Pathways That Make Voices

Hubl, Daniela; Koenig, Thomas; Strik, Werner; Federspiel, Andrea; Kreis, Roland; Boesch, Chris; Maier, Stephan E.; Schroth, Gerhard; Lövblad, Karl-Olof; Dierks, Thomas

doi:10.1001/archpsyc.61.7.658

Cited by 438 publications

(139 citation statements)

References 60 publications

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“…This study also reported that the visual cortex of hallucinators was less responsive to external stimulation, which we also found in the lower N1 VEP of the VH subgroup. Still another possibility is that the correlations between increased phase locking and symptoms ref lects the presence of abnormally increased connectivity in particular neural circuits, as was recently reported for SZ with auditory hallucinations (36).…”

Section: Discussionmentioning

confidence: 69%

Neural synchrony indexes disordered perception and cognition in schizophrenia

Spencer

Nestor²,

Perlmutter³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

552

411

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Current views of schizophrenia suggest that it results from abnormalities in neural circuitry, but empirical evidence in the millisecond range of neural activity has been difficult to obtain. In pursuit of relevant evidence, we previously demonstrated that schizophrenia is associated with abnormal patterns of stimulus-evoked phaselocking of the electroencephalogram in the ␥ band (30 -100 Hz). These patterns may reflect impairments in neural assemblies, which have been proposed to use ␥-band oscillations as a mechanism for synchronization. Here, we report the unique finding that, in both healthy controls and schizophrenia patients, visual Gestalt stimuli elicit a ␥-band oscillation that is phase-locked to reaction time and hence may reflect processes leading to conscious perception of the stimuli. However, the frequency of this oscillation is lower in schizophrenics than in healthy individuals. This finding suggests that, although synchronization must occur for perception of the Gestalt, it occurs at a lower frequency because of a reduced capability of neural networks to support high-frequency synchronization in the brain of schizophrenics. Furthermore, the degree of phase locking of this oscillation is correlated with visual hallucinations, thought disorder, and disorganization in the schizophrenia patients. These data provide support for linking dysfunctional neural circuitry and the core symptoms of schizophrenia.electroencephalogram ͉ ␥ band C ontemporary views of schizophrenia propose that the basis of this disorder lies in the dysfunction of neural microcircuits, rather than specific brain areas or neurotransmitter systems. These views are based on postmortem studies of the brains of schizophrenia patients (SZ), which have reported abnormalities at the cellular level, including inhibitory interneurons (1-3). Moreover, animal studies suggest that such disturbances may involve the hypofunctioning of N-methyl-D-aspartate receptors on inhibitory interneurons because psychotomimetics selectively block this receptor (4, 5). Inhibitory interneurons appear to be crucial elements in the generation of synchronous neural activity in the ␤ (13-30 Hz) and ␥ (30-100 Hz) bands of the electroencephalogram (EEG) (6, 7). Evidence is accumulating that such synchronous oscillations may underlie cognitive functions such as object perception, selective attention, and working memory (8, 9), as well as consciousness (10). Thus, the analysis of high-frequency EEG oscillatory activity may provide functional evidence for neural circuitry abnormalities in schizophrenia.In earlier studies we have found that SZ exhibit deficits in ␥-band neural synchrony as measured by EEG phase locking during auditory steady-state stimulation (11) and during the perception of visual Gestalt patterns (12). In the latter study, SZ displayed several abnormalities in the early visual ␥-band oscillation in comparison with matched healthy control subjects. The most striking finding was that Gestalt stimuli failed to elicit the occipital component of the earl...

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Section: Discussionmentioning

confidence: 69%

Neural synchrony indexes disordered perception and cognition in schizophrenia

Spencer

Nestor²,

Perlmutter³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

552

411

View full text Add to dashboard Cite

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“…AVHs, on the other hand, were attributed to the sensory functions of the language system, since they consist in an abnormal perception of speech [9, 49-51]. …”

Section: Translational Psychopathology: Matching Psychotic Symptoms Wmentioning

confidence: 99%

“…A later diffusion tensor imaging study suggested an increased connectivity within the left arcuate fascicle, which is a major intrahemispheric fiber tract connecting frontal to temporal components of the language system. This finding was specific for schizophrenia patients with frequent hallucinations compared to schizophrenia patients who had never hallucinated as well as healthy controls [49]. Furthermore, it was demonstrated that the effect of phasic activation of Heschl’s gyrus during hallucinations could not be explained by external stimulation, but rather by sequestration of temporal lobe resources by internal processes [88].…”

