Activity In Specific Brain Regions Research Articles

The Effectiveness of Online Messages for Promoting Smoking Cessation Resources: Predicting Nationwide Campaign Effects From Neural Responses in the EX Campaign.

What are the key ingredients that make some persuasive messages resonate with audiences and elicit action, while others fail? Billions of dollars per year are put towards changing human behavior, but it is difficult to know which messages will be the most persuasive in the field. By combining novel neuroimaging techniques and large-scale online data, we examine the role of key health communication variables relevant to motivating action at scale. We exposed a sample of smokers to anti-smoking web-banner messages from a real-world campaign while measuring message-evoked brain response patterns via fMRI, and we also obtained subjective evaluations of each banner. Neural indices were derived based on: (i) message-evoked activity in specific brain regions; and (ii) spatially distributed response patterns, both selected based on prior research and theoretical considerations. Next, we connected the neural and subjective data with an independent, objective outcome of message success, which is the per-banner click-through rate in the real-world campaign. Results show that messages evoking brain responses more similar to signatures of negative emotion and vividness had lower online click-through-rates. This strategy helps to connect and integrate the rapidly growing body of knowledge about brain function with formative research and outcome evaluation of health campaigns, and could ultimately further disease prevention efforts.

The neural basis of individual differences in memory performance in young and older adults: Using the encoding/retrieval flip account as framework

Aging is associated with cognitive decline, specifically in episodic memory. However, there are large individual differences in the extent of this decline and previous research suggests that these are associated with differences in executive functioning (EF). These EF differences, and associated differences in the encoding and retrieval of episodic information, have been linked to differences in the activation of particular brain regions. The “encoding/retrieval flip” (E/R flip) framework assumes deactivation and activation of specific brain regions during successful encoding and retrieval, respectively. The present study assessed whether this framework can be used to explain EF-based individual differences in memory performance of young and older participants. Young adults (N = 19) and older adults (N = 39) performed an incidental semantic encoding and memory recognition task in an fMRI setting, focusing on brain regions that show the E/R flip. The association between an index of EF and fMRI activity in brain regions showing the E/R flip was tested in each age group. EF predicted E/R flip activity in the older, but not young adults. These findings underscore the importance of individual differences in ageing research and provide empirical evidence for the association between EF and the E/R flip.

Chronic treatment with the antipsychotic drug blonanserin modulates the responsiveness to acute stress with anatomical selectivity.

Patients diagnosed with schizophrenia typically receive life-long treatments with antipsychotic drugs (APDs). However, the impact of chronic APDs treatment on neuroplastic mechanisms in the brain remains largely elusive. Here, we focused on blonanserin, a second-generation antipsychotic (SGA) that acts as an antagonist at dopamine D2, D3, and serotonin 5-HT2A receptors, and represents an important tool for the treatment of schizophrenia. We used rats to investigate the ability of chronic treatment blonanserin to modulate the activity of brain structures relevant for schizophrenia, under baseline conditions or in response to an acute forced swim session (FSS). We measured the expression of different immediate early genes (IEGs), including c-Fos, Arc/Arg 3.1, Zif268 and Npas4. Blonanserin per se produced limited changes in the expression of these genes under basal conditions, while, as expected, FSS produced a significant elevation of IEGs transcription in different brain regions. The response of blonanserin-treated rats to FSS show anatomical and gene-selective differences. Indeed, the upregulation of IEGs was greatly reduced in the striatum, a brain structure enriched in dopamine receptors, whereas the upregulation of some genes (Zif268, Npas4) was largely preserved in other regions, such as the prefrontal cortex and the ventral hippocampus. Taken together, our findings show that chronic exposure to blonanserin modulates selective IEGs with a specific anatomical profile. Moreover, the differential activation of specific brain regions under challenging conditions may contribute to specific clinical features of the drug.

Under the Hood: Using Computational Psychiatry to Make Psychological Therapies More Mechanism-Focused.

