Anterior Brain Regions Research Articles

The Lateral Preoptic Area and Its Projection to the VTA Regulate VTA Activity and Drive Complex Reward Behaviors

The ventral tegmental area (VTA) underlies motivation and reinforcement of natural rewards. The lateral preoptic area (LPO) is an anterior hypothalamic brain region that sends direct projections to the VTA and to other brain structures known to regulate VTA activity. Here, we investigated the functional connection between the LPO and subpopulations of VTA neurons and explored the reinforcing and valence qualities of the LPO in rats. We found that the LPO and the LPO→VTA pathway inhibit the activity of VTA GABA neurons and have mixed effects on VTA dopamine neurons. Furthermore, we found that the LPO supports operant responding but drives avoidance, and we explored the apparent discrepancy between these two results. Finally, using fiber photometry, we show that the LPO signals aversive events but not rewarding events. Together, our findings demonstrate that the LPO modulates the activity of the VTA and drives motivated behavior and represents an overlooked modulator of reinforcement.

Rapid Cortical Plasticity Induced by Active Associative Learning of Novel Words in Human Adults.

Human speech requires that new words are routinely memorized, yet neurocognitive mechanisms of such acquisition of memory remain highly debatable. Major controversy concerns the question whether cortical plasticity related to word learning occurs in neocortical speech-related areas immediately after learning, or neocortical plasticity emerges only on the second day after a prolonged time required for consolidation after learning. The functional spatiotemporal pattern of cortical activity related to such learning also remains largely unknown. In order to address these questions, we examined magnetoencephalographic responses elicited in the cerebral cortex by passive presentations of eight novel pseudowords before and immediately after an operant conditioning task. This associative procedure forced participants to perform an active search for unique meaning of four pseudowords that referred to movements of left and right hands and feet. The other four pseudowords did not require any movement and thus were not associated with any meaning. Familiarization with novel pseudowords led to a bilateral repetition suppression of cortical responses to them; the effect started before or around the uniqueness point and lasted for more than 500 ms. After learning, response amplitude to pseudowords that acquired meaning was greater compared with response amplitude to pseudowords that were not assigned meaning; the effect was significant within 144–362 ms after the uniqueness point, and it was found only in the left hemisphere. Within this time interval, a learning-related selective response initially emerged in cortical areas surrounding the Sylvian fissure: anterior superior temporal sulcus, ventral premotor cortex, the anterior part of intraparietal sulcus and insula. Later within this interval, activation additionally spread to more anterior higher-tier brain regions, and reached the left temporal pole and the triangular part of the left inferior frontal gyrus extending to its orbital part. Altogether, current findings evidence rapid plastic changes in cortical representations of meaningful auditory word-forms occurring almost immediately after learning. Additionally, our results suggest that familiarization resulting from stimulus repetition and semantic acquisition resulting from an active learning procedure have separable effects on cortical activity.

Test-retest reliability and reproducibility of long-label pseudo-continuous arterial spin labeling

