However, in order to propose initial theories, the best is probably to start with animal models.
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The overall goal is to understand the interplay between structural, chemical, and electrical signals in the brain, which gives rise to a depressed behaviour in humans. In particular, studies of animal models of depression may be important for performing screening tests to discover and develop new antidepressant drugs. Moreover, animal models are used to simulate and elucidate neurobiological aspects of depressive illness—to induce anhedonia as a core symptom of depression, or to a particular subtype of depression, and to examine mechanisms of depressive syndromes and of various acute and chronic antidepressive treatments Mitchell and Redfern [ 20 ]; Harro [ 21 ]; Sarbadhikari and Sankar [ 22 ]; Willner [ 23 , 24 ]; Porsolt et al.
For instance, disruption of neurochemistry of the noradrenergic locus coeruleus LC is at least one aspect of the pathophysiology of major depression Klimek et al. The mutual role of LC and cerebellum is also bringing new information about motor and non-motor cerebellar processing Culic et al. The fitness of an animal model depends on the similarity with the human disorder with respect to symptomatology, etiology, biochemistry, electrophysiology and response to antidepressive treatment.
It is of vital importance to fully recognize the limitations of such models. Certain behavioural or physiological responses, which are supposed to be important for depression, are measured in animal assay models. Examples of assay models are: muricide, potentiation of yohimbine lethality or amphetamine-induced hyperactivity, antagonism of apomorphine-induced hypothermia, preferential reduction of kindled seizures initiated from the amygdale, and facilitation of circadian rhythm readjustment.
Such models focus on the predictive value for screening of new drugs and other treatments, without trying to create a human disorder in the animal. On the other hand, homologous animal models place less emphasis on correlative approaches and rely more on construct and face validity.
They are based on resemblance to symptoms of human depression although some symptoms can never be mimicked in animals. That EEG correlates of motivation and short term memory STM in cats during an approach-avoidance delayed differentiation task were studied several decades ago Psatta [ 28 , 29 ]. The preparatory cue stimuli were tone and intermittent light stimulation ILS , the delay of ten seconds, and reinforcement was either food or pain.
Under these conditions, motivation changed from one trial to another. EEG activity varying with motivation during the delayed period was statistically confirmed. Changes occurred only in the amygdaloidal and the hypothalamic nuclei. Changes significantly related to STM either prolonged desynchronization or ILS memory traces during the delay period occurred only in the cortical cognitive areas Ectosylvius medius or Marginalis posterior in cats.
The electrical activity in the Hippocampus had complex relationships. Occurrence of theta activity in VH systematically accompanied the motor response. It was concluded that hippocampus exerts a complex sensory-motor integration. DH intervenes in the sensory processing of information, by closing the thalamic gates.
VH exerts an inhibitory motor control on the frontal cortex by uncial fibers. Depression occurred in five out of 13 investigated animals, when the approach-avoidance conflict induced manifestations of experimental neurosis Psatta [ 30 , 31 ]. The most characteristic electrical change in these animals was the constant occurrence of a mid-amplitude very fast rhythm in both DH and VH. Thus depression was attributed to the exaggerated inhibitory control of hippocampus induced by the emotional conflict imposed. Administration of small doses of Reserpine, reducing the cerebral amount of free catecholamines, induced a reoccurrence of the theta rhythm in the hippocampus and of the coordinated motor responses.
Further administration resulted in change in the appearance of higher amplitude fast rhythms in the hippocampus and of exhaustion type of depression. It was concluded that there is an optimal monoamine level a narrow window for which hippocampus acts normally. Administration of Nialamide after Reserpine restored first theta activity and eventually the original aspect of mid amplitude fast rhythms in the hippocampus the anxious type of depression.
A choline-estherase inhibitor eserine in small doses restored in the depressed animals both the DH theta activity and the EEG correlates of STM the memory traces. Atropine after Reserpine induced a release of motor behaviour, but no signs of performing STM. These experiments reveal the difficulty of controlling depression by psychotropic drugs administration. It is also outlined the difficult extrapolation of these results in animals to experimentation in humans in whom subcortical EEG investigation is not possible.
