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BackgroundInfluential theories predict that antidepressant medication and psychological therapies evoke distinct neural changes.AimsTo test the convergence and divergence of antidepressant- and psychotherapy-evoked neural changes, and their overlap with the brain's affect network.MethodWe employed a quantitative synthesis of three meta-analyses (n = 4206). First, we assessed the common and distinct neural changes evoked by antidepressant medication and psychotherapy, by contrasting two comparable meta-analyses reporting the neural effects of these treatments. Both meta-analyses included patients with affective disorders, including major depressive disorder, generalised anxiety disorder and panic disorder. The majority were assessed using negative-valence tasks during neuroimaging. Next, we assessed whether the neural changes evoked by antidepressants and psychotherapy overlapped with the brain's affect network, using data from a third meta-analysis of affect-based neural activation.ResultsNeural changes from psychotherapy and antidepressant medication did not significantly converge on any region. Antidepressants evoked neural changes in the amygdala, whereas psychotherapy evoked anatomically distinct changes in the medial prefrontal cortex. Both psychotherapy- and antidepressant-related changes separately converged on regions of the affect network.ConclusionsThis supports the notion of treatment-specific brain effects of antidepressants and psychotherapy. Both treatments induce changes in the affect network, but our results suggest that their effects on affect processing occur via distinct proximal neurocognitive mechanisms of action.

Significance: Surgical simulators, both virtual and physical, are increasingly used as training tools for teaching and assessing surgical technical skills. However, the metrics used for assessment in these simulation environments are often subjective and inconsistent. Aim: We propose functional activation metrics, derived from brain imaging measurements, to objectively assess the correspondence between brain activation with surgical motor skills for subjects with varying degrees of surgical skill. Approach: Cortical activation based on changes in the oxygenated hemoglobin (HbO) of 36 subjects was measured using functional near-infrared spectroscopy at the prefrontal cortex (PFC), primary motor cortex, and supplementary motor area (SMA) due to their association with motor skill learning. Inter-regional functional connectivity metrics, namely, wavelet coherence (WCO) and wavelet phase coherence were derived from HbO changes to correlate brain activity to surgical motor skill levels objectively. Results: One-way multivariate analysis of variance found a statistically significant difference in the inter-regional WCO metrics for physical simulator based on Wilk’s Λ for expert versus novice, F ( 10,1 ) = 7495.5, p

Significance: Transcranial photobiomodulation (PBM) is a noninvasive neuromodulation technique capable of producing changes in the mitochondrial cytochrome c-oxidase (CCO) activity of neurons. Although the application of PBM in clinical practice and as a neurophysiological tool is increasing, less is known about how different treatment time intervals may result in different outcomes. Aim: We evaluated the effects of different PBM treatment intervals on brain metabolic activity through the CCO and proto-oncogene expression (c-Fos). Approach: We studied PBM effects on brain CCO and c-Fos expression in three groups of animals: Control (CN, n = 8), long interval PBM treatment (LI, n = 5), and short interval PBM treatment (SI, n = 5). Results: Increased CCO activity in the LI group, compared to the SI and CN groups, was found in the prefrontal cortices, dorsal and ventral striatum, and hippocampus. Regarding c-Fos expression, we found a significant increase in the SI group compared to LI and CN, whereas LI showed increased c-Fos expression compared to CN in the cingulate and infralimbic cortices. Conclusions: We show the effectiveness of different PBM interval schedules in increasing brain metabolic activity or proto-oncogene expression.

Significance: Speech processing tasks can be used to assess the integrity and health of many functional and structural aspects of the brain. Despite the potential merits of such behavioral tests as clinical assessment tools, however, the underlying neural substrates remain relatively unclear. Aim: We aimed to obtain a more in-depth portrait of hemispheric asymmetry during dichotic listening tasks at the level of the prefrontal cortex, where prior studies have reported inconsistent results. Approach: To avoid central confounds that limited previous studies, we used diffuse correlation spectroscopy to optically monitor cerebral blood flow (CBF) in the dorsolateral prefrontal cortex during dichotic listening tasks in human subjects. Results: We found that dichotic listening tasks elicited hemispheric asymmetries in both amplitude as well as kinetics. When listening task blocks were repeated, there was an accommodative reduction in the response amplitude of the left, but not the right hemisphere. Conclusions: These heretofore unobserved trends depict a more nuanced portrait of the functional asymmetry that has been observed previously. To our knowledge, these results additionally represent the first direct measurements of CBF during a speech processing task recommended by the American Speech-Language-Hearing Association for diagnosing auditory processing disorders.

