Else-Marie Løberg

Amphetamine-induced psychosis - a separate diagnostic entity or primary psychosis triggered in the vulnerable?

Use of amphetamine and methamphetamine is widespread in the general population and common among patients with psychiatric disorders. Amphetamines may induce symptoms of psychosis very similar to those of acute schizophrenia spectrum psychosis. This has been an argument for using amphetamine-induced psychosis as a model for primary psychotic disorders. To distinguish the two types of psychosis on the basis of acute symptoms is difficult. However, acute psychosis induced by amphetamines seems to have a faster recovery and appears to resolve more completely compared to schizophrenic psychosis. The increased vulnerability for acute amphetamine induced psychosis seen among those with schizophrenia, schizotypal personality and, to a certain degree other psychiatric disorders, is also shared by non-psychiatric individuals who previously have experienced amphetamine-induced psychosis. Schizophrenia spectrum disorder and amphetamine-induced psychosis are further linked together by the finding of several susceptibility genes common to both conditions. These genes probably lower the threshold for becoming psychotic and increase the risk for a poorer clinical course of the disease.The complex relationship between amphetamine use and psychosis has received much attention but is still not adequately explored. Our paper reviews the literature in this field and proposes a stress-vulnerability model for understanding the relationship between amphetamine use and psychosis.

Left temporal lobe structural and functional abnormality underlying auditory hallucinations in schizophrenia.

In this article, we have reviewed recent findings from our laboratory, originally presented in Hugdahl et al. (2008). These findings reveal that auditory hallucinations in schizophrenia should best be conceptualized as internally generated speech mis-representations lateralized to the left superior temporal gyrus and sulcus, not cognitively suppressed due to enhanced attention to the ‘voices’ and failure of fronto-parietal executive control functions. An overview of diagnostic questionnaires for scoring of symptoms is presented together with a review of behavioral, structural, and functional MRI data. Functional imaging data have either shown increased or decreased activation depending on whether patients have been presented an external stimulus during scanning. Structural imaging data have shown reduction of grey matter density and volume in the same areas in the temporal lobe. We have proposed a model for the understanding of auditory hallucinations that trace the origin of auditory hallucinations to neuronal abnormality in the speech areas in the left temporal lobe, which is not suppressed by volitional cognitive control processes, due to dysfunctional fronto-parietal executive cortical networks.

Cannabis use and cognition in schizophrenia

People with schizophrenia frequently report cannabis use, and cannabis may be a risk factor for schizophrenia, mediated through effects on brain function and biochemistry. Thus, it is conceivable that cannabis may also influence cognitive functioning in this patient group. We report data from our own laboratory on the use of cannabis by schizophrenia patients, and review the existing literature on the effects of cannabis on cognition in schizophrenia and related psychosis. Of the 23 studies that were found, 14 reported that the cannabis users had better cognitive performance than the schizophrenia non-users. Eight studies reported no or minimal differences in cognitive performance in the two groups, but only one study reported better cognitive performance in the schizophrenia non-user group. Our own results confirm the overall impression from the literature review of better cognitive performance in the cannabis user group. These paradoxical findings may have several explanations, which are discussed. We suggest that cannabis causes a transient cognitive breakdown enabling the development of psychosis, imitating the typical cognitive vulnerability seen in schizophrenia. This is further supported by an earlier age of onset and fewer neurological soft signs in the cannabis-related schizophrenia group, suggesting an alternative pathway to psychosis.

Auditory hallucinations in schizophrenia: the role of cognitive, brain structural and genetic disturbances in the left temporal lobe

