The P300 event-related potential during propofol sedation: a possible marker for amnesia?

We have studied the effects of conscious sedation with propofolon long latency components of the auditory event-related potential(ERP) in 10 normal volunteers (aged 21–41 yr) receivingpropofol 75 µg kg–1 min–1 i.v. We examinedthe effects of propofol on ERP amplitudes and latencies, andtheir relationship to delayed recognition performance usinga verbal memory test, a selective attention task (button pushing)and serum concentrations of propofol. During infusion of propofol,subjects were mildly sedated, oriented and readily responsiveto verbal commands. ERP were recorded from monopolar F_z, C_zand P_z electrodes. We used a standard paradigm requiring selectiveattention to randomly occurring stimuli associated with a task(button push). The peak-to-peak amplitudes and latencies ofthe N2 and P3 waves were obtained before and during infusion,and 15, 100 and 170min after infusion. Propofol produced a 70%decrease in the amplitude of P3 (P < 0.0001) from baselineand a 50% increase in reaction time. The differential responseto target compared with non-target stimuli was maintained duringinfusion for both N2 and P3. Memory performance correlated morestrongly with changes in P3 amplitude (r = 0.59) than with serumpropofol concentrations (_r = –0.07), although this correlationwith memory did not reach statistical significance (P = 0.08).We conclude that P3 amplitude was profoundly affected by propofolgiven in sedative concentrations.      

A MEASURE OF CONSCIOUSNESS AND MEMORY DURING ISOFLURANE ADMINISTRATION: THE COHERENT FREQUENCY

The coherent frequency (CF) of the auditory evoked response(AER) is derived using auditory clicks presented at frequenciesin the range 5–47 Hz. CF and psychological performancewere measured while seven subjects breathed isoflurane in dosesincreasing from 0% to 0.2%, 0.4% and 0.8% endtidal concentrationand then decreasing to 0%. With increasing doses of isoflurane,CF decreased and there was a decrease in within-list recognition(WLR) and category recognition (CR) scores. There was a correlationbetween changes in CF and WLR (P < 0.05) and between CF andcategory recognition (CR) (P < 0.05). A painful stimulusgiven in conjunction with 0.4% isoflurane caused an increasein CF, WLR and CR in some subjects. This did not reach statisticalsignificance for the group as a whole, apart from the shortword interval scores in the WLR which indicated an increasein attention (P < 0.01). Subjects did not respond with 0.8%isoflurane, either before or after painful stimulation. Reductionof end-tidal isoflurane from 0.8% to 0% caused an increase inthe CF and improved performance on the psychological tests.A category generation task on recovery showed no evidence ofimplicit learning of words presented in conjunction with 0.8%isoflurane. Memory testing after the trial showed a relationshipbetween the CF obtained with isoflurane and subsequent memory:conscious awareness with explicit memory was associated witha median CF (25th–75th centile) of 32.8(28.4–36.7)Hz; conscious awareness without explicit memory was associatedwith a CF 24.8 (21.5–30.6) Hz; absence of both responsivenessand implicit memory was associated with a mean CF of 14.9 (14.2–17.3)Hz. There was a significant difference in CF associated withthese different categories of memory (P < 0.02). We concludethat the coherent frequency of the AER reflects the likelihoodof cognition during anaesthetic inhalation. (Br. J. Anaesth.1993; 71: 633–641)      

Separating intra-modal and across-modal training effects in visual working memory: an fMRI investigation

Working memory training is a useful tool to examine dissociations between specific working memory processes. Although current models propose a distinction between modality-specific working memory processes, to our knowledge no study has directly examined the effects of visual versus auditory working memory training. Functional magnetic resonance imaging was used to investigate whether visual working memory processes can be trained specifically and whether those effects can be separated from across-modal training effects. We found decidedly larger training gains after visual working memory training compared with auditory or no training on a visual 2-back task. These effects were accompanied by specific training-related decreases in the right middle frontal gyrus arising from visual training only. Likewise, visual and auditory training led to decreased activations in the superior portion of the right middle frontal gyrus and the right posterior parietal lobule. We infer that the combination of effects resulted from increased neural efficiency of intra-modal (visual) processes on the one hand and of across-modal (general control) processes on the other hand. Therefore, visual processes of working memory can be trained specifically, and these effects can be functionally dissociated from alterations in general control processes common to both working memory trainings.     

