Anomalies in global network connectivity associated with early recovery from alcohol dependence: A network transcranial magnetic stimulation and electroencephalography study.

Although previous research in alcohol dependent populations identified alterations within local structures of the addiction 'reward' circuitry, there is limited research into global features of this network, especially in early recovery. Transcranial magnetic stimulation (TMS) is capable of non-invasively perturbing the brain network while electroencephalography (EEG) measures the network response. The current study is the first to apply a TMS inhibitory paradigm while utilising network science (graph theory) to quantify network anomalies associated with alcohol dependence. Eleven individuals with alcohol-dependence (ALD) in early recovery and 16 healthy controls (HC) were administered 75 single pulses and 75 paired-pulses (inhibitory paradigm) to both the left and right prefrontal cortex (PFC). For each participant, Pearson cross-correlation was applied to the EEG data and correlation matrices constructed. Global network measures (mean degree, clustering coefficient, local efficiency and global efficiency) were extracted for comparison between groups. Following administration of the inhibitory paired-pulse TMS to the left PFC, the ALD group exhibited altered mean degree, clustering coefficient, local efficiency and global efficiency compared to HC. Decreases in local efficiency increased the prediction of being in the ALD group, while all network metrics (following paired-pulse left TMS) were able to adequately discriminate between the groups. In the ALD group, reduced mean degree and global clustering was associated with increased severity of past alcohol use. Our study provides preliminary evidence of altered network topology in patients with alcohol dependence in early recovery. Network anomalies were predictive of high alcohol use and correlated with clinical features of alcohol dependence. Further research using this novel brain mapping technique may identify useful network biomarkers of alcohol dependence and recovery.

The interactive effects of test-retest and methylphenidate administration on cognitive performance in youth with ADHD: A double-blind placebo-controlled crossover study.

Studies have shown that Methylphenidate (MPH) affects cognitive performance on the neuropsychological tests and clinical symptoms of individuals diagnosed with attention deficit/hyperactivity disorder (ADHD). This study investigated the acute effects of MPH on neuropsychological tests to explore the interaction between MPH and test-retest effects. Twenty youths with ADHD were tested before and after MPH intake in a double-blind placebo-controlled crossover design and compared to twenty matched controls. Participants were tested on a range of standardized tasks including sustained attention to response, N-Back, and Word/Color Stroop. Identical tasks were administered twice each testing day, before and 1 hour after MPH/Placebo administration. Healthy controls were tested similarly with no intervention. Decreases in response time (RT) variability across tasks and in commission errors were found in ADHD after MPH. Conversely, a significant increase in RT variability and increase in omission errors were observed after the placebo. In the control group, RT variability and omission errors increased whereas commission errors decreased, suggesting fatigue and practice effects, respectively. Test-retest reliability was higher in controls than ADHD. It is suggested that cognitive tests are sensitive objective measures for the assessment of responses to MPH in ADHD but are also affected by repetition and fatigue.

Effects of methylphenidate on the ERP amplitude in youth with ADHD: A double-blind placebo-controlled cross-over EEG study.

Methylphenidate (MPH) is a first line drug for attention-deficit/hyperactivity disorder (ADHD), yet the neuronal mechanisms underlying the condition and the treatment are still not fully understood. Previous EEG studies on the effect of MPH in ADHD found changes in evoked response potential (ERP) components that were inconsistent between studies. These inconsistencies highlight the need for a well-designed study which includes multiple baseline sessions and controls for possible fatigue, learning effects and between-days variability. To this end, we employ a double-blind placebo-controlled cross-over study and explore the effect of MPH on the ERP response of subjects with ADHD during a Go/No-Go cognitive task. Our ERP analysis revealed significant differences in ADHD subjects between the placebo and MPH conditions in the frontal-parietal region at 250ms-400ms post stimulus (P3). Additionally, a decrease in the late 650ms-800ms ERP component (LC) is observed in frontal electrodes of ADHD subjects compared to controls. The standard deviation of response time of ADHD subjects was significantly smaller in the MPH condition compared to placebo and correlated with the increased P3 ERP response in the frontoparietal electrodes. We suggest that mental fatigue plays a role in the decrease of the P3 response in the placebo condition compared to pre-placebo, a phenomenon that is significant in ADHD subjects but not in controls, and which is interestingly rectified by MPH.

Human non-olfactory cognition phase-locked with inhalation.

