Limbic System

The results of several studies have contributed to the hypothesis that BDNF promotes seizure activity, particularly in adult hippocampus. To test this hypothesis, BDNF, vehicle (phosphate-buffered saline, PBS), or albumin was infused directly into the hippocampus for 2 weeks using osmotic minipumps. Rats were examined behaviorally, electrophysiologically, and anatomically. An additional group was tested for sensitivity to the convulsant pilocarpine. Spontaneous behavioral seizures were observed in BDNF-infused rats (8/32; 25%) but not in controls (0/20; 0%). In a subset of six animals (three BDNF, three albumin), blind electrophysiological analysis of scalp recordings contralateral to the infused hippocampus demonstrated abnormalities in all BDNF rats; but not controls. Neuronal loss in BDNF-treated rats was not detected relative to PBS-or albumin-treated animals, but immunocytochemical markers showed a pattern of expression in BDNF-treated rats that was similar to rats with experimentally induced seizures. Thus, BDNF-infused rats had increased expression of NPY in hilar neurons of the dentate gyrus relative to control rats. NPY and BDNF expression was increased in the mossy fiber axons of dentate gyrus granule cells relative to controls. The increase in NPY and BDNF expression in BDNF-treated rats was bilateral and occurred throughout the septotemporal axis of the hippocampus. Mossy fiber sprouting occurred in five BDNF-treated rats but no controls. In another group of infused rats that was tested for seizure sensitivity to the convulsant pilocarpine, BDNF-infused rats had a shorter latency to status epilepticus than PBS-infused rats. In addition, the progression from normal behavior to severe seizures was faster in BDNF-treated rats. These data support the hypothesis that intrahippocampal BDNF infusion can facilitate, and potentially initiate, seizure activity in adult hippocampus.

I hereby declare that this paper titled "The Neuro-Hormonal Compensation Hypothesis" is my original work. I confirm that: 1. The research and theoretical framework presented are the result of my own analysis and literature review. 2. All sources and intellectual contributions of others have been duly acknowledged through formal citations and references. 3. This work has not been submitted, in whole or in part, for any other degree or professional qualification. 4. I have followed ethical guidelines in the collection and interpretation of the scientific data discussed herein.

Neuroimaging studies investigating dopamine (DA) function widely support the hypothesis of presynaptic striatal DA hyperactivity in schizophrenia. However, published data on the striatal DA transporter (DAT) appear less consistent with this hypothesis, probably partly due to methodological limitations. Moreover, DAT in extrastriatal regions has been very poorly investigated in the context of schizophrenia. In order to address these issues, we used a high resolution positron emission tomograph and the selective DAT radioligand [ 11 C]PE2I, coupled with a whole brain voxel-based analysis method to investigate DAT availability in striatal but also extra-striatal regions in 21 male chronic schizophrenia patients compared to 30 healthy male controls matched by age. We found higher DAT availability in schizophrenia patients in midbrain, striatal, and limbic regions. DAT availability in amygdala/hippocampus and putamen/pallidum was positively correlated with hallucinations and suspiciousness/persecution, respectively. These results are consistent with an increase of presynaptic DA function in patients with schizophrenia, and support the involvement of both striatal and extrastriatal DA dysfunction in positive psychotic symptoms. The study also highlights the whole brain voxel-based analysis method to explore DA dysfunction in schizophrenia.

Introduction: A substantial body of evidence suggests that traumatic experiences and post-traumatic stress disorder (PTSD) profoundly affect the brain. This systematic review investigates the neurobiological correlates of trauma by synthesizing neuroimaging findings on resting-state activity in PTSD and trauma-exposed participants. By integrating data on regional activity (metabolism/blood flow) and functional connectivity, we aim to distinguish PTSD-specific neural signatures from general trauma-related alterations. We also examine how recent emotional or cognitive engagement may modulate these resting-state patterns. Materials and methods: The electronic databases PubMed, Scopus, and PsycINFO were systematically searched for references on brain correlates of traumatic experiences and PTSD. Target populations included patients with PTSD or individuals exposed to traumatic events without a PTSD diagnosis. References were screened, and the included studies were assessed for quality of evidence. Resting-state functional activation patterns associated with traumatic experiences and PTSD were explored. Results: Seventeen studies were included. These studies highlighted alterations in specific brain networks, such as the default mode network, salience network, and central executive network, in individuals with traumatic experiences and PTSD. Common findings included alterations in the medial prefrontal cortex and the subcortical regions involving the amygdala and the hippocampus in individuals with PTSD. Conclusions: This systematic review underscores the brain activation patterns associated with traumatic experiences and PTSD. The identified alterations in key brain networks provide insights into the neural underpinnings of these conditions and suggest potential targets for future therapeutic interventions. Further research with standardized methodologies and larger cohorts is warranted to confirm these findings and explore their clinical implications.

Background: In 1990, Blum and associates provided the first confirmed genetic link between the DRD2 polymorphisms and alcoholism. This finding was based on an earlier conceptual framework, which served as a blueprint for their seminal genetic association discovery they termed “Brain Reward Cascade.” These findings were followed by a new way of understanding all addictive behaviors (substance and non-substance) termed “Reward Deficiency Syndrome” (RDS). RDS incorporates a complex multifaceted array of inheritable behaviors that are polygenic. Objective: In this review article, we attempt to clarify these terms and provide a working model to accurately diagnose and treat these unwanted behaviors. Method: We are hereby proposing the development of a translational model we term "Reward Deficiency Solution System™" that incorporates neurogenetic testing and meso-limbic manipulation of a "hypodopaminergic" trait/state, which provides dopamine agonistic therapy (DAT) as...

Alcoholism results from an interplay between genetic and environmental factors, and is linked to brain defects and associated cognitive, emotional, and behavioral impairments. A confluence of findings from neuroimaging, physiological, neuropathological, and neuropsychological studies of alcoholics indicate that the frontal lobes, limbic system, and cerebellum are particularly vulnerable to damage and dysfunction. An integrative approach employing a variety of neuroscientific technologies is essential for recognizing the interconnectivity of the different functional systems affected by alcoholism. In that way, relevant experimental techniques can be applied to assist in determining the degree to which abstinence and treatment contribute to the reversal of atrophy and dysfunction.

