Search results for: dorsolateral prefrontal cortex

Authors: Woogul Lee, Johnmarshall Reeve

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Learners’ perceived autonomy predicts learners’ interest, engagement, and learning. To understand these processes, we conducted an fMRI experiment. In this experiment, participants saw the national flag and were asked to rate how much they freely wanted to learn about that particular national flag. The participants then learned the characteristics of the national flag. Results showed that (1) the degree of participants’ perceived autonomy was positively correlated with the degree of insula activity, (2) participants’ early-trial insula activity predicted corresponding late-trial dorsolateral prefrontal cortex activity, and (3) the degree of dorsolateral prefrontal cortex activity was positively correlated with the degree of participants’ learning about the characteristics of the national flag. Results suggest that learners’ perceived autonomy predicts learning through the mediation of insula activity associated with intrinsic satisfaction and 'pure self' processes.

Keywords: insular cortex, autonomy, self-determination, dorsolateral prefrontal cortex

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Authors: Aline M. Dantas, Alexander T. Sack, Elisabeth Bruggen, Peiran Jiao, Teresa Schuhmann

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Risk-taking behavior has been associated with the activity of specific prefrontal regions of the brain, namely the right dorsolateral prefrontal cortex (DLPFC) and the ventromedial prefrontal cortex (VMPFC). While the deactivation of the rDLPFC has been shown to lead to increased risk-taking behavior, the functional relationship between VMPFC activity and risk-taking behavior is yet to be clarified. Correlational evidence suggests that the VMPFC is involved in valuation processes that involve risky choices, but evidence on the functional relationship is lacking. Therefore, this study uses brain stimulation to investigate the role of the VMPFC during risk-taking behavior and replicate the current findings regarding the role of the rDLPFC in this same phenomenon. We used continuous theta-burst stimulation (cTBS) to inhibit either the VMPFC or DLPFC during the execution of the computerized Maastricht Gambling Task (MGT) in a within-subject design with 30 participants. We analyzed the effects of such stimulation on risk-taking behavior, participants’ choices of probabilities and average values, and response time. We hypothesized that, compared to sham stimulation, VMPFC inhibition leads to a reduction in risk-taking behavior by reducing the appeal to higher-value options and, consequently, the attractiveness of riskier options. Right DLPFC (rDLPFC) inhibition, on the other hand, should lead to an increase in risk-taking due to a reduction in cognitive control, confirming existent findings. Stimulation of both the rDLPFC and the VMPFC led to an increase in risk-taking behavior and an increase in the average value chosen after both rDLPFC and VMPFC stimulation compared to sham. No significant effect on chosen probabilities was found. A significant increase in response time was observed exclusively after rDLPFC stimulation. Our results indicate that inhibiting DLPFC and VMPFC separately leads to similar effects, increasing both risk-taking behavior and average value choices, which is likely due to the strong anatomical and functional interconnection of the VMPFC and rDLPFC.

Keywords: decision-making, risk-taking behavior, brain stimulation, TMS

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Authors: Irene M. Arora

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Hypothesis: Attention Deficit Hyperactivity Disorder is the result of an underdeveloped prefrontal cortex which is the primary cause for the signs and symptoms seen as defining features of ADHD. Methods: Through ‘PubMed’, ‘Wiley’ and ‘Google Scholar’ studies published between 2011-2018 were evaluated, determining if a dysfunctional prefrontal cortex caused the characteristic symptoms associated with ADHD. The search terms "prefrontal cortex", "Attention-Deficit/Hyperactivity Disorder", "cognitive control", "frontostriatal tract" among others, were used to maximize the assortment of relevant studies. Excluded papers were systematic reviews, meta-analyses and publications published before 2010 to ensure clinical relevance. Results: Nine publications were analyzed in this review, all of which were non-randomized matched control studies. Three studies found a decrease in the functional integrity of the frontostriatal tract fibers in conjunction with four studies finding impaired frontal cortex stimulation. Prefrontal dysfunction, specifically medial and orbitofrontal areas, displayed abnormal functionality of reward processing in ADHD patients when compared to their normal counterparts. A total of 807 subjects were studied in this review, yielding that a little over half (54%) presented with remission of symptoms in adulthood. Conclusion: While the prefrontal cortex shows the highest consistency of impaired activity and thinner volumes in patients with ADHD, this is a heterogenous disorder implicating its pathophysiology to the dysfunction of other neural structures as well. However, remission of ADHD symptomatology in adulthood was found to be attributable to increased prefrontal functional connectivity and integration, suggesting a key role for the prefrontal cortex in the development of ADHD.

Keywords: prefrontal cortex, ADHD, inattentive, impulsivity, reward processing

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Authors: Alexandre H. Okano, Pedro M. D. Agrícola, Daniel G. Da S. Machado, Luiz I. Do N. Neto, Luiz F. Farias Junior, Paulo H. D. Nascimento, Rickson C. Mesquita, John F. Araujo, Eduardo B. Fontes, Hassan M. Elsangedy, Shinsuke Shimojo, Li M. Li

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The prefrontal cortex is involved in the reward system and the insular cortex integrates the afferent inputs arriving from the body’ systems and turns into feelings. Therefore, modulating neuronal activity in these regions may change individuals’ perception in a given situation such as exercise. We tested whether transcranial direct current stimulation (tDCS) change cerebral oxygenation and pleasure during exercise. Fourteen volunteer healthy adult men were assessed into five different sessions. First, subjects underwent to a maximum incremental test on a cycle ergometer. Then, subjects were randomly assigned to a transcranial direct current stimulation (2mA for 15 min) intervention in a cross over design in four different conditions: anode and cathode electrodes on T3 and Fp2 targeting the insular cortex, and Fpz and F4 targeting prefrontal cortex, respectively; and their respective sham. These sessions were followed by 30 min of moderate intensity exercise. Brain oxygenation was measured in prefrontal cortex with a near infrared spectroscopy. Perceived exertion and pleasure were also measured during exercise. The asymmetry in prefrontal cortex oxygenation before the stimulation decreased only when it was applied over this region which did not occur after insular cortex or sham stimulation. Furthermore, pleasure was maintained during exercise only after prefrontal cortex stimulation (P > 0.7), while there was a decrease throughout exercise (P < 0.03) during the other conditions. We conclude that tDCS over the prefrontal cortex changes brain oxygenation in ventromedial prefrontal cortex and maintains perceived pleasure during exercise. Therefore, this technique might be used to enhance effective responses related to exercise.

