The neural correlates of the visual consciousness in schizophrenia: an fMRI study.

In the current literature, two distinct and opposite models are suggested to explain the consciousness disorders in schizophrenia. The first one suggests that consciousness disorders rely on a low-level processing deficit, when the second model suggests that consciousness disorders rely on disruption in the ability to consciously access information, with preserved unconscious processing. The current study aims to understand the mechanisms associated with visual consciousness disorder in order to pave the road that will settle the debate regarding these hypotheses. During a functional magnetic resonance imaging session, 19 healthy participants (HC) and 15 patients with schizophrenia (SCZ) performed a visual detection task to compare the neural substrates associated with the conscious access to the visual inputs. The visual detection threshold was significantly higher in SCZ than in HC [t(32) = 3.37, p = 0.002]. Whole-brain ANOVA demonstrated that around the visual detection threshold patients with SCZ failed to activate a large network of brain areas compared to HC. (1) During conscious vision, HC engaged more the left cuneus and the right occipital cortex than patients with SCZ, (2) during unconscious vision, HC engaged a large network that patients with SCZ failed to activate, and finally, (3) during the access to consciousness process, patients with SCZ failed to activate the anterior cingulate cortex. These results suggest that the consciousness disorders in schizophrenia rely on specific dysfunctions depending on the consciousness stage. The disorders of the conscious vision are associated with dysfunction of occipital areas while the ones associated with unconscious vision rely on a large widespread network. Finally, the conscious access to the visual inputs is impaired by a dysfunction of the anterior cingulate cortex. The current study suggests that none of the two suggested models can explain consciousness disorders in schizophrenia. We suggest that there is an alternative model supporting that the conscious access to visual inputs is due to a disengagement of the supragenual anterior cingulate during the unconscious processing of the visual inputs associated with a sensory deficit.

[Delusional misidentification syndromes: A factor associated with violence? Literature review of case reports]. / Les syndromes délirants d'identification : un facteur associé à la violence ? Revue de littérature à partir d'études de cas.

OBJECTIVES: Delusional misidentification syndromes (DMS) correspond to the delusional belief of misidentification of familiar persons, places or objects and to the conviction that they have been replaced or transformed. Several cases of patients who developed violent behavior while suffering from DMS have been published. This led some authors to consider patients with DMS at risk of violence. However, only a few studies have focused on the potential relationship between violence and DMS. The aim of our study was to explore this relationship with a literature review of published cases of patients having committed violent acts associated to DMS. METHODS: A systematic literature search was conducted on PubMed up to January 2017 using the following term combination "misidentification" and "violence" Fifteen cases of patients with DMS who had committed violent acts were identified. The data from these descriptions were analyzed and synthetized. RESULTS: Most of the patients were men with a diagnosis of schizophrenia and Capgras syndrome. Acts of violence were severe with a relatively high number of murders or attempted murders. For half of the patients these violent acts were perpetrated with weapons. Victims were regularly the patient's family members and the assaults were usually not planned. Delusional syndromes often progressed for several years. Importantly, substance abuse, which is known to increase the risk of violence in patients with schizophrenia, was only observed in two patients. CONCLUSION: DMS are associated with several risk factors of violence, such as a diagnosis of schizophrenia, specific delusions including megalomania, persecution, negative affects and identified targets. Despite this risk for severe violence, there are no existing guidelines on how to assess and treat DMS in schizophrenia. Accordingly, we propose (1) the establishment of formal diagnostic criteria, (2) the development of rigorous research on these syndromes and (3) the integration of DMS in assessment of violence risk in schizophrenic patients.

The multimodal connectivity of the hippocampal complex in auditory and visual hallucinations.

