Directed connectivity in Parkinson's disease patients during over-ground and treadmill walking.

Treadmill walking is considered a useful therapeutic tool for improving gait in Parkinson's disease (PD) patients. The study investigated the role of top-down, frontal-parietal versus bottom-up parietal-frontal networks, during over-ground and treadmill walking in PD and control subjects, using functional connectivity. To this end, EEG was recorded simultaneously, during a ten-minute period of continuous walking either over-ground or on a treadmill, in thirteen PD patients and thirteen age-matched controls. We evaluated EEG directed connectivity, using phase transfer entropy in three frequency bands: theta, alpha and beta. PD patients showed increased top-down connectivity during over-ground compared with treadmill walking, in the beta frequency range. Control subjects showed no significant differences in connectivity between the two walking conditions. Our results suggest that in PD patients, OG walking was associated with increased allocation of attentional resources, compared with that on the TL. These functional connectivity modulations may shed further light on the mechanisms underlying treadmill versus overground walking in PD.

A lack of timing-dependent effects of transcranial direct current stimulation (tDCS) on the performance of a choice reaction time task.

Anodal transcranial direct current stimulation (tDCS) can enhance the retention of a previously practiced motor skill. However, the effects of tDCS on the performance of the choice reaction time task are not fully understood. We examined the effects of anodal tDCS over the left primary motor cortex (M1) on the retention of a 4-choice visual-motor reaction time task (4-ChRT). Right-handed healthy participants (n = 100) were randomly assigned to five groups: three groups received anodal tDCS: before (tDCSbefore), during (tDCSduring), or after (tDCSafter) motor practice. In addition, there were two control groups: with (CONmp) and without (CON) motor practice. We evaluated the speed and precision of the 4-ChRT task before (PRE), during, and 24 h (POST) after the interventions. All groups, including the non-stimulation (CONmp) and non-practice groups (CON), improved (p < 0.05) motor retention (Δ4-ChRT: 35.8 ± 36.0 ms). These findings suggest that the tDCS effects over M1 may differ for serial versus choice RT tasks, perhaps due to the different brain areas involved in each motor task.

Altered directed connectivity during processing of predictive stimuli in psychiatric patient populations.

OBJECTIVES: The study investigated the role of top-down versus bottom-up connectivity, during the processing of predictive information, in three different psychiatric disorders. METHODS: Electroencephalography (EEG) was recorded during the performance of a task, which evaluates the ability to use predictive information in order to facilitate predictable versus random target detection. We evaluated EEG event-related directed connectivity, in patients with schizophrenia (SZ), major depressive disorder (MDD), and autism spectrum disorder (ASD), compared with healthy age-matched controls. Directed connectivity was evaluated using phase transfer entropy. RESULTS: We showed that top-down frontal-parietal connectivity was weaker in SZ (theta and beta bands) and ASD (alpha band) compared to control subjects, during the processing of stimuli consisting of the predictive sequence. In SZ patients, top-down connectivity was also attenuated, during the processing of predictive targets in the beta frequency band. In contrast, compared with controls, MDD patients displayed an increased top-down flow of information, during the processing of predicted targets (alpha band). CONCLUSIONS: The findings suggest that top-down frontal-parietal connectivity is altered differentially across three major psychiatric disorders, specifically during the processing of predictive stimuli. SIGNIFICANCE: Altered top-down connectivity may contribute to the specific prediction deficits observed in each of the patient populations.

Altered directed connectivity during processing of implicit versus explicit predictive stimuli in Parkinson's disease patients.

The study investigated the role of top-down versus bottom-up connectivity, during the processing of implicit or explicit predictive information, in Parkinson's disease (PD). EEG was recorded during the performance of a task, which evaluated the ability to utilize either implicit or explicit predictive contextual information in order to facilitate the detection of predictable versus random targets. Thus, subjects performed an implicit and explicit session, where subjects were either unaware or made aware of a predictive sequence that signals the presentation of a subsequent target, respectively. We evaluated EEG event-related directed connectivity, in PD patients compared with healthy age-matched controls, using phase transfer entropy. PD patients showed increased top-down frontal-parietal connectivity, compared to control subjects, during the processing of the last (most informative) stimulus of the predictive sequence and of random standards, in the implicit and explicit session, respectively. These findings suggest that PD is associated with compensatory top-down connectivity, specifically during the processing of implicit predictive stimuli. During the explicit session, PD patients seem to allocate more attentional resources to non-informative standard stimuli, compared to controls. These connectivity changes shed further light on the cognitive deficits, associated with the processing of predictive contextual information, that are observed in PD patients.

