How can cognitive remediation therapy modulate brain activations in schizophrenia? An fMRI study

Cognitive remediation therapy (CRT) is a non biological treatment that aims to correct cognitive deficits through repeated exercises. Its efficacy in patients with schizophrenia is well recognized, but little is known about its effect on cerebral activity. Our aim was to explore the impact of CRT on cerebral activation using functional magnetic resonance imaging (fMRI) in patients with schizophrenia. Seventeen patients and 15 healthy volunteers were recruited. Patients were divided into two groups: one group received CRT with Rehacom? software (n=8), while a control group of patients (non-CRT group) received no additional treatment (n=9). The three groups underwent two fMRI sessions with an interval of 3months: they had to perform a verbal and a spatial n-back task at the same performance level. Patients were additionally clinically and cognitively assessed before and after the study. After CRT, the CRT group exhibited brain over-activations in the left inferior/middle frontal gyrus, cingulate gyrus and inferior parietal lobule for the spatial task. Similar but nonsignificant over-activations were observed in the same brain regions for the verbal task. Moreover, CRT patients significantly improved their behavioural performance in attention and reasoning capacities. We conclude that CRT leads to measurable physiological adaptation associated with improved cognitive ability. Trial name: Cognitive Remediation Theraphy and Schizophrenia. http://clinicaltrials.gov/ct2/show/NCT01078129. Registration number: NCT01078129.     

Do brain responses to emotional images and cigarette cues differ? An fMRI study in smokers

Chronic smoking is thought to cause changes in brain reward systems that result in overvaluation of cigarette-related stimuli and undervaluation of natural rewards. We tested the hypotheses that, in smokers, brain circuits involved in emotional processing: (i) would be more active during exposure to cigarette-related than neutral pictures; and (ii) would be less active to pleasant compared with cigarette-related pictures, suggesting a devaluation of intrinsically pleasant stimuli. We obtained whole-brain blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data from 35 smokers during the presentation of pleasant (erotica and romance), unpleasant (mutilations and sad), neutral, and cigarette-related pictures. Whole-brain analyses showed significantly larger BOLD responses during presentation of cigarette-related pictures relative to neutral ones within the secondary visual areas, the cingulate gyrus, the frontal gyrus, the dorsal striatum, and the left insula. BOLD responses to erotic pictures exceeded responses to cigarette-related pictures in all clusters except the insula. Within the left insula we observed larger BOLD responses to cigarette-related pictures than to all other picture categories. By including intrinsically pleasant and unpleasant pictures in addition to neutral ones, we were able to conclude that the presentation of cigarette-related pictures activates brain areas supporting emotional processes, but we did not find evidence of overall reduced activation of the brain reward systems in the presence of intrinsically pleasant stimuli.     

How does brain activation differ in children with unilateral cerebral palsy compared to typically developing children, during active and passive movements, and tactile stimulation? An fMRI study

The aim of the functional magnetic resonance imaging (fMRI) study was to investigate brain activation associated with active and passive movements, and tactile stimulation in 17 children with right-sided unilateral cerebral palsy (CP), compared to 19 typically developing children (TD). The active movements consisted of repetitive opening and closing of the hand. For passive movements, an MRI-compatible robot moved the finger up and down. Tactile stimulation was provided by manually stroking the dorsal surface of the hand with a sponge cotton cloth. In both groups, contralateral primary sensorimotor cortex activation (SM1) was seen for all tasks, as well as additional contralateral primary somatosensory cortex (S1) activation for passive movements. Ipsilateral cerebellar activity was observed in TD children during all tasks, but only during active movements in CP children. Of interest was additional ipsilateral SM1 recruitment in CP during active movements as well as ipsilateral S1 activation during passive movements and tactile stimulation. Another interesting new finding was the contralateral cerebellum activation in both groups during different tasks, also in cerebellar areas not primarily linked to the sensorimotor network. Active movements elicited significantly more brain activation in CP compared to TD children. In both groups, active movements displayed significantly more brain activation compared to passive movements and tactile stimulation.     

