Clinical and neuroimaging correlates in a pilot randomized trial of aerobic exercise for major depression.

BACKGROUND: Aerobic exercise (AE) combined with pharmacotherapy is known to reduce depressive symptoms; however, studies have not focused on long-term AE for volumetric changes of brain regions (amygdala, thalamus, and nucleus accumbens [NAcc]) linked to the control of affective responses and hopelessness in individuals with major depression (MD). In addition, AE with motor complexity (AEMC) would be more effective than AE in causing brain plasticity. We compared the effects of 24 weeks of AE and AEMC combined with pharmacotherapy on clinical and volumetric outcomes in individuals with MD. METHODS: Forty medicated individuals with MD were randomly assigned to nonexercising control (C), AE, and AEMC groups. The training groups exercised for 60 min, twice a week for 24 weeks. Clinical and volumetric outcomes were assessed before and after the 24 weeks. Effect size (ES) and confidence interval (CI) were calculated for within-group and between-groups changes. RESULTS: AE and AEMC reduced hopelessness (ES = -0.73 and ES = -0.62, respectively) and increased affective responses (ES = 1.24 and ES = 1.56, respectively). Only AE increased amygdala (ES = 0.27 left and ES = 0.34 right), thalamus (ES = 0.33 left and ES = 0.26 right) and left NAcc (ES = 0.54) volumes. AE was more effective than the C group in reducing hopelessness and causing brain plasticity. The changes in the right amygdala volume showed a strong trend in explaining 72 % of the changes in affective responses following AE (p = 0.06). LIMITATION: Lack of posttraining follow-up and small sample size. CONCLUSION: These preliminary data indicate that AE combined with pharmacotherapy can cause clinical improvement and brain plasticity in individuals with MD.

Corrigendum: The olfactory tract: Basis for future evolution in response to rapidly changing ecological niches.

[This corrects the article DOI: 10.3389/fnana.2022.831602.].

Involvement of nitric oxide in the neurobiology of fear-like behavior.

Fear is an emotional reaction that arises in dangerous situations, inducing the adaptation to an existing condition. This behavior was conserved in all vertebrates throughout evolution and is observed in mammals, birds, fish, amphibians, and reptiles. The neurocircuitry of fear involves areas of the limbic system, cortical regions, midbrain, and brainstem. These areas communicate with each other so that there is an expression of fear and memory formation to deal with the same situation at another time. The effect of nitric oxide (NO) on fear modulation has been explored. NO is a gaseous compound that easily diffuses through the cell membrane and is produced through the oxidation reaction of l-Arginine to l-citrulline catalyzed by nitric oxide synthase (NOS). Activating the intracellular NO receptor (soluble guanylyl cyclase enzyme - sGC) triggers an enzymatic cascade that can culminate in plastic events in the neuron. NOS inhibitors induce anxiolytic-like responses in fear modulation, whereas NO donors promote fear- and anxiety-like behaviors. This review describes the neurobiology of fear in mammals and non-mammals, how NO is produced in the central nervous system, and how NO acts in fear-like behavior.

The Olfactory Tract: Basis for Future Evolution in Response to Rapidly Changing Ecological Niches.

Within the forebrain the olfactory sensory system is unique from other sensory systems both in the projections of the olfactory tract and the ongoing neurogenic potential, characteristics conserved across vertebrates. Olfaction plays a crucial role in behaviors such as mate choice, food selection, homing, escape from predators, among others. The olfactory forebrain is intimately associated with the limbic system, the region of the brain involved in learning, memory, and emotions through interactions with the endocrine system and the autonomic nervous system. Previously thought to lack a limbic system, we now know that teleost fishes process emotions, have exceptional memories, and readily learn, behaviors that are often associated with olfactory cues. The association of neuromodulatory hormones, and more recently, the immune system, with odor cues underlies behaviors essential for maintenance and adaptation within natural ecological niches. Increasingly anthropogenic perturbations affecting ecosystems are impacting teleost fishes worldwide. Here we examine the role of the olfactory tract as the neural basis for the integration of environmental cues and resulting behaviors necessary for the regulation of biotic interactions that allow for future adaptation as the climate spins out of control.

