Brain connectivity changes occurring following cognitive behavioural therapy for psychosis predict long-term recovery

Little is known about the psychobiological mechanisms of cognitive behavioural therapy for psychosis (CBTp) and which specific processes are key in predicting favourable long-term outcomes. Following theoretical models of psychosis, this proof-of-concept study investigated whether the long-term recovery path of CBTp completers can be predicted by the neural changes in threatbased social affective processing that occur during CBTp. We followed up 22 participants who had undergone a social affective processing task during functional magnetic resonance imaging along with self-report and clinician-administered symptom measures, before and after receiving CBTp. Monthly ratings of psychotic and affective symptoms were obtained retrospectively across 8 years since receiving CBTp, plus self-reported recovery at final follow-up. We investigated whether these long-term outcomes were predicted by CBTp-led changes in functional connections with dorsal prefrontal cortical and amygdala during the processing of threatening and prosocial facial affect. Although long-term psychotic symptoms were predicted by changes in prefrontal connections during prosocial facial affective processing, long-term affective symptoms were predicted by threat-related amygdalo-inferior parietal lobule connectivity. Greater increases in dorsolateral prefrontal cortex connectivity with amygdala following CBTp also predicted higher subjective ratings of recovery at long-term follow-up. These findings show that reorganisation occurring at the neural level following psychological therapy can predict the subsequent recovery path of people with psychosis across 8 years. This novel methodology shows promise for further studies with larger sample size, which are needed to better examine the sensitivity of psychobiological processes, in comparison to existing clinical measures, in predicting long-term outcomes.Wellcome Trust; Biomedical Research Centre for Mental Health at the Institute of Psychiatry, Psychology & Neuroscience, King’s College London and South London and Maudsley NHS Foundation Trust, U

Psychophysical and fMRI measures of shape learning in the human visual cortex

The aim of this study was to investigate the effect of learning in the integration of local elements into coherent visual shapes. Human early (V1, V2, VP, V4) and higher visual areas known to be involved in the analysis of shape information (Lateral Occipital Complex-LOC) have been implicated in the perceptual integration of global shapes. We used event-related fMRI to investigate the effect of learning in the neural representation of shapes across the human visual cortex. The stimuli consisted of symmetrical and asymmetrical closed contours rendered by aligned gabor elements and embedded in random gabor background fields. Two stimuli were presented simultaneously in each trial to the left and right of the fixation point and the subjects were instructed to report which stimulus contained the symmetrical contour. Behavioral and fMRI responses were recorded while observers performed the 2-AFC shape discrimination task in two different sessions, one before and one after three days of training. Observers were shown different sets of novel stimuli in every session and a set of training stimuli rendered in novel backgrounds across trials. Prior to training, no differences were observed in the behavioral performance or the fMRI responses across visual areas for the novel vs. the training stimulus set. However, after training the observers showed significantly improved accuracy in the discrimination task for learned vs. novel shapes. Consistently, fMRI responses in the early and the higher visual areas were significantly stronger for learned than novel stimuli. These results provide evidence for behavioral and neuronal learning-based plasticity in the human visual areas involved in coherent shape perception

Effects of attention on perceptual learning of shapes in the human visual cortex

Perceptual learning and attention have been shown to modulate visual processing in the human brain. This study used fMRI to investigate the effect of these processes in the representation of shapes in early (V1, V2, VP, V4) and higher visual areas known to be involved in shape processing (Lateral Occipital Complex-LOC). The stimuli consisted of closed contours rendered by aligned gabor elements and embedded in two different background types: a) random gabor elements that interfered with the detection and integration of the contour elements (distributed attention condition) or b) uniformly-oriented elements that facilitated these processes (focused attention condition). We measured behavioral and fMRI responses while observers performed a 2-AFC shape discrimination task in two different sessions, one before and one after three days of training. Observers were trained in the distributed attention condition and were tested in both attention conditions on novel and learned shapes. Prior to training, no differences were observed in the behavioral performance or the fMRI responses across early and higher visual areas for the novel vs. the training shapes. After training, the observers showed significantly higher accuracy in the discrimination task for learned vs. novel shapes in both the distributed and the focused attention conditions. fMRI responses across visual areas were significantly stronger for learned than novel stimuli in the distributed attention condition. Interestingly, fMRI responses in the posterior subregion of the LOC (LO), known to be involved in the representation of shape features, showed stronger responses for novel than learned stimuli in the focused attention condition. These results suggest that increased shape saliency due to focused attention may enhance the tuning of the feature representation for familiar shapes and facilitate the representation of novel shape features

Repetition priming in 3-D form and motion recognition

Behavioural studies have highlighted the importance of dynamic information for object recognition: Object motion provides additional views and image features that may facilitate the extraction of 3-D shape. However, even the direction of in-depth rotation that controls for shape and view information affects recognition performance. Here, we used a priming paradigm to investigate the effects of motion direction and form as well as their interaction during dynamic object recognition. Furthermore, two task-contexts were used to investigate the effects of top - down modulation on behavioural priming effects. For these contexts, subjects responded on the basis of object form or motion. Subjects were presented with pairs of successive objects rotating in depth. They performed a two-alternative forced choice form or motion categorisation to the second object. The conditions conformed to a 2 × 2 × 2 factorial design manipulating (i) object form (same/different pairs), (ii) in-depth rotation (same/different pairs), and (iii) task (motion/form). We observed that form and motion priming effects interacted and were enhanced in congruent task context. These findings suggest that dynamic 3-D object recognition is accomplished through interaction of form and motion information. Furthermore, both form and motion priming are influenced by task requirements. Future fMRI studies will investigate these effects at the neuronal level

