Altered brain function directly related to structural abnormalities in people at ultra high risk of psychosis: Longitudinal VBM-fMRI study

Background

Several studies have indicated that people with prodromal signs of psychosis show alterations in the structure and function of the brain when they first present to clinical services. However, the longitudinal course of these abnormalities, and how they relate to subsequent clinical and functional outcome is relatively unclear.

Methods

A cohort of subjects at ultra high risk of psychosis were studied using functional magnetic resonance imaging (fMRI) in conjunction with the N-Back task, and volumetric MRI at first clinical presentation and again after one year. Levels of psychopathology and global functioning were assessed at the same time points using the CAARMS, PANSS, and the GAF scale.

Results

At baseline, the high risk group showed reduced activation during the task in the left middle frontal gyrus, supramarginal gyrus and inferior parietal lobule, and reduced gray matter volume in the left middle and medial frontal gyri, left insula and the right anterior cingulate gyrus. Within the high-risk group, there was a positive correlation between the magnitude of the functional and structural alterations in the left middle frontal gyrus. Between presentation and follow up, the severity of perceptual disorder and thought disorder (rated by the CAARMS), and of general psychopathology (rated by the PANSS general score) decreased, and the level of global functioning improved. This clinical and functional improvement was associated with a longitudinal increase in activation in the anterior cingulate and right parahippocampal gyrus. The change in anterior cingulate response was directly correlated with the improvement in the GAF score.

Conclusions

In subjects presenting with prodromal signs of psychosis, reduced prefrontal activation during a working memory task is associated with a reduction in gray matter volume in the same area. Changes in anterior cingulate activation were correlated with functional improvement in this group, consistent with the role of this region in multiple cognitive and social processes.     

Voxelwise meta-analysis of gray matter reduction in major depressive disorder

Background

Voxel-based morphometry (VBM) has been widely used in studies of major depressive disorder (MDD) and has provided cumulative evidence of gray matter abnormalities in patients relative to controls. Thus we performed a meta-analysis to integrate the reported studies to determine the consistent gray matter alterations in MDD.

Methods

A systematic search was conducted to identify VBM studies which contrasted MDD patients against a comparison group. The coordinates of gray matter change across studies were meta-analyzed using the activation likelihood estimation (ALE) method hybridized with the rank-based Genome Scan Meta-Analysis (GSMA) to quantitatively estimate regional gray matter reductions in MDD.

Results

A total of 20 VBM studies comparing 543 major depressive patients with 750 healthy control subjects were included. Consistent gray matter reductions in all MDD patients relative to healthy controls were identified in the bilateral anterior cingulate cortex (ACC), right middle and inferior frontal gyrus, right hippocampus and left thalamus.

Conclusions

Meta-analysis of all primary VBM studies indicates that significant gray matter reductions in MDD are localized in a distributed neural network which includes frontal, limbic and thalamic regions. Future studies will benefit from the use of a longitudinal approach to examine anatomical and functional abnormalities within this network and their relationship to clinical profile, particularly in first-episode and drug-naive MDD patients.     

Pharmacotherapy impacts functional connectivity among affective circuits during response inhibition in pediatric mania

Objective

The aim of the current study was to determine the influence of implicated affective circuitry disturbance in pediatric bipolar disorder (PBD) on behavioral inhibition. The differential influence of an antipsychotic and an anti-epileptic medication on the functional connectivity across affective and cognitive neural operations in PBD was examined.

Methods

This was a six-week double blind randomized fMRI trial of risperidone plus placebo vs. divalproex plus placebo for patients with mania (n = 22; 13.6 ± 2.5 years). Healthy controls (HC; n = 14, 14.5 ± 2.8 years) were also scanned for normative comparison. Participants performed a response inhibition fMRI task where a motor response, already ‘on the way’ to execution, had to be voluntarily inhibited on trials where a stop signal was presented. Independent component analysis was used to map functional connectivity across the whole brain.