Hallucinations constitute one of the most representative and disabling symptoms of schizophrenia. Several Magnetic Resonance Imaging (MRI) findings support the hypothesis that distinct patterns of connectivity, particularly within networks involving the hippocampal complex (HC), could be associated with different hallucinatory modalities. The aim of this study was to investigate HC connectivity as a function of the hallucinatory modality, that is, auditory or visual. Two carefully selected subgroups of schizophrenia patients with only auditory hallucinations (AH) or with audio-visual hallucinations (A+VH) were compared using the following three complementary multimodal MRI methods: resting state functional MRI, diffusion MRI and structural MRI were used to analyze seed-based Functional Connectivity (sb-FC), Tract-Based Spatial Statistics (TBSS) and shape analysis, respectively. Sb-FC was significantly higher between the HC, the medial prefrontal cortex (mPFC) and the caudate nuclei in A+VH patients compared with the AH group. Conversely, AH patients exhibited a higher sb-FC between the HC and the thalamus in comparison with the A+VH group. In the A+VH group, TBSS showed specific higher white matter connectivity in the pathways connecting the HC with visual areas, such as the forceps major and the inferior-fronto-occipital fasciculus than in the AH group. Finally, shape analysis showed localized hippocampal hypertrophy in the A+VH group. Functional results support the fronto-limbic dysconnectivity hypothesis of schizophrenia, while specific structural findings indicate that plastic changes are associated with hallucinations. Together, these results suggest that there are distinct connectivity patterns in patients with schizophrenia that depend on the sensory-modality, with specific involvement of the HC in visual hallucinations.

Functional integration in schizophrenia: too little or too much? Preliminary results on fMRI data.

The disconnectivity hypothesis proposes that schizophrenia results from poor or miswired anatomical connections. Theoretically, its functional counterpart should be disintegration. Integration is thought to allow segregated neurons to interact as a coherent whole, referred to as the "core", while the non-interacting part of the brain is referred to as the "rest". In this study, it is suggested that schizophrenia is the result of rest noise interfering with core activity. Two possible causes are assessed: (i) defective core integration, making the core more vulnerable to noise from the rest, or (ii) the rest being too highly integrated, meaning that it can interfere with the core. These hypotheses were tested using fMRI data acquired from 13 stabilized medicated schizophrenic subjects compared to 11 matched controls. Subjects were required to perform a series of lexical decision and retrieval tasks in separate sessions. The brain was divided into 90 components. Integration was defined as the amount of information shared between the components of a sub-system. An iterative aggregation procedure made it possible to identify a core on the basis of the functional clustering index, which assesses the integration of the core relative to its integration with the rest. Correlation of component-pairs within the core was also compared between the two groups. This procedure was repeated for each subject and for each task. Cores did not differ between the two groups, either in terms of integration or in terms of functional clustering index. However, the core was still highly integrated with the rest and the rest was overly integrated in schizophrenic subjects. Both anomalies were correlated with the negative symptoms. These findings were consistent regardless of the task considered. Furthermore, within the core, anterior-posterior correlations were lower in patients (between the frontal and the parietal and posterior cingulate cortices), whereas frontal left-right correlations were excessive. No significant correlation was found with the medication. Thus, it appears that schizophrenia entails a deleterious combination of too much "noisy" integration (from the rest) and too little "significant" integration (anterior-posterior functional connectivity).

Neural correlates of implicit object identification.

The present study sought to assess neural correlates of implicit identification of objects by means of fMRI, using tasks that require matching of the physical properties of objects. Behavioural data suggests that there is automatic access to object identity when observers attend to a physical property of the form of an object (e.g. the object's orientation) and no evidence for semantic processing when subjects attend to colour. We evaluated whether, in addition to neural areas associated with decisions to specific perceptual properties, areas associated with access to semantic information were activated when tasks demanded processing of the global configuration of pictures. We used two perceptual matching tasks based on the global orientation or on the colour of line drawings. Our results confirmed behavioural data. Activations in the inferior occipital cortex, fusiform and inferior temporal gyri in both tasks (orientation and colour) account for perceptual and structural processing involved in each task. In contrast, activations in the posterior and medial parts of the fusiform gyrus, shown to be involved in explicit semantic judgements, were more pronounced in the orientation-matching task, suggesting that semantic information from the pictures is processed in an implicit way even when not required by the task. Thus, this study suggests that cortical regions usually involved in explicit semantic processing are also activated when implicit processing of objects occurs.

Electrical stimulation of anterior visual pathways in retinitis pigmentosa.