PurposeArterial spin labeling MRI can quantify the cerebral blood flow (CBF) without exogenous tracer. However, the variation of arterial transit time across different brain regions introduces bias for measuring local CBF, especially for those subjects with long arterial transit time (ATT). Long post-labeling delay (PLD) or multi-PLD methods could mitigate the problem of heterogenous ATT at the expense of the signal-to-noise ratio (SNR). Long-label ASL might address the low SNR problem by increasing the amount of labeled arterial blood. Thus, we hypothesized that with the same relatively long PLD, long-label pCASL may be more robust and reproducible than standard-label pCASL in population with potentially prolonged ATT. The purpose of the study was to investigate the reliability and reproducibility of long-label pCASL in the whole brain and vascular regions of interest in an elderly population, compared with standard-label pCASL. MethodTwenty adult volunteers (14 males, 6 females; age, 56.6 ± 17.2 years) were scanned twice on one 3.0 T scanner by standard-label pCASL (label duration (LD) = 1500 ms, PLD = 2000 ms) and long-label pCASL (LD = 3500 ms, PLD = 2000 ms). The intraclass correlation coefficient (ICC), within-subject coefficient of variation (wsCV), random noise and signal coefficient of variation(CoV) were used to assess global and regional reliability and reproducibility. Measurement agreement and difference were compared in different brain regions using correlation coefficient plots and Bland-Altman plots respectively. ResultsCBF value measured by long-label pCASL was overall higher than standard-label pCASL in all ROIs. Long-label pCASL had higher ICC than standard-label pCASL in most ROIs, and lower wsCV, random noise and CoV in all ROIs. Regardless of ASL method used, anterior circulation flow territories (ICC, 0.93–0.97; wsCV, 0.03–0.06) had higher CBF reliability and reproducibility than posterior circulation flow territories (ICC, 0.89; wsCV, 0.06–0.08). In all ROIs, the correlation analysis showed higher test-retest agreement (rlong-label > rstandard-label) and the Bland-Altman plots demonstrated lower measurement difference in long-label pCASL. ConclusionThe study demonstrated good reliability and reproducibility of long-label pCASL in anterior brain regions in the elderly population. To further improve CBF quantification in a long-ATT population while proper PLD is already used, increasing the label duration may help.

Characterization of monoaminergic neurochemicals in the different brain regions of adult zebrafish

Monoaminergic neurotransmitters are the main components that regulate of a lot of processes in the vertebrate brain. There is growing interest to monitor the changes produced in these neurochemicals due to the large number of exogenous agents, such as pharmaceuticals and drugs of abuse, targeting and affecting this system. Adult zebrafish (Danio rerio) shares the common neurotransmitter pathways and nervous system organization with mammals. Therefore, a method based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has been developed for the first time to study the profile of ten monoaminergic neurochemicals in the anterior, middle and posterior brain regions of adult zebrafish. Moreover, the applied LC-MS/MS method has been studied in terms of quality such as linearity, sensitivity and intra- and inter-day precision. The analytical method based in LC-MS/MS has become a new source in neurotoxicology using adult zebrafish as research model. Significant differences on the levels of these neurotransmitters have been found between the different brain regions. CapsuleThe profile of ten monoaminergic neurochemicals in the main three brain areas of adult zebrafish has been reported for the first time in this manuscript.

Genuine cross-frequency coupling networks in human resting-state electrophysiological recordings.

Phase synchronization of neuronal oscillations in specific frequency bands coordinates anatomically distributed neuronal processing and communication. Typically, oscillations and synchronization take place concurrently in many distinct frequencies, which serve separate computational roles in cognitive functions. While within-frequency phase synchronization has been studied extensively, less is known about the mechanisms that govern neuronal processing distributed across frequencies and brain regions. Such integration of processing between frequencies could be achieved via cross-frequency coupling (CFC), either by phase–amplitude coupling (PAC) or by n:m-cross–frequency phase synchrony (CFS). So far, studies have mostly focused on local CFC in individual brain regions, whereas the presence and functional organization of CFC between brain areas have remained largely unknown. We posit that interareal CFC may be essential for large-scale coordination of neuronal activity and investigate here whether genuine CFC networks are present in human resting-state (RS) brain activity. To assess the functional organization of CFC networks, we identified brain-wide CFC networks at mesoscale resolution from stereoelectroencephalography (SEEG) and at macroscale resolution from source-reconstructed magnetoencephalography (MEG) data. We developed a novel, to our knowledge, graph-theoretical method to distinguish genuine CFC from spurious CFC that may arise from nonsinusoidal signals ubiquitous in neuronal activity. We show that genuine interareal CFC is present in human RS activity in both SEEG and MEG data. Both CFS and PAC networks coupled theta and alpha oscillations with higher frequencies in large-scale networks connecting anterior and posterior brain regions. CFS and PAC networks had distinct spectral patterns and opposing distribution of low- and high-frequency network hubs, implying that they constitute distinct CFC mechanisms. The strength of CFS networks was also predictive of cognitive performance in a separate neuropsychological assessment. In conclusion, these results provide evidence for interareal CFS and PAC being 2 distinct mechanisms for coupling oscillations across frequencies in large-scale brain networks.