Results

While there were no behavioral differences between the groups at pre- or post-drug trial, there was significant improvement on manic symptoms in the patient groups. All participants engaged an evaluative affective circuit (EAC: bilateral inferior frontal gyrus, middle frontal gyrus, anterior cingulate cortex (ACC), middle temporal gyrus, insulae, caudate and putamen) and a reactive affective circuit (RAC: bilateral occipital cortex, amygdala, medial frontal gyrus and insula) during task performance. Within the EAC, post-treatment and relative to HC, greater engagement was seen in left insula in risperidone group and left subgenual ACC in divalproex group. Within the RAC, greater baseline amygdala connectivity in patients did not alter with treatment.

Conclusion

EAC and RAC are two key circuits that moderate emotional influence on response inhibition in PBD. Risperidone and divalproex differentially engage the EAC. Limited change in amygdala activity with treatment in all patients indicates a likely trait deficit in PBD.     

Disrupted regional homogeneity in treatment-resistant depression: a resting-state fMRI study

Background

Using a newly developed regional homogeneity (ReHo) approach, we were to explore the features of brain activity in patients with treatment-resistant depression (TRD) in resting state, and further to examine the relationship between abnormal brain activity in TRD patients and specific symptom factors derived from ratings on the Hamilton Rating Scale for Depression (HRSD).

Methods

24 patients with TRD and 19 gender-, age-, and education-matched healthy subjects participated in the fMRI scans.

Results

1.

Compared with healthy controls, decreased ReHo were found in TRD patients in the left insula, superior temporal gyrus, inferior frontal gyrus, lingual gyrus and cerebellum anterior lobe (culmen) (p < 0.05, corrected).

2.

Compared with healthy controls, increased ReHo were found in the left superior temporal gyrus, cerebellum posterior lobe (tuber), cerebellum anterior lobe (culmen), the right cerebellar tonsil and bilateral fusiform gyrus (p < 0.05, corrected).

3.

There was no correlation between the ReHo values in any brain region detected in our study and the patients' age, years of education, illness duration, HRSD total score and its symptom factors.

Limitation

The influence of antidepressants to the brain activity in TRD patients was not fully eliminated.

Conclusions

The pathogenesis of TRD may be attributed to abnormal neural activity in multiple brain regions.     

Development of left occipitotemporal systems for skilled reading in children after a phonologically- based intervention

Background

A range of neurobiological investigations shows a failure of left hemisphere posterior brain systems to function properly during reading in children and adults with reading disabilities. Such evidence of a disruption in the normal reading pathways provides a neurobiological target for reading interventions. In this study, we hypothesized that the provision of an evidence-based, phonologically mediated reading intervention would improve reading fluency and the development of the fast-paced occipitotemporal systems serving skilled reading.

Methods

Functional magnetic resonance imaging was used to study the effects of a phonologically based reading intervention on brain organization and reading fluency in 77 children aged 6.1-9.4 years (49 with reading disability and 28 control subjects). Children comprised three experimental groups: experimental intervention (n = 37), community intervention (n = 12), and community control subjects (n = 28).

Results

Immediately after the year-long intervention, children taught with the experimental intervention had made significant gains in reading fluency and demonstrated increased activation in left hemisphere regions, including the inferior frontal gyrus and the middle temporal gyrus; 1 year after the experimental intervention had ended these children were activating bilateral inferior frontal gyri and left superior temporal and occipitotemporal regions.

Conclusions

These data indicate that the nature of the remedial educational intervention is critical to successful outcomes in children with reading disabilities and that the use of an evidence-based phonologic reading intervention facilitates the development of those fast-paced neural systems that underlie skilled reading.     

A comparative study of cognition and brain anatomy between two neurodevelopmental disorders: 22q11.2 deletion syndrome and Williams syndrome

Background

22q11.2 deletion syndrome (22q11DS) is associated with intellectual disability, poor social interaction and a high prevalence of psychosis. However, to date there have been no studies comparing cognition and neuroanatomical characteristics of 22q11DS with other syndromes to investigate if the cognitive strengths and difficulties and neuroanatomical differences associated with 22q11DS are specific to the syndrome. Hence, it is difficult to know if the observed features of 22q11DS are simply due to a non-specific effect of having a genetic disorder or are specific to 22q11DS.

Methods

In this study, cognition and brain anatomy of 12 children with 22q11DS were compared to 12 age, gender and full scale IQ (FSIQ) matched children with William syndrome (WS) in order to investigate which cognitive and neuroanatomical features are specific to 22q11DS. We chose WS since the literature suggests that both groups have areas of physical/cognitive/behavioural overlap but as yet there has been no direct comparison of the two groups.

