Laterality, attention and rate effects in the auditory temporal discrimination of chronic schizophrenics: the efffect of treatment with chlorpromazine.
Quarterly Journal of Experimental Psychology, 30, 91— Behavioural Brain Sciences, in press. Google Scholar Huret, J.
Google Scholar Ireland, W. May 30th On the discordant action of the double brain. British Medical Journal, — Google Scholar Johnson, O. Journal of Abnormal Psychology, 91, 45— Functional tests of the corpus callosum in schizophrenia. The corpus callosum and brain function in schizophrenia. Auditory processing in schizophrenia patients. Gruzelier eds. Google Scholar Kugler, B. Laterality effects in the tactile modality in schizophrenia.
Google Scholar La Mettrie, J. Man a machine. French-English Ed. La Salle, Open Court, Google Scholar Lerner, J. Responses of paranoid and non-paranoid schizophrenics in a dichotic listening task. Journal of Nervous and Mental Diseases, , — Dichotic listening in psychiatric patients, British Journal of Psychiatry, , — Brain disconnection, schizophrenia and paranoia.
Journal of Nervous and Mental Disease, , — Google Scholar Milner, B. Lateralised suppression of dichotically presented digit after commissural section in man. Science, , — Hemispheric dysfunction in schizophrenia.
A histological study of the corpus callosum in chronic schizophrenia. Psychiatry Research, 10, — Quantitative brain measurement in chronic schizophrenia. Commissural transmission: maturational changes in humans.
Laterality and voltage in the EEG of psychiatric patients. Voltage Laterality in the EEG of psychiatric patients. Diseases of the Nervous System, 34, — Failure to replicate evoked potential observation suggesting corpus callosum dysfunction in schizophrenia. Inter-hemispheric transmission times in schizophrenics. British Journal of Clinical Psychology.
However, the acute effects of dopamine stimulants include euphoria, alertness and over-confidence; these symptoms are more reminiscent of mania than schizophrenia. This observation was subsequently extended to other antipsychotic drug classes, such as butyrophenones including haloperidol. The link was strengthened by experiments in the s which suggested that the binding affinity of antipsychotic drugs for D2 dopamine receptors seemed to be inversely proportional to their therapeutic dose.
This correlation, suggesting that receptor binding is causally related to therapeutic potency, was reported by two laboratories in However, there was controversy and conflicting findings over whether postmortem findings resulted from drug tolerance to chronic antipsychotic treatment.
Compared to the success of postmortem studies in finding profound changes of dopamine receptors, imaging studies using SPET and PET methods in drug naive patients have generally failed to find any difference in dopamine D2 receptor density compared to controls. Comparable findings in longitudinal studies show: " Particular emphasis is given to methodological limitations in the existing literature, including lack of reliability data, clinical heterogeneity among studies, and inadequate study designs and statistic," suggestions are made for improving future longitudinal neuroimaging studies of treatment effects in schizophrenia  A recent review of imaging studies in schizophrenia shows confidence in the techniques, while discussing such operator error.
In addition, newer antipsychotic medication called atypical antipsychotic medication can be as potent as older medication called typical antipsychotic medication while also affecting serotonin function and having somewhat less of a dopamine blocking effect.
In addition, dopamine pathway dysfunction has not been reliably shown to correlate with symptom onset or severity. HVA levels correlate trendwise to symptoms severity.
During the application of debrisoquin , this correlation becomes significant. Radioligand imaging measurements involve the monomer and dimer ratio, and the 'cooperativity' model.
According to Seeman, " The dysconnection hypothesis per se is a hypothesis about functional synaptic connectivity that is very specific about the pathophysiology; namely, an aberrant modulation of synaptic efficacy.
This is potentially important because it speaks to the molecular basis of synaptic gain control in the context of distributed and hierarchical processing in the brain. The dysconnection hypothesis precludes a primary aetiological role for anatomical disconnections. There are simple reasons for this — because schizophrenic signs and symptoms can be elicited by psychomimetic drugs e. In other words, the fact that psychosis can be induced by simply changing the neuromodulatory status of synaptic integration suggests that the anatomical and neurodevelopmental characteristics of schizophrenia are consequences not causes of the underlying pathophysiology.
Furthermore, while synaptic abnormalities can explain aberrant neurodevelopment e. Clearly, this is a rather polemic argument: for instance, ketamine could just produce a phenocopy or the pathophysiology at play may be manifest throughout development, affecting both synaptic function and neurogenesis Zhang et al. Perhaps the most important aspect of the dysconnection hypothesis is that it disambiguates between proximal aetiologies at the level of synaptic physiology and neurodevelopmental failures of cell migration and morphogenesis, acknowledging that the two levels contextualize each other.
Crucially, if the dysconnection hypothesis can be falsified this would be a great advance — enabling a focus on alternative e.
Having said this, the circumstantial evidence and theoretical support for the dysconnection hypothesis appears to be accumulating as the years pass.
In what follows, we summarize some of the key developments. Before reaching to the phenomenal side, we need to take one more intermediate step, the one related to temporal extension. Temporal extension refers to the degree to which a particular stimulus or task at one particular point in time is extended across different points in time during its encounter with the long phase durations of the infraslow frequency fluctuations in the midline regions.
