased bilateral OFC-NAcc FC. In conclusion, reduced volume of the NAcc and reduced FA and tract length of the OFC-NAcc network suggest structural alterations of the reward network in AUD. Increased OFC-NAcc FC is associated with craving in AUD, and may contribute to situational alcohol-seeking behavior in AUD.

Bi-Temporal Anodal Transcranial Direct Current Stimulation during Slow-Wave Sleep Boosts Slow-Wave Density but Not Memory Consolidation.

Slow-wave sleep (SWS) has been shown to promote long-term consolidation of episodic memories in hippocampo-neocortical networks. Previous research has aimed to modulate cortical sleep slow-waves and spindles to facilitate episodic memory consolidation. Here, we instead aimed to modulate hippocampal activity during slow-wave sleep using transcranial direct current stimulation in 18 healthy humans. A pair-associate episodic memory task was used to evaluate sleep-dependent memory consolidation with face-occupation stimuli. Pre- and post-nap retrieval was assessed as a measure of memory performance. Anodal stimulation with 2 mA was applied bilaterally over the lateral temporal cortex, motivated by its particularly extensive connections to the hippocampus. The participants slept in a magnetic resonance (MR)-simulator during the recordings to test the feasibility for a future MR-study. We used a sham-controlled, double-blind, counterbalanced randomized, within-subject crossover design. We show that stimulation vs. sham significantly increased slow-wave density and the temporal coupling of fast spindles and slow-waves. While retention of episodic memories across sleep was not affected across the entire sample of participants, it was impaired in participants with below-average pre-sleep memory performance. Hence, bi-temporal anodal direct current stimulation applied during sleep enhanced sleep parameters that are typically involved in memory consolidation, but it failed to improve memory consolidation and even tended to impair consolidation in poor learners. These findings suggest that artificially enhancing memory-related sleep parameters to improve memory consolidation can actually backfire in those participants who are in most need of memory improvement.

Increased Anxiety After Stimulation of the Right Inferior Parietal Lobe and the Left Orbitofrontal Cortex.

Sustained anxiety is a key symptom of anxiety disorders and may be associated with neural activation in the right inferior parietal lobe (rIPL), particularly under unpredictable threat. This finding suggests a moderating role of the rIPL in sustained anxiety, which we tested in the current study. We applied cathodal or sham transcranial direct current stimulation (tDCS) to the rIPL as a symptom provocation method in 22 healthy participants in a randomized, double-blind, crossover study, prior to two recordings of cerebral blood flow (CBF). In between, we applied a threat-of-shock paradigm with three conditions: unpredictable (U), predictable (P), or no electric shocks (N). We hypothesized increased anxiety under U, but not under P or N. Furthermore, we expected reduced CBF in the rIPL after tDCS compared to sham. As predicted, anxiety was higher in the U than the P and N conditions, and active tDCS augmented this effect. While tDCS did not alter CBF in the rIPL, it did attenuate the observed increase in brain regions that typically increase activation as a response to anxiety. These findings suggest that the rIPL moderates sustained anxiety as a gateway to brain regions crucial in anxiety. Alternatively, anodal tDCS over the left orbitofrontal cortex (lOFC) may have increased anxiety through disruption of OFC-amygdala interactions.

Functional Connectivity Alterations of the Temporal Lobe and Hippocampus in Semantic Dementia and Alzheimer's Disease.

BACKGROUND: Semantic memory impairments in semantic dementia are attributed to atrophy and functional disruption of the anterior temporal lobes. In contrast, the posterior medial temporal neurodegeneration found in Alzheimer's disease is associated with episodic memory disturbance. The two dementia subtypes share hippocampal deterioration, despite a relatively spared episodic memory in semantic dementia. OBJECTIVE: To unravel mutual and divergent functional alterations in Alzheimer's disease and semantic dementia, we assessed functional connectivity between temporal lobe regions in Alzheimer's disease (n = 16), semantic dementia (n = 23), and healthy controls (n = 17). METHODS: In an exploratory study, we used a functional parcellation of the temporal cortex to extract time series from 66 regions for correlation analysis. RESULTS: Apart from differing connections between Alzheimer's disease and semantic dementia that yielded reduced functional connectivity, we identified a common pathway between the right anterior temporal lobe and the right orbitofrontal cortex in both dementia subtypes. This disconnectivity might be related to social knowledge deficits as part of semantic memory decline. However, such interpretations are preferably made in a holistic context of disease-specific semantic impairments and functional connectivity changes. CONCLUSION: Despite a major limitation owed to unbalanced databases between study groups, this study provides a preliminary picture of the brain's functional disconnectivity in Alzheimer's disease and semantic dementia. Future studies are needed to replicate findings of a common pathway with consistent diagnostic criteria and neuropsychological evaluation, balanced designs, and matched data MRI acquisition procedures.