Neural mechanisms underlying state mental fatigue in multiple sclerosis: a pilot study.

Neuroimaging underpinnings of state (in the moment, transient) mental fatigue in multiple sclerosis (MS) are not well understood. The current pilot study examined the effect of state mental fatigue on brain activation (measured using functional magnetic resonance imaging [fMRI]) during conditions of varying cognitive loads of rapid information processing in persons with MS relative to healthy controls. Nineteen persons with MS and 17 healthy controls underwent fMRI scanning while performing a modified version of the Symbol Digit Modalities Test, which consisted of high and low cognitive load conditions with comparable visual stimulation. State mental fatigue was assessed using the Visual Analog Scale of Fatigue before and after each run of the behavioral task. Results indicated that the healthy control group recruited significantly more anterior brain regions (superior and middle frontal gyri, insula, and superior temporal gyrus) to meet increased task demands during the high cognitive load condition as fatigue level increased (p < 0.05), which was accompanied by shorter response time. In contrast, the MS group did not recruit anterior areas to the same extent as the healthy control group as task demands and fatigue increased. Indeed, the MS group continued to activate more posterior brain regions (precuneus, lingual gyrus, and middle occipital gyrus) for the high cognitive load condition (p < 0.05) with no improvement in speed. In conclusion, persons with MS may allocate neural resources less efficiently than healthy controls when faced with increased task demands, which may result in increased mental fatigue. Results of the current pilot investigation warrant replication with a larger sample size.

Endothelin Receptor Antagonism Increases Cerebral Perfusion in Humans

Microvascular cerebral perfusion (CP) is critical for adequate oxygenation of neuronal tissue in the brain. However, the mechanisms underlying proper CP regulation in humans have yet to be fully defined. Endothelin is a potent endogenous vasoconstrictor and appears to have a modest role in blood flow regulation in many peripheral vascular beds in healthy individuals. We tested the hypothesis that endothelin receptor antagonism will not influence CP in healthy young adults. Six male subjects (age: 24±4 yrs; BMI: 23±2 kg/m2) participated in the single‐blind study in which endothelin receptor antagonist (Ambrisentan, 10 mg) or placebo was administered orally. Only males participated in the current study due to potential teratogenic effects of Ambrisentan. Resting CP was quantified via 3T MRI using pseudo‐continuous arterial spin labeling (ASL) normalized to gray matter volume approximately 120 minutes following dosing. Blood pressure, heart rate, and end‐tidal CO2 were monitored. Data were analyzed via paired t‐tests and reported as mean±SD. Significance was taken as p≤0.05. Heart rate (57±8 vs. 59±7 bpm), mean arterial pressure (81±7 vs. 79±8 mmHg) and end‐tidal CO2 (34±6 vs. 37±3 mmHg) was not different between placebo and Ambrisentan, respectively (all p&gt;0.05). Compared to placebo, Ambrisentan increased cerebral perfusion (31±3 vs. 34±2 mL/100g/min; p&lt;0.05), representing a 8±5% increase. Regionally, Ambrisentan demonstrated a tendency to increase CP in brain regions supplied by the anterior cerebral circulation (frontal lobe: 36±11 vs. 45±5 mL/100g/min, p=0.05; parietal lobe: 35±10 vs. 43±5 mL/100g/min, p=0.08; temporal lobe: 35±10 vs. 43±6 mL/100g/min, p=0.07; basal ganglia: 35±9 vs. 41±5, p=0.09; cingulate: 39±10 vs. 47±5 mL/100g/min, p=0.08). In contrast, CP in regions supplied by the posterior circulation did not increase to a similar extent (occipital lobe: 37±9 vs. 43±7 mL/100g/min, p=0.13; cerebellum 30±16 vs. 38±6 mL/100g/min, p=0.27). Contrary to our hypothesis, these data suggest endothelin contributes to resting CP by increasing microvascular tone, an effect that may be more pronounced in the anterior brain regions. These preliminary findings contribute to resolving potential mechanisms mediating normal CP in healthy individuals and form the basis of future studies exploring the influence of elevated endothelin signaling in conditions like diabetes or heart failure.Support or Funding InformationADA 1‐16‐ICTS‐099