Psychological therapies, such as CBT, are an important part of the treatment of a range of psychiatric disorders such as depression and anxiety. There is a growing desire to understand the mechanisms by which such therapies effect change so as to improve treatment outcomes. Here we argue that adopting a computational framework may be one such approach. Computational psychiatry aims to provide a theoretical framework for moving between higher-level psychological states (like emotions, decisions and beliefs) to neural circuits, by modeling these constructs mathematically. These models are explicit hypotheses that contain quantifiable variables and parameters derived from each individual's behavior. This approach has two advantages. Firstly, some of the variables described by these models appears to reflect the neural activity of specific brain regions. Secondly, the parameters estimated by these models may offer a unique description of a patient's symptoms which can be used to both tailor therapy and track its effect. In doing so this approach may offer some additional granularity in understanding how psychological therapies, such as CBT, are working. Although this field shows significant promise, we also highlight several of the key hurdles that must first be overcome before clinical translation of computational insights can be realized.

Neural Correlates of Internal States that Capture Movement Variability.

The brain lacks the ability to perfectly replicate movements. In particular, if specific movements are cued sequentially, how you perform on past trials may influence how you move on current and future trials. Past trial outcomes may, for example, modulate motivation or attention which can play a significant role in how one moves, yet variability due to such internal factors are often ignored when modeling the sensorimotor control system. In this study, we wish to extract such internal factors by modeling variability in movements during a motor task riddled with unpredictable perturbations. Four subjects performed the task, and we simultaneously obtained Local Field Potential (LFP) activity from nonmotor brain regions via depth electrodes implanted for clinical purposes. We first show that motor behavior depends not only on current trial conditions, but also on internal state variables that accumulate past outcomes involving movement performance, movement speed, and whether or not perturbations have occurred. We further show that these internal states modulate with beta band activity in specific brain regions on a trial-by-trial basis. These results suggest a nontraditional role of nonmotor brain regions and prompt a need for further exploration.

Do Neurodegenerative Diseases Affect Creativity? Divergent Thinking in Frontotemporal Dementia and Parkinson’s Disease

Creativity is considered to be one of the most important characteristics that humans possess. It emerges from fundamental cognitive operations and the activation of specific brain regions. In several neurological disorders, such as frontotemporal dementia (FTD) and Parkinson’s disease (PD), creativity plays an important role in diagnosis and rehabilitation strategies. This study examined the link between creativity and pathology in a sample of neurological patients (idiopathic PD, n = 17; FTD, n = 11 with behavioural or semantic variants), and 15 healthy subjects (Mini Mental State Examination score ≥ 20; age range, 45 to 85 years) using the Divergent Thinking Test. The FTD group exhibited lower scores than the PD and control groups. Furthermore, PD patients performed significantly better on the single DTT factor, originality, than controls. These results are discussed in relation to neurological mechanisms that may influence creative strategies in dementia. Finally, it has been proposed creativity therapy as a cognitive rehabilitation approach, which may help patients enhance and maintain cognitive functions, reduce the severity of emotional disorders, and promote social interactions.

A Breakdown of Imagined Visuomotor Transformations and Its Neural Correlates in Young Elderly Subjects.

Several studies have shown age-related changes in motor imagery (MI) in older adults and the associated compensatory brain activation patterns; most of these studies have used explicit MI tasks or implicit MI tasks focused on mental rotation of body parts. Here, we address the effect of ageing on MI for the more complex visuomotor transformations entailed by mentally simulated hand-tool interactions triggered by a grip selection task (GST) for tools used in daily life. We studied 22 young and 22 elderly subjects performing the GST, in which they were asked to report whether they would grip a portrayed tool with an overhand or an underhand grip. We found a behavioral decline in the elderly group, accompanied by reduced activations of the left posterior parietal lobule, in a subregion associated specifically with reaching behavior by previous investigations. No differences were observed in the temporal cortices associated with object semantics. These results suggested a specific age-related vulnerability of the neural substrates, particularly for the imaginary reaching component of the task, rather than for the semantically driven grasping component. The combination of behavioral deficits and reduced activation of specific brain regions speaks in favor of a specific age-associated deficit for the complex imaginary movements required by the GST.

Design and Validation of an FPGA-Based Configurable Transcranial Doppler Neurofeedback System for Chronic Pain Patients.