Results

Despite being matched on FSIQ the WS group had significantly greater impairment than those with 22q11DS on tests of Performance IQ, while performing significantly better on tasks measuring verbal, social and facial processing skills. Moreover there were significant differences in brain anatomy. Despite similar overall brain volumes, midline anomalies were more common among the 22q11DS group, and regional differences such as increased striatal volumes and reduced cerebellar volumes in the 22q11DS group were detected.

Conclusions

These findings suggest that although the behavioural phenotype is similar in some aspects there are key differences in cognition and neuroanatomy between the two groups. Different neuropsychological profiles need to be considered when designing educational frameworks for working with these children.     

Contributions to singing ability by the posterior portion of the superior temporal gyrus of the non-language-dominant hemisphere: First evidence from subdural cortical stimulation, Wada testing, and fMRI

Introduction

Although the substrates that mediate singing abilities in the human brain are not well understood, invasive brain mapping techniques used for clinical decision making such as intracranial electro-cortical testing and Wada testing offer a rare opportunity to examine music-related function in a select group of subjects, affording exceptional spatial and temporal specificity.

Methods

We studied eight patients with medically refractory epilepsy undergoing indwelling subdural electrode seizure focus localization. All patients underwent Wada testing for language lateralization. Functional assessment of language and music tasks was done by electrode grid cortical stimulation. One patient was also tested non-invasively with functional magnetic resonance imaging (fMRI). Functional organization of singing ability compared to language ability was determined based on four regions-of-interest (ROIs): left and right inferior frontal gyrus (IFG), and left and right posterior superior temporal gyrus (pSTG).

Results

In some subjects, electrical stimulation of dominant pSTG can interfere with speech and not singing, whereas stimulation of non-dominant pSTG area can interfere with singing and not speech. Stimulation of the dominant IFG tends to interfere with both musical and language expression, while non-dominant IFG stimulation was often observed to cause no interference with either task; and finally, that stimulation of areas adjacent to but not within non-dominant pSTG typically does not affect either ability. Functional fMRI mappings of one subject revealed similar music/language dissociation with respect to activation asymmetry within the ROIs.

Conclusion

Despite inherent limitations with respect to strictly research objectives, invasive clinical techniques offer a rare opportunity to probe musical and language cognitive processes of the brain in a select group of patients.     

Aftermath of sexual abuse history on adult patients suffering from chronic functional pain syndromes: An fMRI pilot study

Objective

This preliminary study investigates the neural substrates of empathy-induced pain in multisomatoform pain patients “with vs. without” a history of sexual abuse during childhood.

Methods

Using functional magnetic resonance imaging (fMRI) and behavioral measurements, we compared eight abused with eight nonabused patients using an established empathy-for-pain paradigm.

Results

Higher activations in left lateral and medial superior frontal gyrus as well as a nonsignificant activation of the right supplementary motor area in abused patients were detected. The nonabused participants showed higher activation of left hippocampus. There was no significant difference in subjective pain ratings between the groups.

Conclusion

Although the number of participants still needs to be increased, our main findings mirror the clinical impression and support the notion of perturbed neuroprocessing of grievous stimuli in chronic pain patients with a history of sexual abuse.     

White matter alterations related to P300 abnormalities in individuals at high risk for psychosis: an MRI-EEG study

Background

Psychosis onset is characterized by white matter and electrophysiologic abnormalities. The relation between these factors in the development of illness is almost unknown. We studied the relation between white matter volumes and P300 in prodromal psychosis.

Methods

We assessed white matter volume (detected using magnetic resonance imaging) and electrophysiologic response during an oddball task (P300) in healthy controls and individuals at high clinical risk for psychosis (with an “at-risk mental state” [ARMS]).

