Papez Circuit Research Articles

Diffuse injury of the Papez circuit by focal head trauma: a diffusion tensor tractography study

Diffuse injury of the Papez circuit by focal head trauma: a diffusion tensor tractography study

Early Idiopathic Normal Pressure Hydrocephalus Patients With Neuropsychological Impairment Are Associated With Increased Fractional Anisotropy in the Anterior Thalamic Nucleus.

In this study, we aimed to investigate the reactive changes in diffusion tensor imaging (DTI)-derived diffusion metrics of the anterior thalamic nucleus (AN), a relaying center for the Papez circuit, in early idiopathic normal pressure hydrocephalus (iNPH) patients with memory impairment, as well as its correlation with the patients’ neuropsychological performances. In total, 28 probable iNPH patients with symptom onset within 1 year and 17 control subjects were prospectively recruited between 2010 and 2013 for this institutional review board-approved study. Imaging studies including DTI and a neuropsychological assessment battery were performed in all subjects. Diffusion metrics were measured from the region of the AN using tract-deterministic seeding method by reconstructing the mammillo–thalamo–cingulate connections within the Papez circuit. Differences in diffusion metrics and memory assessment scores between the patient and control group were examined via the Mann–Whitney U test. Spearman correlation analyses were performed to examine associations between diffusion metrics of AN and neuropsychological tests within the patient group. We discovered that early iNPH patients exhibited marked elevations in fractional anisotropy, pure diffusion anisotropy, and axial diffusivity (all P < 0.01), as well as lower neuropsychological test scores including verbal and nonverbal memory (all P < 0.05) compared with normal control. Spearman rank correlation analyses did not disclose significant correlations between AN diffusion metrics and neuropsychological test scores in the patient group, whereas ranked scatter plots clearly demonstrated a dichotic sample distribution between patient and control samples. In summary, our study highlighted the potential compensatory role of the AN by increasing thalamocortical connectivity within the Papez circuit because memory function declines in early iNPH when early shunt treatment may potentially reverse the memory deficits.

중대뇌동맥 허혈에 의한 파페츠 회로 손상과 작화증

중대뇌동맥 허혈에 의한 파페츠 회로 손상과 작화증

Thalamic pathology and memory loss in early Alzheimer's disease: moving the focus from the medial temporal lobe to Papez circuit.

It is widely assumed that incipient protein pathology in the medial temporal lobe instigates the loss of episodic memory in Alzheimer's disease, one of the earliest cognitive deficits in this type of dementia. Within this region, the hippocampus is seen as the most vital for episodic memory. Consequently, research into the causes of memory loss in Alzheimer's disease continues to centre on hippocampal dysfunction and how disease-modifying therapies in this region can potentially alleviate memory symptomology. The present review questions this entrenched notion by bringing together findings from post-mortem studies, non-invasive imaging (including studies of presymptomatic, at-risk cases) and genetically modified animal models. The combined evidence indicates that the loss of episodic memory in early Alzheimer's disease reflects much wider neurodegeneration in an extended mnemonic system (Papez circuit), which critically involves the limbic thalamus. Within this system, the anterior thalamic nuclei are prominent, both for their vital contributions to episodic memory and for how these same nuclei appear vulnerable in prodromal Alzheimer's disease. As thalamic abnormalities occur in some of the earliest stages of the disease, the idea that such changes are merely secondary to medial temporal lobe dysfunctions is challenged. This alternate view is further strengthened by the interdependent relationship between the anterior thalamic nuclei and retrosplenial cortex, given how dysfunctions in the latter cortical area provide some of the earliest in vivo imaging evidence of prodromal Alzheimer's disease. Appreciating the importance of the anterior thalamic nuclei for memory and attention provides a more balanced understanding of Alzheimer's disease. Furthermore, this refocus on the limbic thalamus, as well as the rest of Papez circuit, would have significant implications for the diagnostics, modelling, and experimental treatment of cognitive symptoms in Alzheimer's disease.