How does brain activation differ in children with unilateral cerebral palsy compared to typically developing children,during active and passive movements,and tactile stimulation? An fMRI study

The aim of the functional magnetic resonance imaging (fMRI) study was to investigate brain activation associated with active and passive movements, and tactile stimulation in 17 children with right-sided unilateral cerebral palsy (CP), compared to 19 typically developing children (TD). The active movements consisted of repetitive opening and closing of the hand. For passive movements, an MRI-compatible robot moved the finger up and down. Tactile stimulation was provided by manually stroking the dorsal surface of the hand with a sponge cotton cloth. In both groups, contralateral primary sensorimotor cortex activation (SM1) was seen for all tasks, as well as additional contralateral primary somatosensory cortex (S1) activation for passive movements. Ipsilateral cerebellar activity was observed in TD children during all tasks, but only during active movements in CP children. Of interest was additional ipsilateral SM1 recruitment in CP during active movements as well as ipsilateral S1 activation during passive movements and tactile stimulation. Another interesting new finding was the contralateral cerebellum activation in both groups during different tasks, also in cerebellar areas not primarily linked to the sensorimotor network. Active movements elicited significantly more brain activation in CP compared to TD children. In both groups, active movements displayed significantly more brain activation compared to passive movements and tactile stimulation.     

How do changes in body functions and structures,activity, and participation relate in children with cerebral palsy?

Rehabilitation increasingly addresses the International Classification of Functioning, Disability and Health's (ICF) concepts of activity and participation, but little is known about associations between changes in body functions and structures, activity, and participation. We conducted a before-and-after study of 35 ambulatory children with spastic diplegia or hemiplegic cerebral palsy, mean age 5 years 6 months (SD 2 y 2 mo). Children were in Gross Motor Function Classification System (GMFCS) Levels I (n=11), II (n=12), or III (n=12). We assessed body functions and structures, activity, and participation at baseline and at 2 months and 6 months post-botulinum toxin type A (BoNT-A) injection. Repeated-measures analysis of variance evaluated change, and linear regression assessed relationships. Baseline score relationships were moderate to strong but, despite similar directions of change at 2 months, change score relationships between measures of body functions and structures (spasticity and timed walk), activity (Gross Motor Function Measure and Pediatric Evaluation of Disability Inventory), and participation (Pediatric Outcomes Data Collection Instrument) at 2 months and 6 months were poor to fair (r<0.40). Predictor combinations accounted for <69% of variation in activity and participation change scores. Predictors often pertained to baseline score, GMFCS level, or age. Relationships between changes at different ICF levels are complex, and activity and participation gains post-BoNT-A are likely to be influenced by the child and environment factors.     

Can we relate MeCP2 deficiency to the structural and chemical abnormalities in the Rett brain?

The mutated gene for Rett syndrome, MECP2, has now been identified in ninety percent of cases. Molecular biologists are immersed in the study of this gene's biology determining how its mutation could be responsible for such an enigmatic phenotype. In this paper the same question is considered, re-examining the structural phenotype of the Rett brain and asking; is MeCP2 present at the appropriate time and place in brain development to influence the structural and chemical abnormalities which characterize the Rett brain? Data from the literature and previous research suggest that MeCP2 is expressed during critical periods of brain development at several sites and in different neurons. It supports the idea that inadequate functioning of MeCP2 alters trophic factors and raises the possibility that replacement of these factors might improve brain function. The availability of mouse models now makes it possible to test such ideas.     

How do we process event‐based and time‐based intentions in the brain? an fMRI study of prospective memory in healthy individuals

Prospective memory (PM) refers to the ability to remember to do something in the future, either in response to an event (event‐based) or after a certain amount of time has elapsed (time‐based). While the distinction between event‐ and time‐based PM is widely acknowledged in the literature, little is known about the processes they share and those they do not. This is particularly true concerning their brain substrates, as almost all neuroimaging studies so far have focused on event‐based PM. We proposed a functional magnetic resonance imaging paradigm assessing both event‐based and time‐based PM to 20 healthy young individuals. Analyses revealed that event‐ and time‐based PM both induced activation in the posterior frontal and parietal cortices, and deactivation in the medial rostral prefrontal cortex. In addition, activation more specific to each condition, which may underlie differences in strategic monitoring, was highlighted. Thus, occipital areas were more activated during event‐based PM, probably reflecting target‐checking, while a network comprising the dorsolateral prefrontal cortex, the cuneus/precuneus and, to a lesser extent, the inferior parietal lobule, superior temporal gyrus, and the cerebellum, was more activated in time‐based PM, which may reflect the involvement of time‐estimation processes. These results confirm the allocation of attentional resources to the maintenance of intention for event‐based and time‐based PM, as well as the engagement of distinct mechanisms reflecting the monitoring strategies specific to each condition. Hum Brain Mapp 35:3066–3082, 2014. © 2013 Wiley Periodicals, Inc.     

How do the experiences of the early separated and the early bereaved differ and to what extent do such differences affect outcome?

