RESUMEN
OBJECTIVE: Patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) have episodic memory impairment. Memory has rarely been evaluated using an ecologic measure, even though performance on these tests is more related to patients' memory complaints. We aimed to measure everyday memory of patients with TLE-HS to age- and gender-matched controls. METHODS: We evaluated 31 patients with TLE-HS and 34 healthy controls, without epilepsy and psychiatric disorders, using the Rivermead Behavioral Memory Test (RBMT), Visual Reproduction (WMS-III) and Logical Memory (WMS-III). We evaluated the impact of clinical variables such as the age of onset, epilepsy duration, AED use, history of status epilepticus, and seizure frequency on everyday memory. Statistical analyses were performed using MANCOVA with years of education as a confounding factor. RESULTS: Patients showed worse performance than controls on traditional memory tests and in the overall score of RBMT. Patients had more difficulties to recall names, a hidden belonging, to deliver a message, object recognition, to remember a story full of details, a previously presented short route, and in time and space orientation. Clinical epilepsy variables were not associated with RBMT performance. Memory span and working memory were correlated with worse performance on RBMT. SIGNIFICANCE: Patients with TLE-HS demonstrated deficits in everyday memory functions. A standard neuropsychological battery, designed to assess episodic memory, would not evaluate these impairments. Impairment in recalling names, routes, stories, messages, and space/time disorientation can adversely impact social adaptation, and we must consider these ecologic measures with greater attention in the neuropsychological evaluation of patients with memory complaints.
Asunto(s)
Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/psicología , Hipocampo/patología , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/psicología , Memoria Episódica , Adolescente , Adulto , Epilepsia del Lóbulo Temporal/complicaciones , Femenino , Humanos , Masculino , Trastornos de la Memoria/etiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Esclerosis/complicaciones , Esclerosis/patología , Esclerosis/psicología , Adulto JovenRESUMEN
BACKGROUND: Decision-making abilities have rarely been examined in patients with temporal lobe epilepsy related to hippocampal sclerosis (TLE-HS). We aimed to investigate the ability to delay gratification, a decision-making subdomain, in patients with intractable TLE-HS and to verify the association of delay gratification performance and cool executive function tests. METHODS: We evaluated 27 patients with TLE-HS (mean age: 35.46 [±13.31] years; 7 males) and their cognitive performance was compared with that of 27 age- and gender-matched healthy controls (mean age: 35.33 [±12.05] years; 7 males), without epilepsy and psychiatric disorders. Patients were assessed using the delay discounting task (DDT) and tests of attention, shifting, inhibitory control, and concept formation. Results were correlated with clinical epilepsy variables such as age of onset, epilepsy duration, AED use, history of status epilepticus, febrile seizures, and the presence of generalized seizures. Statistical analysis was performed using one-way ANCOVA with years of education as a confounding factor. RESULTS: Patients and controls demonstrated similar performance on DDT, showing similar discount rate (p=0.935) and probability rate (p=0.585). Delay gratification was not related to cool executive function tests (Digit Span, Stroop Color Test, Trail Making Test, Wisconsin Card Sorting Test, and Connors' CPT). History of status epilepticus, presence of generalized seizures and higher seizure frequency, age at onset, and epilepsy duration had a significant impact on DDT. CONCLUSION: Patients with intractable TLE-HS showed unimpaired delay gratification abilities, being able to accept a higher delay and a lower amount of chance for receiving a higher reward in the future. Clinical variables related to the epilepsy severity impacted the performance on delay gratification. Impairment on cool aspects of executive function was unrelated to this decision-making domain.
Asunto(s)
Toma de Decisiones , Descuento por Demora , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/psicología , Hipocampo/patología , Adolescente , Adulto , Función Ejecutiva , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Esclerosis/patología , Adulto JovenRESUMEN
Several studies have shown that the median raphe nucleus (MRN) is involved in anxiety. However, no study assessed the role of 5-HT mechanisms of MRN in both freezing and fear-potentiated startle (FPS) within a single form of conditioned learning. In this work we examined the effects of neurotoxic lesions of the MRN with NMDA on freezing and FPS of rats submitted to a contextual fear conditioning paradigm, in which they were tested in the same chamber where they received foot-shocks 24 h before. Compared to controls NMDA-injected rats showed a reduction of freezing and FPS in response to contextual cues. Next, we examined the effects of stimulation of 5-HT1A somatodendritic autoreceptors of the MRN with local injections of 8-OH-DPAT either before training or testing sessions conducted 2 or 24 h post-conditioning. Pre-training injections of 8-OH-DPAT intra-MRN reduced both freezing and FPS whereas post-training injections reduced only freezing to the aversive context without changing the FPS. Thus, freezing is easily disrupted by post-training MRN injections of 8-OH-DPAT while memory for FPS remained unchanged. It is proposed that the consolidation of contextual conditioned fear promoting freezing takes place through a slow mechanism of transference of information through 5-HT mechanisms of the MRN-hippocampus pathway. On the other hand, a rapid fear conditioning process operates for FPS, probably through other pathways.