In order to replicate the described experiment, the authors tried the effects of Go-NoGo STM performances in humans using auditory click cue stimuli and slightly delayed motor finger responses. N is larger in NoGo, P is deeper in Go situations. Electroconvulsive therapy ECT is a treatment in which seizures are electrically induced in anesthetized patients for therapeutic purposes. ECT is most often used as a treatment for severe major depression, where patients have not responded to other treatments. The course can be summarized as three events of distinct and sequential phase patterns.
Most ECT studies have investigated the physiological mechanism of action in relation to clinical response [ 34 ]. Studies consist often of about 30 patients who are followed 5—9 times. In order to test various hypotheses of ECT effects e. Microwave exposure is a method in which the electromagnetic radiation at field power densities is much lower than used in ECT is applied for treatment of mental disorders. For example, mood improvement in patients with bipolar depressive disorder has been reported at the field power density within clinical magnetic resonance system limits [ 39 ].
Exposure to MHz microwave radiation modulated at Hz frequency at the field power density 0.
The experiments were carried out on a group of depressive patients 18 females and a control group of healthy volunteers 18 females exposed by microwave radiation during 30 minutes. The average HDRS score for the group was 21 s. All the subjects passed two experimental procedures—with exposure and sham. The resting 9 channel EEG was recorded during the experiment.
As a measure for evaluation of the mood improvement the spectral asymmetry index SASI as a combination of the EEG beta and theta power was selected [ 41 ]. The BAS revealed a minor improvement 11 subjects in subjective mood score after exposure and VAS test revealed significant change between scores before average The EEG analysis detected objective effects of the treatment.
The calculated SASI values were positive for depressive and negative for healthy subjects.
The analysis revealed statistically significant differences between exposed and sham exposed patients. These preliminary results are promising and the SASI method of EEG analysis for mood evaluation as well as microwave exposure for treatment of mental disorders need further investigations. Variations between individuals and within individuals should be investigated and experiments on different groups should be performed.
In this paper we have focused on the neural understanding of depression. The aim is to find a link between physiology and mental disorders. There are several indications for such links, for example between hormone levels and SAD. In the future, we hope to have found models that would manifest connections between depression and bio-markers, bio-signals, and bio-maps, such as hormone levels, EEG, fMRI, and so forth.
In particular, we have to learn how to take into account between and within subject variations in spatio-temporal, parametric or semi-parametric models. National Center for Biotechnology Information , U. Journal List Comput Intell Neurosci v. Comput Intell Neurosci. Published online Jun Author information Article notes Copyright and License information Disclaimer. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract This paper is based on a discussion that was held during a special session on models of mental disorders, at the NeuroMath meeting in Stockholm, Sweden, in September Introduction When studying mental disorders researchers have primarily focused on gathering data, that is, the approach is basically empirical.
Problems in Classifying and Modelling Major Depression — The use of the current classification schemas, including DSM-IV, undoubtedly contributes to the difficulties in finding genes and biological variables for psychiatric disorders. Circadian Rhythms, Melatonin, and Bright Light Therapy Circadian rhythms control, among other things, appetite, energy, mood and sleep.
Statistical Repeated Measurements Models for the Analysis of Circadian Rhythms: An Example of Linear Models Analysis Since there are often repeated measurements on individuals in depression studies one has to apply some of the repeated measurements tools that nowadays are available, and not use standard regression methods. Animal Models for Developing Antidepressive Treatment: A Short Introduction The overall goal is to understand the interplay between structural, chemical, and electrical signals in the brain, which gives rise to a depressed behaviour in humans.
Example 2: An Example with Experimental Neurosis in Cats That EEG correlates of motivation and short term memory STM in cats during an approach-avoidance delayed differentiation task were studied several decades ago Psatta [ 28 , 29 ]. Concluding Remarks In this paper we have focused on the neural understanding of depression. References 1. Neuroscience research agenda to guide development of a sychophysiologically based classification system. Gottesman II, Shields J. Amrein, K. On pairs of projections in a Hilbert space. Linear Algebra Appl.
Andruchow, G. Essentially orthogonal subspaces.
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Theory 79 , 79— Arias, S. Almost sharp quantum effects. Avron, R. Seiler, B. The index of a pair of projections. Algebraic characterizations and statistical implications of the commutativity of orthogonal projectors. Pukkila and S. Puntanen eds. Baksalary, O. Commutativity of projectors. Baksalary, P. Generalizations of a property of orthogonal projectors. Baksalary, T. A property of orthogonal projectors.
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