Significance: Dystonia is a dynamic and complex disorder. Real-time analysis of brain activity during motor tasks may increase our knowledge on its pathophysiology. Functional near-infrared spectroscopy (fNIRS) is a noninvasive method that enables the measurement of cortical hemodynamic activity in unconstrained environments. Aim: We aimed to explore the feasibility of using fNIRS for the study of task-related brain activity in dystonia. Task-related functional magnetic resonance imaging (fMRI) and resting-state functional connectivity were also analyzed. Approach: Patients with idiopathic right-upper limb dystonia and controls were assessed through nonsimultaneous fMRI and fNIRS during a finger-tapping task. Seed-based connectivity analysis of resting-state fMRI was performed in both groups. Results: The fMRI results suggest nonspecific activation of the cerebellum and occipital lobe in dystonia patients during the finger-tapping task with the affected hand. Moreover, fNIRS data show lower activation in terms of oxyhemoglobin and total hemoglobin in the frontal, ipsilateral cortex, and somatosensory areas during this task. In dystonia, both fMRI and fNIRS data resulted in hypoactivation of the frontal cortex during finger tapping with both hands simultaneously. Resting-state functional connectivity analysis suggests that the cerebellar somatomotor network in dystonia has an increased correlation with the medial prefrontal cortex and the paracingulate gyrus. Conclusions: These data suggest that unbalanced activation of the cerebellum, somatosensory, and frontal cortical areas are associated with dystonia. To our knowledge, this is the first study using fNIRS to explore the pathophysiology of dystonia. We show that fNIRS and fMRI are complementary methods and highlight the potential of fNIRS for the study of dystonia and other movement disorders as it can overcome movement restrictions, enabling experiments in more naturalistic conditions.

Significance: Combining transcranial direct-current stimulation (tDCS) with functional near-infrared spectroscopy (fNIRS) is a recent approach to exploring brain activation evoked by neurostimulation. Aim: To critically evaluate studies combining tDCS and fNIRS and provide a consolidated overview of cortical hemodynamic responses to neurostimulation. Approach: Key terms were searched in three databases (MEDLINE, EMBASE, and PsycINFO) with cross-referencing and works from Google Scholar also evaluated. All studies reporting on fNIRS-derived hemoglobin changes evoked by tDCS were included. Results: Literature searches revealed 474 articles, of which 28 were included for final review (22 in healthy individuals: 9 involving rest and 13 with tasks; 6 in the clinical setting). At rest, an overall increase in cortical activation was observed in fNIRS responses at the site of stimulation, with evidence suggesting nonstimulated brain regions are also similarly affected. Conversely, during tasks, reduced cortical activation was observed during online stimulation. Offline and poststimulation effects were less consistent, as is the impact on clinical populations and their symptom correlation. Conclusion: This review explores the methodological frameworks for fNIRS-tDCS evaluations and summarizes hemodynamic responses associated with tDCS in all populations. Our findings provide further evidence of the impact of tDCS on neuronal activation within functionally connected networks.

SignificanceMajor depressive disorder (MDD) affects over 40 million US adults in their lifetimes. Transcranial photobiomodulation (t-PBM) has been shown to be effective in treating MDD, but the current treatment dosage does not account for anatomical head and brain changes due to aging.AimWe study effective t-PBM dosage and its variations across age groups using state-of-the-art Monte Caxrlo (MC) simulations and age-dependent brain atlases ranging between 5 to 85 years of age.ApproachAge-dependent brain models are derived from 18 MRI brain atlases. Two extracranial source positions, F3-F4 and Fp1-Fpz-Fp2 in the EEG 10-20 system, are simulated at five selected wavelengths and energy depositions at two MDD-relevant cortical regions – dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) – are quantified.ResultsAn overall decrease of energy deposition was found with increasing age. A strong negative correlation between the thickness of extra-cerebral tissues (ECT) and energy deposition, suggesting that increasing ECT thickness over age is primarily responsible for reduced energy delivery. The F3-F4 position appears to be more efficient in reaching dlPFC compared to treating vmPFC via the Fp1-Fpz-Fp2 position.ConclusionQuantitative simulations revealed age-dependent light delivery across the lifespan of human brains, suggesting the needs for personalized and age-adaptive t-PBM treatment planning.