Default Mode Network Complexity and Cognitive Decline in Mild Alzheimer's Disease.

The human resting-state is characterized by spatially coherent brain activity at a low temporal frequency. The default mode network (DMN), one of so-called resting-state networks, has been associated with cognitive processes that are directed toward the self, such as introspection and autobiographic memory. The DMN's integrity appears to be crucial for mental health. For example, patients with Alzheimer's disease or other psychiatric conditions show disruptions of functional connectivity within the brain regions of the DMN. However, in prodromal or early stages of Alzheimer's disease, physiological alterations are sometimes elusive, despite manifested cognitive impairment. While functional connectivity assesses the signal correlation between brain areas, multi-scale entropy (MSE) measures the complexity of the blood-oxygen level dependent signal within an area and thus might show local changes before connectivity is affected. Hence, we investigated alterations of functional connectivity and MSE within the DMN in fifteen mild Alzheimer's disease patients as compared to fourteen controls. Potential associations of MSE with functional connectivity and cognitive abilities [i.e., mini-mental state examination (MMSE)] were assessed. A moderate decrease of DMN functional connectivity between posterior cingulate cortex and right hippocampus in Alzheimer's disease was found, whereas no differences were evident for whole-network functional connectivity. In contrast, the Alzheimer's disease group yielded lower global DMN-MSE than the control group. The most pronounced regional effects were localized in left and right hippocampi, and this was true for most scales. Moreover, MSE significantly correlated with functional connectivity, and DMN-MSE correlated positively with the MMSE in Alzheimer's disease. Most interestingly, the right hippocampal MSE was positively associated with semantic memory performance. Thus, our results suggested that cognitive decline in Alzheimer's disease is reflected by decreased signal complexity in DMN nodes, which might further lead to disrupted DMN functional connectivity. Additionally, altered entropy in Alzheimer's disease found in the majority of the scales indicated a disturbance of both local information processing and information transfer between distal areas. Conclusively, a loss of nodal signal complexity potentially impairs synchronization across nodes and thus preempts functional connectivity changes. MSE presents a putative functional marker for cognitive decline that might be more sensitive than functional connectivity alone.

No Effect of Transcranial Direct Current Stimulation of the Auditory Cortex on Auditory-Evoked Potentials.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique to change cortical excitability. Its effects are shown for cognitive processing, and behavior in the motor and perceptual domains. However, evidence of tDCS effects in the perceptual domain particularly for auditory processing is rare. Therefore, and in the context of disturbances in auditory processing in psychiatric populations, e.g., in patients with auditory verbal hallucinations, we aimed to investigate the potential modulatory effect of tDCS on the excitability of left posterior temporal cortex in detail. We included 24 healthy participants in a crossover design, applying sham and anodal stimulation in two measurement sessions 1 week apart. Electroencephalography (EEG) was recorded while participants listened to tones before, during, and after stimulation. Amplitudes and latencies of P50, N100, and P200 auditory-evoked potentials (AEP) were compared between anodal and sham stimulation, and between time points before, during, and after tDCS. In contrast to previous studies, results demonstrate no significant differences between stimulation types or time points for any of the investigated AEP amplitudes or latencies. Furthermore, a topographical analysis did not show any topographical differences during peak time periods of the investigated AEP for stimulation types and time points besides a habituation effect. Thus, our results suggest that tDCS modulation of excitability of the left posterior temporal cortex, targeting the auditory cortex, does not have any effect on AEP. This is particularly interesting in the context of tDCS as a potential treatment for changed electrophysiological parameters and symptoms of psychiatric diseases, e.g., lower N100 or auditory verbal hallucinations in schizophrenia.

Diverging Progression of Network Disruption and Atrophy in Alzheimer's Disease and Semantic Dementia.

The progression of cognitive deficits in Alzheimer's disease and semantic dementia is accompanied by grey matter atrophy and white matter deterioration. The impact of neuronal loss on the structural network connectivity in these dementia subtypes is, however, not well understood. In order to gain a more refined knowledge of the topological organization of white matter alterations in dementia, we used a network-based approach to analyze the brain's structural connectivity network. Diffusion-weighted and anatomical MRI images of groups with eighteen Alzheimer's disease and six semantic dementia patients, as well as twenty-one healthy controls were recorded to reconstruct individual connectivity networks. Additionally, voxel-based morphometry, using grey and white matter volume, served to relate atrophy to altered structural connectivity. The analyses showed that Alzheimer's disease is characterized by decreased connectivity strength in various cortical regions. An overlap with grey matter loss was found only in the inferior frontal and superior temporal areas. In semantic dementia, significantly reduced network strength was found in the temporal lobes, which converged with grey and white matter atrophy. Therefore, this study demonstrated that the structural disconnection in early Alzheimer's disease goes beyond grey matter atrophy and is independent of white matter volume loss, an observation that was not found in semantic dementia.