Small Enhancement of Bimanual Typing Performance after 20 Sessions of tDCS in Healthy Young Adults.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that may improve motor learning. However, the long-term effects of tDCS have not been explored, and the ecological validity of the evaluated tasks was limited. To determine whether 20 sessions of tDCS over the primary motor cortex (M1) would enhance the performance of a complex life motor skill, i.e., typing, in healthy young adults. Healthy young adults (n = 60) were semi-randomly assigned to three groups: the tDCS group (n = 20) received anodal tDCS over M1; the SHAM group (n = 20) received sham tDCS, both while performing a typing task; and the Control group (CON, n = 20) only performed the typing task. Typing speed and errors at maximum (mTT) and submaximal (iTT) speeds were measured before training, and after 10 and 20 sessions of tDCS. Every subject increased maximum typing speed after 10 and 20 tDCS sessions, with no significant differences (p > 0.05) between the groups. The number of errors at submaximal rates decreased significantly (p < 0.05) by 4% after 10 tDCS sessions compared with the 3% increase in the SHAM and the 2% increase in the CON groups. Between the 10th and 20th tDCS sessions, the number of typing errors increased significantly in all groups. While anodal tDCS reduced typing errors marginally, such performance-enhancing effects plateaued after 10 sessions without any further improvements in typing speed. These findings suggest that long-term tDCS may not have functionally relevant effects on healthy young adults' typing performance.

An Integrative Clustering Approach to tDCS Individual Response Variability in Cognitive Performance: Beyond a Null Effect on Working Memory.

Despite the growing interest in the use of transcranial direct current stimulation (tDCS) for the modulation of human cognitive function, there are contradictory findings regarding the cognitive benefits of this technique. Inter-individual response variability to tDCS may play a significant role. We explored the effects of anodal versus sham tDCS over the left prefrontal cortex (LPFC) on working memory performance, taking into account the inter-individual variability. Twenty-nine healthy volunteers received an 'offline' anodal tDCS (1.5 mA, 15 min) to the left prefrontal cortex (F3 electrode site) in an intra-individual, cross-over, sham-controlled experimental design. n-back and Sternberg task performance was assessed before (baseline), immediately after tDCS administration (T1) and 5 min post-T1 (T2). We applied an integrative clustering approach to characterize both the group and individual responses to tDCS, as well as identifying naturally occurring subgroups that may be present within the total sample. Anodal tDCS failed to improve working memory performance in the total sample. Cluster analysis identified a subgroup of 'responders' who significantly improved their performance after anodal (vs. sham) stimulation, although not to a greater extent than the best baseline or sham condition. The proportion of 'responders' ranged from 15% to 59% across task conditions and behavioral outputs. Our findings show a high inter-individual variability of the tDCS response, suggesting that the use of tCDS may not be an effective tool to improve working memory performance in healthy subjects. We propose that the use of clustering methods is more suitable in identifying 'responders' and for evaluating the efficacy of this technique.

Evaluating the causal contribution of fronto-parietal cortices to the control of the bottom-up and top-down visual attention using fMRI-guided TMS.

Previous studies demonstrate that frontal and parietal cortices are involved in bottom-up and top-down attentional processes. However, their respective contribution to these processes remains controversial. The purpose of the current study was to compare the causal contribution of frontal and parietal cortices to the control of bottom-up and top-down visual attention using functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS). Subjects performed visual search for targets that were easy (pop-out) or difficult (non-pop-out) to distinguish from distractors. Three sites of interest were used, based on the individual fMRI activation during the performance of a search task: the right dorsolateral prefrontal cortex (rDLPFC), the right frontal eye field (rFEF) and the right superior parietal lobule (rSPL). Online rTMS stimulation, with the search onset, showed that relative to rTMS over the vertex, rTMS over the rDLPFC, the rFEF and the rSPL increased the search reaction time (RTs) in the non-pop-out condition. In comparison, no TMS effect was found in the pop-out condition. In addition, the search RT cost caused by the non-pop-out condition was larger after the rDLPFC-TMS compared to the vertex-TMS. The findings suggest that the frontal and parietal cortical regions are both involved in attentional processing during top-down visual search, and that the rDLPFC is causally related to the executive control of cognitive load increases between the pop-out and the non-pop-out search.

Functional connectivity abnormalities during processing of predictive stimuli in patients with major depressive disorder.