In this article we review research in our laboratory on auditory hallucinations using behavioral and MRI measure. The review consists of both previously published and new data that for the first time is presented together in a cohesive way. Auditory hallucinations are among the most common symptoms in schizophrenia, affecting more than 70% of the patients. We here advance the hypothesis that auditory hallucinations are internally generated speech perceptions that are lateralized to the left temporal lobe, in the peri-Sylvian region. From this we predict that hallucinating patients should have problems identifying a simultaneously presented external speech sound, as measured through performance on the dichotic listening (DL) paradigm with consonant–vowel syllables, since this technique lateralizes the stimulus input. Across a series of behavioral experiments, we have shown that patients with schizophrenia who experience frequent auditory hallucinations fail to demonstrate an expected right ear advantage on the dichotic listening test. Absence of a right ear advantage is indicative of a functional deficit in the left peri-Sylvian region. The results also revealed that patients with ongoing auditory hallucinations were more impaired than patients with previous hallucinations, and that a higher score on the hallucination item in a standard symptom rating scale (BPRS) correlated negatively with number of correct reports for the right ear stimulus. Moreover, we have found that schizophrenia patients fail to shift attention to the left ear stimulus, when explicitly instructed to focus on the right or left ear stimulus only, thus showing a deficit in inhibition of attention and response-inhibition. The behavioral DL data are substantiated in two MR morphometry studies that revealed significant reductions in grey matter density in the left peri-Sylvian region in hallucinating patients, and patients with reduced left temporal lobe grey matter density. Hallucinating patients also failed to show a right ear advantage in the dichotic listening test. Ongoing fMRI studies are focused on the underlying synaptic and molecular mechanisms by investigating the effects of the glutamate antagonist drug memantine on auditory perception and speech lateralization, and examination of temporal cortex-specific gene expression in the left peri-Sylvian region.

Dichotic listening in schizophrenic patients: effects of previous vs. ongoing auditory hallucinations

Auditory hallucinations (AH) in schizophrenia have been found to be related to both functional and structural brain abnormalities of left temporal lobe language areas. We do not know if these rain abnormalities are state or trait markers for AH. This study tested these alternatives by contrasting schizophrenic patients with ongoing AH and with a previous history of AH. A heterogeneous group of 26 schizophrenic patients was compared with a healthy control group matched for education and age. We used a verbal dichotic listening (DL) test with consonant-vowel syllables to study hemispheric asymmetry and the functional integrity of the left temporal lobe language areas. All subjects were tested during a divided and two focused attention conditions. Our data suggest that abnormal DL asymmetry for language stimuli is a state marker for AH, seen during the perception of AH. In contrast, problems of modulating DL performance by means of attentional control are a trait marker, seen both in patients with ongoing AH and only a history of AH.

Left hemisphere lateralisation of auditory hallucinations in schizophrenia: A dichotic listening study

Introduction. We propose that auditory hallucinations are internally generated speech misrepresentations that are lateralised to the left temporal lobe. If hallucinations are misrepresentations involving the speech perception area of the left temporal lobe, then hallucinating patients should have problems identifying a simultaneously presented external speech sound, especially when the sound is lateralised to the left hemisphere. Lateralisation of speech perception can be experimentally studied with the dichotic listening task with consonant-vowel syllables. We predicted a negative relation between frequency of auditory hallucinations and performance on the dichotic listening task. Method. We studied 87 right-handed patients with schizophrenia. Hallucination scores were taken from the BPRS symptom scale. Right and left ear scores in the dichotic listening task were recorded. A right ear advantage is expected in healthy individuals, indicating left temporal lobe processing superiority. The patients were compared with 36 right-handed healthy reference subjects. Results. A gradual decrease in the ability to process and report the right ear stimulus with increasing frequency of hallucinations was seen in the schizophrenia patients. No such relationship was found for processing and reporting of the left ear stimulus. There were no significant correlations with negative symptoms. Thus, the results were not the consequence of illness severity. There was however a significant correlation with unusual thought content symptom, pointing to a relationship also between delusions and auditory hallucinations. Conclusion. The results support that auditory hallucinations may be internally generated speech misrepresentations, originating in the left temporal lobe.

