Josef Zihl

Gray Matter Increase Induced by Practice Correlates with Task-Specific Activation: A Combined Functional and Morphometric Magnetic Resonance Imaging Study

The neurophysiological basis of practice-induced gray matter increase is unclear. To study the relationship of practice-induced gray matter changes and neural activation, we conducted a combined longitudinal functional and morphometric (voxel-based morphometry) magnetic resonance imaging (MRI) study on mirror reading. Compared with normal reading, mirror reading resulted in an activation of the dorsolateral occipital cortex, medial occipital cortex, superior parietal cortex, medial and dorsolateral prefrontal cortex, as well as anterior insula and cerebellum. Daily practice of 15 min for 2 weeks resulted in an increased performance of mirror reading. After correction for pure performance effects, we found a practice-related decrease of activation at the right superior parietal cortex and increase of activation at the right dorsal occipital cortex. The longitudinal voxel-based morphometry analysis yielded an increase of gray matter in the right dorsolateral occipital cortex that corresponded to the peak of mirror-reading-specific activation. This confirms that short-term gray matter signal increase corresponds to task-specific processing. We speculate that practice-related gray matter signal changes in MRI are primarily related to synaptic remodeling within specific processing areas.

Restitution of visual function in patients with cerebral blindness.

Patients with postchiasmatic visual field defects were trained at the border of their visual field. Using a psychophysical method, light-difference thresholds were determined repeatedly in this visual field area. Improvement in contrast sensitivity and increase in size of the visual field could be obtained by this training procedure. The improvement was confined to the trained visual field area and showed interocular transfer indicating its central nature. Althoughh only contrast sensitivity was trained, the observed improvement was not limited to this visual function. Visual acutity, critical flicker fusion, and colour perception also showed and improvement suggesting an association of these functions. The improvement was restricted to the training period-no spontaneous recovery was observed between or after the periods of training. It is suggested that a lesion in the central visual system does not always result in a complete and permanent loss of function. The critical level of function that normally has to be reached for sufficient neuronal sensitivity may be obtained by systematic visual stimulation in the area between the intact and blind parts of the visual field. This increase in neuronal sensitivity leads to an improvement in visual performance.

“Blindsight”: Improvement of visually guided eye movements by systematic practice in patients with cerebral blindness

Abstract Patients with damage to the geniculo-striate visual pathways were trained to discriminate different positions of targets presented briefly in the blind region of their visual field. The results indicate that the ability to detect and localize stimuli improved markedly after the systematic training of visually evoked saccadic eye movements. It is concluded that even in the absence of the striate cortex detection and localization of stimuli remained still intact, and that this visual capacity is probably mediated by the extrastriate retionotecnal pathway.

Clinical and neurobiological effects of tianeptine and paroxetine in major depression

Selective serotonin reuptake inhibitors (SSRIs) are widely used as effective pharmacological agents to treat depressive disorders. In contrast to the SSRIs, which block the presynaptic serotonin (5-HT) transporter and by this route increase the concentration of serotonin in the synaptic cleft, the antidepressant tianeptine enhances the presynaptic neuronal reuptake of 5-HT and thus decreases serotonergic neurotransmission. Both SSRIs and tianeptine are clinically effective; however, their opposite modes of action challenge the prevailing concepts on the need of enhancement of serotonergic neurotransmission. To better understand the differences between these two opposite pharmacological modes of action, we compared the changes induced by tianeptine and paroxetine on psychopathology, the hypothalamic-pituitary-adrenocortical (HPA) system, and cognitive functions in a double-blind, randomized, controlled trial including 44 depressed inpatients over a period of 42 days. Depressive symptomatology significantly improved in all efficacy measures, with no significant differences between tianeptine and paroxetine. There was a trend toward better response to the SSRI among women. Assessment of the HPA system showed marked hyperactivity before the beginning of treatment, which then normalized in most of the patients, without significant differences between the two antidepressants. Cognitive assessments showed no significant differences between the two drugs investigated. The results of the current study suggest that the initial effect, i.e., enhancement or decrease of 5-HT release, is only indirectly responsible for antidepressant efficacy, and they support the notion that downstream adaptations within and between nerve cells are crucial. The normalization of the HPA system as a common mode of action of different antidepressants seems to be of special interest.

Overweight and Obesity Affect Treatment Response in Major Depression

BACKGROUND Epidemiologic and clinical studies suggest comorbidity between major depressive disorder (MDD) and obesity. To elucidate the impact of weight on the course of depression beyond comorbidity, we investigated psychopathology, attention, neuroendocrinology, weight change, and treatment response in MDD patients, depending on their weight. METHODS Four hundred eight inpatients with MDD participated in the Munich Antidepressant Response Signature Study, designed to discover biomarkers and genotypes that are predictive for clinical outcome. Psychopathology and anthropometric parameters were monitored weekly in 230 patients. In subsamples, combined dexamethasone-corticotropin-releasing hormone and attention tests were conducted at admission and discharge. One thousand twenty-nine diagnosed matched controls served for morphometric comparisons. RESULTS Patients with MDD had a significantly higher body mass index (BMI) compared with healthy controls. Patients with high BMI (> or =25) showed a significantly slower clinical response, less improvement in neuroendocrinology and attention, and less weight gain than did patients with normal BMI (18.5 < or = BMI < 25) during antidepressant treatment. CONCLUSIONS Our findings suggest that overweight and obesity characterize a subgroup of MDD patients with unfavorable treatment outcome.