Von Economo neurons: Cellular specialization of human limbic cortices?

Von Economo neurons (VENs) have been mentioned in the medical literature since the second half of the 19th century; however, it was not until the second decade of the 20th century that their cytomorphology was described in detail. To date, VENs have been found in limbic sectors of the frontal, temporal and insular lobes. In humans, their density seems to decrease in the caudo-rostral and ventro-dorsal direction; that is, from the anterior regions of the cingulate and insular cortices towards the frontal pole and the superior frontal gyrus. Several studies have provided similar descriptions of the shape of the VEN soma, but the size of the soma varies from one cortical region to another. There is consensus among different authors about the selective vulnerability of VENs in certain pathologies, in which a deterioration of the capacities involved in social behaviour is observed. In this review, we propose that the restriction of VENs towards the sectors linked to limbic information processing in Homo sapiens gives them a possible functional role in relation to the structures in which they are located. However, given the divergence in characteristics such as location, density, size and biochemical profile among VENs of different cortical sectors, the activities in which they participate could allow them to partake in a wide spectrum of neurological functions, including autonomic responses and executive functions.

Adult human neurogenesis: early studies clarify recent controversies and go further.

Evidence on adult mammalian neurogenesis and scarce studies with human brains led to the idea that adult human neurogenesis occurs in the subgranular zone (SGZ) of the dentate gyrus and in the subventricular zone (SVZ). However, findings published from 2018 rekindled controversies on adult human SGZ neurogenesis. We systematically reviewed studies published during the first decade of characterization of adult human neurogenesis (1994-2004) - when the two-neurogenic-niche concept in humans was consolidated - and compared with further studies. The synthesis of both periods is that adult human neurogenesis occurs in an intensity ranging from practically zero to a level comparable to adult mammalian neurogenesis in general, which is the prevailing conclusion. Nonetheless, Bernier and colleagues showed in 2000 intriguing indications of adult human neurogenesis in a broad area including the limbic system. Likewise, we later showed evidence that limbic and hypothalamic structures surrounding the circumventricular organs form a continuous zone expressing neurogenesis markers encompassing the SGZ and SVZ. The conclusion is that publications from 2018 on adult human neurogenesis did not bring novel findings on location of neurogenic niches. Rather, we expect that the search of neurogenesis beyond the canonical adult mammalian neurogenic niches will confirm our indications that adult human neurogenesis is orchestrated in a broad brain area. We predict that this approach may, for example, clarify that human hippocampal neurogenesis occurs mostly in the CA1-subiculum zone and that the previously identified human rostral migratory stream arising from the SVZ is indeed the column of the fornix expressing neurogenesis markers.

Surgical Treatment for Refractory Aggression after Bacterial Meningitis Complicated by Stroke: Case Report / Tratamento cirúrgico para agressividade refratária pós-meningite bacteriana complicada por acidente vascular encefálico: Relato de caso

Bacterial meningitis remains a public health problem. One of the complications of this group of diseases is cerebral ischemia, an important indicator of severity and an independent predictor of poor prognosis. It is already known that, in many cases, pathological aggressiveness is the result of brain abnormalities in individuals with mental illnesses. The indication of neurosurgeries for psychiatric disorders (NPDs) relies on numerous studies based on scientific evidence that correlate psychiatric illnesses with the limbic system and the pathophysiology of emotions. The development of sophisticated stereotactic target localization techniques, brain atlases, and imaging methods made stereotaxis possible, a procedure that increased the precision of neurosurgery and reduced brain damage. Nowadays, multiple targets can be treated during NPD, according to the particular characteristics of the patient. Moreover, the combination of lesions leads to more significant improvements compared with isolated procedures. The present study aimed to report the rare case of a patient with a history of bacterial meningitis who developed stroke and chronic pathological aggressiveness refractory to clinical treatment and underwent ablation using the multitarget stereotactic technique.