A Neuroanatomical Construct for the Amnesic Effects of Propofol

Background: This study was designed to identify neuroanatomical locations of propofol's effects on episodic memory by producing minimal and maximal memory impairment during conscious sedation. Drug-related changes in regional cerebral blood flow (rCBF) were located in comparison with rCBF increases during a simple word memory task.

Methods: Regional cerebral blood flow changes were assessed in 11 healthy volunteers using H215O positron emission tomography (PET) and statistical parametric mapping (SPM99) at 600 and 1,000 ng/ml propofol target concentrations. Study groups were based on final recognition scores of auditory words memorized during PET scanning. rCBF changes during propofol administration were compared with those during the word memory task at baseline.

Results: Nonoverlapping memory effects were evident: low (n = 4; propofol concentration 523 +/- 138 ng/ml; 44 +/- 13% decrement from baseline memory) and high (n = 7; 829 +/- 246 ng/ml; 87 +/- 6% decrement from baseline) groups differed in rCBF reductions primarily in right-sided prefrontal and parietal regions, close to areas activated in the baseline memory task, particularly R dorsolateral prefrontal cortex (Brodmann area 46; x, y, z = 51, 38, 22). The medial temporal lobe region exhibited relative rCBF increases.     

High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice

Changes in cortical activity during working memory tasks were examined with electroencephalograms (EEGs) sampled from 115 channels and spatially sharpened with magnetic resonance imaging (MRI)-based finite element deblurring. Eight subjects performed tasks requiring comparison of each stimulus to a preceding one on verbal or spatial attributes. A frontal midline theta rhythm increased in magnitude with increased memory load. Dipole models localized this signal to the region of the anterior cingulate cortex. A slow (low-frequency), parietocentral, alpha signal decreased with increased working memory load. These signals were insensitive to the type of stimulus attribute being processed. A faster (higher-frequency), occipitoparietal, alpha signal was relatively attenuated in the spatial version of the task, especially over the posterior right hemisphere. Theta and alpha signals increased, and overt performance improved, after practice on the tasks. Increases in theta with both increased task difficulty and with practice suggests that focusing attention required more effort after an extended test session. Decreased alpha in the difficult tasks indicates that this signal is inversely related to the amount of cortical resources allocated to task performance. Practice-related increases in alpha suggest that fewer cortical resources are required after skill development. These results serve: (i) to dissociate the effects of task difficulty and practice; (ii) to differentiate the involvement of posterior cortex in spatial versus verbal tasks; (iii) to localize frontal midline theta to the anteromedial cortex; and (iv) to demonstrate the feasibility of using anatomical MRIs to remove the blurring effect of the skull and scalp from the ongoing EEG. The results are discussed with respect to those obtained in a prior study of transient evoked potentials during working memory.      

In vitro functional responses of isolated human vaginal tissue to selective phosphodiesterase inhibitors