Olfactory stimulus acquisition is perfectly synchronized with inhalation, which tunes neuronal ensembles for incoming information. Because olfaction is an ancient sensory system that provided a template for brain evolution, we hypothesized that this link persisted, and therefore nasal inhalations may also tune the brain for acquisition of non-olfactory information. To test this, we measured nasal airflow and electroencephalography during various non-olfactory cognitive tasks. We observed that participants spontaneously inhale at non-olfactory cognitive task onset and that such inhalations shift brain functional network architecture. Concentrating on visuospatial perception, we observed that nasal inhalation drove increased task-related brain activity in specific task-related brain regions and resulted in improved performance accuracy in the visuospatial task. Thus, mental processes with no link to olfaction are nevertheless phase-locked with nasal inhalation, consistent with the notion of an olfaction-based template in the evolution of human brain function.

Electroencephalography Functional Networks Reveal Global Effects of Methylphenidate in Youth with Attention Deficit/Hyperactivity Disorder.

Methylphenidate (MPH) is the leading drug for treatment of attention deficit/hyperactivity disorder (ADHD), yet its underlying neuronal mechanisms are still unclear. Here, we use a dynamical brain networks approach to explore the effects of cognitive effort and MPH on ADHD subjects. Electroencephalography data were recorded from 19 ADHD subjects and 18 controls during a Go/No-Go Task. ADHD subjects completed the task twice a day over 2 days. The second session was administered post-ingestion of placebo/MPH (alternately). Controls performed two tasks in 1 day. The data were divided into 300 ms windows from -300 pre-stimulus until 1200 ms post-stimulus. Brain networks were constructed per subject and window, from which network metrics were extracted and compared across the experimental conditions. We identified an immediate shift of global connectivity and of network segregation after the stimulus for both groups, followed by a gradual return to baseline. Decreased global connectivity was found to be 400-700 ms post-stimulus in ADHD compared with controls, and it was normalized post-MPH. An increase of the networks' segregation occurred post-placebo at 100-400 and 400-700 ms post-stimulus, yet it was inhibited post-MPH. These global alterations resulted mainly from changes in task-relevant frontal and parietal regions. The networks of medicated ADHD subjects and controls exhibited a more significant and lasting change, relative to baseline, compared with those of nonmedicated ADHD. These results suggest impaired network flexibility in ADHD, corrected by MPH.

Altered Brain Network Dynamics in Schizophrenia: A Cognitive Electroencephalography Study.

BACKGROUND: Alterations in the dynamic coordination of widespread brain networks are proposed to underlie cognitive symptoms of schizophrenia. However, there is limited understanding of the temporal evolution of these networks and how they relate to cognitive impairment. The current study was designed to explore dynamic patterns of network connectivity underlying cognitive features of schizophrenia. METHODS: In total, 21 inpatients with schizophrenia and 28 healthy control participants completed a cognitive task while electroencephalography data were simultaneously acquired. For each participant, Pearson cross-correlation was applied to electroencephalography data to construct correlation matrices that represent the static network (averaged over 1200 ms) and dynamic network (1200 ms divided into four windows of 300 ms) in response to cognitive stimuli. Global and regional network measures were extracted for comparison between groups. RESULTS: Dynamic network analysis identified increased global efficiency; decreased clustering (globally and locally); reduced strength (weighted connectivity) around the frontal, parietal, and sensory-motor areas; and increased strength around the occipital lobes (a peripheral hub) in patients with schizophrenia. Regional network measures also correlated with clinical features of schizophrenia. Network differences were prominent 900 ms following the cognitive stimuli before returning to levels comparable to those of healthy control participants. CONCLUSIONS: Patients with schizophrenia exhibited altered dynamic patterns of network connectivity across both global and regional measures. These network differences were time sensitive and may reflect abnormalities in the flexibility of the network that underlies aspects of cognitive function. Further research into network dynamics is critical to better understanding cognitive features of schizophrenia and identification of network biomarkers to improve diagnosis and treatment models.

Shifting gears in hippocampus: temporal dissociation between familiarity and novelty signatures in a single event.

The hippocampus is known to be involved in encoding and retrieval of episodes. However, real-life experiences are expected to involve both encoding and retrieval, and it is unclear how the human hippocampus subserves both functions in the course of a single event. We presented participants with brief movie clips multiple times and examined the effect of familiarity on the hippocampal response at event onset versus event offset. Increased familiarity resulted in a decreased offset response, indicating that the offset response is a novelty-related signature. The magnitude of this offset response was correlated, across hippocampal voxels, with an independent measure of successful encoding, based on nonrepeated clips. This suggests that the attenuated offset response to familiar clips reflects reduced encoding. In addition, the posterior hippocampus exhibited an increased onset response to familiar events, switching from an online familiarity signal to an offline novelty signal during a single event. Moreover, participants with stronger memory exhibited increased reactivation of online activity during familiar events, in line with a retrieval signature. Our results reveal a spatiotemporal dissociation between novelty/encoding and familiarity/retrieval signatures, assumed to reflect different computational modes, in response to the same stimulus.