Significance: Our study reveals that frontal cerebral oxygenation asymmetry (FCOA), i.e. a difference in the oxygenation between the right and left prefrontal cortex (PFC), is a real phenomenon in healthy human subjects at rest. Aim: To investigate FCOA, we performed a study with 134 healthy right-handed subjects with the systemic physiology augmented functional near infrared spectroscopy (SPA-fNIRS) approach. Approach: Subjects were measured 2 to 4 times on different days resulting in an unprecedented number of 518 single measurements of the absolute values of tissue oxygen saturation (StO2) and total hemoglobin concentration ([tHb]) of the right and left PFC. Measurements were performed with frequency-domain functional near-infrared spectroscopy. In addition, the cardiorespiratory parameters were measured simultaneously. Results: We found that (i) subjects showed an FCOA (higher StO2 on the right PFC), but not for tHb; (ii) intrasubject variability was excellent for both StO2 and tHb, and fair for FCOA; (iii) StO2 correlated significantly with blood CO2 concentration, [tHb] with heart rate, respiration rate (RR), and the pulse–respiration quotient (PRQ), and FCOA with RR and PRQ; (iv) FCOA and StO2 were dependent on season and time of day, respectively; (v) FCOA was negatively correlated with the room temperature; and (vi) StO2 and tHb were not correlated with the subjects mood but with their chronotype, whereas FCOA was not dependent on the chronotype. Conclusion: Our study demonstrates that FCOA is real, and it provides unique insights into this remarkable phenomenon.

Dopamine transmission in the prefrontal cortex (PFC) supports working memory (WM), the temporary holding, processing and manipulation of information in one's mind. The gene coding the catechol‐O‐methyltransferase (COMT) enzyme, which degrades dopamine, in particular in the PFC, has a common single nucleotide polymorphism leading to two versions of the COMT enzyme which vary in their enzymatic activity. The methionine (Met) allele has been associated with higher WM performance and lower activation of the PFC in executive function tasks than the valine (Val) allele. In a previous study, COMT genotype was associated with performance on verbal and visuospatial WM tasks in adults, as well as with performance on a novel social WM paradigm that requires participants to maintain and manipulate information about the traits of their friends or family over a delay. Here, data collected in children and adolescents (N = 202) were compared to data from the adult sample (N = 131) to investigate possible age differences in genetic associations. Our results replicate and extend previous work showing that the pattern of superior WM performance observed in Met/Met adults emerges during development. These findings are consistent with a decrease in prefrontal dopamine levels during adolescence. Developmentally moderated genetic effects were observed for both visuospatial and social WM, even when controlling for non‐social WM performance, suggesting that the maintenance and manipulation of social information may also recruit the dopamine neurotransmitter system. These findings show that development should be considered when trying to understand the impact of genetic polymorphisms on cognitive function., Rs4680 is a genetic polymorphism with two allelic variants (Met vs. Val) that affects the enzymatic activity of the catechol‐O‐methyltransferase (COMT) enzyme, which degrades dopamine. Met/Met adults have been found to have better performance and lower prefrontal cortex activity during working memory (WM) tasks. This study shows that the genetic association with visuospatial WM, but not verbal WM performance, emerges during development, and that the same pattern can be observed in a WM task requiring participants to manipulate social information. These results are consistent with a decrease in prefrontal dopamine levels during development and suggest an involvement of dopaminergic neurotransmission in social cognition.

BackgroundA significantly lower fractional anisotropy (FA) value has been shown in anterior parts of the corpus callosum in patients with bipolar disorder.AimsWe investigated the association between abnormal corpus callosum integrity and interhemispheric functional connectivity (IFC) in patients with bipolar disorder.MethodsWe examined the association between FA values in the corpus callosum (CC-FA) and the IFC between homotopic regions in the anterior cortical structures of bipolar disorder (n=16) and major depressive disorder (n=22) patients with depressed or euthymic states.ResultsWe found a positive correlation between the CC-FA and IFC values between homotopic regions of the ventral prefrontal cortex and insula cortex, and significantly lower IFC between these regions in bipolar disorder patients.ConclusionsThe abnormal corpus callosum integrity in bipolar disorder patients is relevant to the IFC between homotopic regions, possibly disturbing the exchange of emotional information between the cerebral hemispheres resulting in emotional dysregulation.