Only little is known as to the significance of the cyclic nucleotide-mediated signal transduction in the control of the function of human vaginal smooth musculature. Recently, the presence of the phosphodiesterase (PDE) isoenzymes 4 (cAMP-PDE) and 5 (cGMP-PDE) in the human vagina was reported. Thus, it was the aim of the study to elucidate the effects of some PDE inhibitors on the tension induced by endothelin 1 (ET-1), as well as on levels of cGMP and cAMP in isolated human vaginal wall tissue. Using the organ bath technique, the ability of norepinephrine (NE), carbachol, serotonin (5-HT), oxytocin and ET-1 to contract isolated vaginal wall muscle strips was evaluated. In another set-up, the effects of the PDE4 inhibitor rolipram and PDE5 inhibitors sildenafil and vardenafil (1 nM–10 μM) on the tension induced by 0.1 μM ET-1 of human vaginal wall tissue strips were investigated. In order to measure drug effects on tissue levels of cGMP and cAMP, vaginal tissue was exposed to different concentrations (0.1, 1 and 10 μM) of the compounds and the accumulation of cyclic nucleotides was determined. The adenylyl cyclase stimulating agents forskolin and nitric oxide donor sodium nitroprusside (SNP) (0.01, 0.1 and 1 μM) were used as reference compounds. While NE, carbachol and oxytocin failed to contract the vaginal tissue, ET-1 and, to a certain degree, 5-HT elicited contractile responses of the isolated strip preparations. The tension induced by 0.1 μM ET-1 was dose-dependently reversed by the drugs. The rank order of efficacy was sildenafil > forskolin > rolipram ≥ vardenafil > SNP. R _max values ranged from 24% (SNP) to 50% (sildenafil). With sildenafil being the only exception, none of the compounds reached an EC₅₀ value. The relaxing effects of the drugs were paralleled by a fourfold to tenfold increase in tissue levels of cGMP and/or cAMP. Our results demonstrate that PDE inhibitors can relax human vaginal tissue and increase levels of cyclic nucleoside monophosphates. The findings with regard to the PDE5 inhibitors may indicate that the NO–cGMP pathway is, to a certain degree, involved in the control of vaginal smooth muscle tone. This might be of significance with regard to the pharmacological treatment of disorders connected with female sexual arousal and the ability to achieve orgasm.     

Modulation of ventral prefrontal cortex functional connections reflects the interplay of cognitive processes and stimulus characteristics

Emerging ideas of brain function emphasize the context-dependency of regional contributions to cognitive operations, where the function of a particular region is constrained by its pattern of functional connectivity. We used functional magnetic resonance imaging to examine how modality of input (auditory or visual) affects prefrontal cortex (PFC) functional connectivity for simple working memory tasks. The hypothesis was that PFC would show contextually dependent changes in functional connectivity in relation to the modality of input despite similar cognitive demands. Participants were presented with auditory or visual bandpass-filtered noise stimuli, and performed 2 simple short-term memory tasks. Brain activation patterns independently mapped onto modality and task demands. Analysis of right ventral PFC functional connectivity, however, suggested these activity patterns interact. One functional connectivity pattern showed task differences independent of stimulus modality and involved ventromedial and dorsolateral prefrontal and occipitoparietal cortices. A second pattern showed task differences that varied with modality, engaging superior temporal and occipital association regions. Importantly, these association regions showed nonzero functional connectivity in all conditions, rather than showing a zero connectivity in one modality and nonzero in the other. These results underscore the interactive nature of brain processing, where modality-specific and process-specific networks interact for normal cognitive operations.     

Dissociable functional cortical topographies for working memory maintenance of voice identity and location

In order to ascertain whether the neural system for auditory working memory exhibits a functional dissociation for spatial and nonspatial information, we used functional magnetic resonance imaging and a single set of auditory stimuli to study working memory for the location and identity of human voices. The subjects performed a delayed recognition task for human voices and voice locations and an auditory sensorimotor control task. Several temporal, parietal, and frontal areas were activated by both memory tasks in comparison with the control task. However, during the delay periods, activation was greater for the location than for the voice identity task in dorsal prefrontal (SFS/PreCG) and parietal regions and, conversely, greater for voices than locations in ventral prefrontal cortex and the anterior portion of the insula. This preferential response to the voice identity task in ventral prefrontal cortex continued during the recognition test period, but the double dissociation was observed only during maintenance, not during encoding or recognition. Together, the present findings suggest that, during auditory working memory, maintenance of spatial and nonspatial information modulates activity preferentially in a dorsal and a ventral auditory pathway, respectively. Furthermore, the magnitude of this dissociation seems to be dependent on the cognitive operations required at different times during task performance.     