Neurofeedback is a self-regulation technique that can be applied to learn to voluntarily control cerebral activity in specific brain regions. In this work, a Transcranial Doppler-based configurable neurofeedback system is proposed and described. The hardware configuration is based on the Red Pitaya board, which gives great flexibility and processing power to the system. The parameter to be trained can be selected between several temporal, spectral, or complexity features from the cerebral blood flow velocity signal in different vessels. As previous studies have found alterations in these parameters in chronic pain patients, the system could be applied to help them to voluntarily control these parameters. Two protocols based on different temporal lengths of the training periods have been proposed and tested with six healthy subjects that were randomly assigned to one of the protocols at the beginning of the procedure. For the purposes of the testing, the trained parameter was the mean cerebral blood flow velocity in the aggregated data from the two anterior cerebral arteries. Results show that, using the proposed neurofeedback system, the two groups of healthy volunteers can learn to self-regulate a parameter from their brain activity in a reduced number of training sessions.

Cerebral oxygenation patterns during walking with wearable hip-assist robot in elderly adults: A fNIRS study

The purpose of this study was to investigate the modulating effect of wearable hip-assist robot, Gait Enhancing Mechatronic System (GEMS, Samsung Electronics Co., Ltd., Korea), on cerebral oxygenation patterns during treadmill gait in elderly adults. Twenty elderly adults participated in this study. Each subject performed treadmill walking task at self-selected speed either with assistance of GEMS (GEMS) or without assistance of GEMS (NoGEMS). An experimental session began with a fixed standing condition (60 s), followed by one of the 2 walking conditions (60 s) and then a resting condition (60 s) for five repetitions. For analyzing the cortical activation, a task period was divided into the early and late phase. Cerebral oxygenation was measured by oxyhemoglobin (OxyHb) concentration using the functional near infrared spectroscopy (fNIRS) imaging system (NIRScout, NIRx Medical Technology, LLC, Germany) covering bilateral prefrontal cortices (PFC), premotor cortices (PMC), supplemental motor areas (SMA), and lower limb sensorimotor cortices (SMC). We observed less OxyHb concentration over the lower limb SMC, SMA and PMC regions in the late phase of gait with GEMS than NoGEMS conditions. In addition, PFC activity demonstrated left side predominance in GEMS condition. Additional brain activity in older compared to younger adults may be a reflection of compensatory mechanism to improve performance in a specific task which is associated with less efficient use of neural resources. Walking with GEMS demonstrated decreased activity of specific brain regions related with gait and might represent increased efficiency of neural resources. In addition, increased hemispheric asymmetry during walking with GEMS might reflect less need for compensation through right prefrontal activity.

Long-term intensive locomotion training with wearable hip-assist robot in elderly adults: A preliminary study

The purpose of this study was to investigate the long-term training effect of wearable hip-assist robot on locomotion function in elderly adults. Seven elderly participants (age means: 74.5 ± 5.78, 3 males) were recruited. The Gait Enhancing Mechatronics System (GEMS, Samsung Electronic Co., Ltd., Korea), which functions as a wearable hip-assist robot was used. All participants received 45-minute gait training with GEMS in various overground environments for 24-sessions during the consecutive 8 weeks. Muscle efforts were acquired and analyzed using the 12-channel surface electromyography system (Desktop DTS system, Noraxon, USA) at preferred speed. Gait functions were determined by 3D motion capture system (Motion Analysis Corporation, USA). Cardiopulmonary metabolic energy consumption measurements were obtained during 6 minutes of treadmill walking using portable cardiopulmonary metabolic system (COSMED K4B 2 , Rome, IT). In addition, cerebral oxygenation was measured using the fNIRS imaging system (NIRSport, NIRx Medical Technologies LLC, Glen Head, NY, USA). The 24-sessions of long-term intensive locomotion training with GEMS significantly improved gait function of elderly adults ( P < 0.05). Metabolic energy consumption during 6 minutes treadmill walking was significantly lower after 24-sessions training ( P < 0.05). Furthermore, long-term intensive locomotion training with GEMS demonstrated decreased activity of specific brain regions related with gait and might represent increased efficiency of neural resources. These gains were maintained for 4 weeks after the cessation of training ( P < 0.05). The results of this preliminary study suggest that long-term intensive locomotion rehabilitation with the GEMS were tolerable and effective for improving gait function, cardiopulmonary metabolic efficiency and cerebral oxygenation patterns during walking in the elderly. Randomized controlled trial with larger participants is invited in near future.