Keywords: affect, brain stimulation, dopamine neuromodulation, pleasure, reward, transcranial direct current stimulation

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Authors: Singh Deepeshwar, Suhas Vinchurkar

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Similar to neuroimaging findings through functional magnetic resonance imaging (fMRI) assessing regional cerebral blood oxygenation, the functional near infrared spectroscopy (fNIRS) has also been used to assess hemodynamic responses in the imaged region of the brain. The present study assessed hemodynamic responses in terms of changes in oxygenation (HbO), deoxygenation (HbR) and total hemoglobin (THb) on the prefrontal cortex (PFC), bilaterally, using fNIRS in 10 participants who performed three voluntary regulated breathing (pranayama) practices viz. (i) Left nostril breathing (LNB), (ii) Right nostril breathing (RNB); and (iii) Alternating nostril breathing (ANB) and compared with normal breathing as baseline (BS). For this, we used 64 channel NIRS system covering left and the right prefrontal cortex. The normal breathing kept as baseline (BS) measures as regressors in the investigation of hemodynamic responses when compared with LNB, RNB and ANB. In the results, we found greater oxygenation in contralateral side i.e., higher activation on the left prefrontal cortex (lPFC) during RNB, and right prefrontal cortex (rPFC) during LNB, whereas ANB showed greater deoxygenation responses on both sides of PFC. Interestingly, LNB showed increased oxygenation on ipsilateral side i.e., lPFC but not during RNB. This suggests that voluntary regulated breathing produced an immediate effect not only on contralateral but ipsilateral sides of the brain as well. In conclusion, breathing practices are tightly coupled to cerebral rhythms of alternating cerebral hemispheric activity during particular nostril breathing. These results of the specific nostril breathing do not support previous findings of contralateral hemispheric improvement while left or right nostril breathing only.

Keywords: hemodynamic responses, brain, pranayama, voluntary regulated breathing practices, prefrontal cortex

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Authors: A. Alli-Oluwafuyi, A. Amin, S. M. Fii, S. O. Amusa, A. Imam, N. T. Asogwa, W. I. Abdulmajeed, F. Olaseinde, B. V. Owoyele

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Chronic stress or prolonged glucocorticoid administration impairs higher cognitive functions in rodents and humans. However, the mechanisms are not fully clear. Insulin and receptors are expressed in the brain and are involved in cognition. Insulin resistance accompanies Alzheimer’s disease and associated cognitive decline. The goal of this study was to evaluate the effects of sub-chronic administration of a glucocorticoid, dexamethasone (DEX) on behavior and biochemical changes in prefrontal cortex (PFC). Male Wistar rats were administered DEX (2, 4 & 8 mg/kg, IP) or saline for seven consecutive days and behavior was assessed in the following paradigms: “Y” maze, elevated plus maze, Morris’ water maze and novel object recognition (NOR) tests. Insulin, lactate dehydrogenase (LDH) and Superoxide Dismutase (SOD) activity were evaluated in homogenates of the prefrontal cortex. DEX-treated rats exhibited impaired prefrontal cortex function manifesting as reduced locomotion, impaired novel object exploration and impaired short- and long-term spatial memory compared to normal controls (p < 0.05). These effects were not consistently dose-dependent. These behavioral alterations were accompanied by a decrease in insulin concentration observed in PFC of 4 mg/kg DEX-treated rats compared to control (10μIU/mg vs. 50μIU/mg; p < 0.05) but not 2mg/kg. Furthermore, we report a modification of brain stress markers LDH and SOD (p > 0.05). These results indicate that prolonged activation of GCs disrupt prefrontal cortex function which may be related to insulin impairment. These effects may not be attributable to a non-specific elevation of oxidative stress in the brain. Future studies would evaluate mechanisms of GR-induced insulin loss.

Keywords: dexamethasone, insulin, memory, prefrontal cortex

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Authors: Wenqiu Cao

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Suicide prevention is a global problem that needs to be taken seriously. Investigating the mechanisms of suicide in major depressive disorder (MDD) separately through neuroimaging technology is essential for effective suicide prevention. And it’s particularly urgent in geriatric depressive patients since older adults are more likely to use rapidly deadly means, and suicidal behavior is more lethal for older adults. The current study reviews five studies related to suicide in geriatric MDD that uses neuroimaging methodology in order to analyze the relevant neurobiological mechanisms. The majority of the studies found significant white matter and grey matter reduction or lesion widespread in multiple brain regions, including the frontal and parietal regions, the midbrain, the external capsule, and the cerebellum. Regarding the cognitive impairment in geriatric MDD, the reward signals were found weakened in the paralimbic cortex. The functional magnetic resonance imaging (fMRI) studies also found hemodynamic changes in the right dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and right frontopolar cortex (FPC) regions in late-life MDD patients with suicidal ideation. Future studies should consider the age of depression onset, more accurate measurements of suicide, larger sample size, and longitudinal design.

Keywords: brain imaging, geriatric major depressive disorder, suicidality, suicide

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Authors: Sang-Sun Yoon, Yea-Hyun Leem, Sangmee Ahn Jo

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The N-acetylated-alpha-linked-acidic (NAAG) peptidase inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) has demonstrated to be neuroprotective against glutamate-mediated neuron degeneration and neurological disorders such as ischemia. Several studies have demonstrated impaired psychiatric function by altered glutamate carboxypeptidase II expression, although 2-PMPA has not yet been studied. Thus, we investigated effect of 2-PMPA on depressive-like phenotype using C57BL/6 mice. Treatment of 2-PMPA (10 mg/kg for 6 days/daily, ip injection) on C57BL/6 naïve mice showed depressive-like symptoms such as decreased social preference, but did not affect the immobility measured by tail suspension test. Reduction of phosphorylated cAMP-responsive element binding (p-CREB) known as a representative marker of depressive-like behavior was observed in layer 1 and piriform cortex subregions of the prefrontal cortex of 2-PMPA-treated mice. The immunoreactivity of metabotropic glutamate receptors 5 (mGluR5) that mediate phosphorylation of CREB was also decreased in layer 1 and piriform cortex subregions of the prefrontal cortex of 2-PMPA injected mice. Thus, our results suggest that dysregulation of the GCPII or NAAG by 2-PMPA treatment is likely to be associated with pathogenesis of depression and further studies are needed to understand whether the reduced NAAG level or enhanced glutamate level in the brain is involved in this response.