Discovering EEG resting state alterations of semantic dementia.

OBJECTIVE: Diagnosis of semantic dementia relies on cost-intensive MRI or PET, although resting EEG markers of other dementias have been reported. Yet the view still holds that resting EEG in patients with semantic dementia is normal. However, studies using increasingly sophisticated EEG analysis methods have demonstrated that slightest alterations of functional brain states can be detected. METHODS: We analyzed the common four resting EEG microstates (A, B, C, and D) of 8 patients with semantic dementia in comparison with 8 healthy controls and 8 patients with Alzheimer's disease. RESULTS: Topographical differences between the groups were found in microstate classes B and C, while microstate classes A and D were comparable. The data showed that the semantic dementia group had a peculiar microstate E, but the commonly found microstate C was lacking. Furthermore, the presence of microstate E was significantly correlated with lower MMSE and language scores. CONCLUSION: Alterations in resting EEG can be found in semantic dementia. Topographical shifts in microstate C might be related to semantic memory deficits. SIGNIFICANCE: This is the first study that discovered resting state EEG abnormality in semantic dementia. The notion that resting EEG in this dementia subtype is normal has to be revised.

Correlation between topographic N400 anomalies and reduced cerebral blood flow in the anterior temporal lobes of patients with dementia.

In Alzheimer's disease (AD) patients, episodic memory impairments are apparent, yet semantic memory difficulties are also observed. While the episodic pathology has been thoroughly studied, the neurophysiological mechanisms of the semantic impairments remain obscure. Semantic dementia (SD) is characterized by isolated semantic memory deficits. The present study aimed to find an early marker of mild AD and SD by employing a semantic priming paradigm during electroencephalogram recordings. Event-related potentials (ERP) of early (P1, N1) and late (N400) word processing stages were obtained to measure semantic memory functions. Separately, baseline cerebral blood flow (CBF) was acquired with arterial spin labeling. Thus, the analysis focused on linear regressions of CBF with ERP topographical similarity indices in order to find the brain structures that showed altered baseline functionality associated with deviant ERPs. All participant groups showed semantic priming in their reaction times. Furthermore, decreased CBF in the temporal lobes was associated with abnormal N400 topography. No significant CBF clusters were found for the early ERPs. Taken together, the neurophysiological results suggested that the automatic spread of activation during semantic word processing was preserved in mild dementia, while controlled access to the words was impaired. These findings suggested that N400-topography alterations might be a potential marker for the detection of early dementia. Such a marker could be beneficial for differential diagnosis due to its low cost and non-invasive application as well as its relationship with semantic memory dysfunctions that are closely associated to the cortical deterioration in regions crucial for semantic word processing.

Electrophysiological and behavioral correlates of stable automatic semantic retrieval in aging.

Previous studies have shown both declining and stable semantic-memory abilities during healthy aging. There is consistent evidence that semantic processes involving controlled mechanisms weaken with age. In contrast, results of aging studies on automatic semantic retrieval are often inconsistent, probably due to methodological limitations and differences. The present study therefore examines age-related alterations in automatic semantic retrieval and memory structure with a novel combination of critical methodological factors, i.e., the selection of subjects, a well-designed paradigm, and electrophysiological methods that result in unambiguous signal markers. Healthy young and elderly participants performed lexical decisions on visually presented word/non-word pairs with a stimulus onset asynchrony (SOA) of 150 ms. Behavioral and electrophysiological data were measured, and the N400-LPC complex, an event-related potential component sensitive to lexical-semantic retrieval, was analyzed by power and topographic distribution of electrical brain activity. Both age groups exhibited semantic priming (SP) and concreteness effects in behavioral reaction time and the electrophysiological N400-LPC complex. Importantly, elderly subjects did not differ significantly from the young in their lexical decision and SP performances as well as in the N400-LPC SP effect. The only difference was an age-related delay measured in the N400-LPC microstate. This could be attributed to existing age effects in controlled functions, as further supported by the replicated age difference in word fluency. The present results add new behavioral and neurophysiological evidence to earlier findings, by showing that automatic semantic retrieval remains stable in global signal strength and topographic distribution during healthy aging.