Osteolipoma of tubercinerium: An incidental finding in a patient with schizophrenia.

A 45-year-old male patient with clinically suspected schizophrenia was referred for an MRI brain to look for organicity. An incidental lesion was noted on the right side of the tubercinerium with suspicious findings of osteolipoma. T1 and T2 weighted sequences showed a hyper-intense lesion suggestive of fatty intensity or hemorrhage. A homogenous blooming artefact was seen on gradient imaging suggestive of a calcific/hemorrhagic element. The referring clinician was conveyed the findings asking about the need for further imaging by CT. The patient was started on antipsychotics for schizophrenia. One week later, a CT head was obtained, which showed a fatty density lesion with a smooth, peripheral rim of hyperdensity. The HU value matched rim calcification suggesting radiological diagnosis of osteolipoma. The patient was kept under close observation and no specific therapy was guided to this lesion. The patient was responding well to pharmacotherapy (in terms of control of symptoms) confirming osteolipoma as an incidental finding. This case report establishes the role of adequate imaging in subtle brain lesions which may mimic primary lesion-producing neurological symptoms. The importance of clinical judgment and follow-up in guiding suitable therapy is also highlighted.

Do the mammillary bodies atrophy with aging? A magnetic resonance imaging study.

PURPOSE: This retrospective study aimed to explore age-related atrophy of the mammillary bodies (MBs) based on their temporal change using magnetic resonance imaging (MRI). MATERIALS AND METHODS: The study included 30 adult outpatients who presented to the hospital and were followed for more than 100 months with annual MRIs. The bi-ventricular width (BVW), third ventricle width (TVW), and bi-mammillary dimension (BMD) were measured on axial T2-weighted imaging and analyzed. RESULTS: The 30 patients comprised 1 in their 40s, 5 in their 50s, 6 in their 60s, 11 in their 70s, 5 in their 80s, and 2 in their 90s. The MBs were consistently detected with left-to-right symmetry. The mean BVW was 32 ± 2.2 mm on the initial (BVW1) and 32 ± 2.4 mm on the last (BVW2) MRI. The mean TVW was 7.0 ± 2.3 mm on the initial (TVW1) and 7.6 ± 2.7 mm on the last (TVW2) MRI. Furthermore, the mean BMD was 9.9 ± 1.3 mm on the initial (BMD1) and 10 ± 1.3 mm on the last (BMD2) MRI. Statistically, no age ranges had a large dimension for BVW1, BVW2, TVW1, TVW2, BMD1, or BMD2. Changes between TVW1 and TVW2 were significantly different in the patients in their 80s; changes between BMD1 and BMD2 were not different for any age range or between sexes. CONCLUSIONS: Aging alone does not seem to promote MB atrophy. In healthy brains, the MBs may be stationary structures throughout life.

Neurochemistry of the mammillary body.

The mammillary body (MB) is a component of the extended hippocampal system and many studies have shown that its functions are vital for mnemonic processes. Together with other subcortical structures, such as the anterior thalamic nuclei and tegmental nuclei of Gudden, the MB plays a crucial role in the processing of spatial and working memory, as well as navigation in rats. The aim of this paper is to review the distribution of various substances in the MB of the rat, with a description of their possible physiological roles. The following groups of substances are reviewed: (1) classical neurotransmitters (glutamate and other excitatory transmitters, gamma-aminobutyric acid, acetylcholine, serotonin, and dopamine), (2) neuropeptides (enkephalins, substance P, cocaine- and amphetamine-regulated transcript, neurotensin, neuropeptide Y, somatostatin, orexins, and galanin), and (3) other substances (calcium-binding proteins and calcium sensor proteins). This detailed description of the chemical parcellation may facilitate a better understanding of the MB functions and its complex relations with other structures of the extended hippocampal system.

Estimates of total neuron number show that neonatal ethanol causes immediate and lasting neuron loss in cortical and subcortical areas.