The study investigated the underlying mechanisms associated with the ability of patients with major depressive disorder (MDD) to utilize predictive contextual information in order to facilitate detection of predictable versus random targets. To this end we evaluated EEG event-related functional connectivity during the processing of predictive stimuli in MDD and control subjects. A target detection task was used where targets were either preceded by randomized sequences of standards, or by sequences that included a predictive sequence. Functional connectivity was evaluated using synchronization likelihood and graph theory. The cluster coefficient and local efficiency values were greater in MDD compared to controls, during the processing of the three stimuli consisting of the predictive sequence, in the beta frequency band, suggesting an increased structured network organization. These changes were associated with increased functional connectivity within frontal networks in MDD patients compared to controls. However, no significant functional connectivity group-changes were observed for target conditions or randomized standards. These findings suggest that MDD is associated with context-specific functional connectivity abnormalities during the processing of predictive stimuli.

Exploring the effects of Transcranial Direct Current Stimulation over the prefrontal cortex on working memory: A cluster analysis approach.

BACKGROUND: The interest in the use of anodal transcranial direct current stimulation (tDCS) for the enhancement of cognitive functioning has increased significantly in recent years. However, the efficacy of this technique remains to be established. OBJECTIVE: The current study explored the effects of anodal vs. sham tDCS over the left dorsolateral prefrontal cortex (DLPFC) during the performance of the digit span backwards task. METHODS: 30 healthy participants received 'offline' anodal tDCS (1.5 mA, 15 min) to the left DLPFC in an intra-individual, cross-over, sham-controlled experimental design. Memory span performance was assessed before (baseline), immediately after tDCS administration (T1) and 10 min post-T1 (T2). We applied cluster analysis in order to characterize individual responses to tDCS, and in order to identify naturally occurring subgroups that may be present. RESULTS: Analysis of all the subjects showed that anodal tDCS failed to improve memory span performance. Cluster analysis revealed the presence of a subgroup of 'responders' that significantly improved their performance after anodal (vs. sham) tDCS in T1 (47%) and T2 (46%). However, there was no significant improvement in performance after anodal tDCS compared to the best baseline performance. CONCLUSION: Our findings suggest that tDCS does not improve memory span performance and highlights the need for better ways to optimize methodological approaches in order to account for inter-individual variability and accurately assess the evidential value of tDCS-linked cognitive outcomes.

Altered predictive contextual processing of emotional faces versus abstract stimuli in adults with Autism Spectrum Disorder.

OBJECTIVES: We investigated the proposition that Autism Spectrum Disorder (ASD) is associated with predictive contextual processing deficits. METHODS: We recorded electroencephalography (EEG) in adults with ASD and controls during the performance of a predictive contextual processing task, using either triangles or emotional faces. Targets were preceded by either randomized sequences (R) or by sequences including a predictive sequence (P). RESULTS: ASD subjects showed an attenuated behavioral facilitation (P versus R) compared with controls (faces). P3b amplitudes of P, R and the predictive sequence (n-1) were attenuated in ASD compared with controls. However, the attenuation of n-1 was more pronounced during the processing of faces. Controls demonstrated shorter peak P3b latencies of P versus R, while this facilitation was absent in ASD subjects. ASD subjects demonstrated functional connectivity alterations during the processing of random (triangles and faces) and predicted targets (faces). These changes were associated with weaker, more randomised, functional connections between frontal and parietal regions in ASD. CONCLUSIONS: We found predictive contextual processing alterations in ASD, which were more pronounced during the processing of emotional faces compared with abstract stimuli. SIGNIFICANCE: We provide novel evidence for the proposition that ASD is associated with deficits of top-down predictions.

Athletes versus video game players: A predictive contextual processing study.

We investigated the effect of abstract and real life meaningful images from sports on predictive contextual processing in professional athletes and video gamers. EEG was recorded in three groups: professional basketball players (BP), professional athletes of individual sports (IA) and experienced action video game players (VG). Two recording sessions, each with a different set of visual stimuli was presented: either triangles facing left, up, right or down or four images of a basketball player throwing a ball. Recording blocks consisted of targets preceded by randomized sequences of standards and by sequences including a predictive sequence signaling the occurrence of a subsequent target event. The gradual increase of P3b amplitudes across the predictive sequence was greater in BP compared with VG, when stimuli consisted of real life images of a basketball player. For the basketball session, we observed increased local modularity and stronger functional connectivity within frontal attentional networks in BP and VG compared with IA, during the processing of the predictive sequence. Our findings suggest increased top-down attentional allocation, during the processing of predictive visual stimuli, in basketball players compared with video gamers and individual sports athletes.

Processing of implicit versus explicit predictive contextual information in Parkinson's disease.

