Telling true from false: cannabis users show increased susceptibility to false memories.

Previous studies on the neurocognitive impact of cannabis use have found working and declarative memory deficits that tend to normalize with abstinence. An unexplored aspect of cognitive function in chronic cannabis users is the ability to distinguish between veridical and illusory memories, a crucial aspect of reality monitoring that relies on adequate memory function and cognitive control. Using functional magnetic resonance imaging, we show that abstinent cannabis users have an increased susceptibility to false memories, failing to identify lure stimuli as events that never occurred. In addition to impaired performance, cannabis users display reduced activation in areas associated with memory processing within the lateral and medial temporal lobe (MTL), and in parietal and frontal brain regions involved in attention and performance monitoring. Furthermore, cannabis consumption was inversely correlated with MTL activity, suggesting that the drug is especially detrimental to the episodic aspects of memory. These findings indicate that cannabis users have an increased susceptibility to memory distortions even when abstinent and drug-free, suggesting a long-lasting compromise of memory and cognitive control mechanisms involved in reality monitoring.

Analysis of automated methods for spatial normalization of lesioned brains.

Normalization of brain images is a crucial step in MRI data analysis, especially when dealing with abnormal brains. Although cost function masking (CFM) appears to successfully solve this problem and seems to be necessary for patients with chronic stroke lesions, this procedure is very time consuming. The present study sought to find viable, fully automated alternatives to cost function masking, such as Automatic Lesion Identification (ALI) and Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL). It also sought to quantitatively assess, for the first time, Symmetrical Normalization (SyN) with constrained cost function masking. The second aim of this study was to investigate the normalization process in a group of drug-resistant epileptic patients with large resected regions (temporal lobe and amygdala) and in a group of stroke patients. A dataset of 500 artificially generated lesions was created using ten patients with brain-resected regions (temporal lobectomy), ten stroke patients and twenty five-healthy subjects. The results indicated that although a fully automated method such as DARTEL using New Segment with an extra prior (the mean of the white matter and cerebro-spinal fluid) obtained the most accurate normalization in both patient groups, it produced a shrinkage in lesion volume when compared to Unified Segmentation with CFM. Taken together, these findings suggest that further research is needed in order to improve automatic normalization processes in brains with large lesions and to completely abandon manual, time consuming normalization methods.

Patterns out of cases using kohonen maps in breast cancer diagnosis.

DESMAI is a framework for helping experts in breast cancer diagnosis. It allows experts to explore digital mammographic image databases according to a certain topology criteria when they need to decide whether a sample is benign or malignant. In this way, they are provided with complementary information to enhance their interpretations and predictions. The core of the application is a SOMCBR system, which is variant of a Case-Based Reasoning system featured by organizing the case memory using a Self-Organizing Map. The article presents a strategy for improving the SOMCBR reliability thanks to the relations between cases and clusters. The approach is successfully applied in DESMAI for estimating, if it is possible, the class of the recovered mammographies.

Performance monitoring in lung cancer patients pre- and post-chemotherapy using fine-grained electrophysiological measures.

No previous event-related potentials (ERPs) study has explored the error-related negativity (ERN) - an ERP component indexing performance monitoring - associated to cancer and chemotherapy-induced cognitive impairment in a lung cancer population. The aim of this study was to examine differences in performance monitoring in a small-cell lung cancer group (SCLC, C +) 1-month following chemotherapy and two control groups: a non-small cell lung cancer patient group (NSCLC, C -) prior to chemotherapy and a healthy control group (HC). Seventeen SCLC (C +) underwent a neuropsychological assessment and an ERP study using a flanker and a stop-signal paradigm. This group was compared to fifteen age-, gender- and education-matched NSCLC (C -) and eighteen HC. Between 20 and 30% of patients in both lung cancer groups (C + and C -) met criteria for cognitive impairment. Concerning ERPs, lung cancer patients showed lower overall hit rate and a severe ERN amplitude reduction compared to HC. Lung cancer patients exhibited an abnormal pattern of performance monitoring thus suggesting that chemotherapy and especially cancer itself, may contribute to cognitive deterioration. ERN appeared as an objective laboratory tool sensitive to cognitive dysfunction in cancer population.

