Inside a synesthete's head: a functional connectivity analysis with grapheme-color synesthetes.

Grapheme-color synesthesia is a condition in which letters are perceived with an additional color dimension. To identify brain regions involved in this type of synesthesia and to analyze functional connectivity of these areas, 18 grapheme-color synesthetes and 18 matched controls were stimulated with letters and pseudo-letters presented in black and color in an event-related fMRI experiment. Based on the activation-differences between synesthetes and non-synesthetic controls regions of interest were defined. In a second analysis step functional connectivity was calculated using beta series correlation analysis for these seed regions. First we identified one seed region in the left inferior parietal (IPL) cortex (BA7) showing activation differences between grapheme-color synesthetes and controls. Furthermore, we found activation differences in brain areas involved in processing of letters and pseudo-letters, in particular the right IPL cortex (BA7), but also two more clusters in the right hemispheric BA 18 and BA 40. Functional connectivity analysis revealed an increased connectivity between the left IPL seed region and primary/secondary visual areas (BA 18) in synesthetes. Also the right BA 7 showed a stronger connectivity with primary/secondary visual areas (BA 18) in grapheme-color synesthetes. The results of this study support the idea that the parietal lobe plays an important role in synesthetic experience. The data suggest furthermore that the information flow in grapheme-color synesthetes was already modulated at the level of the primary visual cortex which is different than previously thought. Therefore, the current models of grapheme-color synesthesia have to be refined as the unusual communication flow in synesthetes is not restricted to V4, fusiform cortex and the parietal lobe but rather involves a more extended network.

Disinhibited feedback as a cause of synesthesia: evidence from a functional connectivity study on auditory-visual synesthetes.

In synesthesia, certain stimuli to one sensory modality lead to sensory perception in another unstimulated modality. In addition to other models, a two-stage model is discussed to explain this phenomenon, which combines two previously formulated hypotheses regarding synesthesia: direct cross-activation and hyperbinding. The direct cross-activation model postulates that direct connections between sensory-specific areas are responsible for co-activation and synesthetic perception. The hyperbinding hypothesis suggests that the inducing stimulus and the synesthetic sensation are coupled by a sensory nexus area, which may be located in the parietal cortex. This latter hypothesis is compatible with the disinhibited feedback model, which suggests unusual feedback from multimodal convergence areas as the cause of synesthesia. In this study, the relevance of these models was tested in a group (n=14) of auditory-visual synesthetes by performing a functional connectivity analysis on functional magnetic resonance imaging (fMRI) data. Different simple and complex sounds were used as stimuli, and functionally defined seed areas in the bilateral auditory cortex (AC) and the left inferior parietal cortex (IPC) were used for the connectivity calculations. We found no differences in the connectivity of the AC and the visual areas between synesthetes and controls. The main finding of the study was stronger connectivity of the left IPC with the left primary auditory and right primary visual cortex in the group of auditory-visual synesthetes. The results support the model of disinhibited feedback as a cause of synesthetic perception but do not suggest direct cross-activation.

Naturalistic pharmacotherapy of acute episodes of schizophrenic disorders in comparison to treatment guidelines.

INTRODUCTION: This study was designed to investigate to what extent guidelines regarding the pharmacological treatment of patients suffering from schizophrenia-like psychosis are adopted in a naturalistic treatment setting. METHODS: Medical records of n=819 patients undergoing inpatient treatment for schizophrenia-like psychosis in 11 psychiatric hospitals in northwestern Germany were retrospectively analyzed and findings were compared to current schizophrenia guideline recommendations. RESULTS: The prescription rate of second generation antipsychotics increased from 47.1% on admission to 62.5% at discharge. Only half the patients (52.3%) received antipsychotic monotherapy while 47.7% took between 2 and 4 antipsychotic substances at a time. Dosage increases occurred most frequently (in 60%) within the first week of inpatient treatment, 16.6% experienced an elevation between days 15 and 29. A change within the atypical medication was found in 19.3%. Clozapine prescriptions increased throughout the treatment but were combined with other antipsychotic substances in the majority of cases. CONCLUSION: Under naturalistic conditions guideline recommendations for treatment of schizophrenia-like psychosis are adhered to only partially. Combination therapy with 2 or more antipsychotic drugs is quite common despite a clear recommendation for monotherapy.

The neural correlates of coloured music: a functional MRI investigation of auditory-visual synaesthesia.