Section: Mapping Symptoms Onto Brain Systems: Empirical Evidence For mentioning

confidence: 99%

Systems Neuroscience of Psychosis: Mapping Schizophrenia Symptoms onto Brain Systems

et al. 2017

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Schizophrenia research has been in a deadlock for many decades. Despite important advances in clinical treatment, there are still major concerns regarding long-term psychosocial reintegration and disease management, biological heterogeneity, unsatisfactory predictors of individual course and treatment strategies, and a confusing variety of controversial theories about its etiology and pathophysiological mechanisms. In the present perspective on schizophrenia research, we first discuss a methodological pitfall in contemporary schizophrenia research inherent in the attempt to link mental phenomena with the brain: we claim that the time-honored phenomenological method of defining mental symptoms should not be contaminated with the naturalistic approach of modern neuroscience. We then describe our Systems Neuroscience of Psychosis (SyNoPsis) project, which aims to overcome this intrinsic problem of psychiatric research. Considering schizophrenia primarily as a disorder of interindividual communication, we developed a neurobiologically informed semiotics of psychotic disorders, as well as an operational clinical rating scale. The novel psychopathology allows disentangling the clinical manifestations of schizophrenia into behavioral domains matching the functions of three well-described higher-order corticobasal brain systems involved in interindividual human communication, namely, the limbic, associative, and motor loops, including their corticocortical sensorimotor connections. The results of several empirical studies support the hypothesis that the proposed three-dimensional symptom structure, segregated into the affective, the language, and the motor domain, can be specifically mapped onto structural and functional abnormalities of the respective brain systems. New pathophysiological hypotheses derived from this brain system-oriented approach have helped to develop and improve novel treatment strategies with noninvasive brain stimulation and practicable clinical parameters. In clinical practice, the novel psychopathology allows confining the communication deficits of the individual patient, shifting attention from the symptoms to the intact resources. We have studied this approach and observed important advantages for therapeutic alliances, personalized treatment, and de-escalation strategies. Future studies will further conjoin clinical definitions of psychotic symptoms with brain structures and functions, and disentangle structural and functional deficit patterns within these systems to identify neurobiologically distinct subsyndromes. Neurobiologically homogeneous patient groups may provide new momentum for treatment research. Finally, lessons learned from schizophrenia research may contribute to developing a comprehensive perspective on human experience and behavior that integrates methodologically distinct, but internally consistent, insights from humanities and neuroscience.

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“…Notwithstanding the overall reduced FA, a higher FA in WM tracts connecting the temporal regions has been consistently associated with worse hallucinations [31]. The involved tracts included the arcuate fasciculus [32,33] and the corpus callosum, superior longitudinal fasciculus and the cingulum bundle [32,34,35]. A higher FA was also observed in dopaminergic tracts in the mesencephalon of drug-naive schizophrenics and of their unaffected relatives [30].…”

Section: Discussionmentioning

confidence: 99%

Sterol Regulatory Element Binding Transcription Factor-1 Gene Variation and Medication Load Influence White Matter Structure in Schizophrenia

et al. 2015

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Background: Diffusion tensor imaging (DTI) studies have shown a widespread disruption of white matter (WM) microstructure in schizophrenia. Furthermore, higher fractional anisotropy (FA) has been consistently correlated with the severity of psychotic symptoms. Antipsychotic drugs (APDs) affect lipid homeostasis. Gene polymorphisms in sterol regulatory element binding transcription factor (SREBF)-1 and SREBF-2 have been associated with schizophrenia. Methods: In a sample of 65 patients affected by chronic schizophrenia, we investigated the effect of ongoing APD medication, SREBF-1 rs11868035polymorphism and SREBF-2 rs1052717 polymorphism on the WM microstructure, using tract-based spatial statistics with threshold-free cluster enhancement. Results: We reported increased FA associated with the risk rs11868035G/G genotype in several WM tracts, mainly located in the left hemisphere, and opposite effects of the APD medication load, with reduced FA and generally increased diffusivity. These opposite effects overlapped in the forceps minor, cingulum, uncinate fasciculus, the superior and inferior longitudinal fasciculi, the corticospinal tract, inferior fronto-occipital fasciculus and the anterior thalamic radiation. Conclusion: We suggest that changes of WM structure could be an as yet poorly explored biomarker of the effects of APDs, to be further investigated in prospective studies correlating long-term clinical effects with changes of DTI measures in specific WM tracts contributing to the functional integrity of the brain.

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Pathways That Make Voices

Cited by 438 publications

References 60 publications

Neural synchrony indexes disordered perception and cognition in schizophrenia

Neural synchrony indexes disordered perception and cognition in schizophrenia

Systems Neuroscience of Psychosis: Mapping Schizophrenia Symptoms onto Brain Systems

Sterol Regulatory Element Binding Transcription Factor-1 Gene Variation and Medication Load Influence White Matter Structure in Schizophrenia

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