A meningite bacteriana continua sendo um problema de saúde pública. Uma das complicações deste grupo de doenças é a isquemia cerebral, um importante indicador de gravidade e um preditor independente de mau prognóstico. Já se sabe que, em muitos casos, a agressividade patológica é o resultado de anormalidades cerebrais em indivíduos com doença mental. A indicação das neurocirurgias para doenças psiquiátricas (NDPs) se fundamenta em inúmeros estudos com base em evidências científicas, os quais correlacionam as enfermidades psiquiátricas com o sistema límbico e a fisiopatologia das emoções. O desenvolvimento de técnicas sofisticadas de localização de alvos estereotáxicos, atlas cerebrais e métodos de imagem tornaram a estereotaxia possível, um procedimento que aumentou a precisão da neurocirurgia e reduziu os danos cerebrais. Atualmente, múltiplos alvos podem ser tratados durante a NDP, de acordo com as características individuais do paciente. Ademais, a combinação das lesões leva a melhorias mais significativas em comparação com os procedimentos isolados. O presente estudo teve como objetivo relatar o caso raro de uma paciente com histórico de meningite bacteriana que evoluiu para acidente vascular encefálico e agressividade patológica crônica refratária ao tratamento clínico e foi submetida a ablação utilizando a técnica estereotáxica de múltiplos alvos.

Upregulation of FosB/ΔFosB in limbic circuits after tooth exodontia-induced occlusal instability in an experimental model of unpredictable chronic stress.

Psychological stress and occlusal alterations are contributing etiologic factors for temporomandibular and muscular disorders in the orofacial area. The neural modulation recruited for this relationship, however, is not elucidated. The aim of this study was to investigate potential central mechanisms involved in the exodontia-induced occlusal instability associated with unpredictable chronic stress (UCS). Male adult Wistar rats were submitted to occlusal instability (unilateral molar teeth extraction) and/or to a UCS protocol and treated with diazepam or vehicle. The anxiety-like behavior was evaluated by elevated plus maze (EPM) and open field (OF) tests. Limbic structures such as the central nucleus of the amygdala (CeA), paraventricular nucleus of the hypothalamus (PVN), dorsal periaqueductal gray matter (dPAG) and nucleus accumbens core (NAc) were analyzed for expression of FosB/ΔFosB (immediate early genes) by immunohistochemistry. Exodontia and/or UCS decreased the time spent in the open arms at the EPM and the distance travelled at the OF, and increased the immobility time at the OF, suggesting anxiety-like behavior. In addition, exodontia induction resulted in an upregulation of FosB/ΔFosB in the CeA, PVN and dPAG, while UCS and exodontia + UCS upregulate FosB/ΔFosB immunoreactivity in the CeA, PVN, dPAG and NAc. Treatment with diazepam decreased the expression of FosB/ΔFosB in all analyzed structures of animals subject to UCS and exodontia + UCS, while promoted a reduction in the FosB/ΔFosB expression in the CeA, PVN and dPAG in animals subject to exodontia. Our findings showed an anxiogenic effect of exodontia and UCS, which is correlated with intranuclear neuron activation of limbic structures in a spatially dependent manner and that is prevented by the administration of diazepam.

Temporomandibular inflammation regulates the matrix metalloproteinases MMP-2 and MMP-9 in limbic structures.