In auditory-visual synaesthesia, all kinds of sound can induce additional visual experiences. To identify the brain regions mainly involved in this form of synaesthesia, functional magnetic resonance imaging (fMRI) has been used during non-linguistic sound perception (chords and pure tones) in synaesthetes and non-synaesthetes. Synaesthetes showed increased activation in the left inferior parietal cortex (IPC), an area involved in multimodal integration, feature binding and attention guidance. No significant group-differences could be detected in area V4, which is known to be related to colour vision and form processing. The results support the idea of the parietal cortex acting as sensory nexus area in auditory-visual synaesthesia, and as a common neural correlate for different types of synaesthesia.

Effects of quetiapine on cognitive functions in schizophrenic patients: a preliminary single-trial ERP analysis.

AIM: The study aimed to explore by means of single-trial event-related potentials (ERPs), whether and how the medication change from older neuroleptics to quetiapine in schizophrenic patients led to a significant cognitive enhancement. This single-trial ERP analysis helps to investigate attention and memory processes in the single patient before and after treatment. PATIENTS AND METHODS: Thirteen schizophrenic patients (mean age: 40.1+/-13.5 years) were followed up for 16 weeks and assessed for changes of clinical symptoms and ERP components P300 representing target detection processes and N400 indexing context integration in word recognition processes. Three subjects had to be excluded from the ERP recording sessions because of excessive blink artefacts and movements. RESULTS: Regarding the P300 components of the target detection, there were significant increases of amplitudes in 5 of 10 patients (50%) at week 16 comparing with week 0. Regarding the N400 components of the word recognition, there were significant increases of amplitudes in 4 of 10 patients (40%) at week 16 comparing with week 0. DISCUSSION: The mean scores of PANSS, MADRS, Bf-S, SCL-90 and CGI-S at the end of study (week 16) showed significant improvements compared to the baselines (week 0) (p<0.05). During the study, no extrapyramidal symptoms as well as akathisia were reported after quetiapine treatment. These preliminary data suggest that quetiapine might partially improve the cognitive functions in the context integration and target detection processing in these patients. This technical procedure (single-trial ERP) may help to differentially assess cognitive enhancements in each single patient under treatment.

[Empirical evidence for the use of anticonvulsants in personality disorders]. / Evidenz für den Einsatz von Antikonvulsiva bei Persönlichkeitsstörungen.

OBJECTIVE: There is a common practice of polypharmacy and an increased use of mood stabilizers in personality disorders (PD). This paper reviews all randomized controlled trials (RCTs) of anticonvulsants to evaluate the evidence base supporting their use in treatment of PD. METHODS: German and English language literature cited in Medline and published between 1970 and 2008 was searched using the following terms: Borderline/personality disorder, anticonvulsant, mood stabilizer, carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenytoine, pregabalin, tiagabine, topiramate, and valproate. RESULTS: Twelve RCTs were identified which included anticonvulsants in treatment of personality disorders. The anticonvulsants valproate and topiramate appeared to have the most empirical support for having a favorable effect on symptoms of borderline personality disorder. Evidence for the use of other anticonvulsants in patients with PD is sparse. CONCLUSIONS: Valproate and topiramate, probably also lamotrigine, carbamazepine, and oxcarbazepine as well, were useful in treating symptoms of affective dysregulation and impulsive aggression in PD. However, further RCTs of anticonvulsants are greatly needed as clinical use of these agents has risen without sufficient evidence supporting their efficacy and safety in personality disorders.

Audiovisual integration of speech is disturbed in schizophrenia: an fMRI study.

Speech perception is an essential part of social interaction. Visual information (lip movements, facial expression) may supplement auditory information in particular under inadvertent listening situations. Schizophrenia patients have been shown to have a deficit in integrating articulatory motions with the auditory speech input. The goal of this study was to investigate the neural basis of this deficit in audiovisual speech processing in schizophrenia patients by using fMRI. Disyllabic nouns were presented in congruent (audio matches visual information) and incongruent conditions in a slow event related fMRI design. Schizophrenia patients (n=15) were compared to age and gender matched control participants. The statistical examination was conducted by analysis of variance with main factors: audiovisual congruency and group membership. The patients' brain activity differed from the control group as evidenced by congruency by group interaction effects. The pertinent brain sites were located predominantly in the right hemisphere and comprised the pars opercularis, middle frontal sulcus, and superior temporal gyrus. In addition, we observed interactions bilaterally in the fusiform gyrus and the nucleus accumbens. We suggest that schizophrenia patients' deficits in audiovisual integration during speech perception are due to a dysfunction of the speech motor system in the right hemisphere. Furthermore the results can be also seen as a reflection of reduced lateralization of language functions to the left hemisphere in schizophrenia.

The myelin-pathogenesis puzzle in schizophrenia: a literature review.