Intact value-based decision-making during intertemporal choice in women with remitted anorexia nervosa? An fMRI study

Extreme restrictive food choice in anorexia nervosa is thought to reflect excessive self-control and/or abnormal reward sensitivity. Studies using intertemporal choice paradigms have suggested an increased capacity to delay reward in anorexia nervosa, and this may explain an unusual ability to resist immediate temptation and override hunger in the long-term pursuit of thinness. It remains unclear, however, whether altered delay discounting in anorexia nervosa constitutes a state effect of acute illness or a trait marker observable after recovery. We repeated the analysis from our previous fMRI investigation of intertemporal choice in acutely underweight patients with anorexia nervosa in a sample of weight-recovered women with anorexia nervosa (n = 36) and age-matched healthy controls (n = 36) who participated in the same study protocol. Follow-up analyses explored functional connectivity separately in both the weight-recovered/healthy controls sample and the acute/healthy controls sample. In contrast to our previous findings in acutely underweight patients with anorexia nervosa, we found no differences between weight-recovered patients with anorexia nervosa and healthy controls at either behavioural or neural levels. New analysis of data from the acute/healthy controls sample sample revealed increased coupling between dorsal anterior cingulate cortex and posterior brain regions as a function of decision difficulty, supporting the hypothesis of altered neural efficiency in the underweight state. This was a cross-sectional study, and the results may be task-specific. Although our results underlined previous demonstrations of divergent temporal reward discounting in acutely underweight patients with anorexia nervosa, we found no evidence of alteration in patients with weight-recovered anorexia nervosa. Together, these findings suggest that impaired valuebased decision-making may not constitute a defining trait variable or “scar” of the disorder.

The incremental processing of focus, givenness and prosodic prominence

This study on German investigates the real-time comprehension of items in First Occurrence Focus (focused and new), Second Occurrence Focus (focused and given), Quasi Second Occurrence Focus (derogatory expressions that are referentially given and lexically new) and Background (non-focused and given), which are marked by different levels of prosodic prominence. While previous electrophysiological research tested mismatches between prosody and information structure, the present study assessed contextually licensed, appropriate prosodic realizations of stimuli. Our EEG experiment revealed distinct topographic profiles for information structure and prosody. As to prosody, we found a biphasic pattern over anterior brain regions for (secondarily prominent) phrase accents (marking Second Occurrence Focus) and deaccentuation (marking Background) but not for pitch accents (marking First Occurrence Focus), indicating an inverse relation between processing effort and the level of perceived prominence. The event-related potentials for Quasi Second Occurrence Focus items resembled First Occurrence Focus items although the former were deaccented. As to information structural contrasts, First Occurrence Focus engendered a pronounced negativity over posterior sites relative to Second Occurrence Focus and Background. Quasi Second Occurrence Focus showed an intermediate negativity. These differences can probably be accounted for by (lexically) new rather than focused information. In general, the data indicate that both prosodic cues and information structural categories influence the incremental processing of spoken language and that pitch accents and newness fulfill independent prominence-lending functions.

Disentangling the Effects of Processing Speed on the Association between Age Differences and Fluid Intelligence.

Several studies have demonstrated that individual differences in processing speed fully mediate the association between age and intelligence, whereas the association between processing speed and intelligence cannot be explained by age differences. Because measures of processing speed reflect a plethora of cognitive and motivational processes, it cannot be determined which specific processes give rise to this mediation effect. This makes it hard to decide whether these processes should be conceived of as a cause or an indicator of cognitive aging. In the present study, we addressed this question by using a neurocognitive psychometrics approach to decompose the association between age differences and fluid intelligence. Reanalyzing data from two previously published datasets containing 223 participants between 18 and 61 years, we investigated whether individual differences in diffusion model parameters and in ERP latencies associated with higher-order attentional processing explained the association between age differences and fluid intelligence. We demonstrate that individual differences in the speed of non-decisional processes such as encoding, response preparation, and response execution, and individual differences in latencies of ERP components associated with higher-order cognitive processes explained the negative association between age differences and fluid intelligence. Because both parameters jointly accounted for the association between age differences and fluid intelligence, age-related differences in both parameters may reflect age-related differences in anterior brain regions associated with response planning that are prone to be affected by age-related changes. Conversely, age differences did not account for the association between processing speed and fluid intelligence. Our results suggest that the relationship between age differences and fluid intelligence is multifactorially determined.