Keywords: depression, GCPII, 2-PMPA, p-CREB, mGluR5

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Authors: Eleni Peristeri, Georgia Fotiadou, Ianthi-Maria Tsimpli

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The local-global dimension has been studied extensively in healthy controls and preference for globally processed stimuli has been validated in both the visual and auditory modalities. Critically, the local-global dimension has an inherent interference resolution component, a type of cognitive control, and left-prefrontal-cortex-damaged (LPFC) individuals have exhibited inability to override habitual response behaviors in item recognition tasks that involve representational interference. Eight patients with damage in the left PFC (age range: 32;5 to 69;0. Mean age: 54;6 yrs) and twenty age- and education-matched language-unimpaired adults (mean age: 56;7yrs) have participated in the study. Distinct performance patterns were found between the language-unimpaired and the LPFC-damaged group which have mainly stemmed from the latter’s difficulty with inhibiting global stimuli in incongruent trials. Overall, the local-global attentional dimension affects LPFC-damaged individuals with non-fluent aphasia in non-language domains implicating distinct types of inhibitory processes depending on the level of processing.

Keywords: left lateral prefrontal cortex damage (LPFC), local-global non-language attention, representational interference, non-fluent aphasia

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Authors: Takashi Kaburagi, Takamasa Komura, Yosuke Kurihara

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Absolute pitch is the ability to identify a musical note without a reference tone. Training for absolute pitch often occurs in preschool education. It is necessary to clarify how well the trainee can make use of synesthesia in order to evaluate the effect of the training. To the best of our knowledge, there are no existing methods for objectively confirming whether the subject is using synesthesia. Therefore, in this study, we present a method to distinguish the use of color-auditory synesthesia from the separate use of color and audition during absolute pitch training. This method measures blood volume in the prefrontal cortex using functional Near-infrared spectroscopy (fNIRS) and assumes that the cognitive step has two parts, a non-linear step and a linear step. For the linear step, we assume a second order ordinary differential equation. For the non-linear part, it is extremely difficult, if not impossible, to create an inverse filter of such a complex system as the brain. Therefore, we apply a method based on a self-organizing map (SOM) and are guided by the available data. The presented method was tested using 15 subjects, and the estimation accuracy is reported.

Keywords: absolute pitch, functional near-infrared spectroscopy, prefrontal cortex, synesthesia

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Authors: Singh Deepeshwar, N. K. Manjunath, M. Avinash

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Meditation is a self-regulated conscious process associated with improved awareness, perception, attention and overall performance. Different traditional origin of meditation technique may have different effects on autonomic activity and brain functions. Based on this quest, the present study evaluated the effect of Tai-Chi Chuan (TCC, a Chines movement based meditation technique) and Cyclic Meditation (CM, an Indian traditional based stimulation and relaxation meditation technique) on the hemodynamic responses of the prefrontal cortex (PFC) and autonomic functions (such as R-R interval of heart rate variability and respiration). These two meditation practices were compared with simple walking. Employing 64 channel near infrared spectroscopy (NIRS), we measured hemoglobin concentration change (i.e., Oxyhemoglobin [ΔHbO], Deoxyhemoglobin [ΔHbR] and Total hemoglobin change [ΔTHC]) in the bilateral PFC before and after TCC, CM and Walking in young college students (n=25; average mean age ± SD; 23.4 ± 3.1 years). We observed the left PFC activity predominantly modulates sympathetic activity effects during the Tai-Chi whereas CM showed changes on right PFC with vagal dominance. However, the changes in oxyhemoglobin and total blood volume change after Tai-Chi was significant higher (p < 0.05, spam t-maps) on the left hemisphere, whereas after CM, there was a significant increase in oxyhemoglobin (p < 0.01) with a decrease in deoxyhemoglobin (p < 0.05) on right PFC. The normal walking showed decrease in Oxyhemoglobin with an increase in deoxyhemoglobin on left PFC. The autonomic functions result showed a significant increase in RR- interval (p < 0.05) along with significant reductions in HR (p < 0.05) in CM, whereas Tai-chi session showed significant increase in HR (p < 0.05) when compared to walking session. Within a group analysis showed a significant reduction in RR-I and significant increase in HR both in Tai-chi and walking sessions. The CM showed there were a significant improvement in the RR - interval of HRV (p < 0.01) with the reduction of heart rate and breath rate (p < 0.05). The result suggested that Tai-Chi and CM both have a positive effect on left and right prefrontal cortex and increase sympathovagal balance (alertful rest) in autonomic nervous system activity.

Keywords: brain, hemodynamic responses, yoga, meditation, Tai-Chi Chuan (TCC), walking, heart rate variability (HRV)

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Authors: Ubaid Ullah Kamgar, Ajaz Ahmed Suhaff, Mohammad Maqbool Dar

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Objective: The aim is to study the association of MRI findings of T₂/FLAIR white matter hyperintensities among patients with psychiatric disorders. Background and Rationale: MRI findings in psychiatric disorders can vary widely depending on specific disorders and individual differences. However, some general patterns have been observed, such as, in Depression - reduced volume in areas such as the prefrontal cortex and hippocampus; in Schizophrenia - enlarged ventricles, abnormalities in frontal and temporal lobes, as well as hippocampus and thalamus; in Bipolar Disorder – reduced volume in the prefrontal cortex and hippocampus and abnormalities in the amygdala; in OCD – abnormalities in the orbitofrontal cortex, anterior cingulate cortex and striatum. However, many patients show findings of white-matter hyper-intensities, which are usually considered non-specific in psychiatry. These hyperintensities are low attenuation in the deep and white matter. The pathogenic mechanisms of white matter hyperintensities are not well-understood and have been attributed to cerebral small vessel disease. The aim of the study is to study the association of the above MRI findings in patients with psychiatric disorders after ruling out neurological disorders (if any are found). Methodology: Patients admitted to psychiatric hospitals or presenting to OPDs with underlying psychiatric disorders, having undergone MRI Brain as part of investigations, and having T₂/FLAIR white-matter hyperintensities on MRI were taken to study the association of the above MRI findings with different psychiatric disorders. Results: Out of the 22 patients having MRI findings of T₂/FLAIR white-matter hyper-intensities, the underlying psychiatric comorbidities were: Major Depressive Disorder in 7 pts; Obsessive Compulsive Disorder in 5 pts; Bipolar Disorder in 5 pts; Dementia (vascular type) in 5pts. Discussion and conclusion: In our study, the white matter hyper-intensities were found mostly in MDD (32%), OCD (22.7%), Bipolar Disorder (22.7%) and Dementia in 22.7% of patients. In conclusion, the presence of white-matter hyperintensities in psychiatric disorders underscores the complex interplay between vascular, neurobiological and psychosocial factors. Further research with a large sample size is needed to fully elucidate their clinical significance.

Keywords: white-matter hyperintensities, OCD, MDD, dementia, bipolar disorder.