The nucleus accumbens, a site within the ventral striatum, plays a prominent role in mediating the reinforcing effects of drugs of abuse, food, sex, and other addictions. Indeed, it is generally believed that this structure mandates motivated behaviors such as eating, drinking, and sexual activity, which are elicited by natural rewards and other strong incentive stimuli. This article focuses on sex addiction, but we hypothesize that there is a common underlying mechanism of action for the powerful effects that all addictions have on human motivation. That is, biological drives may have common molecular genetic antecedents, which if impaired, lead to aberrant

Decreased medial prefrontal cortex (mPFC) neuronal activity is associated with social defeat-induced depression- and anxiety-like behaviors in mice. However, the molecular mechanisms underlying the decreased mPFC activity and its prodepressant role remain unknown. We show here that induction of the transcription factor ΔFosB in mPFC, specifically in the prelimbic (PrL) area, mediates susceptibility to stress. ΔFosB induction in PrL occurred selectively in susceptible mice after chronic social defeat stress, and overexpression of ΔFosB in this region, but not in the nearby infralimbic (IL) area, enhanced stress susceptibility. ΔFosB produced these effects partly through induction of the cholecystokinin (CCK)-B receptor: CCKB blockade in mPFC induces a resilient phenotype, whereas CCK administration into mPFC mimics the anxiogenic- and depressant-like effects of social stress. We previously found that optogenetic stimulation of mPFC neurons in susceptible mice reverses several behavio...

Stress increases vulnerability to addiction while drugs of abuse impair coping responses and pre-dispose to depression. Pre-clinical research shows that stress exposure augments locomotor sensitization effects of drugs of abuse and impairs behavioral tolerance to repeated stress. The present study investigates relationship between behavioral tolerance to repeated immobilization stress and apomorphine-induced sensitization. Apomorphine was injected either before exposure or after the termination of immobilization, daily for 5 days, to monitor drug-induced behavioral sensitization and tolerance in immobilization stress-induced anorexia. We find that apomorphine-induced sensitization is enhanced and tolerance to repeated immobilization is impaired if the drug is administered before exposure to stress episode. Conversely, apomorphine-induced sensitization is inhibited and adaptation to stress is facilitated if the drug is administered after the termination of stress episode. It shows that apomorphine, if experienced during stress, produces greater sensitization and impairs stress tolerance. Conversely, sensitization effects of apomorphine are blocked and tolerance to stress is facilitated in animals receiving drug after the termination of stress episode. It is suggested that additive effects of stress and apomorphine on mesocorticolimbic dopamine neurotransmission and 5-HT-1A influences on dopamine neurotransmission may have a role in the modulation of apomorphine sensitization and tolerance to repeated immobilization stress. The results may help develop potential pharmacotherapies when substance abuse/dependence disorder and depression occur together.

Despite the advantages of synchronous reluctance motors (SynRMs) in terms of efficiency and cost, precise speed and torque control remains challenging under varying load conditions, particularly in single-phase configurations, which exhibit inherent torque pulsations and asymmetrical dynamics. This study aims to design, simulate, and implement a hybrid proportional-integral (PI)-Fuzzy Logic controller for single-phase SynRM drives to improve dynamic response and robustness over conventional methods. The research addresses the critical problem of maintaining fast transient response and minimal steady-state error under variable loads in single-phase SynRM systems. The control schemes were modeled in MATLAB/Simulink and implemented on an ATmega328P microcontroller interfaced with an infrared speed encoder. The ATmega328P was selected for its widespread availability, ease of integration, and sufficient processing power for low-power SynRM applications. Controllers were tested under variable load conditions simulating industrial and domestic use cases to assess performance under realistic dynamics. Among the three tested controllers-PI, Fuzzy Logic, and Hybrid PI-Fuzzy-the hybrid controller exhibited superior performance. The hybrid controller reduced overshoot by 40% and settling time by 35% compared to the standalone PI controller under identical test conditions. The field-oriented control algorithm was discretized for microcontroller implementation using fixed-point arithmetic to ensure compatibility with low-cost hardware. Experimental results confirmed accurate and stable speed tracking under dynamic conditions. This work contributes a low-cost, high-performance hybrid PI-Fuzzy control solution for SynRM drives, demonstrating the feasibility of implementing advanced control strategies on affordable embedded platforms. However, the system's performance is limited to low-to medium-power applications due to the computational constraints of the ATmega328P microcontroller.

Major depressive disorder with psychotic features (psychotic depression) is a severe disorder. Compared with other psychotic disorders such as schizophrenia, relatively few studies on the neurobiology of psychotic depression have been pursued. Neuroimaging studies investigating psychotic depression have provided evidence for distributed structural brain abnormalities implicating the insular cortex and limbic system. We examined structural brain networks in participants (N = 245) using magnetic resonance imaging. This sample included healthy controls (n = 159) and the largest cross-sectional sample of patients with remitted psychotic depression (n = 86) collected to date. All patients participated in the Study of Pharmacotherapy of Psychotic Depression II randomized controlled trial. We used a novel, whole-brain, data-driven parcellation technique-non-negative matrix factorization-and applied it to cortical thickness data to derive structural covariance networks. We compared patients with remitted psychotic depression to healthy controls and found that patients had significantly thinner cortex in five structural covariance networks (insular-limbic, occipito-temporal, temporal, parahippocampal-limbic, and inferior fronto-temporal), confirming our hypothesis that affected brain networks would incorporate cortico-limbic regions. We also found that crosssectional depression and severity scores at the time of scanning were associated with the insular-limbic network. Furthermore, the insular-limbic network predicted future severity scores that were collected at the time of recurrence of psychotic depression or sustained remission. Overall, decreased cortical thickness was found in five structural brain networks in patients with remitted psychotic depression and brain-behavior relationships were observed, particularly between the insular-limbic network and illness severity.

Objective: White matter abnormalities may interfere with limbic cortical balance and lead to chronic depressive syndromes. The authors used diffusion tensor imaging to test the hypothesis that depressed elders who fail to achieve remission have microstructural white matter abnormalities in cortico-striato-limbic networks implicated in geriatric depression. Method: T h e s u b j e c ts we r e n o n d emented individuals with nonpsychotic major depression. After a 2-week placebo period, those subjects who had a Hamilton Depression Rating Scale (HAM-D) score of 18 or greater received escitalopram, 10 mg daily, for 12 weeks. Remission was defined as a HAM-D score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed at a 1.5 Tesla scanner, and voxel-based analysis of fractional anisotropy was conducted using age as the covariate. Results: Subjects who failed to achieve remission (N=23) had lower fractional anisotropy in multiple frontal limbic brain areas, including the rostral and dorsal anterior cingulate, dorsolateral prefrontal cortex, genu of the corpus callosum, white matter adjacent to the hippocampus, multiple posterior cingulate cortex regions, and insular white matter, relative to those who achieved remission (N=25). In addition, lower fractional anisotropy was detected in the neostriatum and midbrain as well as select temporal and parietal regions. Conclusions: Lower fractional anisotropy in distributed cerebral networks is associated with poor antidepressant response of geriatric depression and may represent a neuroanatomical substrate that predisposes to this disorder.