The use of functional near-infrared spectroscopy (fNIRS) in block designs provides measures of cortical activity in ecologically valid environments. However, in some cases, the use of block designs may be problematic when data are not corrected for performance in a time-restricted block. We sought to investigate the effects of task complexity and processing speed on hemodynamic responses in an fNIRS block design. To differentiate the effects of task complexity and processing speed, 20 subjects completed the trail making test (TMT) in two versions (TMT-A versus TMT-B) and three different speed levels (slow versus moderate versus fast). During TMT-A, subjects are asked to connect encircled numbers in numerically ascending order (1-2-3 ... ). In the more complex TMT-B, subjects are instructed to connect encircled numbers and letters in alternating ascending order (1-A-2-B ... ). To illustrate the obscuring effects of processing speed on task complexity, we perform two different analyses. First, we analyze the classical measures of oxygenated blood, and second, we analyze the measures corrected for the number of processed items. Our results show large effects for processing speed within the bilateral inferior frontal gyrus, left dorsolateral prefrontal cortex, and superior parietal lobule (SPL). The TMT contrast did not show significant effects with classical measures, although trends are observed for higher activation during TMT-B. When corrected for processed items, higher activity for TMT-B in comparison to TMT-A is found within the SPL. The results are discussed in light of recent research designs, and simple to use correction methods are suggested. (c) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

© 2017 The Authors. Developmental Science Published by John Wiley & Sons Ltd. Analogical reasoning, or the ability to find correspondences between entities based on shared relationships, supports knowledge acquisition. As such, the development of this ability during childhood is thought to promote learning. Here, we sought to better understand the mechanisms by which analogical reasoning about semantic relations improves over childhood and adolescence (e.g. chalk is to chalkboard as pen is to…?). We hypothesized that age-related differences would manifest as differences in the brain regions associated with one or more of the following cognitive functions: (1) controlled semantic retrieval, or the ability to retrieve task-relevant semantic associations; (2) response control, or the ability to override the tendency to respond to a salient distractor; and/or (3) relational integration, or the ability to consider jointly two mental relations. In order to test these hypotheses, we analyzed patterns of fMRI activation during performance of a pictorial propositional analogy task across 95 typically developing children between the ages of 6 and 18 years old. Despite large age-related differences in task performance, particularly over ages 6–10 but through to around age 14, participants across the whole age range recruited a common network of frontal, parietal and temporal regions. However, activation in a brain region that has been implicated in controlled semantic retrieval – left anterior prefrontal cortex (BA 47/45) – was positively correlated with age, and also with performance after controlling for age. This finding indicates that improved performance over middle childhood and early adolescence on this analogical reasoning task is driven largely by improvements in the ability to selectively retrieve task-relevant semantic relationships.

The temporal evolution of cortical activation and connectivity patterns during a fatiguing handgrip task were studied by functional near-infrared spectroscopy (fNIRS). Twenty-three young adults (18 to 35 years old) were recruited to use a handheld force sensor to perform intermittent handgrip contractions with their dominant hand at their personal maximum voluntary contraction force level for 3.5 s followed by 6.5 s of rest for 120 blocks. Subjects were divided into self-reported physically active and inactive groups, and their hemodynamic activity over the prefrontal and sensory-motor cortices (111 channels) was mapped while they performed this task. Using this fNIRS setup, a more detailed time sequence of cortical activation and connectivity patterns was observed compared to prior studies. A temporal evolution sequence of hemodynamic activation patterns was noted, which was different between the active and the inactive groups. Physically active subjects demonstrated delayed fatigue onset and significantly longer-lasting and more spatially extended functional connectivity (FC) patterns, compared to inactive subjects. The observed differences in activation and FC suggested differences in cortical network adaptation patterns as fatigue set in, which were dependent on subjects’ physical activity. The findings of this study suggest that physical activity increases FC with regions involved in motor task control and correlates to extended fatigue onset and enhanced performance.