A neuroanatomical construct for the amnesic effects of propofol

BACKGROUND: This study was designed to identify neuroanatomical locations of propofol's effects on episodic memory by producing minimal and maximal memory impairment during conscious sedation. Drug-related changes in regional cerebral blood flow (rCBF) were located in comparison with rCBF increases during a simple word memory task. METHODS: Regional cerebral blood flow changes were assessed in 11 healthy volunteers using H215O positron emission tomography (PET) and statistical parametric mapping (SPM99) at 600 and 1,000 ng/ml propofol target concentrations. Study groups were based on final recognition scores of auditory words memorized during PET scanning. rCBF changes during propofol administration were compared with those during the word memory task at baseline. RESULTS: Nonoverlapping memory effects were evident: low (n = 4; propofol concentration 523 +/- 138 ng/ml; 44 +/- 13% decrement from baseline memory) and high (n = 7; 829 +/- 246 ng/ml; 87 +/- 6% decrement from baseline) groups differed in rCBF reductions primarily in right-sided prefrontal and parietal regions, close to areas activated in the baseline memory task, particularly R dorsolateral prefrontal cortex (Brodmann area 46; x, y, z = 51, 38, 22). The medial temporal lobe region exhibited relative rCBF increases. CONCLUSIONS: As amnesia becomes maximal, rCBF reductions induced by propofol occur in brain regions identified with working memory processes. In contrast, medial temporal lobe structures were resistant to the global CBF decrease associated with propofol sedation. The authors postulate that the episodic memory effect of propofol is produced by interference with distributed cortical processes necessary for normal memory function rather than specific effects on medial temporal lobe structures.     

Activation of Human Prefrontal Cortex during Spatial and Nonspatial Working Memory Tasks Measured by Functional MRI

Separate working memory domains for spatial location, and forobjects, faces, and patterns, have been identified in the prefrontalcortex (PFC) of nonhuman primates. We have used functional magneticresonance imaging to examine whether spatial and nonspatialvisual working memory processes are similarly dissociable inhuman PFC. Subjects performed tasks which required them to remembereither the location or shape of successive visual stimuli. Wefound that the mnemonic component of the working memory tasksaffected the hemispheric pattern of PFC activation. The spatial(LOCATION) working memory task preferentially activated themiddle frontal gyrus (MFG) in the right hemisphere, while thenonspatial (SHAPE) working memory task activated the NIFG inboth hemispheres. Furthermore, the area of activation in theleft hemisphere extended into the inferior frontal gyrus forthe nonspatial SHAPE task. A perceptual target (DOT) detectiontask also activated the MFG bilaterally, but at a level approximatelyhalf that of the working memory tasks. The activation in theMFG occurred within 3–6 s of task onset and declined followingtask offset. Time-course analysis revealed a different patternfor the cingulate gyrus, in which activation occurred upon taskcompletion. Cingulate activation was greatest following theSHAPE task and was greater in the left hemisphere. The presentresults support the prominent role of the PFC and, specifically,the MFG in working memory, and indicate that the mnemonic contentof the task affects the relative weighting of hemispheric activation.     

Priming frequencies of transcranial magnetic stimulation over Wernicke's area modulate word detection

Priming stimulations have shown powerful effects on motor cortex behavior. However, the effects over language areas have not been explored. We assessed the effects of different priming frequencies of repetitive transcranial magnetic stimulation (rTMS), 1 Hz rTMS or 50 Hz bursts of rTMS (theta burst stimulation [TBS]), on temporoparietal language areas (i.e., Wernicke's area) localized with functional magnetic resonance imaging. Functional maps were acquired during an auditory word-detection task with native or foreign language sentences in 14 healthy men. Frameless stereotaxy was used to guide the transcranial magnetic stimulation coil position over Wernicke's area. Active and placebo randomized sessions of priming stimulations (1 Hz rTMS or TBS) were applied at rest, and response times (RTs) were recorded during the auditory word-detection task performed subsequently with 1 Hz rTMS. Individual anatomofunctional maps localized activation in Wernicke's area. Repeated-measure analysis of variance for RTs revealed that priming with 1 Hz rTMS facilitated the detection of native words, whereas priming with TBS facilitated the detection of foreign words. Consistent with motor cortex studies, these findings suggest that priming frequency plays a crucial role in word detection in the auditory stream.     

