Pharmacological elevation of catecholamine levels improves perceptual decisions, but not metacognitive insight.

Perceptual decisions are often accompanied by a feeling of decision confidence. Where parietal cortex is known for its crucial role in shaping such perceptual decisions, metacognitive evaluations are thought to additionally rely on (pre-)frontal cortex. Because of this supposed neural differentiation between these processes, perceptual and metacognitive decisions may be divergently affected by changes in internal (e.g., attention, arousal) and external (e.g., task and environmental demands) factors. Although intriguing, causal evidence for this hypothesis remains scarce. Here, we investigated the causal effect of two neuromodulatory systems on behavioral and neural measures of perceptual and metacognitive decision-making. Specifically, we pharmacologically elevated levels of catecholamines (with atomoxetine) and acetylcholine (with donepezil) in healthy adult human participants performing a visual discrimination task in which we gauged decision confidence, while electro-encephalography (EEG) was measured. Where cholinergic effects were not robust, catecholaminergic enhancement improved perceptual sensitivity, while at the same time leaving metacognitive sensitivity unaffected. Neurally, catecholaminergic elevation did not affect sensory representations of task-relevant visual stimuli, but instead enhanced well-known decision signals measured over centroparietal cortex, reflecting the accumulation of sensory evidence over time. Crucially, catecholaminergic enhancement concurrently impoverished neural markers measured over frontal cortex linked to the formation of metacognitive evaluations. Enhanced catecholaminergic neuromodulation thus improves perceptual, but not metacognitive decision-making.Significance statement Perceptual decisions about sensory input and the metacognitive evaluation of the accuracy of such decisions may be inversely affected by neuromodulatory systems regulating organisms' arousal levels. We tested this hypothesis by pharmacologically manipulating two neuromodulator systems (catecholaminergic, cholinergic) in humans, while measuring EEG. Elevated levels of catecholamines, but not acetylcholine, increased the accuracy of perceptual decisions, but not the accuracy of metacognitive evaluations thereof. Further, catecholamines enhanced neural markers over parietal cortex associated with the accumulation of evidence used for perceptual decision-making, while perturbing markers of metacognitive decision-making over frontal cortex. These findings align with current theories of perceptual decision-making, metacognition and cortical functioning and improve our understanding of the important role of neuromodulation in shaping human behavior and cognition.

Slow segmentation of faces in Autism Spectrum Disorder.

Atypical visual segmentation, affecting object perception, might contribute to face processing problems in Autism Spectrum Disorder (ASD). The current study investigated impairments in visual segmentation of faces in ASD. Thirty participants (ASD: 16; Control: 14) viewed texture-defined faces, houses, and homogeneous images, while electroencephalographic and behavioral responses were recorded. The ASD group showed slower face-segmentation related brain activity and longer segmentation reaction times than the control group, but no difference in house-segmentation related activity or behavioral performance. Furthermore, individual differences in face-segmentation but not house-segmentation correlated with score on the Autism Quotient. Segmentation is thus selectively impaired for faces in ASD, and relates to the degree of ASD traits. Face segmentation relates to recurrent connectivity from the fusiform face area (FFA) to the visual cortex. These findings thus suggest that atypical connectivity from the FFA might contribute to delayed face processing in ASD.

Prior Knowledge about Objects Determines Neural Color Representation in Human Visual Cortex.

To create subjective experience, our brain must translate physical stimulus input by incorporating prior knowledge and expectations. For example, we perceive color and not wavelength information, and this in part depends on our past experience with colored objects ( Hansen et al. 2006; Mitterer and de Ruiter 2008). Here, we investigated the influence of object knowledge on the neural substrates underlying subjective color vision. In a functional magnetic resonance imaging experiment, human subjects viewed a color that lay midway between red and green (ambiguous with respect to its distance from red and green) presented on either typical red (e.g., tomato), typical green (e.g., clover), or semantically meaningless (nonsense) objects. Using decoding techniques, we could predict whether subjects viewed the ambiguous color on typical red or typical green objects based on the neural response of veridical red and green. This shift of neural response for the ambiguous color did not occur for nonsense objects. The modulation of neural responses was observed in visual areas (V3, V4, VO1, lateral occipital complex) involved in color and object processing, as well as frontal areas. This demonstrates that object memory influences wavelength information relatively early in the human visual system to produce subjective color vision.

The spatiotemporal profile of cortical processing leading up to visual perception.

