Reduced connectivity of the auditory cortex in patients with auditory hallucinations: a resting state functional magnetic resonance imaging study.

BACKGROUND: Previous research has reported auditory processing deficits that are specific to schizophrenia patients with a history of auditory hallucinations (AH). One explanation for these findings is that there are abnormalities in the interhemispheric connectivity of auditory cortex pathways in AH patients; as yet this explanation has not been experimentally investigated. We assessed the interhemispheric connectivity of both primary (A1) and secondary (A2) auditory cortices in n=13 AH patients, n=13 schizophrenia patients without auditory hallucinations (non-AH) and n=16 healthy controls using functional connectivity measures from functional magnetic resonance imaging (fMRI) data. METHOD: Functional connectivity was estimated from resting state fMRI data using regions of interest defined for each participant based on functional activation maps in response to passive listening to words. Additionally, stimulus-induced responses were regressed out of the stimulus data and the functional connectivity was estimated for the same regions to investigate the reliability of the estimates. RESULTS: AH patients had significantly reduced interhemispheric connectivity in both A1 and A2 when compared with non-AH patients and healthy controls. The latter two groups did not show any differences in functional connectivity. Further, this pattern of findings was similar across the two datasets, indicating the reliability of our estimates. CONCLUSIONS: These data have identified a trait deficit specific to AH patients. Since this deficit was characterized within both A1 and A2 it is expected to result in the disruption of multiple auditory functions, for example, the integration of basic auditory information between hemispheres (via A1) and higher-order language processing abilities (via A2).

Emotional prosodic processing in auditory hallucinations.

Deficits in emotional prosodic processing, the expression of emotions in voice, have been widely reported in patients with schizophrenia, not only in comprehending emotional prosody but also expressing it. Given that prosodic cues are important in memory for voice and speaker identity, Cutting has proposed that prosodic deficits may contribute to the misattribution that appears to occur in auditory hallucinations in psychosis. The present study compared hallucinating patients with schizophrenia, non-hallucinating patients and normal controls on an emotional prosodic processing task. It was hypothesised that hallucinators would demonstrate greater deficits in emotional prosodic processing than non-hallucinators and normal controls. Participants were 67 patients with a diagnosis of schizophrenia or schizoaffective disorder (hallucinating=38, non-hallucinating=29) and 31 normal controls. The prosodic processing task used in this study comprised a series of semantically neutral sentences expressed in happy, sad and neutral voices which were rated on a 7-point Likert scale from sad (-3) through neutral (0) to happy (+3). Significant deficits in the prosodic processing tasks were found in hallucinating patients compared to non-hallucinating patients and normal controls. No significant differences were observed between non-hallucinating patients and normal controls. In the present study, patients experiencing auditory hallucinations were not as successful in recognising and using prosodic cues as the non-hallucinating patients. These results are consistent with Cutting's hypothesis, that prosodic dysfunction may mediate the misattribution of auditory hallucinations.

Reliability and validity of a new Medication Adherence Rating Scale (MARS) for the psychoses.

Medication compliance is one of the foremost problems affecting neuroleptic efficacy in psychiatric patients. To date, compliancy has most commonly been assessed with the Drug Attitude Inventory (DAI) developed by Hogan et al. (Hogan, T.P., Awad, A.G., Eastwood, R., 1983. A self-report scale predictive of drug compliance in schizophrenics: reliability and discriminative validity. Psychol. Med. 13, 177-183). The present study identified several deficiencies in the DAI. Using the partial credit version of the Item Response Theory measurement model, the DAI was refined with the aim of greater validity and clinical utility. The new inventory was administered to 66 patients, the majority of whom were diagnosed with schizophrenia. When available, lithium levels and carer ratings of compliance were also recorded and used to verify compliancy. The new inventory appears to be a valid and reliable measure of compliancy for psychoactive medications.

Extrapyramidal symptoms and oestrogen.

OBJECTIVE: The present study aimed to investigate neuroleptic side-effect severity in women with psychosis, and to investigate their putative association with variations in sex steroids over the menstrual cycle. Based on the oestrogen hypothesis, which postulates a synergistic relationship between oestrogen and neuroleptics, it was hypothesized that oestrogen would exacerbate extrapyramidal symptoms. METHOD: Twenty-five psychotic women were assessed using the ESRS and blood hormone analysis. Testing was conducted twice, 2 weeks apart, in a randomized cross-over design. RESULTS: Contrary to expectation the results indicated that high levels of oestrogen reduce hyperkinetic symptoms in women with psychosis, and this effect appears to be further potentiated when both oestrogen and progesterone are high. CONCLUSION: On the basis of these findings, and receptor studies in animals, it was concluded that oestrogen has different effects on dopamine dynamics in the mesolimbic and mesostriatal pathways.