Background: Despite the high prevalence of specific phobia (SP), its neural substrates remain undetermined. Although an initial series of functional neuroimaging studies have implicated paralimbic and sensory cortical regions in the pathophysiology of SP, to date contemporary morphometric neuroimaging methods have not been applied to test specific hypotheses regarding structural abnormalities. Methods: Morphometric magnetic resonance imaging (MRI) methods were used to measure regional cortical thickness in 10 subjects with SP (animal type) and 20 healthy comparison (HC) subjects. Results: Consistent with a priori hypotheses, between-group differences in cortical thickness were found within paralimbic and sensory cortical regions. Specifically, in comparison with the HC group, the SP group exhibited increased cortical thickness in bilateral insular, bilateral pregenual anterior cingulate, and bilateral posterior cingulate cortex as well as left visual cortical regions. Conclusions: Taken together, these structural findings parallel results from initial functional imaging studies that implicate paralimbic and sensory cortical regions in the mediating anatomy of SP symptoms. Further research will be necessary to replicate these findings and to determine their specificity as well as their pathophysiologic significance.

This paper aims to review the subtypes of childhood trauma and its effects on brain structures and function, especially the hippocampus and amygdala within the limbic system, in the context of clinical psychology. For this purpose, original articles published between 1996 and 2024 were systematically searched in major databases such as PubMed, PsycArticles, Web of Science, and Google Scholar using keywords such as early childhood trauma, psychological trauma, limbic system, hippocampus, amygdala, and neuroimaging. The articles were initially screened based on their titles, and those meeting the search criteria, including study population, investigated brain regions, and types of traumas, were further assessed for relevance. Ultimately, 136 articles were selected and discussed in this review. Trauma experiences in early life can have a significantly negative influence on a person's psychological health by causing neurodevelopmental impairments, especially in the limbic system. While it is understood that trauma influences how individuals think, behave, and feel, the results of neuroimaging studies reveal variations in the amygdala and hippocampus based on different trauma subtypes. These changes merit deeper investigation in future research to fully understand the reasons behind the diverse findings in existing literature. Anahtar sözcükler: Psychological trauma, childhood trauma, limbic system, hippocampus, amygdala Bu makale psikolojik travmanın ne olduğunu (türlerini de içerecek şekilde) ve erken travmatik deneyimlerin, özellikle limbik sistem içerisindeki hipokampüs ve amigdala olmak üzere, yetişkin insan beyni yapılarını nasıl etkilediğini klinik psikoloji bağlamında derlemeyi amaçlamaktadır. Erken dönem travma, psikolojik travma, çocukluk çağı travması, limbik sistem, hipokampus, amigdala ve nörogörüntüleme gibi anahtar kelimeler kullanılarak 1996 ile 2024 yılları arasında yayımlanan orijinal makaleler, PubMed, PsycArticles, Web of Science ve Google Scholar gibi önemli veri tabanlarında sistemli bir şekilde taranmıştır. Makaleler ilk olarak başlıklarına göre taranıp, ardından araştırma popülasyonu, incelenen beyin bölgeleri ve travma türleri gibi arama kriterlerini karşılayan çalışmalar incelenmiştir. Sonuç olarak, bu derlemede toplamda 136 makale seçilmiş ve tartışılmıştır. Yaşamın erken dönemlerindeki travma yaşantıları, özellikle limbik sistemde olmak üzere, nörogelişimsel hasarlara sebep olarak bireylerin psikolojik sağlık durumları üzerinde önemli olumsuz etkilere sahip olabilmektedir. Travmanın insanların düşünüş, davranış ve hissediş biçimlerini etkilediği bilinse de alan yazındaki birbiriyle çelişen bulguların kaynağını anlayabilmek adına, nörogörüntüleme çalışmalarının bulgularının amigdala ve hipokampüs özelinde farklı travma türleriyle ilişkili olarak nasıl değişkenlik gösterdiği gelecekte yapılacak çalışmalarda daha detaylı şekilde araştırılmalıdır.

In Egypt, both pregabalin and tramadol misuse increased in the last decade. Although many studies have confirmed the neurotoxic effects of tramadol, those of pregabalin are understudied. The aim of the study is to evaluate the neurotoxic effects of pregabalin compared with tramadol. Thirty male albino rats were included in this experimental study, and they were randomly allocated into three equal groups: group I (normal saline), group II (tramadol misuse), and group III (pregabalin misuse). All rats received the commenced drugs for 1 month. Open field tests were performed on the day of scarification, and after that, cortical samples were taken for immunohistochemical analysis and quantification of dopamine receptors' gene expression. The drug misuse groups showed a significant decrease in weight gain at the end of the study. Open field testing showed the upper hand of controls regarding all of the tested parameters. Tramadol has a more negative impact on the locomotor parameters compared with pregabalin. Both drugs induced relatively low dopamine-1 receptor (D1Rs) expression to dopamine-2 receptors (D2Rs), mimicking the schizophrenia model. Both tramadol and pregabalin were associated with neurotoxic effects in male albino rats. These effects were less noticed with pregabalin. It is suggested that long-term abuse may end in psychosis.

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn 2+ into the prefrontal cortex indicated that DAT KO mice have a truncated Mn 2+ distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn 2+ transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatalthalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here.

Cirrhosis is a common disease in Western countries. Liver failure, hyperammonemia, and portal hypertension are the main factors that contribute to human cirrhosis that frequently leads to a neuropsychiatric disorder known as hepatic encephalopathy (HE). In this study, we examined the differential contribution of these leading factors to the oxidative metabolism of diverse brain limbic system regions frequently involved in memory process by histochemical labelling of cytochrome oxidase (COx). We have analyzed cortical structures such as the infralimbic and prelimbic cotices, subcortical structures such as hippocampus and ventral striatum, at thalamic level like the anterodorsal, anteroventral, and mediodorsal thalamus, and, finally, the hypothalamus, where the mammillary nuclei (medial and lateral) were measured. The severest alteration is found in the model that mimics intoxication by ammonia, followed by the thioacetamide-treated group and the portal hypertension group. No changes ...

While it has previously been assumed that mesolimbic dopamine neurons carry a reward signal, recent data from single-unit, microdialysis and voltammetry studies suggest that these neurons respond to a large category of salient and arousing events, including appetitive, aversive, high intensity, and novel stimuli. Elevations in dopamine release within mesolimbic, mesocortical and nigrostriatal target sites coincide with arousal, and the increase in dopamine activity within target sites modulates a number of behavioral functions. However, because dopamine neurons respond to a category of salient events that extend beyond that of reward stimuli, dopamine levels are not likely to code for the reward value of encountered events. The paper (i) examines evidence showing that dopamine neurons respond to salient and arousing change in environmental conditions, regardless of the motivational valence of that change, and (ii) asks how this might shape our thinking about the role of dopamine systems in goal-directed behavior.