We investigated the effects of implicit versus explicit local contextual processing in Parkinson's disease (PD) using electrophysiological measures. EEG recording blocks consisted of targets preceded by either randomized sequences of standards or by sequences including a predictive sequence signaling the occurrence of a target event. PD patients ("on" medication) and healthy controls performed two sessions: in the first the regularity of the predictive sequence was implicit, while in the second this regularity was made explicit. PD and control subjects showed shorter reaction times for predicted versus random targets across both the implicit and explicit sessions. Healthy controls showed a facilitation of the P3b latency for predicted targets (compared with random targets) in both the implicit and explicit sessions, while PD patients showed no significant P3b latency differences between the two target conditions across both sessions. In healthy controls the P3b amplitude of the last most-informative stimulus of the predictive sequence (n-1) was larger in the explicit compared to the implicit session, while this difference was absent in PD patients. Functional connectivity measures showed that during the explicit and implicit sessions detection of n-1 was associated with higher gamma values and weaker fronto-central-parietal connections, in the theta band, in PD compared to controls. The findings suggest that implicit and explicit processing of predictive contextual information is altered in PD patients and that this may be associated with functional connectivity abnormalities within top-down frontal networks.

Connectivity maps based analysis of EEG for the advanced diagnosis of schizophrenia attributes.

This article presents a novel connectivity analysis method that is suitable for multi-node networks such as EEG, MEG or EcOG electrode recordings. Its diagnostic power and ability to interpret brain states in schizophrenia is demonstrated on a set of 50 subjects that constituted of 25 healthy and 25 diagnosed with schizophrenia and treated with medication. The method can also be used for the automatic detection of schizophrenia; it exhibits higher sensitivity than state-of-the-art methods with no false positives. The detection is based on an analysis from a minute long pattern-recognition computer task. Moreover, this connectivity analysis leads naturally to an optimal choice of electrodes and hence to highly statistically significant results that are based on data from only 3-5 electrodes. The method is general and can be used for the diagnosis of other psychiatric conditions, provided an appropriate computer task is devised.

The effects of changes in object location on object identity detection: A simultaneous EEG-fMRI study.

Object identity and location are bound together to form a unique integration that is maintained and processed in visual working memory (VWM). Changes in task-irrelevant object location have been shown to impair the retrieval of memorial representations and the detection of object identity changes. However, the neural correlates of this cognitive process remain largely unknown. In the present study, we aim to investigate the underlying brain activation during object color change detection and the modulatory effects of changes in object location and VWM load. To this end we used simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) recordings, which can reveal the neural activity with both high temporal and high spatial resolution. Subjects responded faster and with greater accuracy in the repeated compared to the changed object location condition, when a higher VWM load was utilized. These results support the spatial congruency advantage theory and suggest that it is more pronounced with higher VWM load. Furthermore, the spatial congruency effect was associated with larger posterior N1 activity, greater activation of the right inferior frontal gyrus (IFG) and less suppression of the right supramarginal gyrus (SMG), when object location was repeated compared to when it was changed. The ERP-fMRI integrative analysis demonstrated that the object location discrimination-related N1 component is generated in the right SMG.

Prediction of Conversion from Mild Cognitive Impairment to Alzheimer's Disease Using MRI and Structural Network Features.

Optimized magnetic resonance imaging (MRI) features and abnormalities of brain network architectures may allow earlier detection and accurate prediction of the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). In this study, we proposed a classification framework to distinguish MCI converters (MCIc) from MCI non-converters (MCInc) by using a combination of FreeSurfer-derived MRI features and nodal features derived from the thickness network. At the feature selection step, we first employed sparse linear regression with stability selection, for the selection of discriminative features in the iterative combinations of MRI and network measures. Subsequently the top K features of available combinations were selected as optimal features for classification. To obtain unbiased results, support vector machine (SVM) classifiers with nested cross validation were used for classification. The combination of 10 features including those from MRI and network measures attained accuracies of 66.04, 76.39, 74.66, and 73.91% for mixed conversion time, 6, 12, and 18 months before diagnosis of probable AD, respectively. Analysis of the diagnostic power of different time periods before diagnosis of probable AD showed that short-term prediction (6 and 12 months) achieved more stable and higher AUC scores compared with long-term prediction (18 months), with K-values from 1 to 30. The present results suggest that meaningful predictors composed of MRI and network measures may offer the possibility for early detection of progression from MCI to AD.

Schizophrenia detection and classification by advanced analysis of EEG recordings using a single electrode approach.

Electroencephalographic (EEG) analysis has emerged as a powerful tool for brain state interpretation and diagnosis, but not for the diagnosis of mental disorders; this may be explained by its low spatial resolution or depth sensitivity. This paper concerns the diagnosis of schizophrenia using EEG, which currently suffers from several cardinal problems: it heavily depends on assumptions, conditions and prior knowledge regarding the patient. Additionally, the diagnostic experiments take hours, and the accuracy of the analysis is low or unreliable. This article presents the "TFFO" (Time-Frequency transformation followed by Feature-Optimization), a novel approach for schizophrenia detection showing great success in classification accuracy with no false positives. The methodology is designed for single electrode recording, and it attempts to make the data acquisition process feasible and quick for most patients.