Leveraging calcium imaging to illuminate circuit dysfunction in addiction.

Alcohol and drug use can dysregulate neural circuit function to produce a wide range of neuropsychiatric disorders, including addiction. To understand the neural circuit computations that mediate behavior, and how substances of abuse may transform them, we must first be able to observe the activity of circuits. While many techniques have been utilized to measure activity in specific brain regions, these regions are made up of heterogeneous sub-populations, and assessing activity from neuronal populations of interest has been an ongoing challenge. To fully understand how neural circuits mediate addiction-related behavior, we must be able to reveal the cellular granularity within brain regions and circuits by overlaying functional information with the genetic and anatomical identity of the cells involved. The development of genetically encoded calcium indicators, which can be targeted to populations of interest, allows for in vivo visualization of calcium dynamics, a proxy for neuronal activity, thus providing an avenue for real-time assessment of activity in genetically and anatomically defined populations during behavior. Here, we highlight recent advances in calcium imaging technology, compare the current technology with other state-of-the-art approaches for in vivo monitoring of neural activity, and discuss the strengths, limitations, and practical concerns for observing neural circuit activity in preclinical addiction models.

Zebrafish knockout of Down syndrome gene, DYRK1A, shows social impairments relevant to autism

BackgroundDYRK1A maps to the Down syndrome critical region at 21q22. Mutations in this kinase-encoding gene have been reported to cause microcephaly associated with either intellectual disability or autism in humans. Intellectual disability accompanied by microcephaly was recapitulated in a murine model by overexpressing Dyrk1a which mimicked Down syndrome phenotypes. However, given embryonic lethality in homozygous knockout (KO) mice, no murine model studies could present sufficient evidence to link Dyrk1a dysfunction with autism. To understand the molecular mechanisms underlying microcephaly and autism spectrum disorders (ASD), we established an in vivo dyrk1aa KO model using zebrafish.MethodsWe identified a patient with a mutation in the DYRK1A gene using microarray analysis. Circumventing the barrier of murine model studies, we generated a dyrk1aa KO zebrafish using transcription activator-like effector nuclease (TALEN)-mediated genome editing. For social behavioral tests, we have established a social interaction test, shoaling assay, and group behavior assay. For molecular analysis, we examined the neuronal activity in specific brain regions of dyrk1aa KO zebrafish through in situ hybridization with various probes including c-fos and crh which are the molecular markers for stress response.ResultsMicroarray detected an intragenic microdeletion of DYRK1A in an individual with microcephaly and autism. From behavioral tests of social interaction and group behavior, dyrk1aa KO zebrafish exhibited social impairments that reproduce human phenotypes of autism in a vertebrate animal model. Social impairment in dyrk1aa KO zebrafish was further confirmed by molecular analysis of c-fos and crh expression. Transcriptional expression of c-fos and crh was lower than that of wild type fish in specific hypothalamic regions, suggesting that KO fish brains are less activated by social context.ConclusionsIn this study, we established a zebrafish model to validate a candidate gene for autism in a vertebrate animal. These results illustrate the functional deficiency of DYRK1A as an underlying disease mechanism for autism. We also propose simple social behavioral assays as a tool for the broader study of autism candidate genes.

How changes in brain activity and connectivity are associated with motor performance in people with MS.

People with multiple sclerosis (MS) exhibit pronounced changes in brain structure, activity, and connectivity. While considerable work has begun to elucidate how these neural changes contribute to behavior, the heterogeneity of symptoms and diagnoses makes interpretation of findings and application to clinical practice challenging. In particular, whether MS related changes in brain activity or brain connectivity protect against or contribute to worsening motor symptoms is unclear. With the recent emergence of neuromodulatory techniques that can alter neural activity in specific brain regions, it is critical to establish whether localized brain activation patterns are contributing to (i.e. maladaptive) or protecting against (i.e. adaptive) progression of motor symptoms. In this manuscript, we consolidate recent findings regarding changes in supraspinal structure and activity in people with MS and how these changes may contribute to motor performance. Furthermore, we discuss a hypothesis suggesting that increased neural activity during movement may be either adaptive or maladaptive depending on where in the brain this increase is observed. Specifically, we outline preliminary evidence suggesting sensorimotor cortex activity in the ipsilateral cortices may be maladaptive in people with MS. We also discuss future work that could supply data to support or refute this hypothesis, thus improving our understanding of this important topic.