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Authors: Yi Li, Yinan Zheng, Ya Ke, Yungwing Ho

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Motor learning is a process that frequently happens among humans and rodents, which is defined as the changes in the capability to perform a skill that is conformed to have a relatively permanent improvement through practice or experience. There are many ways to learn a behavior, among which is observational learning. Observational learning is the process of learning by watching the behaviors of others, for example, a child imitating parents, learning a new sport by watching the training videos or solving puzzles by watching the solutions. Many research explores observational learning in humans and primates. However, the neuronal mechanism of which, especially observational motor learning, was uncertain. It’s well accepted that mirror neurons are essential in the observational learning process. These neurons fire when the primate performs a goal-directed action and sees someone else demonstrating the same action, which suggests they have high firing activity both completing and watching the behavior. The mirror neurons are assumed to mediate imitation or play a critical and fundamental role in action understanding. They are distributed in many brain areas of primates, i.e., posterior parietal cortex (PPC), premotor cortex (M2), and primary motor cortex (M1) of the macaque brain. However, few researchers report the existence of mirror neurons in rodents. To verify the existence of mirror neurons and the possible role in motor learning in rodents, we performed customised string-pulling behavior combined with multiple behavior analysis methods, photometry, electrophysiology recording, c-fos staining and optogenetics in healthy mice. After five days of training, the demonstrator (demo) mice showed a significantly quicker response and shorter time to reach the string; fast, steady and accurate performance to pull down the string; and more precisely grasping the beads. During three days of observation, the mice showed more facial motions when the demo mice performed behaviors. On the first training day, the observer reduced the number of trials to find and pull the string. However, the time to find beads and pull down string were unchanged in the successful attempts on the first day and other training days, which indicated successful action understanding but failed motor learning through observation in mice. After observation, the post-hoc staining revealed that the c-fos expression was increased in the cognitive-related brain areas (medial prefrontal cortex) and motor cortices (M1, M2). In conclusion, this project indicated that the observation led to a better understanding of behaviors and activated the cognitive and motor-related brain areas, which suggested the possible existence of mirror neurons in these brain areas.

Keywords: observation, motor learning, string-pulling behavior, prefrontal cortex, motor cortex, cognitive

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Authors: I-Han Hsiao, Chun-Ping Huang, Ching-Liang Hsieh, Yi-Wen Lin

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Epilepsy is chronic brain disorder that results in the sporadic occurrence of spontaneous seizures in the temporal lobe, cerebral cortex, and hippocampus. Clinical antiepileptic medicines are often ineffective or little benefits in the small amount of patients and usually initiate severe side effects. This inflammation contributes to enhanced neuronal excitability and the onset of epilepsy. Auricular electric-stimulation (AES) can increase parasympathetic activity and stimulate the solitary tract nucleus to induce the cholinergic anti-inflammatory pathway. Furthermore, it may be a therapeutic strategy for the treatment of epilepsy. In the present study, we want to investigate the effects of AES on inflammatory mediators in kainic acid (KA)-induced epileptic seizure rats. Experimental KA injection increased expression of TLR-2 pathway associated inflammatory mediators, were further reduced by either 2Hz or 15 Hz AES in the prefrontal cortex, hippocampus, and somatosensory cortex. We suggest that AES can successfully control the epileptic seizure by down-regulation of inflammation signaling pathway.

Keywords: auricular electric-stimulation, epileptic seizures, anti-inflammation

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Authors: Ivette Gonzalez-Rivera, Diana B. Paz-Trejo, Oscar Galicia-Castillo, David N. Velazquez-Martinez, Hugo Sanchez-Castillo

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Prolonged exposure to stress can cause disorders related with dysfunction in the prefrontal cortex such as generalized anxiety and depression. These disorders involve alterations in neurotransmitter systems; the serotonergic system—a target of the drugs that are commonly used as a treatment to these disorders—is one of them. Recent studies suggest that 5-HT1A receptors play a pivotal role in the serotonergic system regulation and in stress responses. In the same way, there is increasing evidence that astrocytes are involved in the pathophysiology of stress. The aim of this study was to examine the effects of 8-OH-DPAT, a selective agonist of 5-HT1A receptors, in the behavioral signs of anxiety and anhedonia as well as in the number of astrocytes in the medial prefrontal cortex (mPFC) after exposure to chronic stress. They used 50 male Wistar rats of 250-350 grams housed in standard laboratory conditions and treated in accordance with the ethical standards of use and care of laboratory animals. A protocol of chronic unpredictable stress was used for 10 consecutive days during which the presentation of stressors such as motion restriction, water deprivation, wet bed, among others, were used. 40 rats were subjected to the stress protocol and then were divided into 4 groups of 10 rats each, which were administered 8-OH-DPAT (Tocris, USA) intraperitoneally with saline as vehicle in doses 0.0, 0.3, 1.0 and 2.0 mg/kg respectively. Another 10 rats were not subjected to the stress protocol or the drug. Subsequently, all the rats were measured in an open field test, a forced swimming test, sucrose consume, and a cero maze test. At the end of this procedure, the animals were sacrificed, the brain was removed and the tissue of the mPFC (Bregma: 4.20, 3.70, 2.70, 2.20) was processed in immunofluorescence staining for astrocytes (Anti-GFAP antibody - astrocyte maker, ABCAM). Statistically significant differences were found in the behavioral tests of all groups, showing that the stress group with saline administration had more indicators of anxiety and anhedonia than the control group and the groups with administration of 8-OH-DPAT. Also, a dose dependent effect of 8-OH-DPAT was found on the number of astrocytes in the mPFC. The results show that 8-OH-DPAT can modulate the effect of stress in both behavioral and anatomical level. Also they indicate that 5-HT1A receptors and astrocytes play an important role in the stress response and may modulate the therapeutic effect of serotonergic drugs, so they should be explored as a fundamental part in the treatment of symptoms of stress and in the understanding of the mechanisms of stress responses.