In neonatal brain development there is a period of normal apoptotic cell death that regulates adult neuron number. At approximately the same period, ethanol exposure can cause a dramatic spike in apoptotic cell death. While ethanol-induced apoptosis has been shown to reduce adult neuron number, questions remain about the regional selectivity of the ethanol effect, and whether the brain might have some capacity to overcome the initial neuron loss. The present study used stereological cell counting to compare cumulative neuron loss 8 h after postnatal day 7 (P7) ethanol treatment to that of animals left to mature to adulthood (P70). Across several brain regions we found that the reduction of total neuron number after 8 h was as large as that of adult animals. Comparison between regions revealed that some areas are more vulnerable, with neuron loss in the anterior thalamic nuclei > the medial septum/vertical diagonal band, dorsal subiculum, and dorsal lateral geniculate nucleus > the mammillary bodies and cingulate cortex > whole neocortex. In contrast to estimates of total neuron number, estimates of apoptotic cell number in Nissl-stained sections at 8 h after ethanol treatment provided a less reliable predictor of adult neuron loss. The findings show that ethanol-induced neonatal apoptosis often causes immediate neuron deficits that persist in adulthood, and furthermore suggests that the brain may have limited capacity to compensate for ethanol-induced neuron loss.

Clinical characteristics and risk factors for bilateral lateral geniculate body pathology: a systematic review of the literature.

BACKGROUND: Case presentation of acute onset bilateral painless vision loss caused by bilateral infarction of the lateral geniculate bodies (LGB) and a systematic review of the literature. METHODS: A descriptive case report is presented on a 17-year-old female diagnosed with acute pancreatitis who developed acute onset bilateral painless vision loss. A systematic literature review of cases with bilateral LGB lesions was conducted across three electronic databases (PubMed/PubMed Central/MEDLINE, Scopus, and ScienceDirect). The review was conducted in concordance with PRISMA guidelines and prospectively registered on PROSPERO (CRD42022362491). RESULTS: The reported 17-year-old female was found to have MRI findings consistent with bilateral hemorrhagic infarction of the LGB and Purtscher-like retinopathy. A systematic literature review of bilateral LGB infarction yielded 23 records for analysis. 19/23 (82.6%) of reported cases occurred in women. Bilateral vision loss was noted in all cases. The average reported age was 27 years old with a range from 2-50. Gastrointestinal pathology (e.g., pancreatitis, gastroenteritis) was present in 8/23 (34.7%) of cases. 8/23 (34.7%) cases had neuroimaging or pathological evidence of hemorrhagic transformation of the infarct. Most cases experienced partial recovery of visual loss; only one case (4.7%) had complete visual recovery. 9/23 (39.1%) cases were reported from the United States and 4/23 (17.3%) from India. CONCLUSIONS: Bilateral LGB lesion is a rare cause of vision loss, typically caused by systemic diseases and with female preponderance. Purported pathophysiology relates to increased vulnerability of the LGB to ischemic and metabolic stress.

Hemosiderin Detection inside the Mammillary Bodies Using Quantitative Susceptibility Mapping on Patients with Wernicke-Korsakoff Syndrome.

Hemorrhage inside the mammillary bodies (MMBs) is known to be one of the findings of Wernicke encephalopathy. Brain MRI of two patients with Wernicke-Korsakoff syndrome (WKS) demonstrated high susceptibility values representing hemosiderin deposition in MMBs by using quantitative susceptibility mapping (QSM). QSM provided additional information of susceptibility values to susceptibility-weighted imaging in diagnosis of WKS.

Mammillary Body Atrophy in Temporal Lobe Epilepsy With Hippocampal Sclerosis.

BACKGROUND AND PURPOSE: We aimed to determine 1) the frequency of mammillary body (MB) atrophy in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS), 2) the clinical significance of MB atrophy, and 3) the association between MB atrophy and volume changes in other subcortical limbic structures. METHODS: We enrolled 69 patients with pathologically confirmed TLE with HS, who underwent a standard anterior temporal lobectomy, as well as 40 healthy controls. We used the FreeSurfer deep-learning tool of U-Net to obtain the volumes of the subcortical limbic structures, including the MB, hypothalamus, basal forebrain, septal nuclei, fornix, and nucleus accumbens. MB atrophy was considered to be present when the MB volume was decreased relative to the healthy controls. RESULTS: MB atrophy was present in 18 (26.1%) of the 69 patients with TLE and HS. Among the clinical characteristics, the mean age at seizure onset was higher (25.5 vs. 15.9 years, p=0.027) and the median duration of epilepsy was shorter (149 vs. 295 months, p=0.003) in patients with than without MB atrophy. The basal forebrain (0.0185% vs. 0.0221%, p=0.004) and septal nuclei (0.0062% vs. 0.0075%, p=0.003) in the ipsilateral hemisphere of HS were smaller in the patients with MB atrophy. CONCLUSIONS: We observed ipsilateral MB atrophy in about one-quarter of patients with TLE and HS. The severity of subcortical limbic structure abnormalities was greater in patients without MB atrophy. These findings suggest that MB atrophy in TLE with HS is not rare, but it has little clinical significance.