The expression of FoxG1 in the early development of the European river lamprey Lampetra fluviatilis demonstrates significant heterochrony with that in other vertebrates

FoxG1, a member of the Fox/Forkhead family of winged helix transcription factors, plays key roles in the induction and spatial compartmentalization of the telencephalon in vertebrates. Loss- and gain-of-function experiments have established FoxG1 as a maintenance factor for neural progenitors and a crucial player in the specification of the ventral telencephalon (subpallium). For the first time in evolution, the telencephalon appeared in the ancestors of vertebrates, including cyclostomes. However, although FoxG1 homologues are present in cyclostomes (i.e., in lampreys and hagfishes), no systematic study of the spatial-temporal expression of FoxG1 during the embryonic development of these animals has been carried out. Given these findings, we have now studied FoxG1 spatial-temporal expression patterns in the early development of the European river lamprey Lampetra fluviatilis. We show that in contrast to other vertebrates, in which the expression of FoxG1 begins during neurulation, the expression of this gene in L. fluviatilis starts after neurulation, first at stage 21 (early head protrusion) in the area of the otic placodes and then, beginning from stage 22, in the telencephalon. Such heterochrony of FoxG1 expression in the lamprey may reflect the fact that in this basally divergent representative of vertebrates, telencephalon specification occurs relatively late. This heterochrony could be related to the evolutionary history of the telencephalon, with a recent appearance in vertebrates as an extension to more ancient anterior brain regions. Another peculiarity of FoxG1 expression in lamprey, compared to other vertebrates, is that it is not expressed in the lamprey optic structures.

The positive impacts of early-life education on cognition, leisure activity, and brain structure in healthy aging.

Education in people’s early lives are positively related to their cognitive function, but its modulating effects on detailed cognition domains, its interaction with leisure activities and the associated brain changes have yet to be investigated. This report used data from 659 cognitively normal community dwelling elderly who completed neuropsychological tests, leisure activities measurement, and 78 of them underwent structural and diffusion MRI scans. We found that: (i) the highly educated elderly had a better cognitive functioning in multi-domains, higher frequencies of participation in knowledge-related leisure activities, and slower age-related reductions of executive function; (ii) the intellectual and social types of leisure activities mediated the association between education and multiple cognitive domains, including memory, language, attention and executive function; (iii) there was a significant age by education interaction on the gray matter volume of the anterior brain regions and white matter integrity; and (iv) the interaction between age and education affected cognition indirectly through white matter integrity analyzed using structural equation model. Overall, our results revealed that high education in early life served as a protective factor in aging that may help to postpone cognitive and brain reserve decline in cognitively normal aging.

Directed Connectivity in Large-scale Brain Networks for Precision Grip Force Control.

Precision grip requires accurate but dynamic control of the magnitude and direction of fingertip forces. It is still not well known whether directed information flow across activated cortical regions could change with different force outputs during precision grip. This study aimed to investigate the directed connectivity in large-scale brain networks for precision grip force control. Eight healthy volunteers participated in the experiment. Totally 32 channel electroencephalography (EEG) signals were recorded during a precision grip task that requires accurate force control following a dynamically changed visual target. The force target changed between 10% and 1% Maximal Voluntary Contraction (MVC). Horizontal visibility graph transfer entropy (HVG-TE) was used to measure the directed connectivity between pairs of EEG channels. In addition, the relative HVG-TE (rHVG-TE) was applied to evaluate the activation of each EEG channel. Results showed relatively higher rHVG-TE values in the posterior brain region but lower rHVG-TE values in the anterior brain region within the whole spectrum (4-70Hz), indicating a posterior-to-anterior information flow. This study revealed that the activation of posterior region is higher than the anterior region. There is a directed functional connectivity of cortex from posterior to anterior region for precision grip force control. This study shed light on how to quantify activation and large-scale connectivity of cortical regions, and reveal the in-depth central mechanisms for peripheral fine motor control.