Anterior Thalamic Deep Brain Stimulation: Functional Activation Patterns in a Large Animal Model

Deep brain stimulation (DBS) of the anterior thalamic nucleus (ATN) exerts its effects by modulating neural circuits involved in seizures. However, these networks remain incompletely characterized. Investigate the effects of ATN DBS on network activity in a large animal model using 3-T fMRI. Anesthetized swine underwent ATN DBS using stimulation parameters applied in the Stimulation of the Anterior Thalamus for the Treatment of Epilepsy (SANTE) trial. Stimulation amplitude, frequency, and temporal paradigm were varied and the resulting blood oxygen level-dependent signal was measured. ATN DBS resulted in activation within temporal, prefrontal, and sensorimotor cortex. An amplitude-dependent increase in cluster volume was observed at 60 Hz and 145 Hz stimulation. ATN DBS in swine induced parameter-dependent activation in cortical regions including but not limited to the Papez circuit. These findings may hold clinical implications for treatment of epilepsy in patients with temporal or extratemporal seizure foci.

Troubles cognitifs liés à l’alcool : nature, impact et dépistage

Alcohol-related neuropsychological deficits result from chronic and excessive alcohol consumption and are associated with structural and functional damage of Papez's circuit and frontocerebellar circuit. Alcohol-related cognitive deficits are heterogeneous but especially affect executive functions and memory abilities. They result in difficulties to change alcohol behavior combined with a tendency for patients to overestimate their capacity to succeed. Alcohol-related cognitive deficits could be a risk-factor for relapse since they hamper patients to benefit fully from treatment (especially when based on relapse prevention). Screening tools usable by non-psychologists are available and can be completed by an extensive neuropsychological examination conducted by a neuropsychologist when necessary. Alcohol treatment should be adjusted to take alcohol-related cognitive deficits into account, by promoting longer treatment in healthy environment for example. Improvements of alcohol treatment options, including specific neuropsychological rehabilitation, are required for patients with persistent alcohol-related cognitive deficits.

Complementary subicular pathways to the anterior thalamic nuclei and mammillary bodies in the rat and macaque monkey brain.

The origins of the hippocampal (subicular) projections to the anterior thalamic nuclei and mammillary bodies were compared in rats and macaque monkeys using retrograde tracers. These projections form core components of the Papez circuit, which is vital for normal memory. The study revealed a complex pattern of subicular efferents, consistent with the presence of different, parallel information streams, whose segregation appears more marked in the rat brain. In both species, the cells projecting to the mammillary bodies and anterior thalamic nuclei showed laminar separation but also differed along other hippocampal axes. In the rat, these diencephalic inputs showed complementary topographies in the proximal–distal (columnar) plane, consistent with differential involvement in object‐based (proximal subiculum) and context‐based (distal subiculum) information. The medial mammillary inputs, which arose along the anterior–posterior extent of the rat subiculum, favoured the central subiculum (septal hippocampus) and the more proximal subiculum (temporal hippocampus). In contrast, anterior thalamic inputs were largely confined to the dorsal (i.e. septal and intermediate) subiculum, where projections to the anteromedial nucleus favoured the proximal subiculum while those to the anteroventral nucleus predominantly arose in the distal subiculum. In the macaque, the corresponding diencephalic inputs were again distinguished by anterior–posterior topographies, as subicular inputs to the medial mammillary bodies predominantly arose from the posterior hippocampus while subicular inputs to the anteromedial thalamic nucleus predominantly arose from the anterior hippocampus. Unlike the rat, there was no clear evidence of proximal–distal separation as all of these medial diencephalic projections preferentially arose from the more distal subiculum.

Functional magnetic resonance imaging in awake transgenic fragile X rats: evidence of dysregulation in reward processing in the mesolimbic/habenular neural circuit.