Isolated Enhancement Effect is the Only MRI Finding for Wernicke's encephalopathy.

Wernicke's encephalopathy (WE) is an acute neuropsychiatric disorder that results from thiamine (vitamin B1) deficiency. The typical clinical manifestations, which occur as triads in 20% of patients with the disorder, are acute mental status changes, ophthalmoplegia, and ataxia. Brain magnetic resonance imaging (MRI) has important value in diagnosis as it can reveal abnormalities in the thalamus, mammillary body, third and fourth ventricles, and periaqueductal area. Here we describe a 44-year-old female patient with WE, in the context of fasting following bowel surgery. The unique neuroimaging findings were symmetrical mammillary body and dorsal midbrain abnormalities, only evident on contrast-enhanced brain MRI.

Impact of Mesial Temporal Lobe Resection on Brain Structure in Medically Refractory Epilepsy.

OBJECTIVE: Surgical resection can decrease seizure frequency in medically intractable temporal lobe epilepsy. However, the functional and structural consequences of this intervention on brain circuitry are poorly understood. We investigated structural changes that occur in brain circuits after mesial temporal lobe resection for refractory epilepsy. Specifically, we used neuroimaging techniques to evaluate changes in 1) contralesional hippocampal and bilateral mammillary body volume and 2) brain-wide cortical thickness. METHODS: Serial T1-weighted brain magnetic resonance images were acquired before and after surgery (1.6 ± 0.5 year interval) in 21 patients with temporal lobe epilepsy (9 women, 12 men; mean age, 39.4 ± 11.5 years) who had undergone unilateral temporal lobe resection (14 anterior temporal lobectomy; 7 selective amygdalohippocampectomy). Blinded manual segmentation of the unresected hippocampal formation and bilateral mammillary bodies was performed using the Pruessner and Copenhaver protocols, respectively. Brain-wide cortical thickness estimates were computed using the CIVET pipeline. RESULTS: Surgical resection was associated with a 5% reduction in contralesional hippocampal volume (P < 0.01) and a 9.5% reduction in mammillary body volume (P = 0.03). In addition, significant changes in cortical thickness were observed in contralesional anterior and middle cingulate gyrus and insula (Pfalse discovery rate < 0.01) as well as in other temporal, frontal, and occipital regions (Pfalse discovery rate < 0.05). Postoperative verbal memory function was significantly associated with cortical thickness change in contralesional inferior temporal gyrus (R2 = 0.39; P = 0.03). CONCLUSIONS: These results indicate that mesial temporal lobe resection is associated with both volume loss in spared Papez circuitry and changes in cortical thickness across the brain.

High ethanol preference and dissociated memory are co-occurring phenotypes associated with hippocampal GABAAR-δ receptor levels.

Alcohol use disorder (AUD) frequently co-occurs with dissociative disorders and disorders with dissociative symptoms, suggesting a common neurobiological basis. It has been proposed that facilitated information processing under the influence of alcohol, resulting in the formation of dissociated memories, might be an important factor controlling alcohol use. Access to such memories is facilitated under the effect of alcohol, thus further reinforcing alcohol use. To interrogate possible mechanisms associated with these phenotypes, we used a mouse model of dissociative amnesia, combined with a high-alcohol preferring (HAP) model of AUD. Dissociated memory was induced by activation of hippocampal extrasynaptic GABA type A receptor delta subunits (GABAAR-δ), which control tonic inhibition and to which ethanol binds with high affinity. Increased ethanol preference was associated with increased propensity to form dissociated memories dependent on GABAAR-δ in the dorsal hippocampus (DH). Furthermore, the DH level of GABAAR-δ protein, but not mRNA, was increased in HAP mice, and was inversely correlated to the level of miR-365-3p, suggesting an miRNA-mediated post-transcriptional mechanism contributing to elevated GABAAR-δ. The observed changes of DH GABAAR-δ were associated with a severe reduction of excitatory projections stemming from GABAAR-δ-containing pyramidal neurons in the subiculum and terminating in the mammillary body. These results suggest that both molecular and circuit dysfunction involving hippocampal GABAAR-δ receptors might contribute to the co-occurrence of ethanol preference and dissociated information processing.