Ketamine disrupts frontal and hippocampal contribution to encoding and retrieval of episodic memory: an fMRI study

The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine produces episodic memory deficits. We used functional magnetic resonance imaging to characterize the effects of ketamine on frontal and hippocampal responses to memory encoding and retrieval in healthy volunteers using a double-blind, placebo-controlled, randomized, within-subjects comparison of two doses of intravenous ketamine. Dissociation of the effects of ketamine on encoding and retrieval processes was achieved using two study-test cycles: in the first, items were encoded prior to drug infusion and retrieval tested, during scanning, on drug; in the second, encoding was scanned on drug, and retrieval tested once ketamine plasma levels had declined. We additionally determined the interaction of ketamine with the depth of processing that occurred at encoding. A number of effects upon task-dependent activations were seen. Overall, our results suggest that left frontal activation is augmented by ketamine when elaborative semantic processing is required at encoding. In addition, successful encoding on ketamine is supplemented by additional non-verbal processing that is incidental to task demands. The effects of ketamine at retrieval are consistent with impaired access to accompanying contextual features of studied items. Our findings show that, even when overt behaviour is unimpaired, ketamine has an impact upon the recruitment of key regions in episodic memory task performance.     

Information Loss over Time Defines the Memory Defect of Propofol: A Comparative Response with Thiopental and Dexmedetomidine

Background: Sedative-hypnotic drugs impair memory, but details regarding the nature of this effect are unknown. The influences of propofol, thiopental, and dexmedetomidine on the performance of a task that isolates specific components of episodic memory function were measured.

Methods: Working (1 intervening item, 6 s) and long-term memory (10 intervening items, 33 s) were tested using auditory words in a continuous recognition task before and during drug administration. Eighty-three volunteer participants were randomly assigned to receive a constant target concentration of drug or placebo, producing sedative effects from imperceptible to unresponsiveness. Responsive participants were categorized as high or low performers, using a median split of long-term memory performance during drug administration. Recognition of words at the end of the study day was assessed.

Results: High performers had acquisition of material into long-term memory when drug was present at the same level as placebo. Retention of this material at 225 min was significantly less for propofol (39 +/- 23% loss of material) than for other drugs (17-23% loss; P < 0.01). Greater sedation in low performers was evident in multiple measures. Memory for words presented before drug was no different from that associated with placebo for all groups.     

Recovery of memory after general anaesthesia: clinical findings and somatosensory evoked responses

Background. Mid-latency somatosensory evoked responses are usedto monitor the integrity of the sensory pathways intra-operatively.They can quantify the effects of anaesthetics on the centralnervous system. Mid-latency auditory evoked responses have beenrelated to cognition during anaesthesia, but there are no detailedstudies using median nerve somatosensory evoked responses (MnSSER). Methods. We studied 49 patients during recovery from generalanaesthesia (isoflurane/nitrous oxide or propofol) to assessimplicit and explicit memory function in relation to mid-latencyMnSSER. The MnSSER recordings were made before anaesthesia,during steady-state anaesthesia, and at the end of the recoveryperiod. The patients were interviewed 24 h later about theirmemory for the immediate wake up phase. Statistical analysiswas by multivariate analysis of variance. Results. Out of 49 patients, 23 recalled the recovery period,11 had implicit memory for an object shown to them during therecovery period, and 15 did not have any memory for the recoveryperiod. At RECOVERY the patients with recall had significantlyshorter MnSSER latencies N45 and P50 and inter-wave conductiontimes LatN35 – LatP45 than patients without memory (P<0.05). Conclusions. We conclude that MnSSER components warrant furtherinvestigation for studying the effects of anaesthetic drugson cognitive function. Br J Anaesth 2002; 88: 362–8     