Computer simulation of electrocortical activity at millimetric scale.

We report a simulation of electrocortical wave activity at millimetric scale, during the "desynchronised" state. Asymmetric sigmoid pulse/wave relations, short-range excitatory/inhibitory interactions and long-range excitatory couplings of pools of cortical cells were modelled. Frequency/wave number analysis of cat electrocorticogram was compared with the results of simulation. Local standing waves, with wave numbers from about 0.25/mm to 3.3/mm independent of temporal frequency, appeared in real and simulated ECoG. These arise from interactions of excitatory and inhibitory cells and reciprocal excitation of pyramidal cells. The simulation also exhibits long wave length activity consistent with that of the real ECoG. Serial relay of excitation gives rise to travelling waves with a velocity of about 0.6 m/sec, which approximates earlier experimental estimates based on coherence. Interaction of the local and travelling waves results in group waves with high phase velocities (32 m/sec at 5 Hz, to 0.6 m/sec at 50 Hz). Such group waves have not yet been experimentally identified and would be readily confused with effects of volume conduction. However, the frequency response characteristics of the simulation, along with the group waves, may account for experimental findings of action potential correlation with local field potentials at 40-50 Hz and long-range synchronisation of action potentials.

Radial coherence, wave velocity and damping of electrocortical waves.

Mean squared coherence was calculated as a function of frequency (1-32 Hz) and electrode separation (1-8 mm) from 64-channel extradural arrays on occipito-parietal association cortex of cats. A 2-parameter theoretical function was then fitted to sets of pooled estimates. The theoretical function described coherences between recording sites of small separation for linear, non-dispersive, dissipative waves moving on an infinite homogeneous plane medium, and driven by spatio-temporally noisy inputs. Residuals of fit were then plotted as a function of frequency and distance, and were found to show no systematic trends with frequency, but an irregular and generally increasing relation to distance. This was the result predicted for linear non-dispersive waves on a surface actually folded, and with significant additional wave action generated between electrodes. Further recordings of coherence from more widely separated electrodes indicated that boundary conditions were absorbing or remote, rather than closed or reentrant. The phase velocity for electrocortical waves obtained from autoregression estimates of temporal damping and parameters of fit to coherence, was found in the range 0.1-0.29 m/sec, and appeared independent of the direction of electrode alignment. This compares with the velocity of 0.33 m/sec for alpha waves earlier found by Lopes da Silva and Storm van Leeuwen.

Autoregression models of EEG. Results compared with expectations for a multilinear near-equilibrium biophysical process.

This paper considers the properties of parameters (natural frequencies and damping coefficients) obtained from segment-by-segment autoregression analysis of ECoG of rat. The use of a reference signal as control for parameter estimate errors, and multiple regression analyses indicate that the dependencies among parameters calculated from ECoG in the alert (desynchronised) state are of a form consistent with imposition of time-invariance assumptions (implicit in autoregression) on an inherently non-stationary, multimodal, linear and near-equilibrium "thermal" process.

Inverse filter computation of the neural impulse giving rise to the auditory evoked potential.

An impulse response hypothesis for evoked potentials is tested. The auditory evoked potential (AEP) is shown to be the consequence of an impulse (the arrival of sensory signals in cortex) giving rise to an impulse response (the resonation of electrocortical activity in the form of group linear waves). To demonstrate this, pre- and post-stimulus EEG activity was recorded from subjects engaged in performance of an auditory odd-ball experiment. For each stimulus, the impulse required to account for the single auditory evoked potential (AEP) as a linear impulse response, was computed by use of the inverse of a filter obtained by autoregression analysis of the pre-stimulus EEG epoch. Single estimations of the impulse were then averaged. The average impulse exhibits a time course and topology consistent with the arrival of neural volleys in the cortex. The physical validity of the hypothesis is supported by a high lag correlation of the following values of the AEP to the average impulse. A further test calculation supports the linear additivity assumptions of the hypothesis.