Music supported therapy promotes motor plasticity in individuals with chronic stroke.

Novel rehabilitation interventions have improved motor recovery by induction of neural plasticity in individuals with stroke. Of these, Music-supported therapy (MST) is based on music training designed to restore motor deficits. Music training requires multimodal processing, involving the integration and co-operation of visual, motor, auditory, affective and cognitive systems. The main objective of this study was to assess, in a group of 20 individuals suffering from chronic stroke, the motor, cognitive, emotional and neuroplastic effects of MST. Using functional magnetic resonance imaging (fMRI) we observed a clear restitution of both activity and connectivity among auditory-motor regions of the affected hemisphere. Importantly, no differences were observed in this functional network in a healthy control group, ruling out possible confounds such as repeated imaging testing. Moreover, this increase in activity and connectivity between auditory and motor regions was accompanied by a functional improvement of the paretic hand. The present results confirm MST as a viable intervention to improve motor function in chronic stroke individuals.

Morphological processing in early bilinguals: an ERP study of regular and irregular verb processing.

Although the age of acquisition of a language has an effect when learning a second language, the similarity between languages may also have a crucial role. The aim of the present study is to understand the influence of this latter factor in the acquisition of morphosyntactic information. With this purpose, two groups of highly proficient early Catalan-Spanish bilinguals were presented with a repetition-priming paradigm with regular and irregular verbs of Spanish. Catalan and Spanish have a similar suffix (-o) for regular verbs and completely different alternations for irregular verbs. Two types of irregular verbs were studied (semi-regular verbs with a systematic diphthong alternation, sentir-siento, and verbs with idiosyncratic changes, venir-vengo). Regular verbs showed the same centro-parietal N400 priming effect in the second-language speakers (L2) as in primary-language (L1) speakers. However, differences between groups, in the ERP pattern and the topography of the N400 effect, were observed for irregular morphology. In L1 speakers, the N400 effect was attenuated only for semi-regular verbs. In contrast, L2 speakers showed a reduced N400 priming effect in both irregular contrasts. This pattern of results suggests that the similarity between languages may help for similar structures but may interfere for dissimilar structures, at least when the two languages have very similar morphological systems.

Brain potentials related to self-generated and external information used for performance monitoring.

OBJECTIVE: Humans need to supervise and adjust their own behavior by means of an error detection and correction system as well as by using externally available information. The purpose of the present study was to compare the electrophysiological effects related to self-generated internal and to external (feedback) information used for performance monitoring. METHODS: Fourteen young normal subjects learned to associate each of several line-drawings with either a left-hand or right-hand response. In the experiment proper multi-channel ERPs were obtained time-locked to (a) the line-drawings, (b) the button-press, and (c) subsequent feedback stimuli. Feedback was either affirmative, negative, or equivocal. Event-related potentials were quantified and statistically evaluated using standard methodology. RESULTS: Response-locked ERPs showed a typical error-related negativity (ERN) for erroneous responses. ERPs to negative and equivocal feedback stimuli contained a negativity with a more posterior distribution than that of the ERN, which occurred earlier and had a higher peak amplitude in the equivocal condition. Dipole modeling suggests that this feedback-related negativity is generated by medial prefrontal and posterior cingulate cortex areas. CONCLUSIONS: Different brain systems support the use of internal and external information necessary for performance monitoring and modification. SIGNIFICANCE: The flexible use of internal and external information for performance control is a core executive function. The delineation of the corresponding brain correlates will further our understanding of executive dysfunction in neurological disorders.

Effects of alprazolam on the acoustic startle response in humans.