Comparing the effects of stimulation and propofol infusion rate on implicit and explicit memory formation

Doubt remains about the conditions under which learning persistsdespite anaesthesia. This study investigated the relative importanceof dose of anaesthetic and stimulation for learning during propofolinfusion before surgery. Thirty-six patients were randomly assignedto three groups. Group 1 received two word lists (category examplesand nonsense words) during infusion of propofol to a targetconcentration of 2 µg ml^–1. Groups 2 and3 received the word lists during infusion of propofol 5 µg ml^–1.Group 2 received nonsense words before tracheal intubation andcategory examples during intubation; Group 3 heard categoryexamples before and nonsense words during intubation. Bispectralindex was recorded as a measure of depth of sedation/anaesthesia.We assessed explicit memory on recovery using a structured interviewand a recognition test. We assessed implicit memory using acategory generation test and a preference rating task. To establishbaseline, a control group of 12 patients completed the categorygeneration test without receiving the category examples duringanaesthesia. Overall, there was no evidence for learning duringpropofol infusion, though the category generation task showeda trend towards more implicit memory for words presented duringintubation than during anaesthesia. We conclude that learningdoes not occur during anaesthesia without surgery. Br J Anaesth 2001; 86: 189–95     

Comparison of the clinical efficacy and safety of the on‐demand use of paroxetine,dapoxetine, sildenafil and combined dapoxetine with sildenafil in treatment of patients with premature ejaculation: A randomised placebo‐controlled clinical trial

The aim of the study was to compare the clinical efficacy and safety of the on‐demand use of paroxetine, dapoxetine, sildenafil and combined dapoxetine with sildenafil in treatment of patients with premature ejaculation (PE). In a single‐blind placebo‐controlled clinical study, 150 PE patients without erectile dysfunction (ED) were included during the period of March 2015 to May 2016. Patients were randomly divided into five groups (30 patients each). On demand placebo, paroxetine (30 mg), dapoxetine (30 mg), sildenafil citrate (50 mg) and combined dapoxetine (30 mg) with sildenafil citrate (50 mg) were given for patients for 6 weeks in each group respectively. All patients were instructed to record intravaginal ejaculatory latency time (IELT) and evaluated with Premature Ejaculation Diagnostic Tool (PEDT) and the patient satisfaction score before and after treatment. The mean of IELT, satisfaction score and PEDT in all groups was significantly improved after treatment (p value = .001). Combined dapoxetine with sildenafil group had the best values of IELT, satisfaction scores and PEDT in comparison with other treatment groups (p value <.001). The combined dapoxetine with sildenafil therapy could significantly improve PE patients without ED as compared to paroxetine alone or dapoxetine alone or sildenafil alone with tolerated adverse effects.     

Hemodynamic Effects of Sildenafil Citrate (Viagra) on Segmental Branches of Bilateral Renal Arteries

Introduction: Erectile dysfunction (ED) is one of the most encountered male health problem and sildenafil citrate is used worlwide for treatment of ED. Aim of the present study was to determine and evaluate hemodynamic effects of sildenafil citrate on segmental branches of bilateral renal arteries of cases with ED.Patients and methods: Total of 35 male patients aging between 34 and 56 years were recruited into study. Patients were evaluated with renal color Doppler sonography (CDS) before and after (45–75 min) peroral sildenafil citrate (50 mg) administration. Peak sistolic flow rate (V_max), end diastolic flow rate (V_min), resistive index (RI) and pulsatility index (PI) of renal artery segmental branches were determined before and after sildenafil citrate administration.Results: V_min measured at right lower segment was significantly reduced after sildenafil administration (p=0.030). Accordingly mean RI and PI of right lower segment of renal artery slightly increased after drug administration (p=0.007 and p=0.012, respectively). The measurements on other segments had no significant change after sildenafil treatment when compared to baseline values. On this single dose administration no side effect was recorded.Conclusion: Findings of the present study demonstrated that peroral sildenafil citrate usage had slight effects on hemodynamic parameters of lower segmental branch of right renal artery. This result could not be interpreted as robust evidence for hemodynamic changes of renal arteries associated with slidenafil usage nevertheless warrants more comprehensive research with larger number of patients.     