Effects of exercise on brain activity during walking in older adults: a randomized controlled trial

BackgroundPhysical activity may preserve neuronal plasticity, increase synapse formation, and cause the release of hormonal factors that promote neurogenesis and neuronal function. Previous studies have reported enhanced neurocognitive function following exercise training. However, the specific cortical regions activated during exercise training remain largely undefined. In this study, we quantitatively and objectively evaluated the effects of exercise on brain activity during walking in healthy older adults.MethodsA total of 24 elderly women (75–83 years old) were randomly allocated to either an intervention group or a control group. Those in the intervention group attended 3 months of biweekly 90-min sessions focused on aerobic exercise, strength training, and physical therapy. We monitored changes in regional cerebral glucose metabolism during walking in both groups using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG).ResultsAll subjects completed the 3-month experiment and the adherence to the exercise program was 100%. Compared with the control group, the intervention group showed a significantly greater step length in the right foot after 3 months of physical activity. The FDG-PET assessment revealed a significant post-intervention increase in regional glucose metabolism in the left posterior entorhinal cortex, left superior temporal gyrus, and right superior temporopolar area in the intervention group. Interestingly, the control group showed a relative increase in regional glucose metabolism in the left premotor and supplemental motor areas, left and right somatosensory association cortex, and right primary visual cortex after the 3-month period. We found no significant differences in FDG uptake between the intervention and control groups before vs. after the intervention.ConclusionExercise training increased activity in specific brain regions, such as the precuneus and entorhinal cortices, which play an important role in episodic and spatial memory. Further investigation is required to confirm whether alterations in glucose metabolism within these regions during walking directly promote physical and cognitive performance.Trial registrationUMIN-CTR (UMIN000021829). Retrospectively registered 10 April 2016.

Executive Network Activation is Linked to Walking Speed in Older Adults: Functional MRI and TCD Ultrasound Evidence From the MOBILIZE Boston Study.

Changes in cerebral blood flow velocity (CBF) in response to a cognitive task (task-related ΔCBF) have been shown by Transcranial Doppler ultrasonography (TCD) to be reduced in slow walkers. However, it is unknown whether reduced task-related ΔCBF is associated with reduced neural activity in specific brain regions, as measured by blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI). We assessed the regional changes in neural activity associated with reduced middle cerebral artery (MCA) task-related ΔCBF to an executive task and slow walking speed in 67 community-dwelling older adults from the MOBILIZE Boston Study. Participants underwent walking assessments and TCD ultrasonography measures of MCA ΔCBF during the n-back task of executive function. A subset of participants (n = 27) completed the same task during fMRI. Individual BOLD activation maps for the n-back task were correlated with TCD measures and network-level averages were associated with TCD and preferred walking speed. Participants with diminished task-related ΔCBF walked more slowly (β = .39, p = .001). fMRI revealed significant associations between task-related ΔCBF and regional BOLD activation in several brain regions/networks supplied by the MCA. Of these regions and networks, those within the executive network were most strongly associated with walking speed (β = .36, p = .01). Task-related ΔCBF during an executive function task is related to activation in several neural networks and impairment in the ability to recruit the executive network in particular is associated with slow walking speed in older adults.