In the present study, we assessed the effects of the potent benzodiazepine alprazolam on the human acoustic startle response in healthy volunteers. Eight undergraduate students received single oral doses of placebo and alprazolam 2 mg on 2 separate days, according to a double-blind balanced crossover design. Electromyographic activity of the orbicularis oculi muscle was recorded 5, 7 and 11 h after drug administration. At each recording time, subjects received 21 acoustic stimuli (1 KHz, 116 dB, 50 ms duration) separated by variable intervals (8-30 s, mean 16.5 s). Consistent with previous results obtained for diazepam in humans, alprazolam significantly reduced the amplitude of the startle reflex. A patent increase in onset latency was also observed, this being a novel effect not previously described for benzodiazepines in human studies. Both effects were maximum at 5 h after dosing, the startle response experiencing a recovery as the drug disappeared from systemic circulation. These results indicate a potent inhibitory effect of alprazolam on baseline startle at the dose used, with a robust time-dependent recovery of initial values effectively counteracting between-session habituation.

Differential effects of alprazolam on the baseline and fear-potentiated startle reflex in humans: a dose-response study.

RATIONALE: The "fear-potentiated startle" paradigm has been extensively used in animal studies, and more recently in human experimental psychopharmacology to evaluate the effects of anxiogenic and anxiety-relieving drugs. Previous human studies have shown that both the baseline and the fear-potentiated responses can be inhibited by anxiety-relieving drugs, suggesting drug activity on two different emotional states, the former reflecting a resting condition and the latter more akin to pathological anxiety. OBJECTIVES: To examine to which extent the reductions induced by a benzodiazepine on the basic and the fear-potentiated startle responses are of equal intensity, and whether or not the drug shows a predominant, i.e., selective, effect on either. METHODS: The effects of three increasing doses of the benzodiazepine alprazolam (0.25, 0.5, and 1.0 mg) were assessed on the human baseline and fear-potentiated startle responses. Twelve healthy volunteers attended the laboratory on four experimental days and received either alprazolam or placebo according to a double-blind crossover balanced design. Startle recordings were undertaken 2 h after drug intake. Fear potentiation was implemented by means of an electric-shock-anticipation experimental procedure. Additionally, subjective self-reports of sedation and anxiety and psychomotor performance were obtained at 2 and 3 h, respectively, after drug administration. RESULTS: Alprazolam dose-dependently impaired psychomotor performance and produced increases in subjective anxiolytic activity and sedation, although the latter did not reach statistical significance. Additionally, the drug reduced the magnitude of the startle response both in the absence and in the presence of a threat-related cue, although a differentially greater inhibitory effect was seen on the fear-potentiated response as the dose increased. CONCLUSIONS: Alprazolam showed a greater inhibitory effect on the fear-potentiated startle than on the baseline reflex, suggesting a more selective action of the drug on those structures mediating potentiation of the behavioral response by anxiety.

Subjective effects and tolerability of the South American psychoactive beverage Ayahuasca in healthy volunteers.

RATIONALE: Ayahuasca is a South American psychoactive beverage that contains the naturally occurring psychedelic agent N,N-dimethyltryptamine (DMT). This "tea" has been used for centuries in religious and medicinal contexts in the rain forest areas of South America and is presently gaining the attention of psychedelic users in North America and Europe. OBJECTIVES: In the present study, the psychological effects and tolerability of ayvahuasca were assessed. METHODS: Three increasing doses of encapsulated freeze-dried ayahuasca (0.5, 0.75, and 1.0 mg DMT/kg body weight) were administered to six healthy male volunteers with prior experience in the use of this tea, in a single-blind crossover placebo-controlled clinical trial. RESULTS: Ayahuasca produced significant dose-dependent increases in five of the six subscales of the Hallucinogen Rating Scale, in the LSD, MBG, and A scales of the Addiction Research Center Inventory, and in the "liking", "good effects" and "high" visual analogue scales. Psychological effects were first noted after 30-60 min, peaked between 60-120 min, and were resolved by 240 min. The tea was well tolerated from a cardiovascular point of view, with a trend toward increase for systolic blood pressure. Modified physical sensations and nausea were the most frequently reported somatic-dysphoric effects. The overall experience was regarded as pleasant and satisfactory by five of the six volunteers, while one volunteer experienced an intensely dysphoric reaction with transient disorientation and anxiety at the medium dose and voluntarily withdrew from the study. CONCLUSIONS: Ayahuasca can be described as inducing changes in the perceptual, affective, cognitive, and somatic spheres, with a combination of stimulatory and visual psychoactive effects of longer duration and milder intensity than those previously reported for intravenously administered DMT.