PURPOSE: To explore electrically induced phosphenes in blind patients with retinitis pigmentosa (RP) in comparison with healthy subjects and to develop a screening test for candidates for an optic nerve visual prosthesis implantation. METHODS: Phosphenes are obtained by charge balanced biphasic pulse stimulations through a surface cathode over the closed eyelids and an anode near the opposite ear. The resulting strength-duration relationship for somatosensory, phosphene, and pain threshold has been recorded in five RP patients as well as in 10 healthy volunteers. RESULTS: In sighted subjects, the average rheobase and chronaxy for phosphene perception are 0.28 mA and 3.07 msec, respectively. For pulse durations longer than 2 msec, phosphenes are usually obtained at current strengths below the level giving rise to any other electrically generated sensation. In RP patients, however, phosphenes are not so easily obtained. One in five had no visual response at all. Another patient reported a flash perception for the longest pulse durations only. Spontaneous phosphenes interfered heavily with the stimulation in a third person. Finally, despite the higher threshold, two patients displayed normally shaped strength-duration curves. CONCLUSIONS: The surface stimulation has proven harmless, adequate, and very helpful to ascertain that the optic nerve can be electrically activated in completely blind individuals. Long-duration stimulation pulses yield very low phosphene thresholds in healthy subjects. Anterior visual pathways activation requires higher currents in RP patients.

Automatic object identification: an fMRI study.

Boucart and Humphreys reported an automatic access to object identity when observers attend to a physical property of the form of an object (e.g. the orientation) but not to its colour. We sought evidence for automatic identification in a brain imaging study using fMRI. In an orientation decision task participants decided whether a picture was vertical or horizontal. In the colour decision task participants decided if a picture was blue or green. Activation of areas 18-19 was found for both color and orientation. Activation of the temporal area 37 occurred more frequently in the orientation than in the colour decision task. This result suggests that automatic identification activates the same brain area as overt processing of semantic information.

The Piéron function in the threshold region.

The Piéron function (Piéron, 1914, 1920, 1952) describes the decay of reaction time (RT) when the intensity of the stimulus is increased. It is generally demonstrated within a suprathreshold range of intensities. However, in some studies, for the lowest range of intensities, the exponent of the function is clearly greater than that for the upper ranges of intensities. Such an increase in the exponent for the lowest intensities is assumed to result from a combined effect of stimulus intensity and of stimulis uncertainty in detection. Our first experiment used luminance levels that covered all the scotopic range and a spatial two-alternative forced-choice task in which both accuracy and RT were measured. It demonstrated a drastic increase in the exponent in the Piéron function when the intensities reached the threshold region. Since the estimates of the threshold region may have been biased by the use of a much larger range of luminances, a second experiment was conducted using luminances that covered only the threshold region. This experiment confirmed the previous estimates for the threshold region.

Response times to Ehrenstein illusions of varying subjective magnitude: complementarity of psychophysical measures.

The following experiments investigate the effects of contrast polarity, inducer spacing, and inducer type on three dependent variables measuring the perception of an illusory surface in Ehrenstein figures: subjective magnitude, response time, and frequency of perception. It was found that response time generally decreased when the other two behavioral indicators increased. However, it was also shown that subjective magnitude provided more discriminating measures of relatively strong illusory percepts, whereas frequency of perception and response time provided more discriminating measures of relatively weak illusory percepts. The findings generally confirm earlier work on the effect of inducer spacing and contrast polarity on the perceived strength of brightness illusions, and in particular reveal the complementarity of subjective magnitude, response time, and frequency of perception as critical measures of configurational effects in the perceptual processing of these phenomena.

Visual sensations produced by optic nerve stimulation using an implanted self-sizing spiral cuff electrode.

A blind volunteer with retinitis pigmentosa was chronically implanted with a self-sizing spiral cuff electrode around an optic nerve. Electrical stimuli applied to the nerve produced localized visual sensations that were broadly distributed throughout the visual field and could be varied by changing the stimulating conditions. These results demonstrate the potential for constructing a visual prosthesis, based on electrical stimulation of the optic nerve, for blind subjects who have intact retinal ganglion cells.

Diurnal rhythmicity for visual sensitivity in humans?