Increased Reading Speed for Stories Presented during General Anesthesia

Background: In the absence of explicit memories such as the recall and recognition of intraoperative events, memory of auditory information played during general anesthesia has been demonstrated with several tests of implicit memory. In contrast to explicit memory, which requires conscious recollection, implicit memory does not require recollection of previous experiences and is evidenced by a priming effect on task performance. The authors evaluated the effect of a standardized anesthetic technique on implicit memory, first using a word stem completion task, and then a reading speed task in a subsequent study.

Methods: While undergoing lumbar disc surgery, 60 patients were exposed to auditory materials via headphones in two successive experiments. A balanced intravenous technique with propofol and alfentanil infusions and a nitrous oxide-oxygen mixture was used to maintain adequate anesthesia. In the first experiment, 30 patients were exposed randomly to one of the two lists of 34 repeated German nouns; in the second experiment, 30 patients were exposed to one of two tapes containing two short stories. Thirty control patients for each experiment heard the tapes without receiving anesthesia. All patients were tested for implicit memory 6-8 h later: A word stem completion task for the words and a reading speed task for the stories were used as measures of implicit memory.

Results: The control group completed the word stems significantly more often with the words that they had heard previously, but no such effect was found in the anesthetized group. However, both the control and patient groups showed a decreased reading time of about 40 ms per word for the previously presented stories compared with the new stories. The patients had no explicit memory of intraoperative events.     

Comparative effect of administration and discontinuation of sildenafil and/or clomipramine on the hepatic,cardiac and testicular tissues of male rats

In this study, we examined the adverse consequences of prolonged treatment with sildenafil and/or clomipramine (CLO) on the hepatic, cardiac and testicular tissues of rats. Additionally, we investigated the potential effects of treatment discontinuation. To this end, 60 adult male rats were randomly assigned into six groups and were orally treated with 4.5 mg sildenafil /kg BW (SLD) and 9 mg/ kg BW (SHD), 2.25 mg CLO/kg BW (CLO), 4.5 mg sildenafil/kg BW + 2.25 mg CLO/kg BW (SLD-CLO) and 9 mg sildenafil/kg BW + 2.25 mg CLO/kg BW (SHD-CLO) while the control rats received 0.5 ml distilled water for 8 weeks. Then, five rats from each group were sacrificed and the other five rats were left untreated for another four weeks to recover from the drug treatment. Long-term administration of sildenafil and/or CLO led to oxidative stress, inflammation and structural changes in the liver, heart and testis, reduction in sperm count and motility, an increase in abnormalities, and a reduction in serum testosterone, FSH and LH levels. All tested parameters returned to the normal state following the four-week discontinuation of sildenafil. Additionally, all the alterations caused by long-term administration of CLO, SLD-CLO and SHD-CLO were significantly improved during the recovery period.     

Roles of attention, memory, and motor preparation in modulating human brain activity in a spatial working memory task

Neuronal activity of the human brain was studied with magnetoencephalography (MEG) in a spatial working memory task similar to those commonly used with nonhuman primates. The subject was required to remember target positions for 3 s and make a same-different judgement with a finger lift comparing the position of the probed target with the probe or to execute a memory-guided saccade to the probed target. In this type of task single-unit studies have shown attention- and memory-related activities independent of movement type during the retention interval in a large number of cortical areas of the primates, including the parietal and prefrontal areas. Consistent with these results, there were strong stimulus-driven transient and sustained responses and modulations of oscillatory activity during the retention period. Although we did not determine the source locations, coarse estimates of the currents responsible for the MEG signals showed activity over a wide area of the cortex, most prominently over the Rolandic, parietal and occipital areas, but also over the frontal area. Some of the activities in these cortical areas reflect processes that may be identified with attention and memory, while others were related to preparation of the overt movements.