Anxiety and social deficits, often involving communication impairment, are fundamental clinical features of fragile X syndrome. There is growing evidence that dysregulation in reward processing is a contributing factor to the social deficits observed in many psychiatric disorders. Hence, we hypothesized that transgenic fragile X mental retardation 1 gene (fmr1) KO (FX) rats would display alterations in reward processing. To this end, awake control and FX rats were imaged for changes in blood oxygen level dependent (BOLD) signal intensity in response to the odor of almond, a stimulus to elicit the innate reward response. Subjects were ‘odor naive' to this evolutionarily conserved stimulus. The resulting changes in brain activity were registered to a three-dimensional segmented, annotated rat atlas delineating 171 brain regions. Both wild-type (WT) and FX rats showed robust brain activation to a rewarding almond odor, though FX rats showed an altered temporal pattern and tended to have a higher number of voxels with negative BOLD signal change from baseline. This pattern of greater negative BOLD was especially apparent in the Papez circuit, critical to emotional processing and the mesolimbic/habenular reward circuit. WT rats showed greater positive BOLD response in the supramammillary area, whereas FX rats showed greater positive BOLD response in the dorsal lateral striatum, and greater negative BOLD response in the retrosplenial cortices, the core of the accumbens and the lateral preoptic area. When tested in a freely behaving odor-investigation paradigm, FX rats failed to show the preference for almond odor which typifies WT rats. However, FX rats showed investigation profiles similar to WT when presented with social odors. These data speak to an altered processing of this highly salient novel odor in the FX phenotype and lend further support to the notion that altered reward systems in the brain may contribute to fragile X syndrome symptomology.

Into the future with little past: exploring mental time travel in a patient with damage to the mammillary bodies/fornix

Objective: Remembering the past and imaging the future are both manifestations of ‘mental time travel’. These processes have been found to be impaired in patients with bilateral hippocampal lesions. Here, we examined the question of whether future thinking is affected by other Papez circuit lesions, namely: damage to the mammillary bodies/fornix.Method: Case (SL) was a 43-year-old woman who developed dense anterograde and retrograde amnesia suddenly, as a result of Wernicke–Korsakoff’s syndrome. A region of interest volumetric Magnetic resonance imaging (MRI) analysis was performed. We assessed past and future thinking in SL and 11 control subjects of similar age and education with the adapted Autobiographical Interview (AI). Participants also completed a battery of neuropsychological tests.Results: Volumetric MRI analyses revealed severely reduced fornix and mammillary body volumes, but intact hippocampi. SL showed substantial, albeit temporally graded retrograde memory deficits on the adapted AI. Strikingly, whilst SL could not provide any specific details of events from the past two weeks or past two years and had impaired recall of events from her late 30s, her descriptions of potential future events were normal in number of event details and plausibility.Conclusions: This dissociation of past and future events’ performance after mammillary body and fornix damage is at odds with the findings of the majority of patients with adult onset hippocampal amnesia. It suggests that these non-hippocampal regions of the Papez circuit are only critical for past event retrieval and not for the generation of possible future events.

Decreased Fronto-Limbic Activation and Disrupted Semantic-Cued List Learning in Major Depressive Disorder.

Individuals with major depressive disorder (MDD) demonstrate poorer learning and memory skills relative to never-depressed comparisons (NDC). Previous studies report decreased volume and disrupted function of frontal lobes and hippocampi in MDD during memory challenge. However, it has been difficult to dissociate contributions of short-term memory and executive functioning to memory difficulties from those that might be attributable to long-term memory deficits. Adult males (MDD, n=19; NDC, n=22) and females (MDD, n=23; NDC, n=19) performed the Semantic List Learning Task (SLLT) during functional magnetic resonance imaging. The SLLT Encoding condition consists of 15 lists, each containing 14 words. After each list, a Distractor condition occurs, followed by cued Silent Rehearsal instructions. Post-scan recall and recognition were collected. Groups were compared using block (Encoding-Silent Rehearsal) and event-related (Words Recalled) models. MDD displayed lower recall relative to NDC. NDC displayed greater activation in several temporal, frontal, and parietal regions, for both Encoding-Silent Rehearsal and the Words Recalled analyses. Groups also differed in activation patterns in regions of the Papez circuit in planned analyses. The majority of activation differences were not related to performance, presence of medications, presence of comorbid anxiety disorder, or decreased gray matter volume in MDD. Adults with MDD exhibit memory difficulties during a task designed to reduce the contribution of individual variability from short-term memory and executive functioning processes, parallel with decreased activation in memory and executive functioning circuits. Ecologically valid long-term memory tasks are imperative for uncovering neural correlates of memory performance deficits in adults with MDD.