Results

We included 41 controls and 39 patients with an ARMS in our study. A psychotic disorder developed in 26% of the ARMS group within the follow-up period of 2 years. The P300 amplitude was significantly lower in the ARMS group than in the control group. The ARMS group showed reduced volume of white matter underlying the left superior temporal gyrus and the left superior frontal gyrus and increased volume of white matter underlying the right insula and the right angular gyrus compared with controls. Relative to individuals who did not later become psychotic, the subgroup in whom psychosis subsequently developed had a smaller volume of white matter underlying the left precuneus and the right middle temporal gyrus and increased volume in the white matter underlying the right middle frontal gyrus. We observed a significant interaction in the right middle frontal gyrus: white matter volume was negatively associated with P300 amplitude in the ARMS group and positively associated with P300 amplitude in the control group.

Limitations

The voxel-based morphometry method alone cannot determine whether abnormal white matter volumes are due to an altered number of axonal connections or decreased myelination.

Conclusion

P300 abnormalities precede the onset of psychosis and are directly related to white matter alterations, representing a correlate of an increased vulnerability to disease.     

Un tremblement d’attitude révélant une maladie de Huntington

Introduction

Initial manifestations of Huntington's disease (HD) are varied and chorea is not always the first motor symptom.

Case report

We report the case of a 44-year-old woman, with a family history of HD, who presented isolated head and upper limbs tremor for 4 years. Genetic testing confirmed the diagnosis of HD and no cause of secondary postural tremor was found. Propanolol was introduced with success.

Conclusion

This kind of presentation is unusual and has mostly been reported in the juvenile form of HD.     

Analysis of Altered Baseline Brain Activity in Drug-Naive Adult Patients with Social Anxiety Disorder Using Resting-State Functional MRI

Objective

We hypothesize that the amplitude of low-frequency fluctuations (ALFF) is involved in the altered regional baseline brain function in social anxiety disorder (SAD). The aim of the study was to analyze the altered baseline brain activity in drug-naive adult patients with SAD.

Methods

We investigated spontaneous and baseline brain activities by obtaining the resting-state functional magnetic resonance imaging data of 20 drug-naïve adult SAD patients and 19 healthy controls. Voxels were used to analyze the ALFF values using one- and two-sample t-tests. A post-hoc correlation of clinical symptoms was also performed.

Results

Our findings show decreased ALFF in the bilateral insula, left medial superior frontal gyrus, left precuneus, left middle temporal gyrus, right middle temporal pole, and left fusiform gyrus of the SAD group. The SAD patients exhibited significantly increased ALFF in the right inferior temporal gyrus, right middle temporal gyrus, bilateral middle occipital gyrus, orbital superior frontal gyrus, right fusiform gyrus, right medial superior frontal gyrus, and left parahippocampal gyrus. Moreover, the Liebowitz Social Anxiety Scale results for the SAD patients were positively correlated with the mean Z values of the right middle occipital and right inferior occipital but showed a negative correlation with the mean Z values of the right superior temporal gyrus and right medial superior frontal gyrus.

Conclusion

These results of the altered regional baseline brain function in SAD suggest that the regions with abnormal spontaneous activities are involved in the underlying pathophysiology of SAD patients.     

Psychological responses to cardiac diagnosis: Changes in illness representations immediately following coronary angiography

Objective

Coronary angiography is a commonly used diagnostic test for ischemic heart disease. Little is known, however, about how undergoing the procedure impacts on the ways in which individuals perceive their illness. We sought to explore patients' reactions to an angiogram in terms of changes in symptom appraisal, perceived consequences of their condition, and patients' illness concern and emotional response to their condition after the receiving diagnostic results.

Methods

The Brief IPQ was administered to patients undergoing a diagnostic coronary angiogram (N=57) before and immediately following the procedure. Changes in illness representations were then compared between patients diagnosed with diseased arteries and patients with normal arteries.

Results

We found that the number of symptoms patients associated with their condition, illness consequences, and illness emotion decreased for patients receiving normal results but remained unchanged for patients receiving results showing diseased arteries. Illness concern decreased significantly for both patient groups.

Conclusions

The results demonstrate that diagnostic results can have clear and immediate effects on how patients' view and emotionally respond to their symptoms. The results also suggest that patients cognitively prepare themselves to receive an unfavorable diagnosis and the pattern suggests those receiving normal results modify their perceptions in a positive direction rather than those receiving an unfavorable diagnosis.     