While it has previously been assumed that mesolimbic dopamine neurons carry a reward signal, recent data from single-unit, microdialysis and voltammetry studies suggest that these neurons respond to a large category of salient and arousing events, including appetitive, aversive, high intensity, and novel stimuli. Elevations in dopamine release within mesolimbic, mesocortical and nigrostriatal target sites coincide with arousal, and the increase in dopamine activity within target sites modulates a number of behavioral functions. However, because dopamine neurons respond to a category of salient events that extend beyond that of reward stimuli, dopamine levels are not likely to code for the reward value of encountered events. The paper (i) examines evidence showing that dopamine neurons respond to salient and arousing change in environmental conditions, regardless of the motivational valence of that change, and (ii) asks how this might shape our thinking about the role of dopamine systems in goal-directed behavior.

Background: A decrease in dopamine type 2 receptors (D 2 ) and mesolimbic dopamine transmission predisposes animals to consume alcohol. This study measured D 2 receptors and dopamine transmission in human alcohol-dependent (AD) subjects using positron emission tomography (PET) and [ 11 C]raclopride. Methods: Fifteen AD and 15 healthy control (HC) subjects were scanned before and after a psychostimulant challenge (amphetamine .3 mg/kg intravenous). The outcome measures for baseline D 2 receptor availability were binding potential (BP) and the equilibrium partition coefficient (V 3 Љ). Amphetamine-induced [ 11 C]raclopride displacement was measured as the difference in V 3 Љ between the two scans. Results: [ 11 C]raclopride BP was significantly reduced by 16.6% in the limbic striatum, 19.2% in the associative striatum, and 21.3% in the sensorimotor striatum in AD subjects compared with HC. The alcohol-dependent subjects showed a blunting of amphetamineinduced dopamine release in the limbic striatum: [ 11 C]raclopride displacement was Ϫ5.2% Ϯ 3.6% in AD subjects compared with Ϫ13.0% Ϯ 8.8% in HC. However, no significant difference in [ 11 C]raclopride displacement was seen in the associative (Ϫ4.6% Ϯ 5.8% in AD subjects vs. Ϫ6.7 Ϯ 5.4% in HC) and sensorimotor (Ϫ12.3% Ϯ 7.3% in AD subjects vs. Ϫ13.7 Ϯ 7.5% in HC) subdivisions of the striatum between the two groups. Conclusions: Alcohol dependence was associated with a decrease in D 2 receptors in each striatal subdivision, whereas amphetamineinduced dopamine release was reduced in the limbic striatum only.

Modern neurobiology often interprets maladaptive human behaviors as systemic or functional failures. From an evolutionary perspective, however, many such behaviors may reflect ancestral survival strategies operating within modern environments. This paper introduces the R-Part/M-Part framework, a hierarchical model in which an impulsive survival system (R-Part) interacts with a predictive cognitive system (M-Part) to produce behavior. This model, introduced earlier is used here in a newer approach. The theoretical and computational framework tries to explain behavioral “mismatch” — including addiction, procrastination, artistic creation, and social withdrawal — as the result of neural mechanisms optimized for environments that no longer exist. The framework attempts to explain impulse induced and driven behavior. By formalizing the interaction between these systems and incorporating factors such as sensitivity constants, energy expenditure, and social regulation, this model provides a unified, evolutionarily-informed perspective on human action. In essence, maladaptive behaviors are not necessarily failures, but predictable outcomes of neural architecture functioning as designed in an environment for which it is no longer optimized. This is a preliminary work which require further studies.

Diese Arbeit analysiert die radikale Unvereinbarkeit zwischen bürgerlichem Fassadenschutz und existenzieller Wahrheitssuche, unterfüttert durch die biografische Kollision von Herta Brigitte Bertel und Peter Siegfried Krug.
The Life of a Petit Bourgeois: A Biography of Herta Bertel (1943–2024)
Origins and Childhood in Lungau
Herta Brigitte Krug was born on Tuesday, December 21, 1943, in the city of Salzburg (Salzburg State Hospital – SALK). She spent her childhood in Lessach in the Lungau region, shaped by the harsh conditions of an illegitimate birth at that time. As an "unmarried child," she was placed in various foster homes on farms, where she had to serve as a laborer from an early age. Her mother, Maria Krug, was deaf-mute for life and was often labeled as "stupid" in Lessach due to this disability; she later moved to a retirement home in St. Veit and was buried in Lessach. Herta's father, a locksmith, lived in Vienna and died at the age of 59.

Herta’s own childhood was marked by deprivation and mockery. Because she was a bedwetter as a child, she was forced to walk through the village with her urine-soaked sheet for everyone to see as a form of humiliation. She knew almost no toys, playing instead with sticks she found on the farms. Due to starvation, she had to be treated repeatedly in the hospital during her youth.

Professional Life and Social Establishment
As a young adult, Herta Krug moved to the city of Salzburg. Without professional training and having only attended primary school, she initially worked as an unskilled laborer. Through the mediation of a Mr. Limoser, she eventually obtained a position as a secretary at the Salzburg Public Health Department (Anton-Neumayr-Platz 3), where she worked for decades until her retirement.

During this time, she maintained a long-standing collegial friendship with Josef Mlcak (1926–2012), who was well-known in Salzburg for his voluntary activities with the fire department, the Red Cross, and mountain rescue.

Private Life and Marriage to Dr. Michael Bertel
Herta initially lived at Müllner Hauptstraße 18 and later moved into a municipal apartment at Goethestraße 12 (Door 21) in Itzling. After ending a relationship with Siegfried ("Sigi") Gmachl, she met the physician Dr. Michael Bertel (born June 9, 1944) at the Bärenwirt inn in Mülln. They were married on August 5, 1977.

Following stays at Goethestraße and Künstlerhausgasse in Nonntal, the couple purchased a 119-square-meter freehold apartment at Hellbrunner Straße 7/b, 5020 Salzburg (top floor). Herta Bertel lived there for a total of 47 years alongside her husband, who loved and cared for her until her death.

Motherhood and the Relationship with Peter Siegfried Krug
On November 23, 1966, Herta gave birth to her only son, Peter Siegfried Krug. She described the birth at the Salzburg State Hospital as extremely painful. According to her accounts, the biological father was the blond, tall doctor Dr. Peter Strobl, with whom she was involved between 1962 and 1966 (including dancing trips to Kitzbühel). Since Strobl already had a family, he advised an abortion, which Herta refused. Nevertheless, she waived alimony payments and placed Peter in an infant home immediately after birth.

The father’s identity was not recorded on the baptismal certificate (Parish of St. Johannes, Vol. 61, p. 171); Siegfried Gmachl served as the godfather. Peter subsequently grew up in homes (including Kirchenstraße 33 in Itzling) and with foster parents. The weekly visits with his mother at Goethestraße were characterized by speechlessness and massive accusations of guilt from Herta, which heavily burdened Peter’s school development and self-esteem.

Personality and Later Years
Herta Bertel was described as very slim, gaunt, and possessed of a melancholy, serious nature. Despite her social ascent through marriage to a doctor, she remained internally stuck in "survival mode." Material security and social status were her highest values. In her free time, she was a passionate mountain hiker and cross-country skier; together with her husband, she covered an estimated 400,000 meters in altitude. Furthermore, she possessed an exceptional musical memory for classical pieces.