Topographical organization of mammillary neurogenesis and efferent projections in the mouse brain.

The mammillary body is a hypothalamic nucleus that has important functions in memory and spatial navigation, but its developmental principles remain not well understood. Here, we identify progenitor-specific Fezf2 expression in the developing mammillary body and develop an intersectional fate-mapping approach to demonstrate that Fezf2+ mammillary progenitors generate mammillary neurons in a rostral-dorsal-lateral to caudal-ventral-medial fashion. Axonal tracing from different temporal cohorts of labeled mammillary neurons reveal their topographical organization. Unsupervised hierarchical clustering based on intrinsic properties further identify two distinct neuronal clusters independent of birthdates in the medial nuclei. In addition, we generate Fezf2 knockout mice and observe the smaller mammillary body with largely normal anatomy and mildly affected cellular electrophysiology, in contrast to more severe deficits in neuronal differentiation and projection in many other brain regions. These results indicate that Fezf2 may function differently in the mammillary body. Our results provide important insights for mammillary development and connectivity.

Acute ethanol induces behavioral changes and alters c-fos expression in specific brain regions, including the mammillary body, in zebrafish.

Ethanol is one of the most commonly abused substances in the world, and ethanol abuse and dependence disorders represent major societal problems. However, appropriate treatment is lacking as we still do not fully understand the molecular bases of these disorders. The zebrafish is one of the model organisms utilized for studying such mechanisms. In this study, we examined the effects of acute ethanol administration on the behavior of zebrafish, and we also analyzed correlated gene expression changes using whole-mount in situ hybridization focusing on a number of genes associated with different neurotransmitter systems, stress response, and neuronal activity. We found ethanol treatment to result in hyperactivity and reduced shoal cohesion compared to control. Analysis of c-fos expression demonstrated altered activity patterns in certain brain regions, including intense activation of the mammillary body in zebrafish with acute ethanol treatment. We also found reduced level of gad1b expression in the cerebellum of ethanol treated fish compared to control. However, we could not detect significant changes in the expression level of other genes, including vglut2b, th, crh, hdc, avp, pomc, and galn in ethanol treated fish compared controls. Our results suggest that zebrafish is a promising animal model for the study of mechanisms underlying alcohol induced behavioral changes and alcohol related human disorders.

F-18 Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Showing Mammillary Body Involvement in a Case of Autoimmune Anti-N-Methyl D-Aspartate Antibody Encephalitis.

Autoimmune encephalitis with antibodies against neuronal cell surface antigens is a group of neuropsychiatric disorders, with anti-N-methyl D-aspartate (NMDAR) encephalitis being one of them. We report a case of a young male patient who presented with complaints of seizures associated with fever, rapidly progressing memory loss, and choreoathetoid movements for 1 month. His serum was strongly positive for anti-NMDAR receptor antibodies. F-18 fluorodeoxyglucose positron-emission tomography/computed tomography for the brain revealed hypermetabolism involving bilateral basal ganglia and bilateral mammillary bodies associated with hypometabolism in bilateral occipital lobes.

Susceptibility and Volume Measures of the Mammillary Bodies Between Mild Cognitively Impaired Patients and Healthy Controls.

PURPOSE: To investigate the baseline values and differences for susceptibility and volume of the mammillary bodies between mild cognitively impaired (MCI) patients and healthy controls (HCs), and further explore their differences in relation to gender, MCI subtypes and apolipoprotein E (APOE) genotypes. METHODS: T1-weighted and multi-echo gradient echo imaging sequences were acquired on a 3T MR scanner to evaluate the T1W based volume and susceptibility differences in the mammillary body for 47 MCI and 47 HCs. T-tests were performed to compare volume and susceptibility between groups, and right and left hemispheres. Correlation analysis was used to relate the volume and mean susceptibility as a function of age in MCI and HC groups separately, and to investigate the relationship of susceptibility with the neuro-psychological scales in the MCI group. RESULTS: Susceptibility was found to be elevated within the right mammillary body in MCI patients compared to HCs (p < 0.05). There were no differences for the mammillary body volumes between the MCI and HC groups, although there was a reduction in volume with age for the MCI group (p = 0.007). Women showed decreased mammillary body volume compared to men in the HC group (p = 0.004). No significant differences were found in relation to MCI subtypes and APOE genotypes. No significant correlations were observed between mammillary body susceptibility with neuro-psychological scales. CONCLUSION: This work provides a quantitative baseline for both the volume and susceptibility of the mammillary body which can be used for future studies of cognitive impairment patients underlying the pathology of the Papez circuit.