What Type Of Exercise Is Appropriate For An Optimistic Affective Mind-set?

PURPOSE: “Affective mind-set” is a mental frame or lens that selectively organizes. Previous reports proved that activation of the left anterior brain region is linked with the optimistic affective mind-set. Aerobic exercise such as moderate-intensity interval training (MIT) and moderate continuous training (MCT) activates the frontal area of the left hemisphere, which gives euphoric feelings. However, whether interval training is appropriate for stimulating an optimistic affective mind-set is unknown. We hypothesized that interval, rather than continuous, training activates the left brain. This study aimed to evaluate which exercise can activate the left brain more by using three different kinds of bicycle exercise. METHODS: The participants were six healthy male volunteers. The three bicycle exercises used were MCT, MIT, and high-intensity interval training (HIT). Exercise intensity was considered in the assessment of the peak heart rate (PHR) induced by the cardiopulmonary exercise test. A 70% PHR was defined as moderate intensity; and 90% PHR, as high intensity. The MCT protocol included 3 min of warm-up (WU) and 40 min of moderate-intensity (70% PHR) continuous exercise, 3 min of cooldown (CD), and 10 min of rest. The MIT protocol was composed of a 3-minute WU, 4 term of moderate-intensity (70% PHR) exercise, active rest (45% PHR), 5-min CD, and 10-min rest. The HIT protocol was composed of a 3-min WU, 4 term of high-intensity (90% PHR) exercise with active rest (70% PHR), 3-min CD, and 10-min rest. Brain activity was measured using electroencephalography (EEG; NegPos, Neuro Sky). EEG was performed during each session. Data were the mean values obtained at WU, CD, and 5-min rest. ⊿CD-WU and ⊿Rest 5-min WU were calculated. The three groups were compared via one-way analysis of variance, with the Bonferroni test for post hoc comparison. RESULTS: A slight difference was observed among the three groups in ⊿Rest 5-min WU (MIT: 42.0±42.6, HIT: −19.5±48.6, MCT:-3.8±14.8, p<0.057). ⊿CD-WU was not significantly different among the groups (MCT: −2.7±15.8, MIT: 39.1±43.7, HIT: −16.2±51.1, p<0.11). WU and CD showed no significance differences among the three groups (WU: p<0.25, CD: p<0.51). CONCLUSION: MIT is the most appropriate exercise for an optimistic affective mind-set. I have no financial relationships to disclose.

Abstract TP146: Intracranial Microvascular Calcification: A Cadaveric Study

Introduction: Stroke and brain ischemia are associated with macrovascular calcification. Microvascular calcification may also contribute to cerebrovascular disease, yet its prevalence and pathophysiological significance remain unclear. Hypothesis: Calcification associated with intracranial microvasculature is prevalent in elderly populations and correlates with calcification of proximal macrovascular supply. Methods: Tissues were dissected from 20 cadavers (16 female, 4 male; median age = 81 y; range = 56-94 y) unilaterally on the left side. Three vascular territories were examined representing anterior, middle, and posterior brain regions supplied by distal M4 branches of the middle cerebral artery (MCA). Proximally, two putaminal regions supplied by lenticulostriate arteries (from M1 of the MCA) were examined. Extra- and intracranial internal carotid arteries (ICA) and M1 segments of the MCA from the same subjects were previously scored for calcium; those data were used for correlation analysis. A sensitive and specific calcium detection protocol (alizarin red) was used in all studies alongside H&amp;E. Light microscopy was performed to grade small- (&lt; 20 micron) and large-caliber (20-200 micron) vessels for calcification. Results: Calcification was detected in all subjects, with 95% in small-caliber and 50% in large-caliber microvessels. Non-parametric Spearman correlation analysis revealed significant correlation between calcification of large-caliber microvessels in M4 (but not M1 putaminal vessels) and medial calcification of the MCA (M1 segment; r = 0.6533, p &lt; 0.05). Contrary to our hypothesis, no correlations were found between microvascular calcification and calcification of the ICA. Additionally, no correlations were found between microvascular calcification and atheromatous calcification of either the MCA (M1 segment) or ICA (extra- and intracranial parts). Conclusions: Our study implies that intracranial microvascular calcification is highly prevalent in elderly populations. Additionally, we discovered significant correlation between microvascular calcification and that of the media in mascrovasculature, suggesting a causal link between medial sclerosis and dysfunction of the neurovascular unit.