Asunto(s)
Miedo/fisiología , Aprendizaje/fisiología , Neuronas/metabolismo , Puente/metabolismo , Núcleos del Rafe/metabolismo , Serotonina/metabolismo , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Animales , Trastornos de Ansiedad/metabolismo , Trastornos de Ansiedad/fisiopatología , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Condicionamiento Psicológico/efectos de los fármacos , Condicionamiento Psicológico/fisiología , Desnervación , Modelos Animales de Enfermedad , Agonistas de Aminoácidos Excitadores , Miedo/efectos de los fármacos , Aprendizaje/efectos de los fármacos , Masculino , N-Metilaspartato , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Neuronas/efectos de los fármacos , Neurotoxinas , Puente/citología , Núcleos del Rafe/citología , Núcleos del Rafe/efectos de los fármacos , Ratas , Ratas Wistar , Receptor de Serotonina 5-HT1A/metabolismo , Reflejo de Sobresalto/efectos de los fármacos , Reflejo de Sobresalto/fisiología , Agonistas del Receptor de Serotonina 5-HT1 , Agonistas de Receptores de Serotonina/farmacologíaRESUMEN
The amplitude of the whole-body acoustic startle response is reliably enhanced when elicited in the presence of foreground signals, such as light, previously paired with footshocks. It has been shown that this enhancement is evident by moderate fear levels, but is less affected by high fear levels. Potentiation of the acoustic startle reflex has also been reported in the presence of background cues previously associated with footshocks. However, the effects of anxiolytic drugs on different levels of fear elicited by moderate and intense contextual fear conditioning associated with startle reflex have not been examined yet. To approach this issue, we examined the effects of the anxiolytic, midazolam, on two intensities of contextual fear; freezing behavior and the startle response to loud noise. First, we compared the magnitude of the freezing behavior and the startle amplitude during the testing sessions in groups of rats submitted to fear conditioning using 0.3 and 0.6 mA as unconditioned stimuli (10 stimuli of 1 s each, intertrial interval from 60 to 180 s). Afterwards, the effects of midazolam (0.5 and 1.0 mg/kg) were assessed in these two conditions. Rats showed a potentiated startle reflex and a significant freezing behavior to moderate fear conditioning, which were both attenuated by midazolam. Higher levels of fear conditioning caused more intense freezing behavior without enhancing the startle reflex. Whereas midazolam reduced this freezing response, the startle response was unaffected. These results are indicative that anxiolytic-sensitive freezing and fear-potentiated startle are triggered by moderate contextual fear conditioning, while contextual conditioning with the use of high footshocks causes a distinct pattern of behavioral responses, which is only partially affected by midazolam. Due to the differential sensitivity to midazolam of these two patterns of startle responses generated as a function of the intensity of contextual fear conditioning, it is proposed that they represent moderate and intense aversive states that may be related to anxiety or panic/phobic conditions, respectively.
Asunto(s)
Estimulación Acústica/métodos , Miedo/fisiología , Inmovilización/fisiología , Reflejo de Sobresalto/fisiología , Animales , Miedo/psicología , Inmovilización/psicología , Masculino , Ratas , Ratas WistarRESUMEN
It has previously been shown that the median raphe nucleus (MR) is one of the main sources of projections to the septum and hippocampus. 5-HT projections from this nucleus to the hippocampus are implicated in the acquisition and expression of contextual fear (background stimuli), as assessed by freezing. It has also been reported that amygdala is involved in the acquisition of conditioned fear to foreground cues such as light, used as CS. As the MR projects to the hippocampus and amygdala, the role of this raphe nucleus in fear conditioning to contextual and classical fear conditioning remains to be elucidated. The present study examined the involvement of the MR serotonergic mechanisms in the expression of two distinct types of conditioned fear responses: contextual freezing and fear conditioning to explicit cue (light) measured in a fear-potentiated startle (FPS) procedure. Animals received MR electrolytic lesions of or microinjections of 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino tetralin) (1 microg/0.2 microl) into the MR, 1 or 7 days after two consecutive training sessions in which they received 10 pairings of the CS (light, 4 s)-US (foot-shocks 0.6 mA, 1s) and were tested in a contextual fear paradigm and in a FPS procedure. The startle was clearly potentiated in the presence of light-CS in animals bearing lesions of or microinjected with 8-OH-DPAT into MR at 1 or 7 days post-training. However, animals bearing MR electrolytic lesions or microinjections of 8-OH-DPAT into the MR at 1 day, but not at 7 days post-training, showed a significant decrease in time spent in freezing than control ones. Thus, the memory for contextual conditioned fear seems to be formed during a time-window shorter than 1 week. As FPS may be produced in lesioned rats unable to freeze to fear contextual stimuli, dissociable systems seem to be recruited in each condition. Thus, the production of contextual freezing and fear-potentiated startle are conveyed by distinct 5-HT-mediated circuits of the MRN.