Visual sensitivity rhythm has been assessed by several authors in animals. It shows an intrinsic circadian rhythm of some retinal mechanisms that could account for fluctuating sensitivity to light during the day in these species. However, very little is known concerning a possible circadian rhythm of visual sensitivity in humans. The present experiment was designed to assess a diurnal rhythm of visual sensitivity using psychophysical methods. Two different detection threshold measures (adaptive and constant methods) were applied on 7 highly entrained subjects. The results show a strongly increased visual detection threshold in the morning (8:00 h) in 4 of 7 subjects, followed by an important improvement at 10:00 h, after which time it remains almost constant whatever the method used. But 3 subjects had constant thresholds throughout the day. A "first session" effect as well as a "chronotype" effect were ruled out. The results are discussed in terms of a possible effect of sleep inertia, suggesting a long-lasting effect probably dependent on the type of task.

On the relation between stimulus intensity and processing time: Piéron's law and choice reaction time.

Piéron (1914, 1920, 1952) demonstrated that simple reaction time (SRT) decays as a hyperbolic function of luminance in detection tasks. However, whether such a relationship holds equally for choice reaction time (CRT) has been questioned (Luce, 1986; Nissen, 1977), at least when the task is not brightness discrimination. In two SRT and three CRT experiments, we investigated the function that relates reaction time (RT) to stimulus intensity for five levels of luminance covering the entire mesopic range. The psychophysical experiments consisted of simple detection, two-alternative forced choice (2 AFC) with spatial uncertainty, 2 AFC with semantic categorization, and 2 AFC with orientation discrimination. The results of the experiments showed that mean RT increases with task complexity. However, the exponents of the functions relating RT to stimulus intensity were found to be similar in the different experiments. This finding indicates that Piéron's law holds for CRT as well as for SRT. It describes RT as a power function of stimulus intensity, with similar exponents, regardless of the complexity of the task.

Determinants of deranged sodium and water homeostasis in decompensated cirrhosis.

Previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant central hypervolemia induced by water immersion to the neck (NI) results in a significant natriuresis, kaliuresis, and diuresis. The NI model was utilized to assess the role of "effective volume" and hyperaldosteronism in the impairment of sodium and water handling in cirrhosis. Eleven cirrhotic patients were studied twice while in balance on a 10 mEq. Na, 100 mEq. K diet: control and NI. The conditions of seated posture and time of day were identical. UNaV was constant throughout C, ranging from 1 to 2 muEq per minute. During NI, UNaV increased progressively from 1 +/- 1 (S.E.M.) during the prestudy hour to 89 +/- 32 muEq per minute during hour 5 of NI (p less than 0.02), greatly exceeding the comparable value found in normal subjects on an identical diet. (See article).

Failure of water immersion to influence parathyroid hormone secretion and renal phosphate handling in normal man.

Previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant relative central hypervolemia induced by water immersion to the neck (NI) results in a significant natriuresis which is quantitatively identical to that induced by the acute administration of 2 L. of saline. Since the central hypervolemia induced by NI occurs without concomitant alterations in serum ionized calcium concentration (Ca++), the NI model was utilized to assess the role of volume in the regulation of PTH secretion in man. Seven normal subjects were studied following 11 hours of dehydration on two occasions, control and NI. The conditions of seated posture and time of day were identical. Blood for ionized calcium and PTH was obtained at 30-minute intervals for 6 hours. NI resulted in a significant increase in UNaV from a prestudy value of 78 +/- 12 (S.E.M.) to 222 +/- 20 muEq per minute (p less than 0.001). Concomitantly, Ca++ remained constant, ranging between 4.57 to 4.71 mg. per cent. Despite the volume-induced natriuresis, PTH was not altered throughout 5 hours of NI, ranging from 36 +/- 7 to 45 +/- 5 mul-Eq. per milliliter. Phosphate excretion remained constant. These data indicate that central volume expansion does not alter PTH in normal man when the variables of ionized calcium, posture, and time of day are controlled. Furthermore, the current demonstration of the absence of phosphaturia during immersion despite the probability that the distal delivery of phosphate was enhanced, permits consideration of the possibility that the concept of a distal tubular reabsorptive site for phosphate may be applicable to man.