Temporomandibular disorder (TMD) is characterized by acute or chronic orofacial pain, which can be associated with inflammatory processes in the temporomandibular joint (TMJ) and emotional disorders. Peripheral and central sensitization in painful orofacial processes is common, and it can be triggered by peripheral inflammatory challenge with consequent neuroinflammation phenomena. Such neuroinflammation comes from inflammatory products from supportive cells, blood-brain barrier, and extracellular matrix. Here, we evaluated the possible recruitment of limbic structures for modified matrix metalloproteinases (MMPs) expression and activity during temporomandibular inflammation-induced orofacial persistent pain. The inflammatory process in TMJs of rats was induced by Freund's Complete Adjuvant (CFA) administration. The activity and expression of MMPs-2 and 9 were assessed by in situ zymography and conventional zymography, respectively. A glial colocalization with the MMPs was performed using immunofluorescence. The results evidenced both short- and long-term alterations on MMP-2 and -9 expression in the limbic structures following CFA-induced temporomandibular inflammation. The gelatinolytic activity was increased in the central amygdala, hippocampus, hypothalamus, ventrolateral periaqueductal gray (vlPAG), superior colliculus, and inferior colliculus. Finally, an increase of colocalization of MMP-2/GFAP and MMP-9/GFAP in CFA-induced inflammation groups was observed when compared with saline groups in the central amygdala and vlPAG. It is possible to suggest that glial activation is partly responsible for the production of gelatinases in the persistent orofacial pain, and it is involved in the initiation and maintenance of this process, indicating that inhibition of MMPs might be pursued as a potential new therapeutic target for TMD.

AMPAr GluA1 Phosphorylation at Serine 845 in Limbic System Is Associated with Cardiac Autonomic Tone.

The central autonomic network, which is connected to the limbic system structures including the amygdala (AMY) and anterior hippocampus (aHIP), regulates the sympathetic and parasympathetic modulation of visceromotor, neuroendocrine, pain, and behavior manifestations during stress responses. Heart rate variability (HRV) is useful to estimate the cardiac autonomic tone. The levels of phosphorylation on the Ser831 and Ser845 sites of the GluA1 subunit of the AMPAr (P-GluA1-Ser845 and P-GluA1-Ser831) are useful markers of synaptic plasticity. The relation between synaptic plasticity in the human limbic system structures and autonomic regulation in humans is unknown. This study investigated the association between HRV and neurochemistry biomarkers of synaptic plasticity in AMY and aHIP. HRV indices were obtained from the resting state electrocardiogram of patients with drug-resistant mesial temporal lobe epilepsy (MTLE, n = 18) and the levels of P-GluA1-Ser845 and P-GluA1-Ser831 in the AMY and aHIP resected during the epilepsy surgery. A backward stepwise multiple linear regression models were used to analyze the association between HRV and synaptic plasticity biomarkers controlling for imbalances in the distribution of sociodemographic, clinical, neuroimaging, and neurosurgical variables. P-GluA1-Ser845 levels in AMY show a negative association (p < 0.05) with the 3 investigated parasympathetic autonomic HRV indices (SDNN, rMSSD, and HF) predicting 24 to 40% of their variation. The final multiple linear regression models include disease duration and levels of P-GluA1-Ser845 and predict 24 to 56% of cardiac autonomic tone variation (p < 0.01). P-GluA1-Ser845 levels in AMY and aHIP are negatively associated with the resting HRV in MTLE-HS indicating that increased synaptic efficiency in amygdala is associated with a parasympathetic cardiac autonomic tone impairment. The results suggest that specific changes in synaptic plasticity may be involved in the brain-heart axis regulation by the limbic system.

CRF1 and CRF2 receptors in the lateral hypothalamus differently modulate the baroreflex function in unanesthetized rats.

The lateral hypothalamus (LH) is a diencephalic structure that has been considered part of the central circuitry regulating the baroreflex function. However, the local neurochemical mechanisms involved in baroreflex control by this hypothalamic area are poorly understood. Therefore, in the present study we investigated the role of corticotropin-releasing factor (CRF) neurotransmission within the LH acting via local CRF1 and CRF2 receptors in cardiac baroreflex responses in unanesthetized rats. For this, the baroreflex activity was assessed using two approaches: i) the pharmacological approach via intravenous infusion of vasoactive agents, and ii) the sequence analysis technique that evaluates reflex responses during spontaneous arterial pressure variations. The sequence analysis technique indicated that LH treatment with the selective CRF1 receptor antagonist CP376395 decreased the baroreflex effectiveness index, whereas the selective CRF2 receptor antagonist antisauvagine-30 increased the reflex shortening of pulse interval during spontaneous arterial pressure decreases. However, the pharmacological approach did not indicate effect of the bilateral microinjection of either CP376395 or antisauvagine-30 into the LH in the tachycardia evoked by blood pressure decrease or the reflex bradycardia caused by blood pressure increase. Overall, these findings indicate that CRF neurotransmission within the LH controls baroreflex function during a narrow range of physiological arterial pressure variations. Besides, results provide evidence that CRF1 and CRF2 receptors in the LH oppositely modulate the spontaneous baroreflex activity through different mechanisms.