Keywords: anxiety, prefrontal cortex, serotonergic system, stress

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Authors: Asmaa Tahiri, Mouktafi Amine

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A substantial number of traditional medical research has been put forward to managing and treating mental disorders. At the present time, to our best knowledge, it is believed that fundamental understanding of the underlying causes of the majority psychological disorders needs to be explored further to inform early diagnosis, managing symptoms and treatment. The emerging field of evolutionary psychology is a promising prospect to address the origin of mental disorders, potentially leading to more effective treatments. Schizophrenia as a topical mental disorder has been linked to the evolutionary adaptation of the human brain represented in the brain connectivity and asymmetry directly linked to humans higher brain cognition in contrast to other primates being our direct living representation of the structure and connectivity of our earliest common African ancestors. As proposed in the evolutionary psychology scientific literature the pathophysiology of schizophrenia is expressed and directly linked to altered connectivity between the Hippocampal Formation (HF) and Dorsolateral Prefrontal Cortex (DLPFC). This research paper presents the results of the use of tractography analysis using multiple open access Diffusion Weighted Imaging (DWI) datasets of healthy subjects, schizophrenia-affected subjects and primates to illustrate the relevance of the aforementioned brain regions connectivity and the underlying evolutionary changes in the human brain. Deterministic fiber tracking and streamline analysis were used to generate connectivity matrices from the DWI datasets overlaid to compute distances and highlight disconnectivity patterns in conjunction with other fiber tracking metrics; Fractional Anisotropy (FA), Mean Diffusivity (MD) and Radial Diffusivity (RD).

Keywords: tractography, evolutionary psychology, schizophrenia, brain connectivity

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Authors: Ana Munguia, Gerardo Ortiz, Guadalupe Gonzalez, Fiacro Jimenez

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Parkinson's disease (PD) is a neurodegenerative disorder that causes motor and cognitive symptoms. The first-choice treatment for these patients is pharmacological, but this generates several side effects. Because of that new treatments were introduced such as Repetitive Transcranial Magnetic Stimulation (rTMS) in order to improve the life quality of the patients. Several studies suggest significant changes in motor symptoms. However, there is a great diversity in the number of pulses, amplitude, frequency and stimulation targets, which results in inconsistent data. In addition, these studies do not have an analysis of the neuropsychological effects of the treatment. The main purpose of this study is to evaluate the impact of rTMS on the cognitive performance of 6 patients with H&Y III and IV (45-65 years, 3 men and 3 women). An initial neuropsychological and neurological evaluation was performed. Patients were randomized into two groups; in the first phase one received rTMS in the supplementary motor area, the other group in the dorsolateral prefrontal cortex contralateral to the most affected hemibody. In the second phase, each group received the stimulation in the area that he had not been stimulated previously. Reassessments were carried out at the beginning, at the end of each phase and a follow-up was carried out 6 months after the conclusion of the stimulation. In these preliminary results, it is reported that there's no statistically significant difference before and after receiving rTMS in the neuropsychological test scores of the patients, which suggests that the cognitive performance of patients is not detrimental. There are even tendencies towards an improvement in executive functioning after the treatment. What added to motor improvement, showed positive effects in the activities of the patients' daily life. In a later and more detailed analysis, will be evaluated the effects in each of the patients separately in relation to the functionality of the patients in their daily lives.

Keywords: Parkinson's disease, rTMS, cognitive, treatment

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Authors: Dileep G., Akash Singh, Dalchand Ahirwar, Arkadeep Ghosh, Ashutosh Purohit, Gaurav Guleria, Kshatriya Om Prashant, Pushkar Patel, Saksham Kumar, Vanshaj Nathani, Vikas Dangi, Shubhajit Roy Chowdhury, Varun Dutt

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Transcranial direct current stimulation (tDCS) has shown promise as a novel approach to enhance cognitive performance and provide therapeutic benefits for various brain disorders. However, the exact underlying brain mechanisms are not fully understood. We conducted a study to examine the brain's functional changes when subjected to simultaneous tDCS and music (Indian classical raga). During the study, participants in the experimental group underwent a 20-minute session of tDCS at two mA while listening to music (raga) for a duration of seven days. In contrast, the control group received a sham stimulation for two minutes at two mA over the same seven-day period. The objective was to examine whether repetitive tDCS could lead to the formation of additional functional connections between the medial prefrontal cortex (the stimulated area) and the auditory cortex in comparison to a sham stimulation group. In this study, 26 participants (5 female) underwent pre- and post-intervention scans, where changes were compared after one week of either tDCS or sham stimulation in conjunction with music. The study revealed significant effects of tDCS on functional connectivity between the stimulated area and the auditory cortex. The combination of tDCS applied over the mPFC and music resulted in newly formed connections. Based on our findings, it can be inferred that applying anodal tDCS over the mPFC enhances functional connectivity between the stimulated area and the auditory cortex when compared to the effects observed with sham stimulation.

Keywords: fNIRS, tDCS, neuroplasticity, music

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Authors: Spyridon Komaitis, Christos Koutsarnakis, Evangelos Drosos, Aristotelis Kalyvas

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This study opts to investigate the intrinsic architecture, morphology, and spatial relationship of the subcortical pathways implicated in the connectivity of the motor/premotor cortex and SMA/pre-SMA complex. Twenty normal, adult, formalin-fixed cerebral hemispheres were explored through the fiber micro-dissection technique. Lateral to medial and medial to lateral dissections focused on the area of interest were performed in a tandem manner and under the surgical microscope. We traced the subcortical architecture, spatial relationships, and axonal connectivity of four major pathways: a) the dorsal component of the SLF (SLF-I) was found to reside in the medial aspect of the hemisphere and seen to connect the precuneus with the SMA and pre-SMA complex, b) the frontal longitudinal system (FLS) was consistently encountered as the natural anterior continuation of the SLF-II and SLF-III and connected the premotor and prefrontal cortices c) the fronto-caudate tract (FCT), a fan-shaped tract, was documented to participate in connectivity of the prefrontal and premotor cortices to the head and body of the caudate nucleus and d) the cortico-tegmental tract(CTT) was invariably recorded to subserve the connectivity of the tegmental area with the fronto-parietal cortex. No hemispheric asymmetries were recorded for any of the implicated pathways. Sub-segmentation systems were also proposed for each of the aforementioned tracts. The structural connectivity and functional specialization of motor and premotor areas in the human brain remain vague to this day as most of the available evidence derives either from animal or tractographic studies. By using the fiber-microdissection technique as our main method of investigation, we provide sound structural evidence on the delicate anatomy of the related white matter pathways.