A preliminary investigation of impulsivity, aggression and white matter in patients with bipolar disorder and a suicide attempt history

BackgroundImpulsivity and aggression may be associated with suicide attempts in bipolar disorder (BD), but findings have been inconsistent. Abnormalities in anterior white matter tracts that project to the frontal lobes mediate top-down regulation of emotion and may contribute to this clinical phenomenology. MethodsWe assessed white matter (i.e., fractional anisotropy) in anterior and posterior brain regions using diffusion tensor imaging in 18 patients with BD and no prior suicide attempt (BD-S), 12 patients with BD and a prior suicide attempt (BD+S), and 12 healthy volunteers. Patients completed the Urgency, Premeditation, Perseverance, Sensation Seeking, Positive Urgency (UPPS-P) Impulsive Behavior Scale and Impulsive Premeditated Aggression Scale (IPAS). All individuals completed the Barratt Impulsiveness Scale (BIS-11). ResultsPatients with BD+S had higher overall impulsivity (assessed using both the UPPS-P Impulsive Behavior Scale and BIS-11) and premeditated aggression compared to patients with BD-S. There were no significant group differences on measures of fractional anisotropy (FA). In patients with BD+S, however, higher FA in the anterior (but not the posterior) brain regions correlated with greater overall impulsivity on the UPPS-P Impulsive Behavior Scale. There were no significant correlations between either anterior or posterior brain regions with clinical measures in patients with BD-S. LimitationsCross-sectional study, sample size and possible contribution of psychotropic medications. ConclusionImpulsivity and aggression may be risk factors for a suicide attempt in BD. White matter in the anterior limb of the internal capsule and anterior corona radiata may play a role in this phenomenology.

Directed functional connections underlying spontaneous brain activity.

Neuroimaging studies have shown that spontaneous brain activity is characterized as changing networks of coherent activity across multiple brain areas. However, the directionality of functional interactions between the most active regions in our brain at rest remains poorly understood. Here, we examined, at the whole-brain scale, the main drivers and directionality of interactions that underlie spontaneous human brain activity by applying directed functional connectivity analysis to electroencephalography (EEG) source signals. We found that the main drivers of electrophysiological activity were the posterior cingulate cortex (PCC), the medial temporal lobes (MTL), and the anterior cingulate cortex (ACC). Among those regions, the PCC was the strongest driver and had both the highest integration and segregation importance, followed by the MTL regions. The driving role of the PCC and MTL resulted in an effective directed interaction directed from posterior toward anterior brain regions. Our results strongly suggest that the PCC and MTL structures are the main drivers of electrophysiological spontaneous activity throughout the brain and suggest that EEG-based directed functional connectivity analysis is a promising tool to better understand the dynamics of spontaneous brain activity in healthy subjects and in various brain disorders.

Ultrafast Cortical Gain Adaptation in the Human Brain by Trial-To-Trial Changes of Associative Strength in Fear Learning.