How do the increased degrees of neuronal synchronization and temporal continuity impact temporal extension of particular stimuli in time as for instance during mental time travel with prospection and retrospection see refs 50 and The extrinsic stimulus encounters an intrinsic resting state activity with increased neuronal synchronization and temporal continuity where, as presumed, the long phase durations of low-frequency fluctuations predominate. One would then suggest that the extrinsic stimuli should be more extended in time by the long phase durations.
Such temporal extension is possible, however, only if the extrinsic stimuli interact with and induce some change, eg, temporal flow in the ongoing midline resting state activity. Accordingly, increased temporal continuity during resting state activity entails reduced temporal extension during task-evoked or stimulus-induced activity. Owing to the changes in opposite directions, one may say that temporal continuity and temporal extension of midline neural activity dissociate from each other in schizophrenia see figures 2a and 2b.
View large Download slide Abnormal relationship between changes in neural activity and temporal extension and how they are modulated by high- and low-frequency fluctuations a and the abnormal continuum of changes in neural activity b in schizophrenia.
The low-frequency fluctuations are then complemented by the stimulus-related high-frequency fluctuations middle left that show much shorter phase durations and allow for temporal flow of neural activity middle right , which is significantly reduced in schizophrenia dotted thin lines. Temporal extension is based on a balance between temporal flow and continuity of neural activity as reflected in the inverted u-shape curve dotted lines in healthy subjects.
Taken in this sense, sensible continuity is obviously closely related to temporal extension: the higher the degree of temporal extension of neural activity as related to particular stimuli or tasks, the more that stimulus or tasks can be extended neurally in time, and the higher the degree of subsequent sensible continuity on the phenomenal level of consciousness. Therefore, temporal extension and sensible continuity are positively and directly proportional related to each other.
Reduced degree of temporal extension should entail reduced sensible continuity. The stimulus or task can no longer be extended in time and is therefore less continuous with previous mental contents as associated with the preceding stimuli and tasks on the phenomenal level of consciousness. The contents of consciousness as resulting externally from the stimuli and tasks should consequently be less continuous in time and with each other—they should be more segregated from each other in subjective experience.
This is exactly one form and way how schizophrenic patients experience time besides other ways that cannot be described in detail here; see my hint at the end of the Methodological Remark section.
Although we leave other forms and ways of time experience in schizophrenia as described in subtle details by psychiatrists like Minkowski, Gebsattel, Binswanger, and Strauss as mentioned earlier, there is a more refined neurophenomenal investigation kept aside for future.. Let us specify experience of temporal fragmentation in the following text. Decreased temporal extension may lead to decreased temporal extension of the respective stimulus or task in the neural activity.
The various mental contents occurring at different discrete points in time can consequently no longer be connected, linked, and glued temporally to each other. Instead of being connected as distinct parts of a homogenous stream of consciousness, the different mental contents are now experienced as temporally disconnected or fragmented with no temporal linkage or glue connecting them anymore in consciousness.
Things go too quickly for my mind. They get blurred and it is like being blind. There are no longer any temporal transitions between the different discrete points in time and space associated with the different contents, eg, pictures. Instead of temporal transitions, there are temporal gaps, which lead to temporal delays in linking the different contents and putting them together. Metaphorically speaking, the pictures are, as it were, experienced as pearls without an underlying chain.
Time is running strangely.
Psychosomatics 24 4 , A study by Spencer et al 46 reported that gamma-band power in auditory cortex during an auditory task was modulated by the phase of delta oscillations in a significantly lower degree in schizophrenic patients. Unfortunately, only a combined functional magnetic resonance imaging fMRI —EEG resting state study allowing for combined measurement of infraslow 0. SLPE distinguishes itself from schizophrenia by a relative absence of negative symptoms and better premorbid as well as long term functioning [ 16 , 17 ]. SPET study of verbal fluency in schizophrenia and epilepsy.
In either case, our findings support the hypothesis that dopamine receptor abnormalities are present in untreated schizophrenic patients. It is still thought that dopamine mesolimbic pathways may be hyperactive, resulting in hyperstimulation of D2 receptors and positive symptoms. This review mainly discussed the clinical characters; diagnose approaches, and predisposing factors of schizophrenia-like psychosis in epilepsy SLPE , which is one of the most severe comorbidity in epilepsy. Crucially, the dysconnection hypothesis explains how the physiological consequences of abnormal modulation of NMDAR-mediated plasticity such as altered pyramidal cell gain translate into computational impairments at the level of neuronal circuits — and how this leads to false inference and psychomotor poverty. Temporal continuity is increased and predominates over temporal flow that is decreased. Behav 5 5 ,
In other words, the fact that psychosis can be induced by simply changing the neuromodulatory status of synaptic integration suggests that the anatomical and neurodevelopmental characteristics of schizophrenia are consequences not causes of the underlying pathophysiology. Behav 6 1 , Early studies often looked at the presence or absence of a history of psychiatric treatment or hospitalization, because of the lack of standardized methods [ 5 ]. Res 73 2 , The disconnection hypothesis.
Therefore, the current neurophenomenal hypotheses may be considered tentative as suggestions for bridging the neurophenomenal gap which may be refined in the future by more direct and explicit experimental paradigms. This is a direct result of the abnormal dopaminergic input to the striatum, thus indirectly disinhibition of thalamic activity. Individual alterations are produced by differences within glutamatergic pathways within the limbic system, which are also implicated in other psychotic syndromes.
It fells apart and no longer progresses. Interictal psychopathology in epilepsy: Prevalence and pattern in a Nigerian clinic.