Neural correlates of local contextual processing across stimulus modalities and patient populations.

The objective of the current review is to integrate information from a series of studies, employing a paradigm that evaluates local contextual processing using electrophysiological measures. Collectively these studies provide an overview of how utilization of predictive context changes as a function of stimulus modality and across different patient populations, as well as the networks that may be critical for this function. The following aspects of local contextual processing will be discussed and reviewed: (i) the correlates associated with contextual processing that have been identified in healthy adults, (ii) stimulus modality effects, (iii) specific alterations and deficits of local contextual processing in aging and across different neurological and psychiatric patient populations, including patients with prefrontal cortex lesions, Parkinson's disease, schizophrenia, and major depressive disorder, (iv) the potential for utilizing the correlates of local context as biomarkers for frontal cognitive dysfunction and (v) the role of frontal networks in the processing of contextual information. Overall findings show that behavioral and neural correlates associated with processing of local context are comparable across stimulus modalities, but show specific alterations in aging and across different neurological and psychiatric disorders.

The functional anatomy of schizophrenia: A dynamic causal modeling study of predictive coding.

This paper tests the hypothesis that patients with schizophrenia have a deficit in selectively attending to predictable events. We used dynamic causal modeling (DCM) of electrophysiological responses - to predictable and unpredictable visual targets - to quantify the effective connectivity within and between cortical sources in the visual hierarchy in 25 schizophrenia patients and 25 age-matched controls. We found evidence for marked differences between normal subjects and schizophrenia patients in the strength of extrinsic backward connections from higher hierarchical levels to lower levels within the visual system. In addition, we show that not only do schizophrenia subjects have abnormal connectivity but also that they fail to adjust or optimize this connectivity when events can be predicted. Thus, the differential intrinsic recurrent connectivity observed during processing of predictable versus unpredictable targets was markedly attenuated in schizophrenia patients compared with controls, suggesting a failure to modulate the sensitivity of neurons responsible for passing sensory information of prediction errors up the visual cortical hierarchy. The findings support the proposed role of abnormal connectivity in the neuropathology and pathophysiology of schizophrenia.

Local contextual processing in major depressive disorder.

OBJECTIVE: The study investigated local contextual processing in patients with major depressive disorder (MDD). This was defined as the ability to utilize predictive contextual information to facilitate detection of predictable versus random targets. METHOD: We recorded EEG in 15 MDD patients and 14 age-matched controls. Recording blocks consisted of targets preceded by randomized sequences of standards and by sequences of standards that included a predictive sequence signaling the occurrence of a subsequent target event. RESULTS: Both MDD patients and age-matched controls demonstrated a significant reaction time (RT) and P3b latency differences between predicted and random targets. However, patients demonstrated a specific prolongation of these measures during processing of predicted targets, as well as an attenuation of P3b amplitudes for the predictive sequence. In addition, patients target N1 amplitudes were attenuated compared with controls. CONCLUSION: MDD patients were able to utilize predictive context in order to facilitate processing of deterministic targets, however, this ability was limited compared to controls, as demonstrated by context-dependent P3b deficits. SIGNIFICANCE: These findings suggest that patients with major depression have altered processing of local contextual processing.

Functional connectivity abnormalities during contextual processing in schizophrenia and in Parkinson's disease.

Functional connectivity was evaluated in patients with schizophrenia (SC) and in patients with Parkinson's disease (PD) during the performance of a local contextual processing paradigm, to investigate the proposition that functional disconnection is involved with contextual processing deficits in these populations. To this end, we utilized event-related EEG signals, synchronization likelihood and graph theoretical analysis. Local context was defined as the occurrence of a predictive sequence of stimuli before the presentation of a target event. In the SC patients, we observed a decrease in path length (L) in the beta band, for the predictive sequence and for predicted and random targets, compared with controls. These abnormalities were associated with weaker frontal-temporal-parietal connections. In the PD patients we found longer L (theta band) for predicted targets, and higher cluster coefficients for both the predictive sequence (theta band) and predicted targets (alpha and theta bands), compared with controls. Detection of predicted targets was associated with weaker frontal-parietal connections in PD. No group differences were found for randomized standard stimuli in both SC and PD patients. These findings provide evidence of task-specific functional connectivity abnormalities within frontal networks during local contextual processing.