Summary From a survey of 40- to 49-year-old women from Chichester, West Sussex, 45 were selected whose mothers died before they were aged 11, 38 who were evacuated from their mothers during the 1939–1945 War and 45 who were separated from their mothers for other reasons for at least a year before they were aged 10. A series of 69 non-mother-bereaved or non-mother-separated controls of similar age-range was also collected. Each subject was interviewed at home and asked to complete the Middlesex Hospital Questionnaire, a modified Zung Depression Scale and the Navran Dependency Scale of the MMPI. There were significant differences between the groups in terms of place of birth, age of the mother at time of the initial break and size of the original sibship. Significantly more evacuees were cared for by foster mothers and significantly more of the other separations had a poor relationship with their natural mother. For all groups increased test scores were associated with lower parental social class and poor replacement care. Poor outcome was also associated with being later born for the early bereaved, having a poor relationship with the natural mother for the evacuees and being separated after age 4 for the other separations.     

Age-related variables in childhood epilepsy: How do they relate to each other and to quality of life?

How do age of onset and duration of epilepsy correlate with each other and with patient-reported outcomes? To address this question, we explored whether age of onset, duration, and proportion of life with epilepsy are either similar or relatively independent variables that can be used as markers on how children experience the complexity of epilepsy and adjustment.Three hundred ninety-one Canadian and 266 Hong Kong youth with epilepsy completed the childhood epilepsy-specific quality of life (QOL) measure (CHEQOL-25). Each cohort was separately stratified by tertiles for age of onset, life proportion with epilepsy, and duration of epilepsy. Pearson's r was used for correlation analysis.The epilepsy age-related variables correlated strongly with each other among children with epilepsy onset ≤ 4 years (r = 0.53–0.66). The correlation between these variables was weaker with an onset ≥ 9 years (r = 0.22–0.35). Correlation with QOL was clinically non-significant.These variables appear to measure the same phenomenon only in children with early epilepsy onset (< 4 years) and explain little variance in QOL.     

Abnormal body perception and neural activity in the insula in depression: An fMRI study of the depressed “material me”

Abstract

Objectives. In addition to affective-cognitive symptoms, patients with major depressive disorder (MDD) suffer from somato-vegetative symptoms, suggesting abnormal interoceptive awareness of their “material me”. While recent imaging studies have extensively investigated affective-cognitive symptoms in MDD, the neural correlates of somato-vegetative symptoms and abnormal interoception remain unclear. Since the “material me” has been especially associated with the anterior insula in healthy subjects, we hypothesized abnormalities in this region during interoceptive awareness in MDD. Methods. We therefore investigated behavioural and neural correlates of interoception in healthy and depressed subjects using the Body Perception Questionnaire (BPQ) and a well established heartbeat perception task in fMRI. Results. MDD patients showed significantly higher scores in the BPQ and reduced neural activity during rest periods, particularly in the bilateral anterior insula. In contrast to healthy subjects, BPQ scores no longer correlated with activity during rest periods in the anterior insula. Both BPQ scores and left anterior insula signal changes correlated with depression severity. Conclusions. We demonstrate for the first time abnormal body perception and altered activity in the insula during rest in MDD. Our results suggest that these behavioural and neural abnormalities are closely related to these patients’ somato-vegetative abnormalities and their abnormal “material me”.     

How does a specific learning and memory system in the mammalian brain gain control of behavior?

This review addresses a fundamental, yet poorly understood set of issues in systems neuroscience. The issues revolve around conceptualizations of the organization of learning and memory in the mammalian brain. One intriguing, and somewhat popular, conceptualization is the idea that there are multiple learning and memory systems in the mammalian brain and they interact in different ways to influence and/or control behavior. This approach has generated interesting empirical and theoretical work supporting this view. One issue that needs to be addressed is how these systems influence or gain control of voluntary behavior. To address this issue, we clearly specify what we mean by a learning and memory system. We then review two types of processes that might influence which memory system gains control of behavior. One set of processes are external factors that can affect which system controls behavior in a given situation including task parameters like the kind of information available to the subject, types of training experience, and amount of training. The second set of processes are brain mechanisms that might influence what memory system controls behavior in a given situation including executive functions mediated by the prefrontal cortex; switching mechanisms mediated by ascending neurotransmitter systems, the unique role of the hippocampus during learning. The issue of trait differences in control of different learning and memory systems will also be considered in which trait differences in learning and memory function are thought to potentially emerge from differences in level of prefrontal influence, differences in plasticity processes, differences in ascending neurotransmitter control, differential access to effector systems like motivational and motor systems. Finally, we present scenarios in which different mechanisms might interact. This review was conceived to become a jumping off point for new work directed at understanding these issues. The outcome of this work, in combination with other approaches, might improve understanding of the mechanisms of volition in human and non‐human animals. © 2013 Wiley Periodicals, Inc.     