Emotion unfolded by motion: a role for parietal lobe in decoding dynamic facial expressions

Facial expressions convey important emotional and social information and are frequently applied in investigations of human affective processing. Dynamic faces may provide higher ecological validity to examine perceptual and cognitive processing of facial expressions. Higher order processing of emotional faces was addressed by varying the task and virtual face models systematically. Blood oxygenation level-dependent activation was assessed using functional magnetic resonance imaging in 20 healthy volunteers while viewing and evaluating either emotion or gender intensity of dynamic face stimuli. A general linear model analysis revealed that high valence activated a network of motion-responsive areas, indicating that visual motion areas support perceptual coding for the motion-based intensity of facial expressions. The comparison of emotion with gender discrimination task revealed increased activation of inferior parietal lobule, which highlights the involvement of parietal areas in processing of high level features of faces. Dynamic emotional stimuli may help to emphasize functions of the hypothesized 'extended' over the 'core' system for face processing

Categorization of complex dynamic patterns in the human brain

The ability to categorize actions is critical for interacting in complex environments. Previous studies have examined the neural correlates of categorization using static stimuli. The goal of our study was to investigate the neural substrates that mediate learning of complex movement categories in the human brain. We used novel dynamic patterns that were generated by animation of an artificial skeleton model and presented as point-light displays. We created prototypical stimuli that differed in the spatial arrangement of their segments and their kinematics. Intermediate stimuli between the prototypes were generated by a weighted linear combination of the prototypical trajectories in space-time. We compared fMRI activations when the observers performed a categorization vs. a spatial discrimination task on the same stimuli. In the categorization task, the observers discriminated whether each stimulus belonged to one of four prototypical classes. In the spatial discrimination task, the observers judged whether each stimulus was rotated (or translated) leftwards vs. rightwards. These tasks were matched for difficulty based on the observers? Performance during a practice session. We observed significantly stronger fMRI activations for the categorization than the spatial discrimination tasks in the dorsal, inferior parietal and the medial, inferior frontal cortex, consistent with previous findings on the categorization of static stimuli. Interestingly, we also observed activations in visual motion areas (V3a, hMT+/V5), higher-order motion areas in the intraparietal sulcus (VOIPS, POIPS, DIPSM, DIPSA) and parieto-frontal areas (supramarginal gyrus, postcentral gyrus, ventral and dorsal premotor cortex) thought to be involved in action observation and imitation. These findings suggest that categorization of complex dynamic patterns may modulate processing in areas implicated in the analysis of visual motion and actions

Categorization of complex dynamic patterns in the human brain

The ability to categorize actions is critical for interacting in complex environments. Previous studies have examined the neural correlates of categorization using static stimuli. The goal of our study was to investigate the neural substrates that mediate learning of complex movement categories in the human brain. We used novel dynamic patterns that were generated by animation of an artificial skeleton model and presented as point-light displays. We created prototypical stimuli that differed in the spatial arrangement of their segments and their kinematics. Intermediate stimuli between the prototypes were generated by a weighted linear combination of the prototypical trajectories in space-time. We compared fMRI activations when the observers performed a categorization vs. a spatial discrimination task on the same stimuli. In the categorization task, the observers discriminated whether each stimulus belonged to one of four prototypical classes. In the spatial discrimination task, the observers judged whether each stimulus was rotated (or translated) leftwards vs. rightwards. These tasks were matched for difficulty based on the observers? Performance during a practice session. We observed significantly stronger fMRI activations for the categorization than the spatial discrimination tasks in the dorsal, inferior parietal and the medial, inferior frontal cortex, consistent with previous findings on the categorization of static stimuli. Interestingly, we also observed activations in visual motion areas (V3a, hMT+/V5), higher-order motion areas in the intraparietal sulcus (VOIPS, POIPS, DIPSM, DIPSA) and parieto-frontal areas (supramarginal gyrus, postcentral gyrus, ventral and dorsal premotor cortex) thought to be involved in action observation and imitation. These findings suggest that categorization of complex dynamic patterns may modulate processing in areas implicated in the analysis of visual motion and actions

Evaluation of anti-melanogenic activity of Ziziphus jujuba fruits obtained by two different extraction methods

Abstract Background and objectives: Dried pulps and peels of Ziziphus jujuba fruits are commonly applied as food because of their high nutritional value. It has been widely used in traditional medicine as laxative, tonic, wound healing agent and appetizer. The aim of this study was to evaluate the antimelanogenic effects of Z. jujuba fruit. Methods: Fruit extracts were obtained by two different extraction methods, percolation (cold extraction) and soxhlet (hot extraction) using methanol 80% as the solvent. The total phenolic and flavonoid contents, DPPH radical scavenging activity and antityrosinase capacity of the MeOH extracts from Z. jujuba fruits were evaluated in vitro. In addition, the effects of fruit extracts on the melanin content and cytotoxicity on human melanoma SKMEL-3 cells were determined after 72 hours. Results: The amount of total phenolic and flavonoid contents of the cold extract were found higher in comparison to the hot extract. Moreover, the antioxidant (SC 50 =1.40 mg/mL) and anti-tyrosinase activities (IC 50 = 0.54 mg/mL) of the cold extract were significantly stronger than the hot extract. At the dose of 500 μg/mL, the cold extract showed weaker toxicity to the melanoma cells than the hot extract. Melanin content of the cold extract was reduced to 30% at this concentration, while the hot extract had no inhibitory effect on melanin formation. Conclusion: The results showed that the percolation method was more suitable for extraction of the (poly) phenolics from Z. jujuba fruits. In addition, the results of tyrosinase activity and melanin content assays suggested that the cold extract of Z. jujuba fruit can be considered as a dermatological whitening agent in skin care products