Effect of unilateral amygdalotomy and hypothalamotomy in patients with refractory aggressiveness.

BACKGROUND: Neurosurgical treatment, although controversial, is considered a useful resource in the treatment of chronic psychiatric diseases such as refractory aggressiveness. OBJECTIVE: To evaluate the clinical results and side effects of posteromedial hypothalamotomy associated with amygdalotomy in patients with refractory aggressiveness. METHOD: A clinical trial was conducted in patients with chronic aggressiveness and refractory to pharmacological treatment. A central amygdalotomy associated with posteromedial hypothalamotomy was performed using thermo-coagulation by radiofrequency. The degree of aggressiveness was quantified by the Yudofsky's global scale of aggression. Postoperative changes in aggressive behavior continued to be evaluated every 6 months for at least 36 months. RESULTS: A statistically significant change in aggressive behavior was observed during 36 months of follow-up. The collateral effects of the association of both procedures are described, the most frequent being drowsiness and some cases of reduction in sexual behavior. CONCLUSION: Symmetric and simultaneous unilateral lesions of the central nucleus of the amygdala and the posteromedial hypothalamus contralateral to motor dominance give the same clinical effect in the reduction of the pathological aggression that the bilateral lesions.

Forced normalization: A systematic review.

OBJECTIVE: Forced normalization (FN) is an intriguing phenomenon characterized by the emergence of psychiatric disturbances following the establishment of seizure control or reduction in the epileptic activity in a patient with previous uncontrolled epilepsy. We aim to describe the clinical characteristics of the condition. METHODS: We conducted a systematic review on MEDLINE, EMBASE, Cochrane, and Scielo from January 1953 to January 2018. Clinical, electrographic, and imaging data were gathered. We considered all outcomes in children and adults. We performed no meta-analyses due to the limited available data. RESULTS: Of 2606 abstracts identified, 36 fulfilled the FN diagnostic criteria; 193 FN episodes were evaluated and 77 of them were analyzed extensively. Sixty percent of cases were female. Mean age ± standard deviation (SD) was 28.3 ± 14.2 years. The majority of patients had focal (80%) symptomatic (44%) epilepsy. Most patients reported a high ictal frequency (58%) and were on polytherapy (51%). Patients presented psychosis (86.4%), mood disorders (25.8%), and dissociation (4.5%) as the main manifestations. In the psychosis group, persecutory (52.6%) and reference (47.3%) delusions were frequent. FN was provoked by an antiepileptic drug (AED) (48.5%) mainly levetiracetam, epilepsy surgery (31.8%), or vagus nerve stimulation (13.6%). Treatment was homogeneous including anticonvulsant withdrawal (47%) or taper (25%); antipsychotics were initiated in the majority of cases (73%). Psychiatric symptoms were partially controlled in 35%, with complete resolution of symptoms in the remaining 65% of cases. The majority of patients (87%) with AED trigger and withdrawal presented complete resolution of symptoms in comparison to 28.5% of patients triggered by surgery. SIGNIFICANCE: Forced normalization is an entity whose pathophysiology remains uncertain. Antipsychotic drug use does not predict complete resolution of psychiatric symptoms in comparison with AED withdrawal. Although there is a positive response to treatment in patients with FN triggered by drugs, the prognosis is obscure in patients with surgery triggered FN.