Subcortical control of visual thresholds in humans: evidence for modality specific and retinotopically organized mechanisms of selective attention.

SummaryThe present experiments were designed to study the control of visual thresholds in relation to selective attention and goal directed saccadic eye movements in human subjects. The results demonstrate that visual thresholds increase by about 0.5–1 log unit when targets are repeatedly presented in the periphery of the visual field while the subjects are fixating. The diameter of the adapted area and the amplitude of the threshold elevation increase with retinal eccentricity but do not depend on other stimulus parameters such as target size or target luminosity. Irrespective of target size the diameter of the adapted field is in the range of 5 ° close to the fovea and reaches up to 20 ° in the visual field periphery. This elevation of detection thresholds can be reset either by adapting a mirror symmetric area in the contralateral visual field or by directing a saccadic eye movement towards a target which is presented in an area mirror symmetric to the adapted field. When saccades are performed in the absence of the target stimulus or when they are directed towards targets outside the mirror symmetric area no resetting occurs. Adaptation is further prevented when the subject is allowed to saccade towards the adapting target. Measurements in patients with cortical hemianopia indicate, that these phenomena are mediated by subcortical visual centers since they can be influenced by stimulation in the blind hemifield. Participation of subcortical centers, especially of the tectum, is further suggested by the numerous correlations between the present psychophysical observations and the available neurophysiological data on subcortical visual pathways. It is concluded that it is one of the functions of the retino-tectal system to determine detection thresholds in a retinotopically organized way and to guide visual attention towards particular areas within the visual field. The observations in hemianopic patients suggest that these operations are accomplished in parallel to cortical analysis and remain functional after striatal lesions. They are, however, inaccessible to conscious experience.

Persistent cognitive impairment in depression: the role of psychopathology and altered hypothalamic-pituitary-adrenocortical (HPA) system regulation

BACKGROUND Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system and cognitive impairment are consistent findings in depression. This study examines the associations between HPA system regulation, cognitive functioning, and psychopathology in depressed inpatients on admission and at discharge. METHODS The HPA system dysregulation was evaluated with the dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test. Cognitive assessment included speed of information processing, divided and selective attention, as well as short-term and working memory. Psychopathology was evaluated with the Hamilton Rating Scale for Depression (HAMD). Data from 75 depressed inpatients are reported, 51 (68%) of them achieved remission. RESULTS Despite a significant reduction of depressive symptoms between admission and discharge, a high rate of patients remained cognitively impaired. Selective attention improved significantly in remitters and nonremitters, while speed of information processing increased only in remitters. The cortisol response to the DEX/CRH test decreased significantly only in remitters, which was uncorrelated with cognitive performance. In nonremitters, severity of depression was significantly correlated with information processing time while improvement in short-term memory was negatively associated with the cortisol response at discharge. CONCLUSIONS Our data support the assumption that psychopathological symptoms and the HPA system dysregulation can be dissociated in their impact on cognitive functioning in depressed patients.

Visual motion perception after brain damage: I. Deficits in global motion perception

We report on the test results of a group of 32 mostly unilaterally brain-damaged patients examined for global visual motion perception. Three of these patients had severely impaired visual motion perception in their contralateral visual half-field, a deficit remarkably similar to the perceptual defects found in V5-lesioned monkeys. Two of these three patients had a right-hemisphere lesion; the remaining one had a left-hemisphere lesion. We conclude that both hemispheres of the human brain contain an area, functionally equivalent to V5, which subserves visual motion perception in the contralateral visual half-field. Lesion analysis revealed that this area is located in the posterior medial temporal gyrus.

Top-down selective visual attention: a neurodynamical approach.

We propose a system of interconnected modules consisting of populations of neurons for modelling the underlying mechanisms involved in selective visual attention. We demonstrate that it is plausible to build a neural system for visual search, which works across the visual field in parallel, but, due to the intrinsic dynamics of the system, resembles apparent modes of visual attention, namely the serial focal and the parallel spread over the space mode. Thus, neither explicit serial focal search nor saliency maps need to be assumed. A focal attentional spotlight is not included in the system but rather focal attention emerges due to the convergence of the dynamic behaviour of the neural networks. The dynamics of the system can be interpreted as a mechanism for routing information from the sensory input.

Visual motion perception after brain damage: II. Deficits in form-from-motion perception

We investigated form-from-motion perception (FFM perception) in a sample of 39 patients with acquired brain damage. Pronounced FFM deficits were found in two patients (FM1 and FM2) with biparietal lesions. Both patients were able to identify the relevant figure, when it was not embedded in obstructive texture. Moreover, they could localize the figures in the FFM condition, although they could not reliably identify them. The two patients had normal motion coherence thresholds. Their performance in a static figure-ground task did not differ from that of other patients. These findings imply that the FFM deficits are not caused by impairment of basic visual motion or form perception but are the consequence of damage to a parietal brain structure involved in the combined analysis of visual motion and form information. The nature and functional role of this brain structure as well as the implications of our results for models of FFM perception are discussed.