Suppression of plasma renin and plasma aldosterone during water immersion in normal man.

Previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant relative central hypervolemia induced by water immersion to the neck (NI) results in a significant natriuresis which is quantitative identical to that induced by the acute administration of 2 liters of saline. Since the central hypervolemia induced by NI occurs without concomitant alterations in serum sodium and potassium concentration, the NI model was utilized to assess the role of volume in the regulation of both plasma renin (PRA) and plasma aldosterone (PA) in man. Nine normal subjects were studied on two occasions while in balance on a 10 meq Na, 100 meq K diet; Control and NI. The conditions of seated posture and time of day were identical. Blood for PRA and PA was obtained at 30-min intervals for 6 h. NI produced a profound suppression of PRA as early as 30 min with maximal suppression (62%) by 180 min (P less than 0.001). Recovery from NI was associated with a prompt return to pre-study levels. The changes in PA paralleled those of PRA with regard to both the rapidity and magnitude of the suppression (r = 0.993: P less than 0.001). These data emphasize the importance of central volume per se as a primary determinant of PRA and PA regulation in normal man. Furthermore, the current studies confirm the importance of the renin-angiotensin axis in the control of volume-related changes in PA in normal man. The ability of NI to induce a prompt and parallel suppression of PRA and PA without concomitant alterations in plasma composition, suggests that NI may be a preferred investigative tool for assessing the effects of volume expansion on renin-aldosterone.

Comparison of water immersion and saline infusion as a means of inducing volume expansion in man.

Although previous studies have demonstrated that water immersion to the neck (NI) results in both central hypervolemia and a significant natriuresis, it is unclear whether the magnitude of the "volume stimulus" of NI is comparable to that induced by the extracellular fluid volume expansion (ECVE) induced by acute saline administration. The present study was undertaken therefore to compare the natriuresis induced by these two different stimuli. All subjects were studied on four occasions while in balance on a diet containing 150 meq of sodium and 80 meq of potassium daily: seated control; seated immersion; and saline administration in both the seated and recumbent posture. The increment in UNaV during NI was indistinguishable from that of seated saline. Similarly, the kaliuretic response during NI was similar to that induced by seated saline infusion. In contrast, supine saline infusion resulted in a greater increment in UNaV than either NI or seated saline. The present data indicate that the "volume stimulus" of immersion is identical with that of standard saline-induced ECVE in normal seated subjects. Furthermore, the ability of NI to induce a natriuresis without a concomitant increase in total blood volume and with a decrease in body weight, rather than the increase which attends saline infusion, suggests that NI may be a preferred investigative tool for assessing the effects of ECVE in man.

Suppression of ADH during water immersion in normal man.

Since previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant relative central hypervolemia induced by water immersion to the neck causes a profound natriuresis and a suppression of the renin-aldosterone system, it was of interest to assess whether the diuresis induced by immersion was mediated by an analogous inhibition of ADH. The effects of water immersion on renal water handling and urinary ADH excretion were assessed in 10 normal male subjects studied following 14 h of overnight dehydration on two occasions, control and immersion. The conditions of seated posture and time of day were identical. During control ADH persisted at or above prestudy values. Immersion resulted in a progressive decrease in ADH excretion from 80.1 plus or minus 7 (SEM) to 37.3 plus or minus 6.3 muU/min (P smaller than 0.025). Cessation of immersion was associated with a marked increase in ADH from 37.3 +/- 6.3 muU/min to 176.6 +/- 72.6 muU/min during the recovery hour (P smaller than 0.05). Concomitant with these changes urine osmolality decreased significantly beginning as early as the initial hour of immersion from 1044 +/- 36 to 542 +/- 66 mosmol/kg H2O during the final hour of immersion (P smaller than 0.001). Recovery was associated with a significant mean increase in Uosm of 190 +/- 40 mosmol/kg H2O over the final hour of immersion (P smaller than 0.001). The suppression of ADH occurred without concomitant changes in plasma tonicity. These studies are consistent with the suggestion that in hydrated subjects undergoing immersion suppression of ADH release contributes to the enhanced free water clearance, which has been previously documented.