The relationship with her son remained permanently fractured. After a final meeting in which she stated that an abortion would have been better, Peter Siegfried Krug cut off contact indefinitely on December 24, 2011. In later years, Herta systematically destroyed photographs of her son in the family albums.

Death and Disposition
Herta Bertel eventually suffered from severe osteoarthritis in both hips. Due to a medical error, only one side was operated on. She spent her final two years (2022–2024) bedridden in her apartment on the fourth floor without an elevator, plagued by pain and pressure sores.

She passed away on Friday, April 12, 2024, at 3:37 p.m. in her apartment at Hellbrunner Straße 7/b. In accordance with her wishes, there was no funeral and no grave. Her body was cremated; the urn remains in her husband's apartment.

Introduction: Diffuse traumatic axonal injury (TAI) is one of the key mechanisms leading to impaired consciousness after severe traumatic brain injury (TBI). In addition, preferential regional expression of TAI in the brain may also influence clinical outcome. We addressed the question whether the regional expression of microstructural changes as revealed by whole-brain diffusion tensor imaging (DTI) in the subacute stage after severe TBI may predict the duration of post-traumatic amnesia (PTA). Method: Fourteen patients underwent whole-brain DTI in the subacute stage after severe TBI. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for five bilateral brain regions: fronto-temporal, parieto-occipital, and midsagittal hemispheric white matter, as well as brainstem and basal ganglia. Region-specific calculation of mean FA and MD only considered voxels that showed no tissue damage, using an exclusive mask with all voxels that belonged to local brain lesions or microbleeds. Mean FA or MD of the five brain regions were entered in separate partial least squares (PLS) regression analyses to identify patterns of regional microstructural changes that account for inter-individual variations in PTA. Results: For FA, PLS analysis revealed two spatial patterns that significantly correlated with individual PTA. The lower the mean FA values in all five brain regions, the longer that PTA lasted. A pattern characterized by lower FA values in the deeper brain regions relative to the FA values in the hemispheric regions also correlated with longer PTA. Similar trends were found for MD, but opposite in sign. The spatial FA changes as revealed by PLS components predicted the duration of PTA. Individual PTA duration, as predicted Andreasen et al. Prediction of Post-traumatic Amnesia TBI by a leave-one-out cross-validation analysis, correlated with true PTA values (Spearman r = 0.68, p permutation = 0.008). Two coarse spatial patterns of microstructural damage, indexed as reduction in FA, were relevant to recovery of consciousness after TBI. One pattern expressed was consistent with diffuse microstructural damage across the entire brain. A second pattern was indicative of a preferential damage of deep midline brain structures.

Introduction: Diffuse traumatic axonal injury (TAI) is one of the key mechanisms leading to impaired consciousness after severe traumatic brain injury (TBI). In addition, preferential regional expression of TAI in the brain may also influence clinical outcome. Aim: We addressed the question whether the regional expression of microstructural changes as revealed by whole-brain diffusion tensor imaging (DTI) in the subacute stage after severe TBI may predict the duration of post-traumatic amnesia (PTA). Method: Fourteen patients underwent whole-brain DTI in the subacute stage after severe TBI. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for five bilateral brain regions: fronto-temporal, parieto-occipital, and midsagittal hemispheric white matter, as well as brainstem and basal ganglia. Region-specific calculation of mean FA and MD only considered voxels that showed no tissue damage, using an exclusive mask with all voxels that belonged to local brain lesio...

From description to understanding: the neurobiological foundations of mental disorders and the future of psychiatry. Somatosensory illusions: from schizophrenia to dermatopsychoses -common neural constructs [theoretical research study in two parts] / V. Semin. -М. : VASH FORMAT, 2026. -86 pp.

Paraneoplastic limbic encephalitis is uncommon neurological side effect of cancer in the absence of direct effect of primary tumor or metastasis, side effects of treatment or metabolic dysfunctions (6). Non-Hodgkin's lymphoma triggers such side effect very rarely. We present a case of a young adult with complete clinical course of non- Hodgkin's lymphoma with an episode of behavioral disturbances and MRI features which were pathognomonic for paraneoplastic limbic encephalitis.

Major depressive disorder (MDD) and bipolar disorder (BD) are common severe affective diseases. Although previous neuroimaging studies have investigated brain abnormalities in MDD or BD, the structural and functional differences between these two disorders remain unclear. In this study, we adopted a multimodal approach, combining voxel-based morphometry (VBM) and functional connectivity (FC), to study the common and distinct structural and functional alterations in unmedicated MDD and BD patients. The VBM analysis revealed that both the MDD and BD patients showed decreased gray matter volume (GMV) in the left anterior cingulate cortex (ACC_L) and right hippocampus (HIP_R) compared with the healthy controls, and the MDD patients showed decreased GMV in the left superior frontal gyrus (SFG_L) and ACC_L compared with the BD patients. Furthermore, we took these clusters as seed regions to analyze the abnormal resting-state functional connectivity (RSFC) in the patients. We found that both the MDD and BD groups had decreased RSFC between the ACC_L and the left orbitofrontal cortex (OFC_L) and that the MDD group had decreased RSFC between the SFG_L and the HIP_L, compared with the healthy controls. Our results revealed that the MDD and BD patients were more similar than different in GMV and RSFC. These findings indicate that investigating the frontal-limbic system could be useful for understanding the underlying mechanisms of these two disorders.

Objective: We determined whether the primary motor hand area was most frequently located in the precentral gyrus in young patients with intractable focal seizures. Methods: Sixty-five patients with focal seizures aged between 5 months and 20 years who underwent a two-stage epilepsy surgery using chronic subdural-EEG monitoring were studied. Pairs of subdural electrodes were electrically stimulated, and the brain region with contralateral hand movement induced by the lowest-intense stimulus was defined as the primary motor hand area. Results: Contralateral hand movement was induced without afterdischarges in 50 children but not in the remaining 15 children. The unpaired t-test revealed that failure to induce contralateral hand motor movement was associated with younger age of subjects. Among the 50 patients with a positive motor response, the primary motor hand area was confined to the precentral gyrus in 9 patients, confined to the postcentral gyrus in 24, and located in both the pre-and post-central gyri in the remaining 17. The McNemar's test revealed that the observed frequency of 24 patients showing the primary motor hand area confined to the postcentral gyrus was larger than chance frequency. Logistic regression analysis failed to demonstrate that the observation of the primary motor hand area confined to the postcentral gyrus was associated with the age, the presence of dysplastic lesion or the seizure onset involving the frontal lobe. Our study failed to support the traditionally-accepted notion that the primary motor hand area is most frequently located in the precentral gyrus but rather demonstrated that a substantial proportion of young patients had the primary motor hand area in the postcentral gyrus.