Schizophrenia is a serious and disabling mental disorder with symptoms such as auditory hallucinations, disordered thinking and delusions, avolition, anhedonia, blunted affect and apathy. In this review article we seek to present the current scientific findings from linkage studies and susceptible genes and the pathophysiology of white matter in schizophrenia. The article has been reviewed in two parts. The first part deals with the linkage studies and susceptible genes in schizophrenia in order to have a clear-cut picture of the involvement of chromosomes and their genes in schizophrenia. The genetic linkage results seem to be replicated in some cases but in others are not. From these results, we cannot draw a fine map to a single locus or gene, leading to the conclusion that schizophrenia is not caused by a single factor/gene. In the second part of the article we present the oligodendrocyte-related genes that are associated with schizophrenia, as we hypothesize a potential role of oligodendrocyte-related genes in the pathology of the disorder.

Perazine and carbamazepine in comparison to olanzapine in schizophrenia.

Atypical antipsychotics like olanzapine are more efficacious in treating negative symptoms and have less side effects. Nevertheless, important adverse effects of olanzapine are, for example, weight gain and hyperglycemia. Perazine in combination with carbamazepine has shown satisfying results in several single-schizophrenia patients, leading to the hypothesis of being equal or even superior to atypical antipsychotic monotherapy. The aim of the present study was to survey the hypothesis that perazine in combination with carbamazepine have an outcome and risk of side effects comparable to olanzapine. Eleven patients with DSM-IV schizophrenia received 14.0 +/- 5.0 mg/day olanzapine and 12 patients received 360.0 +/- 196.0 mg/day perazine in combination with 404.0 +/- 229.0 mg/day carbamazepine. Symptoms and neuropsychological state were assessed 3 times (days 0, 7, 21) using the Positive and Negative Syndrome Scale and the Brief Psychiatric Rating Scale. The neuropsychological state was assessed by the following neuropsychological tests: Benton, d2, ZVT, VLMT and MWT-B. Data were analyzed of variance for multiple dependent variables and repeated-measures multivariate analysis of variance. Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores showed superior improvement in the group receiving olanzapine. Olanzapine offers a more favorable response in positive symptoms than does perazine in combination with carbamazepine. The effect on negative symptoms is favorable in both forms of therapy and no significant differences between the groups could be determined. In both groups, treatment was associated with improved performance in cognitive tests; however, no differences were determined in the effects of the drugs. Results suggest that olanzapine offers a better response in positive symptoms than perazine in combination with carbamazepine.

Systems-theory of psychosis--the relevance of "internal censorship".

The different aspects of the neurobiology of psychotic disorders are presently discussed under the perspective of Arvid Calssons neurochemical theory of mesolimbic/cortico-thalamic loops. In this regard the question as to whether--neuropsychologically--a "filter-defect" or a disturbance of "internal censorship" is causative for psychoses. This topic is discussed in the present paper.

Oxcarbazepine versus carbamazepine in the treatment of alcohol withdrawal.

In a single-blinded and randomized pilot study efficacy and tolerability of oxcarbazepine versus carbamazepine were investigated in 29 patients during therapy of alcohol withdrawal. No initial differences were found regarding sociodemographic data and alcohol-related parameters, indicating successful randomization. The oxcarbazepine group showed a significant decrease of withdrawal symptoms and reported significantly less 'craving for alcohol' compared to the carbamazepine group. Subjectively experienced side effects, normalization of vegetative parameters and improvement in the cognitive processing speed did not reveal differences for both groups. Therefore, oxcarbazepine might be an interesting alternative to carbamazepine, and having almost no addictive potential, no clinically relevant interaction with alcohol and no prominent sedatory effect, possibly also to other drugs such as benzodiazepines or clomethiazole, in the treatment of alcohol withdrawal syndrome.

[Accidental intraartrial injection of diacethylmorphine (heroin) in drug addicts -- three case reports]. / Akzidentelle intraarterielle Injektion von Diacetylmorphin (Heroin) bei Drogenabhängigen -- 3 Fallberichte.

Accidental intrarterial injections are not uncommon in medical treatments. This is also true for uncontrolled injections by drug-addicts. Since 2002 a number of 600 heavy opiate addicts in Germany are substituted in a country-wide study with pure diacetylmorphine (Heroine). We report the course and outcome of three cases of accidental intraarterial injections of pure diacetylmorphine under controlled conditions. After initial symptoms of vasospasms, all cases were without symptoms within one hour and no obvious loss of tissue was observed. After discussing the literature about medical literature and treatment options in intraarterial injections it is concluded, that the cause of major complications after intraarterial injections may not be the pure diacetylmorphine but additional substances in impure "street-heroin" samples.

Treatment of alcohol withdrawal: chlormethiazole vs. carbamazepine and the effect on memory performance--a pilot study.

