Paola Bucci

The cortical generators of P3a and P3b: a LORETA study.

The P3 is probably the most well known component of the brain event-related potentials (ERPs). Using a three-tone oddball paradigm two different components can be identified: the P3b elicited by rare target stimuli and the P3a elicited by the presentation of rare non-target stimuli. Although the two components may partially overlap in time and space, they have a different scalp topography suggesting different neural generators. The present study is aimed at defining the scalp topography of the two P3 components by means of reference-independent methods and identifying their electrical cortical generators by using the low-resolution electromagnetic tomography (LORETA). ERPs were recorded during a three-tone oddball task in 32 healthy, right-handed university students. The scalp topography of the P3 components was assessed by means of the brain electrical microstates technique and their cortical sources were evaluated by LORETA. P3a and P3b showed different scalp topography and cortical sources. The P3a electrical field had a more anterior distribution as compared to the P3b and its generators were localized in cingulate, frontal and right parietal areas. P3b sources included bilateral frontal, parietal, limbic, cingulate and temporo-occipital regions. Differences in scalp topography and cortical sources suggest that the two components reflect different neural processes. Our findings on cortical generators are in line with the hypothesis that P3a reflects the automatic allocation of attention, while P3b is related to the effortful processing of task-relevant events.

Reliability and validity of the DSM-IV diagnostic category of schizoaffective disorder: Preliminary data

BACKGROUND Concerns have been expressed about the reliability and validity of the DSM-IV criteria for schizoaffective disorder, but no systematic study has been published up to now. METHODS The Cohens kappa for the individual items of the DSM-IV definition of schizoaffective disorder, manic episode and major depressive episode was evaluated in 150 patients independently interviewed by two psychiatrists using the Composite International Diagnostic Interview. The two-year outcome of patients with a consensus DSM-IV diagnosis of schizoaffective disorder was compared to that of patients with DSM-IV schizophrenia and schizophreniform disorder, using the Strauss-Carpenter Outcome Scale. RESULTS The Cohens kappa was 0.22 for the diagnosis of schizoaffective disorder, 0.71 for that of manic episode, and 0.82 for that of major depressive episode. Schizoaffective patients had a significantly better outcome than those with schizophrenia but a worse outcome than those with schizophreniform disorder. CONCLUSIONS The inter-rater reliability of the DSM-IV criteria for schizoaffective disorder is not satisfactory. The better outcome of DSM-IV schizoaffective disorder compared with schizophrenia seems to depend more on the inclusion, in the definition of schizophrenia but not in that of schizoaffective disorder, of the six-month duration and functional impairment criteria than on the different symptomatological patterns of the two conditions. LIMITATION The size of the sample of patients fulfilling DSM-IV criteria for schizoaffective disorder was small. CLINICAL RELEVANCE The study suggests that the clinical implications of the currently problematic diagnosis of schizoaffective disorder may be modest.

The influence of illness-related variables, personal resources and context-related factors on real-life functioning of people with schizophrenia.

In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real‐life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real‐life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness‐related variables, personal resources and context‐related factors. Some of these variables were never investigated before in relationship with real‐life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real‐life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real‐life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real‐life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real‐life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia.

Persistent negative symptoms in first episode patients with schizophrenia: Results from the European First Episode Schizophrenia Trial

Negative symptoms that do not improve following antipsychotic treatment represent a challenge for development of effective treatments. Few studies have been carried out so far, especially in first-episode schizophrenia patients, to clarify prevalence, correlates and impact of persistent negative symptoms (PNS) on short- and long-term outcome of the disease. All patients from EUFEST study for whom both baseline and 12-month assessments were available were included (N=345). PNS were defined as the presence of at least one negative symptom of moderate or higher severity, not confounded by depression or parkinsonism, at baseline and after 1 year of treatment. Patients with PNS were compared to those with at least one negative symptom of moderate or higher severity at the baseline, not persisting after 1 year, on demographic, clinical, neurocognitive, global functioning and quality of life measures. PNS not confounded by depression or parkinsonism were present in 6.7% of the sample. The symptom that more often persisted was blunted affect. Patients with PNS differed from those without PNS for a longer duration of untreated psychosis (DUP) and a more frequent discontinuation of study treatment; they also had a poorer psychopathological outcome and a worse global functioning after 1 year of treatment. The presence of PNS was associated to poorer improvement of all psychopathological dimensions and worse global functioning after 1 year of treatment. The longer DUP in subjects with PNS suggests that programs aimed at shortening DUP might reduce the prevalence of PNS and improve prognosis of schizophrenia.