Atrophy of the ipsilateral mammillary body in unilateral hippocampal sclerosis shown by thin-slice-reconstructed volumetric analysis.

PURPOSE: Conventional volumetric analysis could not detect ipsilateral atrophy of the mammillary body in patients with unilateral hippocampal sclerosis. By using thin-slice-reconstructed volumetric analysis, we investigated whether the mammillary body volume is smaller on the hippocampal sclerosis side than in healthy subjects or the non-hippocampal sclerosis side. METHODS: This retrospective study included 45 patients with unilateral hippocampal sclerosis and 30 healthy subjects. Three-dimensional T1WI of 1 mm thicknesses were oversampled to a thickness of 0.2 mm (thin-slice-reconstructed images), and the mammillary bodies were segmented manually to determine mammillary body volume on each side. Mammillary body volumes on the hippocampal sclerosis side were compared with those in healthy subjects or the non-hippocampal sclerosis side. RESULTS: In patients with right hippocampal sclerosis, right mammillary body volume was both significantly smaller than that in healthy subjects (30.3 ± 10.3 vs. 43.3 ± 8.07 mm3, P < 0.001) and significantly smaller than the left mammillary body volume in each patient (30.3 ± 10.3 vs. 41.4 ± 10.1 mm3, P < 0.001). Similarly, in patients with left hippocampal sclerosis, left mammillary body volume was both significantly smaller than that in healthy subjects (37.7 ± 11.2 vs. 47.0 ± 8.65 mm3, P < 0.001) and significantly smaller than right mammillary body volume in each patient (37.7 ± 11.2 vs. 42.5 ± 7.78 mm3, P = 0.044). CONCLUSIONS: In this study, thin-slice-reconstructed volumetric analysis showed that, in patients with unilateral hippocampal sclerosis, mammillary body volume on the hippocampal sclerosis side is smaller than that in healthy subjects and the non-hippocampal sclerosis side.

An autopsied case of MM1-type sporadic Creutzfeldt-Jakob disease with pathology of Wernicke encephalopathy.

An 83-year-old Japanese man presented with gait disturbance followed by rapidly-progressive cognitive impairment. Magnetic resonance diffusion-weighted images showed extensive hyperintense regions in the cerebral cortex. Four weeks after symptom onset, myoclonus appeared, and the patient developed difficulty swallowing; intravenous peripheral continuous infusions without vitamin supplementation were administered during the last two months of the patient's life. The patient reached the akinetic mutism state and died 12 weeks after symptom onset due to sepsis. The brain weighed 940 g and showed general cerebral atrophy. Extensive spongiform change were observed in the cerebral cortex, striatum, thalamus, and cerebellar cortex, but gliosis was generally mild. Numerous newly-developed hemorrhage foci were observed in the mammillary body, the areas adjacent to the third and fourth ventricles, and the periaqueduct of the midbrain; however, proliferation of capillaries and endothelium and collections of macrophages were relatively inconspicuous. These findings suggested comorbidity with the acute stage of Wernicke encephalopathy (WE). Immunostaining showed extensive diffuse synaptic-type prion protein deposition in the gray matter. According to the neuropathological, genetic, and molecular findings, the present case was finally diagnosed as MM1-type sporadic Creutzfeldt-Jakob disease (CJD) with WE. We should remain alert to the diagnosis of WE when CJD is suspected, and it is necessary to consider the complications of both diseases. This report emphasizes the importance of pathological investigations for the diagnosis of CJD, WE, and the coexistence of both.

The limbic-reticular coupling theory of memory processing in the brain and its greater compatibility over other theories.