Correction to: How do you perceive threat? It’s all in your pattern of brain activity

Brain Imaging and Behavior - The author found a mistake in their published article. They observed that Fig.&nbsp;2 presented some mistakes as follow.     

How does social functioning in the early stages of psychosis relate to depression and social anxiety?

Aims: The study aims to compare social functioning in young people considered to be at risk of psychosis with those meeting criteria for first episode psychosis (FEP) and controls, and to determine the association between social functioning and positive and negative symptoms, depressive symptoms, and social anxiety. Methods: This study examined social functioning in 20 individuals at risk of psychosis, 20 FEP patients and 20 healthy controls. Social functioning was measured using the Social Functioning Scale and World Health Organization Disability Assessment Scale. Psychiatric variables were also measured using the Comprehensive Assessment of At‐Risk Mental States, the Brief Psychiatric Rating Scale, the Brief Social Phobia Scale, and the Depression Anxiety and Stress Scale. Results: At‐risk individuals had comparable social deficits to the FEP group, and both patient groups had significantly poorer social functioning than controls. Importantly, social functioning was most strongly associated with depressive and social anxiety symptoms and to a lesser extent with positive symptoms. However, negative symptoms did not appear to relate to social functioning. Conclusion: Social functioning impairments precede the onset of full‐threshold psychosis and may therefore be a significant marker for the illness. Additionally, associated psychiatric symptoms such as depression and social anxiety may provide an avenue for early interventions of social functioning deficits in psychosis.     

The day-night differences in ERK1/2, GSK3β activity and c-Fos levels in the brain,and the responsiveness of various brain structures to morphine

As with other drugs or pharmaceuticals, opioids differ in their rewarding or analgesic effects depending on when they are applied. In the previous study, we have demonstrated the day/night difference in the sensitivity of the major circadian clock in the suprachiasmatic nucleus to a low dose of morphine, and showed the bidirectional effect of morphine on pERK1/2 and pGSK3β levels in the suprachiasmatic nucleus depending on the time of administration. The main aim of this study was to identify other brain structures that respond differently to morphine depending on the time of its administration. Using immunohistochemistry, we identified 44 structures that show time-of-day specific changes in c-Fos level and activity of ERK1/2 and GSK3β kinases in response to a single dose of 1 mg/kg morphine. Furthermore, comparison among control groups revealed the differences in the spontaneous levels of all markers with a generally higher level during the night, that is, in the active phase of the day. We thus provide further evidence for diurnal variations in the activity of brain regions outside the suprachiasmatic nucleus indicated by the temporal changes in the molecular substrate. We suggest that these changes are responsible for generating diurnal variation in the reward behavior or analgesic effect of opioid administration.     

Does fMRI repetition suppression reveal mirror neuron activity in the human brain? Insights from univariate and multivariate analysis

Mirror neurons (MN) have been proposed as the neural substrate for a wide range of clinical, social and cognitive phenomena. Over the last decade, a commonly used tool for investigating MN activity in the human brain has been functional magnetic resonance (fMRI) repetition suppression (RS) paradigms. However, the available evidence is mixed, largely owing to inconsistent application of the methodological criteria necessary to infer MN properties. This raises concerns about the degree to which one can infer the presence (or absence) of MN activity from earlier accounts that adopted RS paradigms. We aimed to clarify this issue using a well‐validated fMRI RS paradigm and tested for mirror properties by rigorously applying the widely accepted criteria necessary to demonstrate MN activity using traditional univariate techniques and Multivariate Pattern Analysis (MVPA). While univariate whole brain analysis in healthy adults showed uni‐modal RS effects within the supplementary motor area, no evidence for cross‐modal RS effects consistent with mirror neuron activity was found. MVPA on the other hand revealed a region along the anterior intraparietal sulcus that met the criteria for MN activity. Taken together, these results clarify disparate evidence from earlier RS studies, highlighting that traditional univariate analysis of RS data may not be sensitive for detecting MN activity when rigorously applying the requisite criteria. In light of these findings, we recommend that short of increasing sample sizes substantially, future studies using RS paradigms to investigate MNs across the human brain consider the use of MVPA.     

How do children ascribe gender to nouns? A study of Spanish‐speaking children with and without specific language impairment

The purpose of this investigation was to identify how Spanish‐speaking preschool children with and without specific language impairment (SLI) use the various cues available for ascribing a noun's inherent gender in the language. Via an invented word task, four types of cues were isolated and presented to each child: (1) two types of noun‐internal cues (semantic transparency and word ending), and (2) two types of noun‐external cues (article gender and adjective gender). Eleven children with typical language skills, 11 children with SLI, and 11 adults participated in the study. Results indicated, as expected, that adults outperformed both child groups. Significant differences were observed in the children's use of article cues, with the typical children outperforming the children with SLI. Individual data also indicate that most children with SLI were using the noun‐internal cue of word ending effectively. Discussion of previous research in the area of gender agreement in Spanish‐speaking children with SLI and explanations of potential reasons for the children's performance are addressed.     