Auditory verbal hallucinations in schizophrenia as aberrant lateralized speech perception: Evidence from dichotic listening

We report evidence that auditory verbal hallucinations (AVH) in schizophrenia patients are perceptual distortions lateralized to the left hemisphere. We used a dichotic listening task with repeated presentations of consonant-vowel syllables, a different syllable in the right and left ear. This task produces more correct reports for the right ear syllable in healthy individuals, indicative of left hemisphere speech processing focus. If AVHs are lateralized to the left hemisphere language receptive areas, then this should interfere with correct right ear reports in the dichotic task, which would result in significant negative correlations with severity of AVHs. We correlated the right and left ear correct reports with the PANSS hallucination symptom, and a randomly selected negative symptom, in addition to the sum total of the positive and negative symptoms, in 160 patients with schizophrenia. The results confirmed the predictions with significant negative correlations for the right ear scores with the PANSS hallucination item, and for the sum total of positive symptoms, while all other correlations were close to zero. The results are unambiguous evidence for AVHs as aberrant speech perceptions originating in the left hemisphere.

Positive symptoms and duration of illness predict functional laterality and attention modulation in schizophrenia.

Objective:  Dichotic listening (DL) performance in schizophrenia, reflecting hemispheric asymmetry and the functional integrity of the left temporal lobe, can vary with clinical characteristics. Previous studies have not taken the co‐linearity of clinical variables into account. The aim of the present study was to evaluate the roles of positive symptoms and duration of illness in DL through Structural Equation Modeling (SEM), thus allowing for complex relationships between the variables.

Patients with Schizophrenia Fail to Up-Regulate Task-Positive and Down-Regulate Task-Negative Brain Networks: An fMRI Study Using an ICA Analysis Approach

Recent research suggests that the cerebral correlates of cognitive deficits in schizophrenia are nested in the activity of widespread, inter-regional networks rather than being restricted to any specific brain location. One of the networks that have received focus lately is the default mode network. Parts of this network have been reported as hyper-activated in schizophrenia patients (SZ) during rest and during task performance compared to healthy controls (HC), although other parts have been found to be hypo-activated. In contrast to this network, task-positive networks have been reported as hypo-activated compared in SZ during task performance. However, the results are mixed, with, e.g., the dorsolateral prefrontal cortex showing both hyper- and hypo-activation in SZ. In this study we were interested in signal increase and decrease differences between a group of SZ and HC in cortical networks, assuming that the regulatory dynamics of alternating task-positive and task-negative neuronal processes are aberrant in SZ. We compared 31 SZ to age- and gender-matched HC, and used fMRI and independent component analysis (ICA) in order to identify relevant networks. We selected the independent components (ICs) with the largest signal intensity increases (STG, insula, supplementary motor cortex, anterior cingulate cortex, and MTG) and decreases (fusiform gyri, occipital lobe, PFC, cingulate, precuneus, and angular gyrus) in response to a dichotic auditory cognitive task. These ICs were then tested for group differences. Our findings showed deficient up-regulation of the executive network and a corresponding deficit in the down-regulation of the anterior default mode, or effort network during task performance in SZ when compared with HC. These findings may indicate a deficit in the dynamics of alternating task-dependent and task-independent neuronal processes in SZ. The results may cast new light on the mechanisms underlying cognitive deficits in schizophrenia, and may be of relevance for diagnostics and new treatments.

Neurobiology of cognitive remediation therapy for schizophrenia: a systematic review

Cognitive impairment is an important aspect of schizophrenia, where cognitive remediation therapy (CRT) is a promising treatment for improving cognitive functioning. While neurobiological dysfunction in schizophrenia has been the target of much research, the neural substrate of cognitive remediation and recovery has not been thoroughly examined. The aim of the present article is to systematically review the evidence for neural changes after CRT for schizophrenia. The reviewed studies indicate that CRT affects several brain regions and circuits, including prefrontal, parietal, and limbic areas, both in terms of activity and structure. Changes in prefrontal areas are the most reported finding, fitting to previous evidence of dysfunction in this region. Two limitations of the current research are the few studies and the lack of knowledge on the mechanisms underlying neural and cognitive changes after treatment. Despite these limitations, the current evidence suggests that CRT is associated with both neurobiological and cognitive improvement. The evidence from these findings may shed light on both the neural substrate of cognitive impairment in schizophrenia, and how better treatment can be developed and applied.