Keywords: neuroanatomy, premotor, motor, connectivity

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Authors: Bernice Lottering, Yi-Wen Lin

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Chronic pain and depression have an estimated 80% rate of comorbidity with unsatisfactory treatment interventions signifying the importance of developing effective therapeutic interventions for a serious chronic condition affecting a large majority of the global population. Chronic pain is defined as persistent pain presenting for over 3 months. This disease state increases the risk of developing depression in comparison to healthy individuals. In the current study, complete Freund’s adjuvant (CFA) was used to induce cell-mediated chronic inflammatory pain in a murine model. Significant mechanical and thermal hyperalgesia was induced, alongside observable depression-like behaviors. These conditions were attenuated through the use of electroacupuncture (EA). Similarly, these effects were also investigated with respect to the transient receptor potential vanilloid 1 (TRPV1), by analyzing the effects of TRPV1 gene deletion on the comorbidity of chronic pain and depression. The expression of the TRPV1 inflammatory response, and related downstream molecules, including protein kinases (PKs), mitogen-activated protein kinase (MAPKs), and transcriptional factors, were significantly reduced in the thalamus, prefrontal cortex (PFC), hippocampus, and periaqueductal gray (PAG) of CFA-treated mice. In addition, phosphorylated N-methyl-D-aspartate (NMDA) receptor 1 was also found to be reduced in the aforementioned areas, suggesting potential application and validity in a clinical setting. Our study determined the prospective therapeutic effects of EA in the treatment of chronic inflammatory pain and depression comorbidity and provides a novel and detailed mechanism underlying EA-mediated analgesia. These findings may be relevant in the utilization of clinical intervention approaches related to chronic pain and depression comorbidity.

Keywords: chronic pain, depression, NMDA, prefrontal cortex, TRPV1

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Authors: Arezou Hajhashemi, Karim Asgari, Masoud Etemadifar, Maryam Keyvani, Ali Hekmatnia

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Multiple Sclerosis (MS) is one of the most prevalent demyelinating diseases in CNS. As in other chronic cerebral diseases, impairment in cognitive functioning and in memory is popular. Because of the inflammatory and demyelinating nature of the disease, the localization of plaques in different parts of the Prefrontal and Limbic System, may lead to memorial symptoms. This investigation was intended to study relationship between frequency of plaques and memorial symptoms arising from dysfunction limbic system and prefrontal of patients with MS. The sample was selected randomly from patients with MS with memory problem, who have been referred to Isfahan Multiple Sclerosis Society. Brain System Test and Memory Test was administered to the sample, and their MRI's were analyzed by specialist in order to indentify two different parts of plaques. The data was analyzed by SPSS. The results showed that there were significant relationship between MS plaques and prefrontal's dysfunction and memorial symptom related to prefrontal area; however, there were no significant relationship between MS plaques and limbic system's dysfunction and memorial symptoms related to limbic system area. The results of this study suggest that memorial symptoms due to injury regions of the brain have the most significant relationship to prefrontal. Better judgment about these results needs more studies in future.

Keywords: multiple sclerosis, magnetic image, brain injury, behavior disorder

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Authors: Jun Young Moon, Hyeonggeon Lee, Jong Tae Kim

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In this paper, we present Cortex-M3 based virtual platform which can virtualize wearable hardware platform and evaluate hardware performance. Cortex-M3 is very popular microcontroller in wearable devices, hardware sensors and display devices. This platform can be used to implement software layer for specific hardware architecture. By using the proposed platform the software development process can be parallelized with hardware development process. We present internal mechanism to implement the proposed virtual platform and describe how to use the proposed platform to develop software by using case study which is low cost wearable device that uses Cortex-M3.

Keywords: electronic system level design, software development, virtual platform, wearable device

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Authors: Rahele Mesbah, Nic Van Der Wee, Manja Koenders, Erik Giltay, Albert Van Hemert, Max De Leeuw

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Introduction: Patients with bipolar disorder (BD), characterized by depressive and manic episodes, often suffer from cognitive dysfunction. An up-to-date meta-analysis of functional Magnetic Resonance Imaging (fMRI) studies examining cognitive function in BD is lacking. Objective: The aim of the current fMRI meta-analysis is to investigate brain functioning of bipolar patients compared with healthy subjects within three domains of emotion processing, reward processing, and working memory. Method: Differences in brain regions activation were tested within whole-brain analysis using the activation likelihood estimation (ALE) method. Separate analyses were performed for each cognitive domain. Results: A total of 50 fMRI studies were included: 20 studies used an emotion processing (316 BD and 369 HC) task, 9 studies a reward processing task (215 BD and 213 HC), and 21 studies used a working memory task (503 BD and 445 HC). During emotion processing, BD patients hyperactivated parts of the left amygdala and hippocampus as compared to HC’s, but showed hypoactivation in the inferior frontal gyrus (IFG). Regarding reward processing, BD patients showed hyperactivation in part of the orbitofrontal cortex (OFC). During working memory, BD patients showed increased activity in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Conclusions: This meta-analysis revealed evidence for activity disturbances in several brain areas involved in the cognitive functioning of BD patients. Furthermore, most of the found regions are part of the so-called fronto-limbic network which is hypothesized to be affected as a result of BD candidate genes' expression.

Keywords: cognitive functioning, fMRI analysis, bipolar disorder, fronto-limbic network

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Authors: Sijie Chen, Xiaofang Chen, Juan Wang, Yingying Zhang, Yu Hong, Wanyu Zhuang, Xinxin Huang, Ping Ou, Longsheng Huang

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Purpose: Autistic symptom improvement can be observed in children treated with acupuncture, but the mechanism is still being explored. In the present study, we used scalp acupuncture to treat autism rat model, and then their improvement in the abnormal behaviors and specific mechanisms behind were revealed by detecting animal behaviors, analyzing the RNA sequencing of the prefrontal cortex(PFC), and observing the ultrastructure of PFC neurons under the transmission electron microscope. Methods: On gestational day 12.5, Wistar rats were given valproic acid (VPA) by intraperitoneal injection, and their offspring were considered to be reliable rat models of autism. They were randomized to VPA or VPA-acupuncture group (n=8). Offspring of Wistar pregnant rats that were simultaneously injected with saline were randomly selected as the wild-type group (WT). VPA_acupuncture group rats received acupuncture intervention at 23 days of age for 4 weeks, and the other two groups followed without intervention. After the intervention, all experimental rats underwent behavioral tests. Immediately afterward, they were euthanized by cervical dislocation, and their prefrontal cortex was isolated for RNA sequencing and transmission electron microscopy. Results: The main results are as follows: 1. Animal behavioural tests: VPA group rats showed more anxiety-like behaviour and repetitive, stereotyped behaviour than WT group rats. While VPA group rats showed less spatial exploration ability, activity level, social interaction, and social novelty preference than WT group rats. It was gratifying to observe that acupuncture indeed improved these abnormal behaviors of autism rat model. 2. RNA-sequencing: The three groups of rats differed in the expression and enrichment pathways of multiple genes related to synaptic function, neural signal transduction, and circadian rhythm regulation. Our experiments indicated that acupuncture can alleviate the major symptoms of ASD by improving these neurological abnormalities. 3. Under the transmission electron microscopy, several lysosomes and mitochondrial structural abnormalities were observed in the prefrontal neurons of VPA group rats, which were manifested as atrophy of the mitochondrial membran, blurring or disappearance of the mitochondrial cristae, and even vacuolization. Moreover, the number of synapses and synaptic vesicles was relatively small. Conversely, the mitochondrial structure of rats in the WT group and VPA_acupuncture was normal, and the number of synapses and synaptic vesicles was relatively large. Conclusion: Acupuncture effectively improved the abnormal behaviors of autism rat model and the ultrastructure of the PFC neurons, which might worked by improving their abnormal synaptic function, synaptic plasticity and promoting neuronal signal transduction.