Does somatosensory discrimination activate different brain areas in children with unilateral cerebral palsy compared to typically developing children? An fMRI study

Aside from motor impairment, many children with unilateral cerebral palsy (CP) experience altered tactile, proprioceptive, and kinesthetic awareness. Sensory deficits are addressed in rehabilitation programs, which include somatosensory discrimination exercises. In contrast to adult stroke patients, data on brain activation, occurring during somatosensory discrimination exercises, are lacking in CP children. Therefore, this study investigated brain activation with functional magnetic resonance imaging (fMRI) during passively guided somatosensory discrimination exercises in 18 typically developing children (TD) (age, M = 14 ± 1.92 years; 11 girls) and 16 CP children (age, M = 15 ± 2.54 years; 8 girls). The demographic variables between both groups were not statistically different. An fMRI compatible robot guided the right index finger and performed pairs of unfamiliar geometric shapes in the air, which were judged on their equality. The control condition comprised discrimination of music fragments. Both groups exhibited significant activation (FDR, p < .05) in frontoparietal, temporal, cerebellar areas, and insula, similar to studies in adults. The frontal areas encompassed ventral premotor areas, left postcentral gyrus, and precentral gyrus; additional supplementary motor area (SMA_proper) activation in TD; as well as dorsal premotor, and parietal operculum recruitment in CP. On uncorrected level, p < .001, TD children revealed more left frontal lobe, and right cerebellum activation, compared to CP children. Conversely, CP children activated the left dorsal cingulate gyrus to a greater extent than TD children. These data provide incentives to investigate the effect of somatosensory discrimination during rehabilitation in CP, on clinical outcome and brain plasticity.     

How did the human brain evolve? A proposal based on new evidence from in vivo brain imaging during attention and ideation

It is proposed that brain evolution in nonhuman primates and humans was facilitated by heritable differences in neuroplasticity and in the number of neurons and synapses available during childhood and adolescence, therefore, in differences in modifiability and elaboration of neuronal networks in brains of immature primate genotypes. These differences were exploited when a primate population was forced to adapt to a new cognitively or behaviorally demanding milieu, to select more cognitively and brain competent adults who could best compete and reproduce in this new milieu, extending their genes within the population. Two recently solidified concepts suggest a mechanism for this evolutionary process: (1) "Association" neocortex can be activated by attention and ideation in the absence of sensory or motor contributions, as demonstrated by in vivo imaging and direct brain recording. (2) Activation of the immature brain can promote and stabilize neuronal networks that would disappear or otherwise lose their function by adulthood. Taking these two ideas together, it is proposed that the "thought" processes of attention and ideation, when used by immature primates to adapt to new cognitive or behavioral stresses, led by the repeated selection of genotype to more cognitively able, larger-brained species with more extensive "association" cortex and related regions.     

How do spatial learning and memory occur in the brain? Coordinated learning of entorhinal grid cells and hippocampal place cells

Spatial learning and memory are important for navigation and formation of episodic memories. The hippocampus and medial entorhinal cortex (MEC) are key brain areas for spatial learning and memory. Place cells in hippocampus fire whenever an animal is located in a specific region in the environment. Grid cells in the superficial layers of MEC provide inputs to place cells and exhibit remarkable regular hexagonal spatial firing patterns. They also exhibit a gradient of spatial scales along the dorsoventral axis of the MEC, with neighboring cells at a given dorsoventral location having different spatial phases. A neural model shows how a hierarchy of self-organizing maps, each obeying the same laws, responds to realistic rat trajectories by learning grid cells with hexagonal grid firing fields of multiple spatial scales and place cells with unimodal firing fields that fit neurophysiological data about their development in juvenile rats. The hippocampal place fields represent much larger spaces than the grid cells to support navigational behaviors. Both the entorhinal and hippocampal self-organizing maps amplify and learn to categorize the most energetic and frequent co-occurrences of their inputs. Top-down attentional mechanisms from hippocampus to MEC help to dynamically stabilize these spatial memories in both the model and neurophysiological data. Spatial learning through MEC to hippocampus occurs in parallel with temporal learning through lateral entorhinal cortex to hippocampus. These homologous spatial and temporal representations illustrate a kind of "neural relativity" that may provide a substrate for episodic learning and memory.