Neural patterns in ecological momentary assessment of social stressors

BackgroundSuicidal behaviors result from a complex interaction between social stressors and individual vulnerability. Ecological Momentary Assessment (EMA) provides the opportunity to investigate the relationship between social stressors in daily life and the occurrence of negative thoughts leading to suicidal ideation. fMRI showed that a neural network supports the sensitivity to social stressors in suicide attempters.ObjectiveA joint fMRI/EMA study investigated whether individual differences in brain reactivity to scanner-based social rejection was related to social rejection during real-world social interactions.MethodSixty women were included: euthymic women with a history of depression with or without suicidal behavior and healthy controls. The Cyberball Game was used as a social exclusion paradigm. Following the fMRI, subjects used EMA for seven days, providing data on environmental, contextual and emotional factors.ResultsIn the fMRI study, in comparison to patients without any history of suicide attempt and healthy controls, suicide attempters showed decreased activation in the posterior cingulate cortex, insula and superior temporal gyrus during the exclusion vs. inclusion condition. In the EMA study, social stressors were specific predictors of suicidal ideation in suicide attempters. We will examine here if individuals who show greater activity in specific brain regions during scanner-based social rejection reported a greater social distress during their daily social interactions.Conclusionsthis study used a combined technique to assess whether neural reactivity to experimental social rejection in the scanner is related to real-world social experience, and if it may help to understand the sensitivity to social stress in suicidal behavior.Disclosure of interestThe authors declare that they have no competing interest.

Changes in the Brain’s Intrinsic Organization in the Resting State with Real-Time fMRI Neurofeedback Training of Posterior Cingulate Cortex Activity

Real-time functional magnetic resonance imaging (rtfMRI) technology has been widely used to train subjects to actively regulate the activity of specific brain regions. Although many previous studies have demonstrated that neurofeedback training alters the functional connectivity between brain regions in the task state and resting state, it is unclear how the regulation of the key hub of the default mode network (DMN) affects the topological properties of the resting-state brain network. The current study aimed to investigate what topological changes would occur in the large-scale intrinsic organization of the resting state after the real-time down-regulation of the posterior cingulate cortex (PCC). The results indicated that the down-regulation of the PCC in the DMN reduced the functional connectivity of the PCC with the nodes outside of the DMN and reduced functional connectivity between the superior medial frontal gyrus (SFGmed) and parahippocampal gyrus (PHG) in the experimental group. Moreover, the nodal graph properties of the SFGmed were reduced, while that of the PHG showed the opposite alteration after the down-regulation of the PCC. These findings possibly suggest that the regulation of the key hub of the DMN, the PCC, mainly changed the information transfer of the SFGmed and PHG.

Chronic stress and moderate physical exercise prompt widespread common activation and limited differential activation in specific brain regions

Chronic stress in rodents produces depressive behaviors, whereas moderate physical exercise counteracts stress-induced depressive behaviors. Chronic stress and physical exercise appear to produce such opposing effects by changing the neural activity of specific brain regions. However, the detailed mechanisms through which the two different types of stimuli regulate brain function in opposite directions are not clearly understood. In the present study, we attempted to explore the neuroanatomical substrates mediating stress-induced behavioral changes and anti-depressant effects of exercise by examining stimulus-dependent c-Fos induction in the brains of mice that were exposed to repeated stress or exercise in a scheduled manner. Systematic and integrated analyses of c-Fos expression profiles indicated that various brain areas, including the prelimbic cortex, lateral septal area, and paraventricular nuclei of hypothalamus were commonly and strongly activated by both stress and exercise, while the lateral habenula and hippocampus were identified as being preferentially activated by stress and exercise, respectively. Exercise-dependent c-Fos expression in all regions examined in the brain occurred in both glutamatergic and GABAergic neurons. These results suggest that chronic stress and moderate exercise produce counteractive effects on mood behaviors, along with prompting widespread common activation and limited differential activation in specific brain regions.

EP 131. Real-time fMRI neurofeedback training in elderly leads to cognitive improvement and changes in cerebral connectivity