Keywords: autism spectrum disorder, acupuncture, animal behavior, RNA sequencing, transmission electron microscope

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Authors: Khushboo Shah

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Categorical bans on the death penalty and life-without-parole sentences for juvenile offenders in a growing number of countries have established a new era in juvenile jurisprudence. This has been brought about by integration of the growing knowledge in cognitive neuroscience and appreciation of the inherent differences between adults and adolescents over the last ten years. This evolving understanding of being a child in the criminal system can be aptly reflected through policies that incorporate the mitigating traits of youth. First, the presentation will delineate the structures in cognitive neuroscience and in particular, focus on the prefrontal cortex, the amygdala, and the basal ganglia. These key anatomical structures in the brain are linked to three mitigating adolescent traits—an underdeveloped sense of responsibility, an increased vulnerability to negative influences, and transitory personality traits—that establish why juveniles have a lessened culpability. The discussion will delve into the details depicting how an underdeveloped prefrontal cortex results in the heightened emotional angst, high-energy and risky behavior characteristic of the adolescent time period or how the amygdala, the emotional center of the brain, governs different emotional expression resulting in why teens are susceptible to negative influences. Based on this greater understanding, it is incumbent that policies adequately reflect the adolescent physiology and psychology in the criminal system. However, it is important to ensure that these views are appropriately weighted while considering the jurisprudence for the treatment of children in the law. To ensure this balance is appropriately stricken, policies must incorporate the distinctive traits of youth in sentencing and legal considerations and yet refrain from the potential fallacies of absolving a juvenile offender of guilt and culpability. Accordingly, three policies will demonstrate how these results can be achieved: (1) eliminate housing of juvenile offenders in the adult prison system, (2) mandate fitness hearings for all transfers of juveniles to adult criminal court, and (3) use the post-disposition review as a type of rehabilitation method for juvenile offenders. Ultimately, this interdisciplinary approach of science and law allows for a better understanding of adolescent psychological and social functioning and can effectuate better legal outcomes for juveniles tried as adults.

Keywords: criminal law, Juvenile Justice, interdisciplinary, neuroscience

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Authors: Beata Spilakova, Daniel J. Shaw, Radek Marecek, Milan Brazdil

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Hyperscanning affords a unique insight into the brain dynamics underlying human interaction by simultaneously scanning two or more individuals’ brain responses while they engage in dyadic exchange. This provides an opportunity to observe dynamic brain activations in all individuals participating in interaction, and possible interbrain effects among them. The present research aims to provide an experimental paradigm for hyperscanning research capable of delineating among different forms of interaction. Specifically, the goal was to distinguish between two dimensions: (1) interaction structure (concurrent vs. turn-based) and (2) goal structure (competition vs cooperation). Dual-fMRI was used to scan 22 pairs of participants - each pair matched on gender, age, education and handedness - as they played the Pattern Game. In this simple interactive task, one player attempts to recreate a pattern of tokens while the second player must either help (cooperation) or prevent the first achieving the pattern (competition). Each pair played the game iteratively, alternating their roles every round. The game was played in two consecutive sessions: first the players took sequential turns (turn-based), but in the second session they placed their tokens concurrently (concurrent). Conventional general linear model (GLM) analyses revealed activations throughout a diffuse collection of brain regions: The cooperative condition engaged medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC); in the competitive condition, significant activations were observed in frontal and prefrontal areas, insula cortices and the thalamus. Comparisons between the turn-based and concurrent conditions revealed greater precuneus engagement in the former. Interestingly, mPFC, PCC and insulae are linked repeatedly to social cognitive processes. Similarly, the thalamus is often associated with a cognitive empathy, thus its activation may reflect the need to predict the opponent’s upcoming moves. Frontal and prefrontal activation most likely represent the higher attentional and executive demands of the concurrent condition, whereby subjects must simultaneously observe their co-player and place his own tokens accordingly. The activation of precuneus in the turn-based condition may be linked to self-other distinction processes. Finally, by performing intra-pair correlations of brain responses we demonstrate condition-specific patterns of brain-to-brain coupling in mPFC and PCC. Moreover, the degree of synchronicity in these neural signals related to performance on the game. The present results, then, show that different types of interaction recruit different brain systems implicated in social cognition, and the degree of inter-player synchrony within these brain systems is related to nature of the social interaction.

Keywords: brain-to-brain coupling, hyperscanning, pattern game, social interaction

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Authors: Esshili Awatef, Manitz Marie-Pierre, Eßlinger Manuela, Gerhardt Alexandra, Plümper Jennifer, Wachholz Simone, Friebe Astrid, Juckel Georg

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Maternal immune activation (MIA) resulting from maternal viral infection during pregnancy is a known risk factor for schizophrenia. The neural mechanisms by which maternal infections increase the risk for schizophrenia remain unknown, although the prevailing hypothesis argues that an activation of the maternal immune system induces changes in the maternal-fetal environment that might interact with fetal brain development. It may lead to an activation of fetal microglia inducing long-lasting functional changes of these cells. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, we hypothesize that prenatal treatment with the inflammatory agent Poly(I:C) during embryogenesis at contributes to microglial activation in the offspring, which may, therefore, represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options. Pregnant rats were treated with intraperitoneal injections a single dose of Poly(I:C) or saline on gestation day 17. Brains of control and Poly(I:C) offspring, were removed and into 20-μm-thick coronal sections were cut by using a Cryostat. Brain slices were fixed and immunostained with ba1 antibody. Subsequently, Iba1-immunoreactivity was detected using a secondary antibody, goat anti-rabbit. The sections were viewed and photographed under microscope. The immunohistochemical analysis revealed increases in microglia cell number in the prefrontal cortex, in offspring of poly(I:C) treated-rats as compared to the controls injected with NaCl. However, no significant differences were observed in microglia activation in the cerebellum among the groups. Prenatal immune challenge with Poly(I:C) was able to induce long-lasting changes in the offspring brains. This lead to a higher activation of microglia cells in the prefrontal cortex, a brain region critical for many higher brain functions, including working memory and cognitive flexibility. which might be implicated in possible changes in cortical neuropil architecture in schizophrenia. Further studies will be needed to clarify the association between microglial cells activation and schizophrenia-related behavioral alterations.