Is avolition in schizophrenia associated with a deficit of dorsal caudate activity? A functional magnetic resonance imaging study during reward anticipation and feedback

Background The neurobiological underpinnings of avolition in schizophrenia remain unclear. Most brain imaging research has focused on reward prediction deficit and on ventral striatum dysfunction, but findings are not consistent. In the light of accumulating evidence that both ventral striatum and dorsal caudate play a key role in motivation, we investigated ventral striatum and dorsal caudate activation during processing of reward or loss in patients with schizophrenia. Method We used functional magnetic resonance imaging to study brain activation during a Monetary Incentive Delay task in patients with schizophrenia, treated with second-generation antipsychotics only, and in healthy controls (HC). We also assessed the relationships of ventral striatum and dorsal caudate activation with measures of hedonic experience and motivation. Results The whole patient group had lower motivation but comparable hedonic experience and striatal activation than HC. Patients with high avolition scores showed lower dorsal caudate activation than both HC and patients with low avolition scores. A lower dorsal caudate activation was also observed in patients with deficit schizophrenia compared to HC and patients with non-deficit schizophrenia. Dorsal caudate activity during reward anticipation was significantly associated with avolition, but not with anhedonia in the patient group. Conclusions These findings suggest that avolition in schizophrenia is linked to dorsal caudate hypoactivation.

Double dissociation of N1 and P3 abnormalities in deficit and nondeficit schizophrenia

It has been proposed that the presence of enduring, idiopathic negative symptoms define a group of patients with a disease (deficit schizophrenia, DS) that is separate from other forms of schizophrenia (nondeficit schizophrenia, NDS). Although several findings support this hypothesis, the possibility that DS represents the severe end of a single schizophrenia continuum cannot be excluded yet. We tested the hypothesis that DS and NDS differ relative to event-related potentials (ERPs). Amplitude, scalp topography and cortical sources of the ERP components were assessed in clinically stable DS and NDS outpatients and in matched healthy subjects (HCS). Twenty subjects per group were recruited. Among the subjects who completed the target detection task, there were no group difference in accuracy. For N1, only patients with DS, as compared with HCS, showed an amplitude reduction over the scalp central leads and a reduced current source density in cingulate and parahippocampal gyrus. For P3, only patients with NDS, as compared with HCS, showed a lateralized amplitude reduction over the left posterior regions and reduced current source density in left temporal and bilateral frontal, cingulate and parietal areas. The DS and NDS groups differed significantly from each other with regard to N1 amplitude and topography, as well as P3 amplitude and cortical sources. The N1 was affected in DS but not in NDS patients, whereas P3 was affected in NDS only. This double dissociation is consistent with the hypothesis that DS represents a separate disease entity within schizophrenia.