The limbic-reticular coupling theory suggests that the hippocampus and amygdala regulate such descending limbic structures as the mammillary bodies, septum, hypothalamus and epithalamus to regulate the ascending noradrenergic, serotonergic, dopaminergic and cholinergic systems, performing declarative memory consolidation and recall. Recent studies have revealed that, less sensitive to familiarity, the hippocampus functions via the fornix, mammillary bodies and hypothalamus for memory recall. Lesions to the thalamic nuclei were complicated with damage to adjacent fornix, stria medullaris and habenula, simultaneously destroying two kinds of structures respectively for familiarity and recall. Furthermore, the orbitofrontal cortex was shown to be clinically irrelevant for memory recall. Electrophysiologically, the hippocampus regulates the raphe nuclei in complex ways, and the hippocampal theta wave activates the dopaminergic cells in ventral tegmental area and cholinergic neurons in basal forebrain, while cholinergic-modulated theta-gamma coupling mediates cortical recall. These concurrent advances support the limbic-reticular coupling theory for elucidation of memory recall.

A teoria do acoplamento límbico-reticular sugere que o hipocampo e a amígdala regulam estruturas límbicas descendentes como os corpos mamilares, septum, hipotálamo e epitálamo para regular os sistemas ascendentes noradrenérgico, serotoninérgico, dopaminérgico e colinérgico, realizando a consolidação da memória declarativa e a recordação. Estudos recentes revelaram que, menos sensível à familiaridade, o hipocampo funcionava via fórnice, corpos mamilares e hipotálamo para a recordação da memória. Lesões aos núcleos talâmicos são complicadas com danos ao fórnice, estria medullaris e habenula adjacentes, destruindo simultaneamente dois tipos de estruturas, respectivamente, para familiaridade e recordação. Além disso, o córtex orbitofrontal mostrou-se clinicamente irrelevante para a recordação da memória. Eletrofisiologicamente, o hipocampo regula os núcleos da rafe de maneiras complexas, e a onda teta hipocampal ativa as células dopaminérgicas na área tegmentar ventral e os neurônios colinérgicos no prosencéfalo basal, enquanto que o acoplamento teta-gama colinergicamente modulado medeia a evocação cortical. Esses avanços concorrentes sugerem que a teoria do acoplamento límbico-reticular apropriada para a elucidação da recordação da memória.

The limbic-reticular coupling theory of memory processing in the brain and its greater compatibility over other theories / A teoria do acoplamento límbico-reticular do processamento de memória no cérebro e sua maior compatibilidade com outras teorias

Abstract The limbic-reticular coupling theory suggests that the hippocampus and amygdala regulate such descending limbic structures as the mammillary bodies, septum, hypothalamus and epithalamus to regulate the ascending noradrenergic, serotonergic, dopaminergic and cholinergic systems, performing declarative memory consolidation and recall. Recent studies have revealed that, less sensitive to familiarity, the hippocampus functions via the fornix, mammillary bodies and hypothalamus for memory recall. Lesions to the thalamic nuclei were complicated with damage to adjacent fornix, stria medullaris and habenula, simultaneously destroying two kinds of structures respectively for familiarity and recall. Furthermore, the orbitofrontal cortex was shown to be clinically irrelevant for memory recall. Electrophysiologically, the hippocampus regulates the raphe nuclei in complex ways, and the hippocampal theta wave activates the dopaminergic cells in ventral tegmental area and cholinergic neurons in basal forebrain, while cholinergic-modulated theta-gamma coupling mediates cortical recall. These concurrent advances support the limbic-reticular coupling theory for elucidation of memory recall.

Resumo A teoria do acoplamento límbico-reticular sugere que o hipocampo e a amígdala regulam estruturas límbicas descendentes como os corpos mamilares, septum, hipotálamo e epitálamo para regular os sistemas ascendentes noradrenérgico, serotoninérgico, dopaminérgico e colinérgico, realizando a consolidação da memória declarativa e a recordação. Estudos recentes revelaram que, menos sensível à familiaridade, o hipocampo funcionava via fórnice, corpos mamilares e hipotálamo para a recordação da memória. Lesões aos núcleos talâmicos são complicadas com danos ao fórnice, estria medullaris e habenula adjacentes, destruindo simultaneamente dois tipos de estruturas, respectivamente, para familiaridade e recordação. Além disso, o córtex orbitofrontal mostrou-se clinicamente irrelevante para a recordação da memória. Eletrofisiologicamente, o hipocampo regula os núcleos da rafe de maneiras complexas, e a onda teta hipocampal ativa as células dopaminérgicas na área tegmentar ventral e os neurônios colinérgicos no prosencéfalo basal, enquanto que o acoplamento teta-gama colinergicamente modulado medeia a evocação cortical. Esses avanços concorrentes sugerem que a teoria do acoplamento límbico-reticular apropriada para a elucidação da recordação da memória.