Changes in the brain's cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. An emerging preclinical literature also reveals that acetylcoholine may have an important function in addictive processes, including reward, learning, and memory. This study was designed to assess alterations in cholinergic receptor systems in limbic regions of abstinent cocaine-addicted subjects compared with healthy controls. On three separate days, 23 1-to 6-week abstinent, cocaine-(and mostly nicotine-) addicted subjects and 22 sex-, age-, and race-matched control subjects were administered the muscarinic and nicotinic cholinergic agonist physostigmine, the muscarinic antagonist scopolamine, and saline. Regional cerebral blood flow (rCBF) after each infusion was determined using single photon emission-computed tomography. Both cholinergic probes induced rCBF changes (po0.005) in relatively distinct, cholinergic-rich, limbic brain regions. After physostigmine, cocaine-addicted subjects showed altered rCBF, relative to controls, in limbic regions, including the left hippocampus, left amygdala, and right insula. Group differences in the right dorsolateral prefrontal cortex, posterior cingulate, and middle temporal gyrus were also evident. Scopolamine also revealed group differences in the left hippocampus and right insula as well as the posterior cingulate and middle temporal gyrus. Cocaine addicted and controls differ in their subcortical, limbic, and cortical response to cholinergic probes in areas relevant to craving, learning, and memory. Cholinergic systems may offer a pharmacologic target for cocaine addiction treatment.

Objective: Major depressive disorder occurs in 15%-30% of patients who have had a myocardial infarction (MI), but the neurobiological mechanisms involved are not well understood. Previously, we found early intracellular signalling changes in the limbic system after acute MI in rats. The aim of the present study was to test the presence of behavioural deficits compatible with animal models of depression after acute MI in rats and to verify whether this is associated with apoptosis vulnerability markers. Methods: Occlusion of the left-anterior descending artery was induced for 40 minutes under anesthesia in adult male Sprague-Dawley rats. Control sham rats underwent the same surgical procedure without occlusion. After surgery, subgroups of MI and sham rats were treated with desipramine, 10 mg/kg, intraperitoneally for 14 days. All rats were tested on measures of behavioural depression 14 days after surgery with a sucrose preference test, a forced swimming test, and a memory test (Morris water maze [MWM]). The rats were sacrificed, and the MI size was determined; apoptosis was estimated in the prefrontal cortex, hypothalamus, amygdala and hippocampus by measuring Bax:Bcl-2 ratio and caspase-3 activity. Results: Untreated MI rats drank significantly less sucrose and swam significantly less than sham rats. No difference was found on the MWM. Behavioural depression was prevented by desipramine. Bax:Bcl-2 ratio was significantly increased in the prefrontal cortex and hypothalamus of MI rats, compared with sham rats; caspase-3 activity showed no difference between the 2 groups. Bax:Bcl-2 ratio in the prefrontal cortex was correlated with swim time in the forced swim test. Conclusion: Behavioural impairment and limbic apoptotic events observed after a myocardial infarct are consistent with a model of human post-MI depression.

BACKGROUND. Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior.

Trace amine-associated receptors (TAAR) recognize organic compounds, including primary, secondary, and tertiary amines. The TAAR5 receptor is known to be involved in the olfactory sensing of innate socially relevant odors encoded by volatile amines. However, emerging data point to the involvement of TAAR5 in brain functions, particularly in the emotional behaviors mediated by the limbic system which suggests its potential contribution to the pathogenesis of neuropsychiatric diseases. TAAR5 expression was explored in datasets available in the Gene Expression Omnibus, Allen Brain Atlas, and Human Protein Atlas databases. Transcriptomic data demonstrate ubiquitous low TAAR5 expression in the cortical and limbic brain areas, the amygdala and the hippocampus, the nucleus accumbens, the thalamus, the hypothalamus, the basal ganglia, the cerebellum, the substantia nigra, and the white matter. Altered TAAR5 expression is identified in Down syndrome, major depressive disorder, or HIV-associated encephalitis. Taken together, these data indicate that TAAR5 in humans is expressed not only in the olfactory system but also in certain brain structures, including the limbic regions receiving olfactory input and involved in critical brain functions. Thus, TAAR5 can potentially be involved in the pathogenesis of brain disorders and represents a valuable novel target for neuropsychopharmacology.

BACKGROUND: Bipolar disorder (BD) is characterized by a dysregulation of affect and impaired integration of emotion with cognition. These traits are also expressed in probands at high genetic risk of BD. The inferior frontal gyrus (IFG) is a key cortical hub in the circuits of emotion and cognitive control, and it has been frequently associated with BD. Here, we studied resting-state functional connectivity of the left IFG in participants with BD and in those at increased genetic risk. METHODS: Using resting-state functional magnetic resonance imaging we compared 49 young BD participants, 71 individuals with at least one first-degree relative with BD (at-risk), and 80 control subjects. We performed betweengroup analyses of the functional connectivity of the left IFG and used graph theory to study its local functional network topology. We also used machine learning to study classification based solely on the functional connectivity of the IFG. RESULTS: In BD, the left IFG was functionally dysconnected from a network of regions, including bilateral insulae, ventrolateral prefrontal gyri, superior temporal gyri, and the putamen (p , .001). A small network incorporating neighboring insular regions and the anterior cingulate cortex showed weaker functional connectivity in at-risk than control participants (p , .006). These constellations of regions overlapped with frontolimbic regions that a machine learning classifier selected as predicting group membership with an accuracy significantly greater than chance. CONCLUSIONS: Functional dysconnectivity of the IFG from regions involved in emotional regulation may represent a trait abnormality for BD and could potentially aid clinical diagnosis.

Addictive diseases, including addiction to heroin, prescription opioids, or cocaine, pose massive personal and public health costs. Addictions are chronic relapsing diseases of the brain caused by drug-induced direct effects and persisting neuroadaptations at the epigenetic, mRNA, neuropeptide, neurotransmitter, or protein levels. These neuroadaptations, which can be specific to drug type, and their resultant behaviors are modified by various internal and external environmental factors, including stress responsivity, addict mindset, and social setting. Specific gene variants, including variants encoding pharmacological target proteins or genes mediating neuroadaptations, also modify vulnerability at particular stages of addiction. Greater understanding of these interacting factors through laboratory-based and translational studies have the potential to optimize early interventions for the therapy of chronic addictive diseases and to reduce the burden of relapse. Here, we review the molecular neurobiology and genetics of opiate addiction, including heroin and prescription opioids, and cocaine addiction.