Although relatively little attention has been paid to the question how acute alcohol withdrawal might affect cognitive functions, this factor remains of particular interest because it influences psychotherapeutic treatment during detoxification. The clinical outcome and neuropsychological state of 37 inpatients with alcohol withdrawal was investigated in a randomized single-blind approach. Two different medical strategies [chlormethiazole (CMZ) vs. carbamazepine (CBZ)] in the treatment of inpatients with alcohol withdrawal syndrome were compared. Among comparable groups (related to gender, age, initial alcohol level, severity of abuses, severity of initial withdrawal symptoms such as tremor, perspiration, psychomotor agitation, hallucinations, orientation, intelligence, patient demographics), CBZ is just as potent as CMZ in therapy of withdrawal symptoms (circulatory function, vegetative function, psychomotor activity). Patients in both groups showed initial impairments in some neuropsychological tests (d2, Zahlen-Verbundings test, Beck Depression Inventory, Anxiety Sensitivity Index) with significant improvement during detoxification. Additionally, CBZ-treated patients showed significantly better verbal memory performance during the first days of treatment. Without any addictive potential, CBZ therapy could be very supportive in alcohol detoxification. In addition a higher verbal memory performance state could be favourable for a psychotherapeutic approach.

Lamotrigine in the treatment of confusion psychosis. A case report.

We report on the successful treatment of four patients suffering from confusion psychosis according to the classification of Leonhard. The patients did not sufficiently respond to neuroleptic treatment or mood stabilizers like carbamazepine and valproate, but improved when lamotrigine was added, showing a marked reduction in clinical signs and symptoms. The implications of these findings including the possible mechanisms involved are discussed.

Psychotic disorders and gonadal function: evidence supporting the oestrogen hypothesis.

OBJECTIVE: The aim of this study was to further evaluate the oestrogen hypothesis of schizophrenia, which postulates low oestradiol levels to be a risk factor for these disorders. A possible influence of neuroleptic-induced hyperprolactinaemia was to be addressed. METHOD: Sex hormones were measured and cycle phase assessed in 50 acutely psychotic women on admission and for four consecutive weeks as well as in three control groups. RESULTS: Psychotic women were more likely to be admitted during a low oestrogen phase of their cycle and exhibited markedly reduced oestradiol levels, compared with 23 healthy controls, as well as 50 women suffering from other psychiatric disorders. Oestradiol variability was reduced over the menstrual cycle in women suffering from psychotic disorders. CONCLUSION: These results support the oestrogen hypothesis. Hyperprolactinaemia due to neuroleptic treatment does not appear to account for the findings.

[Oxcarbazepine in the treatment of affective and schizoaffective disorders]. / Oxcarbazepin in der Behandlung affektiver und schizoaffektiver Erkrankungen.

The therapeutic value of anticonvulsants in affective and schizoaffective disorders was documented in several clinical trials. Oxcarbazepine (OXC), a keto-derivative of carbamazepine, which appears to have a preferable side effect profile compared to carbamazepine, has also shown antimanic efficacy in affective and schizoaffective disorders in clinical studies since the early 80's, but was not further investigated regarding these indications. Therefore, the value of OXC in the treatment of affective and schizoaffective disorders requires evaluation. Literature was reviewed with regard to pharmacokinetic and pharmacodynamic characteristics of OXC, drug-drug interactions relevant in pharmacopsychiatry, and clinical effects in these disorders. According to the literature OXC is regarded effective in acute mania and appears to allow reduction of the neuroleptic medication required for the treatment of affective and schizoaffective disorders. In addition, it has a preferable pharmacokinetic profile with less severe side effects compared to other anticonvulsants and neuroleptics. Furthermore, it appears to be well tolerated if augmented to neuroleptics or antidepressants, since OXC does not interact substantially with the cytochrome P450-enzyme-system. However, despite promising effects of OXC, few clinical studies have been published in the last 16 years. We conclude that further studies should validate the antimanic efficacy of OXC and evaluate possible pharmacopsychiatric indications as well as limitations of this psychotropic compound.

[Towards a neuropsychology of autonomy: re-presenting forgetting, subliminality and freedom]. / Skizzen zu einer Neuropsychologie der Autonomie: Vergegenwärtigendes Vergessen, Subliminalität und Freiheit.

Recent neurobiological concepts about sensomotor processes in animals exhibit that voluntary motor behavior is not due primarily to external cues but to internal activation-processes ("initial activity"). Thus questions are raised as to the role of internal "limbic" valuation-processes in relation to contexts of the past. These are not limited to the actual memorial contents but also relate to subliminal aspects of the past. The inclusion of processes of "re-presenting forgetting" means a re-evaluation of autonomy within a neuropsychological theory of freedom. Consequently, subjective freedom may be realized by intrapsychic processes of re-presentation of the past.