Troubles cognitifs dans l’alcoolodépendance : intérêt du dépistage dans l’optimisation des prises en charge

Alcohol-related cognitive impairments are largely underestimated in clinical practice, even though they could limit the benefit of alcohol treatment and hamper the patient's ability to remain abstinent or to respect his/her therapeutic contract. These neuropsychological deficits can impact the management of patients well before the development of the well-known Korsakoff's syndrome. Indeed, even in the absence of ostensible neurological complications, excessive and chronic alcohol consumption results in damage of brain structure and function. The frontocerebellar circuit and the circuit of Papez, respectively involved in motor and executive abilities and episodic memory, are mainly affected. Those brain dysfunctions are associated with neuropsychological deficits, including deficits of executive functions, episodic memory, social cognition, as well as visuospatial and motor abilities. Such cognitive disorders can interfere with the motivation process to abandon maladjusted drinking behavior in favor of a healthier lifestyle (such as abstinence or controlled alcohol consumption). They can also limit the patient's capacity to fully benefit from treatment (notably psychoeducation and cognitive-behavioural treatments) currently widely proposed in French Addiction departments. In addition, they may contribute to relapse which is multi-determinated. A neuropsychological assessment appears therefore crucial to take relevant clinical decisions. However, very few addiction departments have the human and financial resources to conduct an extensive neuropsychological examination of all patients with alcohol dependence. Some brief screening tools can be used, notably the MOntreal Cognitive Assessment and the Brief Evaluation of Alcohol-Related Neuropsychological Impairments, which has been especially designed to assess cognitive and motor deficits in alcoholism. These tools can be used by non-psychologist clinicians to detect alcohol-related cognitive deficits, which require an extensive cognitive examination conducted by a neuropsychologist. The presence of cognitive dysfunctions in patients early in abstinence should encourage clinicians to adjust the modalities of the treatment. The fact to favor recovery of cognitive functions and brain volumes with abstinence or drastic reduction of alcohol consumption could be a first way to make it possible for patients to be cognitively able to benefit from treatment. Further studies are required to determine whether specifically designed cognitive remediation could boost (accelerate or increase) the recovery of brain functioning. Additionally, a potential effect of thiamine to limit alcohol-related cognitive deficits before the development of neurological complications remains to be determined. In this review, we presented the pattern of structural brain damage and the associated cognitive and motor impairments in alcohol-dependent patients. We then emphasized the harmful effects of neuropsychological deficits in the management of these patients. We also pointed how relevant it is to screen patients with neuropsychological impairments and we focused on the presentation of two brief screening tools for cognitive impairments, especially designed for alcohol-related deficits or not. Finally, we reported how these neuropsychological impairments could be taken into consideration the treatment of alcohol addiction by adjusting its timing and modalities.

Recovery of injured fornical crura following neurosurgical operation of a brain tumor: a case report.

Recovery of injured fornical crura following neurosurgical operation of a brain tumor: a case report.

Should stimulation parameters be individualized to stop seizures: Evidence in support of this approach.

Deep-brain electrical stimulation (DBS) is a treatment modality being explored for many neurologic diseases and is a potentially potent means of disrupting the aberrant rhythms that arise during the epileptic seizures that afflict >1% of the population. However, current DBS protocols typically employed are formulated a priori and do not reflect the electrophysiologic dynamics within the brain as seizures arise, which may underlie their limited efficacy. This study investigates how the efficacy of DBS could be improved using endogenous dynamics to inform stimulation protocols. Multisite brain dynamics within the circuit of Papez were calculated in a chronic rat limbic epilepsy model induced via lithium chloride/pilocarpine intraperitoneal injections. Stimulation/recording electrodes were placed in the CA3 region of the left and right hippocampi and the anteromedial nucleus of the left thalamus. Deconvolution of local field potentials using empirical mode decomposition (EMD) and phase synchrony analysis revealed multisite coherence as seizures approached natural termination that could not be detected with Fourier analysis. Multisite stimulation used charge-neutral biphasic square waves at frequencies observed during natural termination. Synchronization of electrical activity across sites occurred as both spontaneous and evoked seizures naturally terminated. Furthermore, the location and frequency of the synchrony varied between subjects but was stable in time within each animal. DBS protocols were significantly more effective at rapidly stopping seizures when the frequency and location of multisite stimulation reflected the endogenous synchrony dynamics observed in each subject as seizures naturally terminated. These results strongly support the approach of tailoring DBS protocols to individual endogenous rhythms that may represent how brains naturally resolve epileptic seizures. This approach may significantly improve the overall efficacy of this potentially important therapy.