In fear conditioning, more efficient sensory processing of a stimulus (the conditioned stimulus, CS) that has acquired motivational relevance by being paired with an aversive event (the unconditioned stimulus, US) has been associated with increased cortical gain in early sensory brain areas (Miskovic and Keil, 2012). Further, this sensory gain modulation related to short-term plasticity changes occurs independently of aware cognitive anticipation of the aversive US, pointing toward implicit learning mechanisms (Moratti and Keil, 2009). However, it is unknown how quickly the implicit learning of CS-US associations results in the adaptation of cortical gain. Here, using steady-state visually evoked fields derived from human Magnetoencephalography (MEG) recordings in two experiments (N = 33, 17 females and 16 males), we show that stimulus-driven neuromagnetic oscillatory activity increases and decreases quickly as a function of associative strength within three or four trials, as predicted by a computationally implemented Rescorla-Wagner model with the highest learning rate. These ultrafast cortical gain adaptations are restricted to early visual cortex using a delay fear conditioning procedure. Short interval (500 ms) trace conditioning resulted in the same ultrafast activity modulations by associative strength, but in a complex occipito-parieto-temporo-frontal network. Granger causal analysis revealed that reverberating top-down and bottom-up influences between anterior and posterior brain regions during trace conditioning characterized this network. Critically, in both delay and trace conditioning, ultrafast cortical gain modulations as a function of associative strength occurred independently of conscious US anticipation.SIGNIFICANCE STATEMENT In ever-changing environments, learned associations between a cue and an aversive consequence must change under new stimulus-consequence contingencies to be adaptive. What predicts potential dangers now might be meaningless in the next situation. Predictive cues are prioritized, as reflected by increased sensory cortex activity for these cues. However, this modulation also must adapt to altered stimulus-consequence contingencies. Here, we show that human visual cortex activity can be modulated quickly according to ultrafast contingency changes within a few learning trials. This finding extends to frontal brain regions when the cue and the aversive event are separated in time. Critically, this ultrafast updating process occurs orthogonally to aware aversive outcome anticipation and therefore relies on unconscious implicit learning mechanisms.

Looking but not seeing: Increased eye fixations in behavioural-variant frontotemporal dementia

Face processing plays a central role in human communication, with the eye region a particularly important cue for discriminating emotions. Indeed, reduced attention to the eyes has been argued to underlie social deficits in a number of clinical populations. Despite well-established impairments in facial affect recognition in behavioural-variant frontotemporal dementia, whether these patients also have perturbed facial scanning is yet to be investigated. The current study employed eye tracking to record visual scanning of faces in 20 behavioural-variant frontotemporal dementia patients and 21 controls. Remarkably, behavioural-variant frontotemporal dementia patients displayed more fixations to the eyes of emotional faces, compared to controls. Neural regions associated with fixations to the eyes included the left inferior frontal gyrus, right cerebellum and middle temporal gyrus. Our study is the first to show such compensatory functions in behavioural-variant frontotemporal dementia and suggest a feedback-style network, including anterior and posterior brain regions, is involved in early face processing.

The dynamics of error processing in the human brain as reflected by high-gamma activity in noninvasive and intracranial EEG

Error detection in motor behavior is a fundamental cognitive function heavily relying on local cortical information processing. Neural activity in the high-gamma frequency band (HGB) closely reflects such local cortical processing, but little is known about its role in error processing, particularly in the healthy human brain. Here we characterize the error-related response of the human brain based on data obtained with noninvasive EEG optimized for HGB mapping in 31 healthy subjects (15 females, 16 males), and additional intracranial EEG data from 9 epilepsy patients (4 females, 5 males). Our findings reveal a multiscale picture of the global and local dynamics of error-related HGB activity in the human brain. On the global level as reflected in the noninvasive EEG, the error-related response started with an early component dominated by anterior brain regions, followed by a shift to parietal regions, and a subsequent phase characterized by sustained parietal HGB activity. This phase lasted for more than 1 s after the error onset. On the local level reflected in the intracranial EEG, a cascade of both transient and sustained error-related responses involved an even more extended network, spanning beyond frontal and parietal regions to the insula and the hippocampus. HGB mapping appeared especially well suited to investigate late, sustained components of the error response, possibly linked to downstream functional stages such as error-related learning and behavioral adaptation. Our findings establish the basic spatio-temporal properties of HGB activity as a neural correlate of error processing, complementing traditional error-related potential studies.