[Efecto de la amigdalotomía e hipotalamotomía unilateral en pacientes con agresividad refractaria].

BACKGROUND: Neurosurgical treatment, although controversial, is considered a useful resource in the treatment of chronic psychiatric diseases such as refractory aggressiveness. OBJECTIVE: To evaluate the clinical results and side effects of posteromedial hypothalamotomy associated with amygdalotomy in patients with refractory aggressiveness. METHOD: A clinical trial was conducted in patients with chronic aggressiveness and refractory to pharmacological treatment. A central amygdalotomy associated with posteromedial hypothalamotomy was performed using thermo-coagulation by radiofrequency. The degree of aggressiveness was quantified by the Yudofsky's global scale of aggression. Postoperative changes in aggressive behavior continued to be evaluated every 6 months for at least 36 months. RESULTS: A statistically significant change in aggressive behavior was observed during 36 months of follow-up. The collateral effects of the association of both procedures are described, the most frequent being drowsiness and some cases of reduction in sexual behavior. CONCLUSION: Symmetric and simultaneous unilateral lesions of the central nucleus of the amygdala and the posteromedial hypothalamus contralateral to motor dominance give the same clinical effect in the reduction of the pathological aggression that the bilateral lesions.

ANTECEDENTES: El tratamiento neuroquirúrgico, aunque polémico, se considera un recurso útil en el tratamiento de enfermedades psiquiátricas crónicas como la agresividad refractaria. OBJETIVO: Evaluar los resultados clínicos y los efectos colaterales de la hipotalamotomía posteromedial (HPM) asociada a amigdalotomía en pacientes con agresividad refractaria. MÉTODO: Se realizó un ensayo clínico en pacientes con agresividad crónica y refractaria a tratamiento farmacológico. Se les realizó amigdalotomía central asociada a HPM mediante termocoagulación por radiofrecuencia. El grado de agresividad se cuantificó mediante la escala global de agresividad de Yudofsky. Los cambios postoperatorios en la conducta agresiva continuaron siendo evaluados cada 6 meses durante al menos 36 meses. RESULTADOS: Se observó un cambio estadísticamente significativo de la conducta agresiva, a lo largo de 36 meses de seguimiento. Se describen los efectos colaterales de la asociación de ambos procedimientos, siendo el de mayor frecuencia la somnolencia y algunos casos de reducción en la conducta sexual. CONCLUSIÓN: Las lesiones unilaterales simétricas y simultáneas del núcleo central de la amígdala y del hipotálamo posteromedial contralaterales a la dominancia motora dan el mismo efecto clínico en la reducción de la agresividad patológica que las lesiones bilaterales.

Efecto de la amigdalotomía e hipotalamotomía unilateral en pacientes con agresividad refractaria / Effect of tonsillotomy and unilateral hypothalamotomy in patients with refractory aggressiveness

Resumen Antecedentes: El tratamiento neuroquirúrgico, aunque polémico, se considera un recurso útil en el tratamiento de enfermedades psiquiátricas crónicas como la agresividad refractaria. Objetivo: Evaluar los resultados clínicos y los efectos colaterales de la hipotalamotomía posteromedial (HPM) asociada a amigdalotomía en pacientes con agresividad refractaria. Método: Se realizó un ensayo clínico en pacientes con agresividad crónica y refractaria a tratamiento farmacológico. Se les realizó amigdalotomía central asociada a HPM mediante termocoagulación por radiofrecuencia. El grado de agresividad se cuantificó mediante la escala global de agresividad de Yudofsky. Los cambios postoperatorios en la conducta agresiva continuaron siendo evaluados cada 6 meses durante al menos 36 meses. Resultados: Se observó un cambio estadísticamente significativo de la conducta agresiva, a lo largo de 36 meses de seguimiento. Se describen los efectos colaterales de la asociación de ambos procedimientos, siendo el de mayor frecuencia la somnolencia y algunos casos de reducción en la conducta sexual. Conclusión: Las lesiones unilaterales simétricas y simultáneas del núcleo central de la amígdala y del hipotálamo posteromedial contralaterales a la dominancia motora dan el mismo efecto clínico en la reducción de la agresividad patológica que las lesiones bilaterales.