The increase in the number of patients with mental disorders with depressive symptoms has become a significant problem. To prevent people developing those disorders and help with the effective recovery, it is important to quantitatively and objectively monitor an individual’s mental state. Previous studies have shown the relationship between negative or depressive mood state and human prefrontal cortex (PFC) activation during verbal and spatial working memory tasks based on a near-infrared spectroscopy imaging technique. In this study, we aimed to explore a biomarker of the mental state of people in remission of mental disorders with depressive symptoms using this technique. We obtained the PFC activation of return-to-work (RTW) trainees in remission of those disorders, compared that of healthy controls, and obtained subjective questionnaire scores with the Profile of Mood States. We compared the PFC activation with the questionnaire scores by receiver operating characteristic analysis using a logistic-regression model. The results showed that the PFC activation indicates a healthy state compared to that of the RTW trainees evaluated by area-under-curve analysis. This study demonstrates that our PFC measurement technique will be useful as a quantitative and objective assessment of mental state.

Working memory (WM) plays a crucial role in human brain functions. The application of brain connectivity analysis helps to understand the brain network properties in WM. Combination of functional and effective connectivity can provide new insights for exploring network attributes. Nevertheless, few studies have combined these two modes in WM. Near-infrared spectroscopy was used to investigate the connectivity properties in the prefrontal cortex (PFC) during n-back (0-back and 2-back) tasks by combining functional and effective connectivity analysis. Our results demonstrated that the PFC network showed small-world properties in both WM tasks. The characteristic path length was significantly longer in the 2-back task than in the 0-back task, while there was no obvious difference in the clustering coefficient between two tasks. Regarding the effective connectivity, the Granger causality (GC) was higher for right PFC→left PFC than for left PFC→right PFC in the 2-back task. Compared with the 0-back task, GC of right PFC→left PFC was higher in the 2-back task. Our findings show that, along with memory load increase, long range connections in PFC are enhanced and this enhancement might be associated with the stronger information flow from right PFC to left PFC.

Autism spectrum disorder (ASD) is characterized by impairment in social communication and the presence of restricted and repetitive behaviors and interests. Executive function impairment is reportedly partially responsible for these symptoms. Executive function includes planning, flexibility, and inhibitory control. Although planning and flexibility in ASD have been consistently reported as atypical, the atypicality of inhibitory control remains controversial. As most previous studies have used nonsocial stimuli to investigate inhibitory control in ASD, the effects of socially relevant information on the inhibitory control system in individuals with ASD remain unclear. Therefore, we developed a go/no-go task with gaze stimuli and measured hemodynamic responses in the right prefrontal cortex (PFC), involved in inhibitory processing in both typically developing (TD) children and children with ASD, using functional near-infrared spectroscopy. Direct gaze induced commission errors to similar extents in both groups. Contrary to the behavioral responses, neural activation in the right PFC was modulated by gaze direction only in the TD group. These findings suggest that the gaze-processing mechanisms in the prefrontal region may be affected by atypical gaze processing in other brain regions during an inhibitory control task with socially relevant information in ASD.

Background: Clinical assessment of cerebral concussion relies on the presence and duration of post concussive symptoms (PCS). Given that these PCS are subjective reports and not always specific to concussion, their usefulness remains to be validated. Objective: To evaluate the usefulness of self-reported PCS by means of cognitive tests and functional MRI (fMRI). Method: 28 male athletes with and without concussion were grouped according to their PCS score. They were then administered a computerised cognitive test battery and submitted to an fMRI session where cerebral activations associated with verbal and non-verbal working memory tasks were analysed. Results: Behaviourally, response accuracy and speed on the cognitive test battery were comparable for the control and low PCS group. The moderate PCS group showed significantly slower response times than the control group on the matching (p

Background: Huntington’s disease is a progressive neurodegenerative disorder that results in deterioration and atrophy of various brain regions. Aim: To assess the functional connectivity between prefrontal brain regions in patients with Huntington’s disease, compared with normal controls, using functional magnetic resonance imaging. Patients and methods: 20 patients with Huntington’s disease and 17 matched controls performed a Simon task that is known to activate lateral prefrontal and anterior cingulate cortical regions. The functional connectivity was hypothesised to be impaired in patients with Huntington’s disease between prefrontal regions of interest, selected from both hemispheres, in the anterior cingulate and dorsal lateral prefrontal cortex. Results: Controls showed a dynamic increase in interhemispheric functional connectivity during task performance, compared with the baseline state; patients with Huntington’s disease, however, showed no such increase in prefrontal connectivity. Overall, patients with Huntington’s disease showed significantly impaired functional connectivity between anterior cingulate and lateral prefrontal regions in both hemispheres compared with controls. Furthermore, poor task performance was predicted by reduced connectivity in patients with Huntington’s disease between the left anterior cingulate and prefrontal regions. Conclusions: This finding represents a loss of synchrony in activity between prefrontal regions in patients with Huntington’s disease when engaged in the task, which predicted poor task performance. Results show that functional interactions between critical prefrontal regions, necessary for cognitive performance, are compromised in Huntington’s disease. It is speculated whether significantly greater levels of activation in patients with Huntington’s disease (compared with controls) observed in several brain regions partially compensate for the otherwise compromised interactions between cortical regions.