Event-related brain responses to morphological violations in Catalan.

The ERP (event-related potential) violation paradigm was used to investigate brain responses to morphologically correct and incorrect verb forms of Catalan. Violations of stem formation and inflectional processes were examined in separate experimental conditions. Our most interesting finding is that misapplications of stem formation rules elicit an early left preponderant negativity. This complements our previous ERP results on morphological violations in other languages in which misapplications of inflectional rules were shown to produce such effects. We make use of the linguistic distinction between lexically stored and rule-based word forms and suggest a unified interpretation of the experimental results, arguing that these negativities vary as a function of processes involved in morpho-syntactic structure building.

Electrophysiological estimates of semantic and syntactic information access during tacit picture naming and listening to words.

We investigated the relative time courses of the accessibility of semantic and syntactic information in speaking and comprehension via event-related brain potentials (ERPs). Native German speakers either viewed a series of pictures (tacit picture naming experiment) or heard a series of nouns (listening experiment) and made dual choice go/nogo decisions based on each item's semantic and syntactic features. N200 peak latency results indicate that access to meaning has temporal precedence over access to syntactic information in both speaking (approximately 80 ms) and comprehension (approximately 70 ms), and are discussed in the context of current psycholinguistic theories.

Abnormalities of the acoustic startle reflex and reaction time in gilles de la tourette syndrome.

OBJECTIVE: To study the startle reflex and the effect of the startle reflex stimulus over reaction time (start-react effect) in Gilles de la Tourette syndrome (GTS). METHOD: Ten GTS patients and ten matched healthy volunteers underwent a simple RT paradigm (4 blocks of 50 trials). Forty acoustic startle reflex stimuli (110 dB) were randomly delivered with a 20% occurrence probability and presented unexpectedly at the same time as the imperative stimuli of the RT. Variables of interest were: amplitude, onset latency, degree of spread and rate of habituation of the startle response, and RT and the start-react effect caused by the startle stimuli. RESULTS: GTS patients showed a significantly higher amplitude, a major degree of spread and fewer habituation phenomena of the startle reflex. GTS patients showed poorer non statistically significant RT performance compared to controls, with a significant correlation between RT and severity of the disease. The start-react effect was significantly less pronounced in GTS patients. CONCLUSIONS: The present study confirms that GTS has an exaggerated startle reflex response and extend the spectrum of abnormalities to the start-react effect. A state of dopaminergic hyperactivity may have contributed to these results.

Psychometric assessment of the Hallucinogen Rating Scale.

Reliability and convergent-discriminant validity of a Spanish version of the Hallucinogen Rating Scale (HRS) were assessed in two differentiated populations of hallucinogen users involving the retrospective assessment of drug effects. In Study 1 (immediate assessment), 75 European users of the South American hallucinogenic drink ayahuasca answered the HRS 4 h after drug intake in their habitual setting. In Study 2 (delayed assessment), 56 adult polydrug users answered the HRS and a short form of the Addiction Research Center Inventory (ARCI) recalling the effects they experienced when they last took a hallucinogen, in order to test the convergent-discriminant validity of HRS with the scales of the standard questionnaire used in most studies involving psychoactive drugs. The HRS scales showed increases after both the immediate and delayed retrospective assessment of drug effects. Reliability data indicated that four of the six scales show an acceptable level of internal consistency. Significant but limited correlations were found between the Perception and Somaesthesia scales and the ARCI LSD scale, pointing out the questionnaire's construct validity. Thus, the HRS was sensitive to hallucinogenic drug effects other than those elicited by intravenous N,N-dimethyltryptamine (DMT), for which it was originally designed, and showed reasonable reliability and convergent validity. Results suggest its usefulness in the evaluation of subjective effects elicited by psychoactive drugs with hallucinogenic properties, and constitute a preliminary approach to the effects of ayahuasca in European subjects.