Abstract Background: Neurosurgical treatment, although controversial, is considered a useful resource in the treatment of chronic psychiatric diseases such as refractory aggressiveness. Objective: To evaluate the clinical results and side effects of posteromedial hypothalamotomy associated with amygdalotomy in patients with refractory aggressiveness. Method: A clinical trial was conducted in patients with chronic aggressiveness and refractory to pharmacological treatment. A central amygdalotomy associated with posteromedial hypothalamotomy was performed using thermo-coagulation by radiofrequency. The degree of aggressiveness was quantified by the Yudofsky's global scale of aggression. Postoperative changes in aggressive behavior continued to be evaluated every 6 months for at least 36 months. Results: A statistically significant change in aggressive behavior was observed during 36 months of follow-up. The collateral effects of the association of both procedures are described, the most frequent being drowsiness and some cases of reduction in sexual behavior. Conclusion: Symmetric and simultaneous unilateral lesions of the central nucleus of the amygdala and the posteromedial hypothalamus contralateral to motor dominance give the same clinical effect in the reduction of the pathological aggression that the bilateral lesions.

Chronic REM Sleep Restriction in Juvenile Male Rats Induces Anxiety-Like Behavior and Alters Monoamine Systems in the Amygdala and Hippocampus.

Adolescence is marked by major physiological changes, including those in the sleep-wake cycle, such as phase delay, which may result in reduced sleep hours. Sleep restriction and/or deprivation in adult rats activate stress response and seem to be a risk factor for triggering emotional disorders. In the present study, we sought to evaluate the behavioral and neurobiological consequences of prolonged REM sleep restriction in juvenile male rats. Immediately after weaning, on postnatal day 21, three males from each litter were submitted to REM sleep deprivation and the other three animals were maintained in their home-cages. REM sleep restriction (REMSR) was accomplished by placing the animals in the modified multiple platform method for 18 h and 6 h in the home-cage, where they could sleep freely; the sleep restriction lasted 21 consecutive days, during which all animals were measured and weighed every 3 days. After the end of this period, all animals were allowed to sleep freely for 2 days, and then the behavioral tests were performed for evaluation of depressive and anxiety-like profiles (sucrose negative contrast test and elevated plus maze, EPM). Blood sampling was performed 5 min before and 30 and 60 min after the EPM for determination of corticosterone plasma levels. The adrenals were weighed and brains collected and dissected for monoamine levels and receptor protein expression. REMSR impaired the physical development of adolescents, persisting for a further week. Animals submitted to REMSR exhibited higher basal corticosterone levels and a greater anxiety index in the EPM, characteristic of an anxious profile. These animals also exhibited higher noradrenaline levels in the amygdala and ventral hippocampus, without any change in the expression of ß1-adrenergic receptors, as well as higher serotonin and reduced turnover in the dorsal hippocampus, with diminished expression of 5-HT1A. Finally, greater concentration of BDNF was observed in the dorsal hippocampus in chronically sleep-restricted animals. Chronic REMSR during puberty impaired physical development and induced anxiety-like behavior, attributed to increased noradrenaline and serotonin levels in the amygdala and hippocampus.