Introduction During past years real-time functional MRI (rtfMRI) has been shown to be a feasible tool for neurofeedback (NFB). This is a technique, which aims at subjects learning to voluntarily modulate activation of specific brain regions. It has already been applied successfully clinically and non-clinically. We conducted rtfMRI NFB training of the left parahippocampal gyrus (PHG) in healthy elderly with the hypothesis subjects are indeed able to modulate left PHG activation and that this training leads to increased cognitive performance. Here, we also focus on brain connectivity over the course of the training. Methods 16 subjects (mean age 63.5 y, 9 male) completed the protocol of five examination days (T1–T5). On T1 the neuropsychological pre-test was done (see table), followed by the encoding of a real-world footpath (one out of three variants). On T2–T4 the rtfMRI NFB training was carried out. Activation of the left PHG was fed back visually by a thermometer bar. The task alternated between upregulation (recalling the path encoded on T1) and baseline (counting backwards). Three rtfMRI NFB runs were done per day. On T5 the neuropsychological post-test was done. For analysis of neuropsychological data ANCOVAs with examination day and variant of the footpath as factors and age, education and gender as covariates were calculated. For fMRI data a general linear model with upregulation as predictor was computed with BrainVoyager QX for each NFB run and the activation was then averaged across all runs. Activation was limited to a threshold of Bonferroni-corrected p . 05 and two voxels of cluster size. To conduct an analysis of connectivity, activation time courses were extracted from clusters active during upregulation and averaged for each day and region. With the statistical software R, a Granger-Causality-Analysis (GCA) for each training day was conducted for each combination of active regions (306 connections) with a lag size of 1 volume (2000 ms). P-values were corrected using the Bonferroni-Holm method. Results Subjects showed improvements in the following neuropsychological tests: a visuo-spatial-memory task from the VVM (F(1,13) = 8.378, p = .013), the backward-digit-span task from the WMS (F(1,13) = 6.919, p = .021) and the MoCA (F(1,13) = 12.204, p = .004). Functional MRI analysis revealed that during NFB training the left PHG was indeed activated. Activation was further found in the right PHG, the left posterior cingulate, bilaterally in the precuneus, superior occipital lobe, middle frontal gyrus and the cerebellum. GCA revealed 133 connections on T2, 206 on T3 and 156 on T4. The main findings were: (1) activation was chiefly driven by both anterior lobes of the cerebellum, the left posterior cingulate and a cluster within the right precuneus, but these regions received only few input from other regions; (2) there was no connectivity between both PHG; (3) the amount of connections to both PHG increased over time, while the amount of connections from both PHG to other regions such as the right cerebellum and the right precuneus tended to decrease. Conclusions The neuropsychological, activation and connectivity data from our NFB training in elderly suggest the following: (1) subjects were able to modulate left PHG activation; (2) the conducted training lead to increased cognitive performance; (3) GCA revealed a complex underlying neuronal network, mainly driven by a small number of regions and with a changing role of the target region of the training over time.

Hypocretin Neurotransmission Within the Central Amygdala Mediates Escalated Cocaine Self-administration and Stress-Induced Reinstatement in Rats

BackgroundCocaine addiction is characterized by patterns of compulsive drug-taking, including preoccupation with obtaining cocaine and loss of control over drug intake. The lateral hypothalamic hypocretin/orexin (HCRT) system has been implicated in drug-taking and the reinstatement of drug-seeking. Evidence suggests that HCRT may drive drug-seeking through activation of specific brain regions implicated in stress system dysfunction, including the central amygdala (CeA). The role of HCRT in the persistence of compulsive-like cocaine-taking has yet to be fully elucidated. MethodsSystemic and intra-CeA microinfusions of the HCRT-receptor 1 antagonist, SB-334867, were administered to rats allowed either short (1 hour; ShA) or long (6 hours; LgA) access to cocaine self-administration. Animals were tested for fixed and progressive ratio responding for cocaine and stress-induced reinstatement of drug-seeking. In addition, using electrophysiological techniques on in vitro slices, we investigated gamma-aminobutyric acidergic (GABAergic) neurotransmission in the medial CeA and the sensitivity of GABAergic synapses to modulation of the HCRT system in ShA or LgA rats. ResultsWe found systemic administration of SB-334867 (0, 7.5, 15, 30 mg/kg) dose dependently decreased cocaine intake specifically in LgA rats but not in ShA rats. Microinjections of SB-334867 (20 nmol) bilaterally into the CeA significantly reduced cocaine intake in LgA rats. We also observed a significant attenuation of yohimbine-induced reinstatement of cocaine-seeking after intra-CeA SB-334867 (10 nmol) administration. Finally, electrophysiological data indicated enhanced GABAergic neurotransmission within the medial CeA in LgA rats, which was blocked with SB-334867 (10 μmol/L). ConclusionsThese findings suggest that HCRT neurotransmission within the CeA is implicated in compulsive-like cocaine-seeking.