Motor circuitry re-organization after pallidotomy in Parkinson disease: a neurophysiological study of the bereitschaftspotential, contingent negative variation, and N30.

The aim of the study was to evaluate the reorganization changes in the motor circuitry of the basal ganglia following unilateral posteroventral pallidotomy in Parkinson disease (PD) patients using neurophysiological paradigms. Eight advanced PD patients received a neurophysiological battery 2 months prior and 6 months after unilateral pallidotomy. Examinations were all performed in the practically defined "off" situation. Bereitschaftspotential (BP) and N30 were recorded for each hand alternately. Contingent negative variation (CNV) was obtained using a visual Go/no-Go paradigm. ANOVAs (electrode position; surgery) were applied for BP and CNV results. N30 data were analyzed using Wilcoxon matched-pair tests. A significant increase in amplitude of the late component (NS') of the BP was evidenced with patient performing with the hand contralateral to pallidotomy. No significant amplitude differences were found in CNV after surgery in any lead, or in any of the time windows tested. A trend toward significance was observed corresponding to a postsurgical numerical increase in amplitude of the N30 peak in the hand contralateral to pallidotomy. These results suggest that neurophysiological changes after pallidotomy are mainly in the last stages of movement preparation and execution.

[Our experience in neuroma surgery]. / Nuestra experiencia en cirugía del neurinoma.

Our 24-year experience with acoustic neuroma surgery is reported. Three approaches were used in 34 patients: translabyrinthine (11 cases), transtemporal (2 cases), and retrosigmoid (21 cases). Prolonged facial paralysis occurred in 27% of patients with the translabyrinthine approach and in 15% with the retrosigmoid approach. Facial nerve monitoring was used in all operations with the retrosigmoid approach. In the translabyrinthine approach, 5 patients had CSF leak, 2 required secondary surgery, and 2 developed meningitis. With the retrosigmoid approach, 5 patients had CSF leak, 2 required secondary surgery, 3 developed meningitis (1 died), and 1 patient required emergency reoperation for posterior cranial fossa hematoma. Auditory function was preserved in one patient. The advantages of the retrosigmoid approach have become apparent: good exposure, speed, and preservation of the facial and cochlear nerves.

Tracking post-error adaptation in the motor system by transcranial magnetic stimulation.

The commission of an error triggers cognitive control processes dedicated to error correction and prevention. Post-error adjustments leading to response slowing following an error ("post-error slowing"; PES) might be driven by changes in excitability of the motor regions and the corticospinal tract (CST). The time-course of such excitability modulations of the CST leading to PES is largely unknown. To track these presumed excitability changes after an error, single pulse transcranial magnetic stimulation (TMS) was applied to the motor cortex ipsilateral to the responding hand, while participants were performing an Eriksen flanker task. A robotic arm with a movement compensation system was used to maintain the TMS coil in the correct position during the experiment. Magnetic pulses were delivered over the primary motor cortex ipsilateral to the active hand at different intervals (150, 300, 450 ms) after correct and erroneous responses, and the motor-evoked potentials (MEP) of the first dorsal interosseous muscle (FDI) contralateral to the stimulated hemisphere were recorded. MEP amplitude was increased 450 ms after the error. Two additional experiments showed that this increase was neither associated to the correction of the erroneous responses nor to the characteristics of the motor command. To the extent to which the excitability of the motor cortex ipsi- and contralateral to the response hand are inversely related, these results suggest a decrease in the excitability of the active motor cortex after an erroneous response. This modulation of the activity of the CST serves to prevent further premature and erroneous responses. At a more general level, the study shows the power of the TMS technique for the exploration of the temporal evolution of post-error adjustments within the motor system.