Abuse of stimulant drugs such as methamphetamine (METH) and cocaine has been associated with long-lasting persistent behavioral alterations. Although METH-induced changes in the striatal dopaminergic system might play a role in these effects, the potential underlying neuroanatomical substrate for the chronic cognitive dysfunction in METH users is unclear. To investigate the involvement of non-dopaminergic systems in the neurotoxic effects of METH, we treated rats with an escalating dose-multiple binge regimen, which we have suggested may more closely simulate human METH exposure profiles. Combined neuropathological and stereological analyses showed that 30 days after the last binge, there was shrinkage and degeneration in the pyramidal cell layers of the frontal cortex and in the hippocampal CA3 region. Further immunocytochemical analysis showed that METH exposure resulted in loss of calbindin interneurons in the neocortex and selective damage to pyramidal neurons in the CA3 region of the hippocampus and granular cells in the dentate gyrus that was accompanied by microglial activation. Taken together, these studies suggest that selective degeneration of pyramidal neurons and interneurons in the neocortex and limbic system might be involved in the cognitive alterations in METH users.

Abuse of stimulant drugs such as methamphetamine (METH) and cocaine has been associated with long-lasting persistent behavioral alterations. Although METH-induced changes in the striatal dopaminergic system might play a role in these effects, the potential underlying neuroanatomical substrate for the chronic cognitive dysfunction in METH users is unclear. To investigate the involvement of non-dopaminergic systems in the neurotoxic effects of METH, we treated rats with an escalating dose-multiple binge regimen, which we have suggested may more closely simulate human METH exposure profiles. Combined neuropathological and stereological analyses showed that 30 days after the last binge, there was shrinkage and degeneration in the pyramidal cell layers of the frontal cortex and in the hippocampal CA3 region. Further immunocytochemical analysis showed that METH exposure resulted in loss of calbindin interneurons in the neocortex and selective damage to pyramidal neurons in the CA3 region of the hippocampus and granular cells in the dentate gyrus that was accompanied by microglial activation. Taken together, these studies suggest that selective degeneration of pyramidal neurons and interneurons in the neocortex and limbic system might be involved in the cognitive alterations in METH users.

PAX6 is a master regulatory gene involved in neuronal cell fate specification. It also plays a critical role in early eye field and subsequent limbal stem cell determination during eye development. Defects of PAX6 cause aniridia and limbal stem cell deficiency in humans, and the Small eye (Sey) phenotype in mice. However, how PAX6 specifies limbal stem cell (LSC) and corneal fates during eye development is not well understood. Here we show that PAX6 is expressed in the primitive eye cup and later in corneal tissue progenitors in early embryonic development. In contrast, P63 expression commences after that of PAX6 in ocular adnexal and skin tissue progenitors, and later on in LSCs. By using an in vitro feeder-free culture system, we show that PAX6 knockdown in LSCs leads to an upregulation of skin epidermal specific keratins Concomitant with differentiation to a skin fate. Using gene expression analysis, we identified involvement of Notch, WNT and TGFb signaling pathways in LSC fate ...

CONTEXT The pathophysiologic mechanism of major depressive disorder (MDD) has been consistently associated with altered catecholaminergic function, especially with decreased dopamine neurotransmission, by various sources of largely indirect evidence. An instructive paradigm for more directly investigating the relationship between catecholaminergic function and depression has involved the mood response to experimental catecholamine depletion (CD). OBJECTIVES To determine whether catecholaminergic dysfunction represents a trait abnormality in MDD and to identify brain circuitry abnormalities involved in the pathophysiologic mechanism of MDD. DESIGN Randomized, double-blind, placebo-controlled, crossover, single-site experimental trial. SETTING Psychiatric outpatient clinic. PARTICIPANTS Fifteen unmedicated subjects with MDD in full remission (hereinafter referred to as RMDD subjects) and 13 healthy controls. INTERVENTION Induction of CD by oral administration of alpha-methylparatyrosi...

Interleukin (IL)-18 is a pro-inflammatory cytokine that is proposed to be involved in physiological as well as pathological conditions in the adult brain. IL-18 acts through a heterodimer receptor comprised of a subunit alpha (IL-18Rα) required for binding, and a subunit beta (IL-18Rβ) necessary for activation of signal transduction. We recently demonstrated that the canonical alpha binding chain, and its putative decoy isoform, are expressed in the mouse central nervous system (CNS) suggesting that IL-18 may act on the brain by directly binding its receptor. Considering that the co-expression of the beta chain seems to be required to generate a functional receptor and, a short variant of this chain has been described in rat and human brain, in this study we have extended our investigation to IL-18Rβ in mouse. Using a multi-methodological approach we found that: 1) a short splice variant of IL-18Rβ was expressed in the CNS even if at lower levels compared to the full-length IL-18Rβ variants 2) the canonical IL-18Rβ is expressed in the CNS particularly in areas and nuclei belonging to the limbic system as previously observed for IL-18Rα, finally 3) we have also demonstrated that both IL-18Rβ isoforms are up-regulated in different brain areas three hours after a single lipopolysaccharide (LPS) injection suggesting that IL-18Rβ in the CNS might be involved in mediating the endocrine and behavioral effects of LPS. Our data highlight the considerable complexity of the IL-18 regulation activity in the mouse brain and further support an important central role for IL-18.

Background: Diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) MRI have high sensitivity and specificity for Creutzfeldt-Jakob disease (CJD). No studies, however, have demonstrated how MRI can distinguish CJD from nonprion causes of rapidly progressive dementia (npRPD). We sought to determine the diagnostic accuracy of MRI for CJD compared to a cohort of npRPD subjects. Methods: Two neuroradiologists blinded to diagnosis assessed DWI and FLAIR images in 90 patients with npRPD (n = 29) or prion disease (sporadic CJD [sCJD], n = 48, or genetic prion disease [familial CJD, n = 6, and Gerstmann-Sträussler-Scheinker, n = 7]). Thirty-one gray matter regions per hemisphere were assessed for abnormal hyperintensities. The likelihood of CJD was assessed using our previously published criteria. Results: Gray matter hyperintensities (DWI > FLAIR) were found in all sCJD cases, with certain regions preferentially involved, but never only in limbic regions, and ra...

Background: Patients with psychogenic amnesia generally suffer from episodic memory deficits associated with an impairment of self-identity. While the first is generally attributed to limbic dysfunction, the latter might be related to posterior parietal cortex. Methods and Results: In a patient with acute repetitive psychogenic amnesia, three different functional investigations (fMRI, electrical-neuroimaging, PET) during both resting-state and a behavioural paradigm testing Ôtime-travelÕ showed left posterior parietal activation, unlike in 12 control subjects. Conclusion: Impairment of self-identity and episodic memory in psychogenic amnesia may be associated with functional alterations of left posterior parietal cortex.