Objectives: To explore the neural substrates corresponding to the perseverative errors in the Wisconsin Card Sorting Test (WCST). Methods: The study examined the correlations between the WCST performances and the SPECT measurements of regional cerebral blood flow (rCBF) in subjects with neurodegenerative dementia. Negative non-linear correlations between the rCBF and the two different types of the perseverative errors ("stuck-in-set" and "recurrent" perseverative errors) were calculated on a voxel basis and volume-of-interest basis in the mixed groups of 72 elderly and dementia patients. Results: The stuck-in-set perseverative error was associated with the reduced rCBF in the rostrodorsal prefrontal cortex, whereas the recurrent perseverative error was related to the left parietal activity but not to the prefrontal activity. Conclusions: These findings augment evidence that the rostrodorsal prefrontal cortex crucially mediates attentional set shifting, and suggest that the stuck-in-set perseverative errors would be a true pathognomonic sign of frontal dysfunction. Moreover, this study shows that the recurrent perseverative errors may not be associated closely with the prefrontal function, suggesting that this error and the stuck-in-set error should be differentially estimated in the WCST.

Background: Both Asperger's disorder and the social-emotional processing disorder (SEPD), a form of non-verbal learning disability, are associated with executive function deficits. SEPD has been shown to be associated with deficient saccadic inhibition. Objective: To study two executive functions in Asperger's disorder and SEPD, inhibition and task switching, using a single saccadic paradigm. Methods: 22 control subjects and 27 subjects with developmental social processing disorders—SEPD, Asperger's disorder, or both syndromes—performed random sequences of prosaccades and anti- saccades. This design resulted in four trial types, prosaccades and antisaccades, that were either repeated or switched. The design allowed the performance costs of inhibition and task switching to be isolated. Results: Subjects with both Asperger's disorder and SEPD showed deficient inhibition, as indicated by increased antisaccade errors and a disproportionate increase in latency for antisaccades relative to prosaccades. In contrast, task switching error and latency costs were normal and unrelated to the costs of inhibition. Conclusions: This study replicates the finding of deficient saccadic inhibition in SEPD, extends it to Asperger's disorder, and implicates prefrontal cortex dysfunction in these syndromes. The finding of intact task switching shows that executive function deficits in Asperger's disorder and SEPD are selective and suggests that inhibition and task switching are mediated by distinct neural networks.

Background: Individuals with Prader–Willi syndrome (PWS) exhibit severe disturbances in appetite regulation, including delayed meal termination, early return of hunger after a meal, seeking and hoarding food and eating of non-food substances. Brain pathways involved in the control of appetite in humans are thought to include the hypothalamus, frontal cortex (including the orbitofrontal, ventromedial prefrontal, dorsolateral prefrontal and anterior cingulate areas), insula, and limbic and paralimbic areas. We hypothesised that the abnormal appetite in PWS results from aberrant reward processing of food stimuli in these neural pathways. Methods: We compared functional MRI blood oxygen level dependent (BOLD) responses while viewing pictures of food in eight adults with PWS and eight normal weight adults after ingestion of an oral glucose load. Results: Subjects with PWS demonstrated significantly greater BOLD activation in the ventromedial prefrontal cortex than controls when viewing food pictures. No significant differences were found in serum insulin, glucose or triglyceride levels between the groups at the time of the scan. Conclusions: Individuals with PWS had an increased BOLD response in the ventromedial prefrontal cortex compared with normal weight controls when viewing pictures of food after an oral glucose load. These findings suggest that an increased reward value for food may underlie the excessive hunger in PWS, and support the significance of the frontal cortex in modulating the response to food in humans. Our findings in the extreme appetite phenotype of PWS support the importance of the neural pathways that guide reward related behaviour in modulating the response to food in humans.