Much controversy exists around the locus of conscious visual perception in human cortex. Some authors have proposed that its neural correlates correspond with recurrent processing within visual cortex, whereas others have argued they are located in a frontoparietal network. The present experiment aims to bring together these competing viewpoints. We recorded EEG from human subjects that were engaged in detecting masked visual targets. From this, we obtained a spatiotemporal profile of neural activity selectively related to the processing of the targets, which we correlated with the subjects' ability to detect those targets. This made it possible to distinguish between those stages of visual processing that correlate with human perception and those that do not. The results show that target induced extra-striate feedforward activity peaking at 121 ms does not correlate with perception, whereas more posterior recurrent activity peaking at 160 ms does. Several subsequent stages show an alternating pattern of frontoparietal and occipital activity, all of which correlate highly with perception. This shows that perception emerges early on, but only after an initial feedforward volley, and suggests that multiple reentrant loops are involved in propagating this signal to frontoparietal areas.

Masking disrupts reentrant processing in human visual cortex.

In masking, a stimulus is rendered invisible through the presentation of a second stimulus shortly after the first. Over the years, authors have typically explained masking by postulating some early disruption process. In these feedforward-type explanations, the mask somehow "catches up" with the target stimulus, disrupting its processing either through lateral or interchannel inhibition. However, studies from recent years indicate that visual perception--and most notably visual awareness itself--may depend strongly on cortico-cortical feedback connections from higher to lower visual areas. This has led some researchers to propose that masking derives its effectiveness from selectively interrupting these reentrant processes. In this experiment, we used electroencephalogram measurements to determine what happens in the human visual cortex during detection of a texture-defined square under nonmasked (seen) and masked (unseen) conditions. Electro-encephalogram derivatives that are typically associated with reentrant processing turn out to be absent in the masked condition. Moreover, extrastriate visual areas are still activated early on by both seen and unseen stimuli, as shown by scalp surface Laplacian current source-density maps. This conclusively shows that feedforward processing is preserved, even when subject performance is at chance as determined by objective measures. From these results, we conclude that masking derives its effectiveness, at least partly, from disrupting reentrant processing, thereby interfering with the neural mechanisms of figure-ground segmentation and visual awareness itself.

Long-term residual complaints and psychosocial sequelae after remission of hyperthyroidism.

The issue of residual complaints after treatment for hyperthyroidism in current euthyroid patients was investigated by means of a survey. Patients treated for hyperthyroidism were selected from medical records of the previous 6 years in two Dutch University Clinics. After the exclusion of patients with comorbidity, 303 one-time hyperthyroid respondents were included in the analysis. A total of 77% of these patients had been diagnosed with Graves' Disease. The newly developed Hyperthyroidism Complaint Questionnaire (HCQ), was used to quantify problems of somatic and mental functioning. The SymptomsCheckList-90 (SCL-90) was used to assess self-reported psychopathological symptoms, the Nottingham Health Profile was used to measure perceived health/quality of life. Dysthyroid patients (n = 20) had a mean HCQ-score of 14.5 (+/- 8.1) complaints; patients who reported euthyroidism for less than 12 months (n = 171) had a mean of 9.3 (+/- 7.6) residual complaints; patients who reported euthyroidism for more than 12 months (n = 54) a mean of 6.6 (+/- 6.8) residual complaints. On each dimension of psychopathology covered by the SCL-90, including depression and anxiety, approximately one third of the total sample had a score exceeding 80% of adult females. According to the NHP lack of energy was evident in 53% of all respondents. Over one third of patients with a full-time job were unable to resume the same work after treatment. It appears that many of these patients are in need of psychological support.

Signs of emotional disturbance three years after early hospitalization.

Tested by a retrospective study the hypothesis that children in the 6-36 months age range in case of lengthy (> 3 days) or repeated (more than once) hospitalization are susceptible to persistent emotional disturbances. Families of children with such a "risky" hospitalization history were approached by mail, several years (M = 36 months, SD = 10) after the latest discharge. The parents of these children (N = 40; mean age 59 months) and of a control group without a risky hospitalization history (N = 73; mean age 58 months) reported about current problem behavior of their child. Scores on the Behaviour Checklist (Richman et al., 1982) were significantly (p < .05) elevated in the sample. Specific signs were poor concentration, immoderate attention seeking, deficits of bowel control, and fearfulness. Cases of surgery significantly exceeded others in signs of disturbance. Although the protective value of parental attendance could not be demonstrated in this study, on the basis of prior research, rooming-in is recommended as a necessary precaution in the 6-36 months age range.