Reduction of prefrontal thickness in military police officers with post-traumatic stress disorder

Abstract Background Brain-imaging studies in post-traumatic stress disorder (PTSD) have consistently revealed alterations in brain structure and function and this is correlated to symptomatology. However, few studies have investigated the role of biomarkers in PTSD some specific groups, as police officers. Objective To evaluate prefrontal and limbic volumes, and cortical thickness of police officers exposed to trauma during work who developed post-traumatic stress disorder, resilient matched controls (without PTSD), and compared to healthy civilians. Methods Prefrontal and limbic volumes, and cortical thickness of 12 police officers with PTSD, 12 resilient police officers, and 12 healthy civilians who underwent brain MRI were analyzed. Results Differences in limbic structures volume were not significative after Bonferroni correction. A significant reduction in cortical thickness on right rostral cingulate, right and left middle frontal gyrus, left superior frontal, left lingual, calcarine and cuneus were observed in PTSD group in comparison to controls was observed. Discussion Although preliminary, our results suggested not only the association between cortical thickness and PTSD, but also indicated that patients and controls have anatomical differences.

Neurobiology of emotions: an update.

The 'nature' of emotions is one of the archaic themes of Western thought, thematized in different cultural manifestations - such as art, science, philosophy, myths and religion -, since Ancient times. In the last decades, the advances in neurosciences have permitted the construction of hypotheses that explain emotions, especially through the studies involving the limbic system. To present an updated discussion about the neurobiology of processes relating to emotions - focusing (1) on the main neural structures that relate to emotions, (2) the paths and circuits of greater relevance, (3) the implicated neurotransmitters, (4) the connections that possess neurovegetative control and (5) the discussion about the main emotions - is the objective of this present article.

Hippocampal subareas arranged in the dorsoventral axis modulate cardiac baroreflex function in a site-dependent manner in rats.

NEW FINDINGS: What is the central question of this study? Classically, areas of the brainstem are involved in the cardiac baroreceptor reflex. However, forebrain areas, such as the hippocampus, may also modulate the cardiac baroreflex function. What is the main finding and its importance? According to the hippocampal subarea recruited dorsoventrally, the baroreflex function can be either facilitated or inhibited. These results are according to the new topographical division proposed for the hippocampus, i.e. it can be divided into functionally and anatomically different regions along its dorsoventral axis. From a neuroanatomical point of view, we may split the hippocampal formation into the dorsal (DH) and ventral hippocampus (VH). Although the basic intrinsic circuitry of the hippocampus seems to be maintained throughout its longitudinal axis, dorsal and ventral portions connect differently with cortical and subcortical areas and express different gene patterns, being functionally distinct. Differential stimulation of the DH or VH can evoke either an increase or a decrease in blood pressure, heart rate and sympathetic activity. However, to the best of our knowledge, specific involvement of the hippocampus and its different subareas in the baroreflex function remains to be investigated. In the present work, therefore, we evaluated the involvement of hippocampal subareas arranged on the dorsoventral axis in cardiac baroreflex modulation. Our results suggest that inhibition of hippocampal subareas by CoCl2 , a calcium-dependent synaptic neurotransmission blocker, differentially affects baroreflex sensitivity; administration of CoCl2 into the DH increased cardiac baroreflex function, whereas it diminished cardiac baroreflex function when administered into the VH. In contrast, administration of CoCl2 into intermediate portions of the hippocampus did not affect the baroreflex response. Our findings suggest that the hippocampus influences baroreflex function according to the hippocampal subarea recruited dorsoventrally.

Migraine, Osmophobia, and Anxiety.

OBJECTIVES: To evaluate the association between osmophobia and the characteristics of patients and their headaches, among migraine patients. METHODS: This was a cross-sectional study. Patients who consecutively sought medical attendance in a primary care unit were asked about their headaches over the last 12 months. Those who had migraine were included. A semi-structured interview, the Headache Impact Test and the Hospital Anxiety and Depression Scale were used. RESULTS: 147 patients had migraine; 78 had osmophobia; 60 had significant anxiety symptoms; and 78 had significant depression symptoms. The mean age of these patients was 43.2 years (± 13.7); 91.2% were women. The mean length of time with complaints of headache was 13.8 years (± 12). Among the migraine patients, those with anxiety, more years of headache history, and phonophobia presented significantly more osmophobia (multivariate logistic regression). CONCLUSION: Osmophobia in migraine patients is associated with significant anxiety symptoms, length of headache history, and phonophobia.