Dominant Thalamus and Aphasia

Many studies have shown that lesions of the dominant thalamus precipitate language disorders in a similar manner to transcortical aphasias, in a phenomenon known as "thalamic aphasia." In some cases, however, aphasia may not occur or may appear transiently following thalamic lesions. Furthermore, dominant thalamic lesions can produce changes in character, as observed in patients with amnesic disorder. Previous work has explored the utility of thalamic aphasia as a discriminative feature for classification of aphasia. Although the thalamus may be involved in the function of the brainstem reticular activating system and play a role in attentional network and in memory of Papez circuit or Yakovlev circuit, the mechanism by which thalamic lesion leads to the emergence of aphasic disorders is unclear. In this review, we we survey historical and recent literature on thalamic aphasia in an attempt to understand the neural processes affected by thalamic lesions.

Brain structural imaging study in schizophrenia patients with violent aggressive behaviors

Objective To review recent neuroimaging studies of aggressive/violent behaviors in schizophrenia and related the neural circuits of aggressive behaviors, focusing on structure magnetic resonance imaging(MRI) method, published from 2000 to 2014. Methods A systematic literature search was conducted using articles from PsycINFO, Embase, Pubmed and Cnki published between 2000 and 2014, we usedaggressive,violent,schizophrenia,structure MRIas the key words, to explore the relationship between schizophrenia of aggressive/violent behaviors and the related neural circuits. Results Of the 18 studies included in the analysis, mostly were case-control studies, two were written in Chinese.The neuroimaging literature on aggression in schizophrenia revealed the related grey matter volume of brain areas which contained the frontal lobe, temporal lobe, amygdala, hippocampus, cerebelum and caudate nucleus. Conclusion Findings from the current reviews suggest that the occurrence of violent/aggressive behaviors of schizophrenia were related with serval neural circuits as the frontal-temporal cognitive circuit, Papez circuit, cerebellum advanced cognitive circuit and caudate nucleus-reward seeking circuits. However, the precise violent/aggressive neural mechanism has yet to be studied further. Key words: Violent/aggressive behavior; Schizophrenia; Structure magnetic resonance imaging

FOC7-3RELATIONSHIP BETWEEN PERFORMANCE ON BEARNI AND GREY MATTER VOLUME IN ALCOHOLISM

Alcoholism leads to neuropsychological deficits associated with shrinkage of the Papez's circuit and frontocerebellar circuit. BEARNI is a new tool devised to detect alcohol-related neuropsychological impairments. The objective of the present study was to examine the links between performances on BEARNI and grey matter volume in ‘uncomplicated’ alcoholics (UA) …

A new semantic list learning task to probe functioning of the Papez circuit

Introduction: List learning tasks are powerful clinical tools for studying memory, yet have been relatively underutilized within the functional imaging literature. This limits understanding of regions such as the Papez circuit that support memory performance in healthy, nondemented adults. Method: The current study characterized list learning performance in 40 adults who completed a semantic list learning task (SLLT) with a Brown–Peterson manipulation during functional magnetic resonance imaging (fMRI). Cued recall with semantic cues and recognition memory were assessed after imaging. Internal reliability, convergent, and discriminant validity were evaluated. Results: Subjects averaged 38% accuracy in recall (62% for recognition), with primacy but no recency effects observed. Validity and reliability were demonstrated by showing that the SLLT was correlated with the California Verbal Learning Test (CVLT), but not with executive functioning tests, and by high intraclass correlation coefficient across lists for recall (.91). fMRI measurements during encoding (vs. silent rehearsal) revealed significant activation in bilateral hippocampus, parahippocampus, and bilateral anterior and posterior cingulate cortex. Post hoc analyses showed increased activation in anterior and middle hippocampus, subgenual cingulate, and mammillary bodies specific to encoding. In addition, increasing age was positively associated with increased activation in a diffuse network, particularly frontal cortex and specific Papez regions for correctly recalled words. Gender differences were specific to left inferior and superior frontal cortex. Conclusions: This is a clinically relevant list learning task that can be used in studies of groups for which the Papez circuit is damaged or disrupted, in mixed or crossover studies at imaging and clinical sites.