Pharmaco-EEG in Psychiatry

In spite of its origins deeply rooted in the discipline, pharmaco-EEG applications in psychiatry remain limited to its achievements in the field of psychotropic drugs classification and, in few instances, discovery. In the present paper two attempts to transfer pharmaco-EEG methods to psychiatric clinical routine will be described: 1) monitoring of psychotropic drug toxicity at the central nervous system level, and 2) prediction of clinical response to treatment with psychotropic drugs. Both applications have been the object of several investigations providing promising and sometimes consistent findings which, however, had no impact on clinical practice. For the first topic, the review is limited to antipsychotics, lithium and recreational drugs, as for other psychotropic drugs mostly case studies are available, while for the response prediction it will include antipsychotics, antidepressants, anxiolytics, psychostimulants and nootropics. In spite of several methodological limitations, pharmaco-EEG studies dealing with monitoring of antipsychotic- and lithium-induced EEG abnormalities went close to, but never became, a clinical routine. EEG studies of recreational drugs are flawed by several limitations, and failed, so far, to identify reliable indices of CNS toxicity to be used in clinical settings. Several QEEG studies on early predictors of treatment response to first generation antipsychotics have produced consistent findings, but had no clinical impact. For other psychotropic drug classes few and inconsistent reports have appeared. Pharmaco-EEG had the potential for important clinical applications, but so far none of them entered clinical routine. The ability to upgrade theories and methods and promote large scale studies represent the future challenge.

Computerized EEG topography findings in schizophrenic patients before and after haloperidol treatment

An increase of delta and fast beta activity in schizophrenic patients when compared with normal controls has been consistently reported. Topography of these abnormalities, in particular a possible frontal localization of delta, and their relationship to drug treatment and clinical status are still debated. In order to assess these issues, a multilead CEEG investigation was carried out in a group of 20 DSM-III-R schizophrenics, both before and after haloperidol treatment. All findings are described in terms of amplitude and relative power. Drug-free schizophrenics, when compared with a group of normal controls, showed a generalized increase of delta and fast beta, and a decrease of alpha 2 relative power. After acute treatment, patients showed a significant decrease of delta, and an increase of theta 2, beta 1, and beta 2. After 28 days of haloperidol treatment, similar changes were observed for delta, together with an increase of alpha 1, and a decrease of fast beta.

Executive hypercontrol in obsessive-compulsive disorder: electrophysiological and neuropsychological indices

OBJECTIVE Neuropsychological, brain imaging and electrophysiological research have consistently shown a dysfunction of fronto-striato-thalamic pathways in subjects with obsessive-compulsive disorder (OCD). The functional meaning of the observed dysfunction in the pathogenesis of OCD is still debated. In the present study the hypothesis that it might be related to a hyperactive executive control is explored by means of neuropsychological and electrophysiological measures. METHODS Multilead quantitative EEG (QEEG) characteristics and neuropsychological performance on tests exploring executive functions, attention, short-term memory and the ability to learn supraspan recurring sequences were investigated in 32 drug-free patients with DSM-IV OCD. Multilead QEEG characteristics were also investigated in 32 healthy controls, matched with patients for age, gender and handedness. RESULTS A decrease of the slow alpha-band power in OCD as compared to healthy subjects was observed. A significant negative correlation between the slow alpha-band power and the time to complete a neuropsychological test exploring executive functions was found: the more reduced the slow alpha-band power, the slower the performance on this test. CONCLUSIONS The topographic distribution of the observed QEEG abnormalities, as well as their correlations with neuropsychological indices, suggest an increased activation of frontal networks in OC patients. SIGNIFICANCE Study findings support the presence of a hyperactivity of attention/executive control mechanisms in obsessive-compulsive patients.

QEEG alpha1 changes after a single dose of high-potency neuroleptics as a predictor of short-term response to treatment in schizophrenic patients

Baseline quantitative electroencephalographic (QEEG) characteristics and their changes after a single test dose of either haloperidol or clopenthixol were investigated in a group of 29 schizophrenics as possible predictors of short-term response to those drugs. On baseline QEEG assessment, responders (R) to subsequent treatment showed fewer slow and more fast activities than nonresponders (NR). A large overlap between R and NR with respect to these measures was observed, however, revealing their practical inadequacy to predict short-term response in individual patients. On the contrary, changes in alpha 1, observed 6 hr after the administration of a single test dose of either haloperidol or clopenthixol, discriminated to a very large extent between R and NR, correctly identifying 17 out of 18 R and 8 out of 10 NR. The QEEG test dose procedure might be used in the selection of the most appropriate antipsychotic drug for individual schizophrenic patients.