Keywords: Microglia, neuroinflammation, PolyI:C, schizophrenia

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Authors: Sarah A. Harris, Fleur L. McIntyre, Paola T. Chivers, Benjamin G. Piggott, Fiona H. Farringdon

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Australian Rules Football (ARF) is an invasion based, contact field sport with over one million participants. The contact nature of the game increases exposure to all injuries, including head trauma. Evidence suggests that both concussion and sub-concussive traumas such as head knocks may damage the brain, in particular the prefrontal cortex. The prefrontal cortex may not reach full maturity until a person is in their early twenties with males taking longer to mature than females. Repeated trauma to the pre-frontal cortex during maturation may lead to negative social, cognitive and emotional effects. It is also during this period that males exhibit high levels of risk taking behaviours. Risk propensity and the incidence of injury is an unexplored area of research. Little research has considered if the level of player’s (especially younger players) risk propensity in everyday life places them at an increased risk of injury. Hence the current study, investigated if a relationship exists between risk propensity and self-reported injuries including diagnosed concussion and head knocks, among male ARF players aged 18 to 31 years. Method: The study was conducted over 22 weeks with one West Australian Football League (WAFL) club during the 2015 competition. Pre-season risk propensity was measured using the 7-item self-report Risk Propensity Scale. Possible scores ranged from 9 to 63, with higher scores indicating higher risk propensity. Players reported their self-perceived injuries (concussion, head knocks, upper body and lower body injuries) fortnightly using the WAFL Injury Report Survey (WIRS). A unique ID code was used to ensure player anonymity, which also enabled linkage of survey responses and injury data tracking over the season. A General Linear Model (GLM) was used to analyse whether there was a relationship between risk propensity score and total number of injuries for each injury type. Results: Seventy one players (N=71) with an age range of 18.40 to 30.48 years and a mean age of 21.92 years (±2.96 years) participated in the study. Player’s mean risk propensity score was 32.73, SD ±8.38. Four hundred and ninety five (495) injuries were reported. The most frequently reported injury was head knocks representing 39.19% of total reported injuries. The GLM identified a significant relationship between risk propensity and head knocks (F=4.17, p=.046). No other injury types were significantly related to risk propensity. Discussion: A positive relationship between risk propensity and head trauma in contact sports (specifically WAFL) was discovered. Assessing player’s risk propensity therefore, may identify those more at risk of head injuries. Potentially leading to greater monitoring and education of these players throughout the season, regarding self-identification of head knocks and symptoms that may indicate trauma to the brain. This is important because many players involved in WAFL are in their late teens or early 20’s hence, may be at greater risk of negative outcomes if they experience repeated head trauma. Continued education and research into the risks associated with head injuries has the potential to improve player well-being.

Keywords: football, head injuries, injury identification, risk

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Authors: Sandy Bao, Yankang Bao

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The understanding of information that is being processed in the brain, especially in the lateral geniculate nucleus (LGN), has been proven challenging for modern neuroscience and for researchers with a focus on how neurons process signals and images. In this paper, we are proposing a method to image process different colors within different layers of LGN, that is, green information in layers 4 & 6 and red & blue in layers 3 & 5 based on the surface dimension of layers. We take into consideration the images in LGN and visual cortex, and that the edge detected information from the visual cortex needs to be considered in order to return back to the layers of LGN, along with the image in LGN to form the new image, which will provide an improved image that is clearer, sharper, and making it easier to identify objects in the image. Matrix Laboratory (MATLAB) simulation is performed, and results show that the clarity of the output image has significant improvement.

Keywords: lateral geniculate nucleus, matrix laboratory, neuroscience, visual cortex

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Authors: Chien-Ho Lin, Ho-Ching Yang, Barbara Knowlton, Shin-Leh Huang, Ming-Chang Chiang

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Practicing motor tasks arranged in an interleaved order (interleaved practice, or IP) generally leads to better learning than practicing tasks in a repetitive order (repetitive practice, or RP), an example of how desirable difficulty during practice benefits learning. Greater difficulty during practice, e.g. IP, is associated with greater brain activity measured by higher blood-oxygen-level dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) in the sensorimotor areas of the brain. In this study resting-state fMRI was applied to investigate whether increase in resting-state brain connectivity immediately after practice predicts the benefit of desirable difficulty to motor learning. 26 healthy adults (11M/15F, age = 23.3±1.3 years) practiced two sets of three sequences arranged in a repetitive or an interleaved order over 2 days, followed by a retention test on Day 5 to evaluate learning. On each practice day, fMRI data were acquired in a resting state after practice. The resting-state fMRI data was decomposed using a group-level spatial independent component analysis (ICA), yielding 9 independent components (IC) matched to the precuneus network, primary visual networks (two ICs, denoted by I and II respectively), sensorimotor networks (two ICs, denoted by I and II respectively), the right and the left frontoparietal networks, occipito-temporal network, and the frontal network. A weighted resting-state functional connectivity (wRSFC) was then defined to incorporate information from within- and between-network brain connectivity. The within-network functional connectivity between a voxel and an IC was gauged by a z-score derived from the Fisher transformation of the IC map. The between-network connectivity was derived from the cross-correlation of time courses across all possible pairs of ICs, leading to a symmetric nc x nc matrix of cross-correlation coefficients, denoted by C = (pᵢⱼ). Here pᵢⱼ is the extremum of cross-correlation between ICs i and j; nc = 9 is the number of ICs. This component-wise cross-correlation matrix C was then projected to the voxel space, with the weights for each voxel set to the z-score that represents the above within-network functional connectivity. The wRSFC map incorporates the global characteristics of brain networks measured by the between-network connectivity, and the spatial information contained in the IC maps measured by the within-network connectivity. Pearson correlation analysis revealed that greater IP-minus-RP difference in wRSFC was positively correlated with the RP-minus-IP difference in the response time on Day 5, particularly in brain regions crucial for motor learning, such as the right dorsolateral prefrontal cortex (DLPFC), and the right premotor and supplementary motor cortices. This indicates that enhanced resting brain connectivity during the early phase of memory consolidation is associated with enhanced learning following interleaved practice, and as such wRSFC could be applied as a biomarker that measures the beneficial effects of desirable difficulty on motor sequence learning.

Keywords: desirable difficulty, functional magnetic resonance imaging, independent component analysis, resting-state networks

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