ObjectiveIn this study, empathy is quantified using a novel social test. Empathy and prosocial behavior are linked to the expression of oxytocin in humans and rodent models. Specifically, prosocial behavior in prairie voles (Microtus ochrogaster) has been linked to the expression of oxytocin in the paraventricular nucleus of the hypothalamus. The animal’s behavior was considered empathic if it spends significantly more time attempting to remove a loos fitting restraint (tether) from the stimulus animal than time in contact with a, simultaneously presented, non-social object similar to the tether. The behavioral data was cross-referenced with the number of neurons expressing oxytocin and arginine vasopressin, as well as the density of dopaminergic neurons (identified by the expression of tyrosine hydroxylase), in the paraventricular nucleus of the hypothalamus. These proteins influence empathic behavior in humans, non-human primates, rats, mice, and prairie voles.ResultsThe consisten...

Human brain imaging studies from various clinical cohorts show that chronic pain is associated with large-scale brain functional and morphological reorganization. However, how the rat whole-brain network is topologically reorganized to support persistent pain-like behavior following neuropathic injury remains unknown. Here we compare resting state fMRI functional connectivity-based whole-brain network properties between rats receiving spared nerve injury (SNI) vs. sham injury, at 5 days (n511 SNI; n512 sham) and 28 days (n511 SNI; n512 sham) post-injury. Similar to the human, the rat brain topological properties exhibited small world features and did not differ between SNI and sham. Local neural networks in SNI animals showed minimal disruption at day 5, and more extensive reorganization at day 28 post-injury. Twenty-eight days after SNI, functional connection changes were localized mainly to within the limbic system, as well as between the limbic and nociceptive systems. No connectivity changes were observed within the nociceptive network. Furthermore, these changes were lateralized and in proportion to the tactile allodynia exhibited by SNI animals. The findings establish that SNI is primarily associated with altered information transfer of limbic regions and provides a novel translational framework for understanding brain functional reorganization in response to a persistent neuropathic injury. ecent human brain imaging studies show that chronic pain is associated with large-scale brain functional and morphological reorganization 1 . Rodent neuroimaging studies potentially provide a pathway for backtranslation of findings from humans to model preparations, wherein more invasive mechanistic experiments can be performed. In rodents, functional magnetic resonance imaging (fMRI) has revealed brain regions related to acute nociceptive processing. The most consistently observed responses are localized to primary and secondary somatosensory cortices, insular cortex, cingulate gyrus, thalamus and periaqueductal gray 2 . However, rodent brain properties that characterize the transition to neuropathic pain remain unknown, and thus it is unclear whether rodent models show appropriate parallels to the human brain reorganization with chronic pain. Human and rodent brains have complex topological attributes that are thought to provide the physiological basis of information processing . Resting-state fMRI (rsfMRI) has been extensively used to map the topological properties of brain networks 6 , and importantly it has been determined that these functional properties are susceptible to various pathological disruptions 7 . Unlike conventional evoked-response fMRI, rsfMRI relies on identifying changes in intrinsic fluctuations of the fMRI signal. Given that the brains of chronic pain patients are continuously encoding and processing spontaneous pain, the approach provides a powerful tool with which to detect fundamental aspects of functional brain reorganization associated with chronic pain. To date, changes in resting-state properties have been observed for multiple chronic pain conditions in humans 8-14 . In contrast, little is known about rsfMRI in animal models of persistent pain. Studies in rodent models of persistent pain show widespread reorganization along the neuraxis . Whereas most studies have examined afferent nociceptors and spinal cord pathways, more recent investigations focus on brain circuitry. Various rodent models for persistent pain show morphological, functional, and molecular changes in limbic circuitry, including the hippocampus 18-21 , striatum , frontal cortex , and amygdala 28 . Based on these results and on recent human imaging data , we hypothesized that persistent neuropathic pain-like behavior in the rodent is primarily associated with functional reorganization of brain regions within the limbic system, including the hippocampus, amygdala, and striatum. To test this hypothesis, we used rsfMRI to examine the intrinsic reorganization of rat brain functional connectivity following spared nerve injury (SNI). We compared longitudinal changes in topology and functional connectivity of resting-state neural networks between SNI and sham animals following peripheral injury.

Previous studies have demonstrated that migraine is associated with enhanced perception and altered cerebral processing of sensory stimuli. More recently, it has been suggested that this sensory hypersensitivity might reflect a more general enhanced response to aversive emotional stimuli. Using functional magnetic resonance imaging and emotional face stimuli (fearful, happy and sad faces), we compared whole-brain activation between 41 migraine patients without aura in interictal period and 49 healthy controls. Migraine patients showed increased neural activation to fearful faces compared to neutral faces in the right middle frontal gyrus and frontal pole relative to healthy controls. We also found that higher attack frequency in migraine patients was related to increased activation mainly in the right primary somatosensory cortex (corresponding to the face area) to fearful expressions and in the right dorsal striatal regions to happy faces. In both analyses, activation differences r...

Increase in dopamine (DA) neurotransmission resulting from blockade of the DA transporter (DAT) after administration of cocaine is believed to play a major role in mediating its behavioral and reinforcing effects. Since it was hypothesized that drugs that block the DAT have cocaine-like behavioral effects, it was of interest to study in the present article the stimulant effects of cocaine on locomotor activity and on pattern of activation of DA neurotransmission in different DAergic terminal areas in rats and compare these effects with those of 4Ј-chloro-3␣-(diphenylmethoxy)-tropane (4-Cl-BZT), a benztropine analog showing higher affinity for the DAT, but reduced behavioral effects compared with cocaine. Administration of cocaine resulted in a dose-dependent stimulation of locomotor activity and DA neurotransmission in the nucleus accumbens shell and Portions of this paper were presented at a meeting on Monitoring Molecules in Neuroscience, Stockholm, Sweden, June 2003 and the 33rd Annual Meeting of the Society for Neuroscience, 2003. Article, publication date, and citation information can be found at .

Stanford, Ian M., Roger D. Traub, and John G. R. Jefferys. Limbic gamma rhythms. II. Synaptic and intrinsic mechanisms underlying spike doublets in oscillating subicular neurons. J. Neurophysiol. 80: 162–171, 1998. Gamma oscillations were evoked in the subiculum in rat transverse hippocampal slices by tetanic stimulation (200 ms/100 Hz) of either CA1 or subiculum. Gamma oscillations in the subiculum differed from those in CA1 in containing population spike doublets as well as singlets. The present study addresses the origin of this more complex form of gamma oscillation in the subiculum. Intracellular recordings from subicular neurons revealed that 63% of them fired double action potentials on cycles of the gamma oscillation that generated population spike doublets after tetanic stimulation of either CA1 or subiculum. The remaining cells produced excitatory postsynaptic potentials (EPSPs), and occasional single spikes, on each cycle. Neurons that fired occasional single action poten...

An experiment is described in which the ability of 1-month-old infants to recognize their mothers visually was explored with the live faces of mother and stranger presented in three different poses. The en face and half-profile poses resulted in significant visual preferences for the mother being demonstrated, but the profile pose did not. The temporal stability of the observed memory is discussed along with potential methodological artifacts.