Behavioral effects of deep brain stimulation of different areas of the Papez circuit on memory- and anxiety-related functions

Deep brain stimulation (DBS) has gained interest as a potential therapy for advanced treatment-resistant dementia. However, possible targets for DBS and the optimal stimulation parameters are not yet clear. Here, we compared the effects of DBS of the CA1 sub-region of the hippocampus, mammillothalamic tract, anterior thalamic nucleus, and entorhinal cortex in an experimental rat model of dementia. Rats with scopolamine-induced amnesia were assessed in the object location task with different DBS parameters. Moreover, anxiety-related side effects were evaluated in the elevated zero maze and open field. After sacrifice, we applied c-Fos immunohistochemistry to assess which memory-related regions were affected by DBS. When comparing all structures, DBS of the entorhinal cortex and CA1 sub-region was able to restore memory loss when a specific set of stimulation parameters was used. No anxiety-related side effects were found following DBS. The beneficial behavioral performance of CA1 DBS rats was accompanied with an activation of cells in the anterior cingulate gyrus. Therefore, we conclude that acute CA1 DBS restores memory loss possibly through improved attentional and cognitive processes in the limbic cortex.

The papez circuit in first-episode, treatment-naive adults with major depressive disorder: combined atlas-based tract-specific quantification analysis and voxel-based analysis.

Previous findings suggest that the Papez Circuit may have a role in major depressive disorders. We used atlas-based tract-specific quantification analysis and voxel-based analysis to examine the integrity of white matter tracts involved in mood regulation (including tracts in the Papez Circuit). Diffusion tensor imaging acquired from 35 first-episode, treatment-naive adults with major depressive disorders and 34 healthy adult controls were compared. Our statistical approach compared structural integrity of 11 major white matter tracts between the major depressive disorder and adult controls, as well as illness duration influence in patients. Fractional anisotropy was decreased in the hippocampal cingulum and in the anterior thalamic radiation according to both analytical approaches, all of which were important tracts included in the Papez Circuit. Our results support the role of the Papez Circuit in major depressive disorders with the minimal probability of false positive due to similar findings in both analyses that have complementary advantages. Dysfunction of the Papez Circuit may be a potential marker for studying the pathogenesis of major depressive disorders.

Behavioral effects of deep brain stimulation of the anterior nucleus of thalamus, entorhinal cortex and fornix in a rat model of Alzheimer's disease.

Background:Recent clinical and preclinical studies have suggested that deep brain stimulation (DBS) can be used as a tool to enhance cognitive functions. The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit, including the anterior nucleus of thalamus (ANT), the entorhinal cortex (EC), and the fornix (FX), on cognitive behaviors in an Alzheimer's disease (AD) rat model.Methods:Forty-eight rats were subjected to an intrahippocampal injection of amyloid peptides 1-42 to induce an AD model. Rats were divided into six groups: DBS and sham DBS groups of ANT, EC, and FX. Spatial learning and memory were assessed by the Morris water maze (MWM). Recognition memory was investigated by the novel object recognition memory test (NORM). Locomotor and anxiety-related behaviors were detected by the open field test (OF). By using two-way analysis of variance (ANOVA), behavior differences between the six groups were analyzed.Results:In the MWM, the ANT, EC, and FX DBS groups performed differently in terms of the time spent in the platform zone (F(2,23) = 6.04, P < 0.01), the frequency of platform crossing (F(2,23) = 11.53, P < 0.001), and the percent time spent within the platform quadrant (F(2,23) = 6.29, P < 0.01). In the NORM, the EC and FX DBS groups spent more time with the novel object, although the ANT DBS group did not (F(2,23) = 10.03, P < 0.001). In the OF, all of the groups showed a similar total distance moved (F(1,42) = 1.14, P = 0.29) and relative time spent in the center (F(2,42) = 0.56, P = 0.58).Conclusions:Our results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently than ANT DBS. In addition, hippocampus-independent recognition memory was enhanced by EC and FX DBS. None of the targets showed side-effects of anxiety or locomotor behaviors.