Background: A comprehensive characterisation of grey and white matter changes in progressive supranuclear palsy (PSP), the second most common extrapyramidal syndrome after Parkinson disease, is still not available. Objective: To evaluate grey and white matter changes in mild PSP patients by voxel based morphometry (VBM) and diffusion tensor imaging (DTI), respectively. Methods: 14 mild PSP patients and 14 healthy controls entered the study and underwent a clinical and neuropsychological evaluation according with a standardised assessment. Each subject had a structural magnetic resonance imaging (MRI) study. Processing analysis of MRI data was carried out according to optimised VBM and fractional anisotropy was determined. Results: Compared with the controls, in PSP patients VBM analysis showed a significant clusters of reduced grey matter in premotor cortex, frontal operculum, anterior insula, hippocampus, and parahippocampal gyrus, bilaterally. With regard to subcortical brain regions, the pulvinar, dorsomedial and anterior nuclei of the thalamus, and superior and inferior culliculum were affected bilaterally. A bilateral decrease in fractional anisotropy in superior longitudinal fasciculus, anterior part of corpus callosum, arcuate fascicolus, posterior thalamic radiations, and internal capsule, probably involving the cortico-bulbar tracts, was present in PSP patients. Conclusions: These data provide evidence for both grey and white matter degeneration in PSP from the early disease stage. These structural changes suggest that atrophy of cortical and subcortical structures and neurodegeneration of specific fibre tracts contribute to neurological deficits in PSP.

Background: Rivastigmine enhances cholinergic activity and has been shown in clinical trials to decrease the rate of deterioration in Alzheimer's disease. It remains unclear where in the brain it exerts its effect. Functional magnetic resonance imaging (fMRI) can be used to measure changes in brain function and relate these to cognition. Objectives: To use fMRI to study brain activation with rivastigmine treatment. Methods: The effect on brain activation of a single dose of rivastigmine was tested in seven patients with mild Alzheimer's disease using fMRI during face encoding, and in five patients during a parametric working memory task. Results: During face encoding, rivastigmine increased bilateral activation in the fusiform gyrus. Brain activation was also enhanced in the prefrontal cortex in a simple working memory task. When working memory load was further increased, not only was increased activation seen, but in certain areas there was also decreased activation. Conclusions: These findings link the previously observed increase in cognitive performance in Alzheimer's disease after treatment with a cholinesterase inhibitor to altered brain activation. Although the results cannot be generalised to the Alzheimer's disease population at large, they provide evidence that in mild Alzheimer's disease, rivastigmine enhances brain activation in the fusiform and frontal cortices. This is compatible with the concept of cholinergic circuitry.

Objectives: Depression is a common psychiatric disorder in late life. Cerebrovascular disease has been postulated as an important aetiological factor in many cases (the "vascular depression" hypothesis). Consistent with this, an inflammatory response, most probably representing ischaemia, has been reported with increases in intercellular adhesion molecule 1 (ICAM-1), in the dorsolateral prefrontal cortex (DLPFC) in postmortem tissue from elderly depressed subjects. As ischaemia is known to cause astrogliosis, this study has further tested the "vascular depression hypothesis" by investigating the distribution of the astrocytic marker glial fibrillary acidic protein (GFAP) in the DLPFC and in the anterior cingulate cortex (ACC). Methods: Postmortem tissue was obtained from 20 elderly patients with a history of major depressive disorder (MDD) and 20 control subjects. Sections were stained for GFAP using standard immunocytochemistry. Sets of images were obtained from all cortical layers in the DLPFC and ACC with the exception of layer IV in the ACC, and from gyral and deep white matter in both regions. The percentage of the area of each image occupied by GFAP was calculated using true colour image analysis, and mean values obtained for each region examined. Results: Immunoreactivity for GFAP was low in grey matter (for example, Mean (SEM) 0.76 (0.2)% in DLPFC layer V in depressed subjects), but higher in white matter (for example, 12.02 (2.2)% in DLPFC deep white matter in depressed subjects). Pronounced gliosis was observed within grey matter in a few cases only. GFAP immunoreactivity was significantly higher in layer I of the DLPFC in depressed subjects 15.8 (2.6)% than in controls 9.7 (1.3)% (t=2.2; df=27.5, p=0.04). No difference was detected in any other region. Conclusions: The data suggest any increase in GFAP in elderly MDD patients is limited to layer 1 of the DLPFC. These results provide some support for the vascular depression hypothesis and further implicate DLPFC abnormalities in depression.