Altered white matter integrity and development in children with autism: a combined voxel-based morphometry and diffusion imaging study

Background

A combined protocol of voxel-based morphometry (VBM) and diffusion-weighted imaging (DWI) was applied to investigate the neurodevelopment of gray and white matter in autism.

Methods

Twenty children with autism (mean age = 7 ± 2.75 years old; age range: 4-14; 2 girls) and 22 matched normally developing children (mean age = 7.68 ± 2.03 years old; age range: 4-11; 2 girls) underwent magnetic resonance imaging (MRI). VBM was employed by applying the Template-o-Matic toolbox (TOM), a new approach which constructs the age-matched customized template for tissue segmentation. Also, the apparent diffusion coefficients (ADC) of water molecules were obtained from the analysis of DWI. Regions of interests (ROIs), standardized at 5 pixels, were placed in cortical lobes and corpus callosum on the non-diffusion weighted echo-planar images (b = 0) and were then automatically transferred to the corresponding maps to obtain the ADC values.

Results

Compared to normal children, individuals with autism had significantly: (1) increased white matter volumes in the right inferior frontal gyrus, the right fusiform gyrus, the left precentral and supplementary motor area and the left hippocampus, (2) increased gray matter volumes in the inferior temporal gyri bilaterally, the right inferior parietal cortex, the right superior occipital lobe and the left superior parietal lobule, and (3) decreased gray matter volumes in the right inferior frontal gyrus and the left supplementary motor area. Abnormally increased ADC values in the bilateral frontal cortex and in the left side of the genu of the corpus callosum were also reported in autism. Finally, age correlated negatively with lobar and callosal ADC measurements in individuals with autism, but not in children with normal development.

Conclusions

These findings suggest cerebral dysconnectivity in the early phases of autism coupled with an altered white matter maturation trajectory during childhood potentially taking place in the frontal and parietal lobes, which may represent a neurodevelopmental marker of the disorder, possibly accounting for the cognitive and social deficits.     

Brain glucose metabolism difference between bipolar and unipolar mood disorders in depressed and euthymic states

Background

Functional brain imaging studies have consistently demonstrated abnormalities in regional cerebral glucose metabolism in the prefrontal cortex in patients with mood disorders (MD). These studies, however, have not clarified the differential characteristics of glucose metabolism between depressed and euthymic states, or between bipolar mood disorder (BP) and unipolar mood disorder (UP).

Methods

We used [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) to evaluate the differences in glucose metabolism at resting state. We compared 30 depressed and 17 euthymic female patients with mood disorders with age-, IQ-, and socioeconomically matched 20 healthy controls (HCs). Then, BP and UP patients were separately analyzed. The PET data were objectively analyzed by statistical parametric mapping (SPM).

Results

Compared with HCs, the depressed MD patients showed significantly lower glucose metabolism in the bilateral frontal gyri, left cingulate gyrus, bilateral temporal gyri, right insula, bilateral inferior parietal lobules, and right occipital gyrus. In contrast, the euthymic MD patients demonstrated fewer areas with significant reduction. When the depressed BP patients were separately compared with HCs, the glucose metabolism was found to be significantly lower in the bilateral frontal gyri, right cingulate gyrus, and bilateral inferior parietal lobules. Meanwhile, the depressed UP patients showed a significantly lower metabolism in the bilateral frontal gyri, left cingulate gyrus, bilateral temporal gyri, bilateral insulae, bilateral inferior parietal lobules, and right occipital gyrus.

Conclusions

The results of this study provide evidence of persistent hypometabolism in depressed MD patients, particularly in the frontal gyrus. Although the conclusions are limited in the cross-sectional study, these findings suggest that abnormalities in the right frontal gyrus, left temporal gyrus, and left cingulate gyrus tend to normalize as the depression symptoms improve, although those in the left frontal gyrus, right cingulate gyrus, and right temporal gyrus persist. This study also elucidated the cerebral hypofunction specific to each BP and UP. BP patients showed a decrease in glucose metabolism in the right anterior cingulate and UP patients did in the right temporal gyrus, right insula, and left posterior cingulate. This study clarified the differences between subtypes.     

Voxel-wise meta-analysis of fMRI studies in patients at clinical high risk for psychosis

Background

Reliable neurofunctional markers of increased vulnerability to psychosis are needed to improve the predictive value of psychosis risk syndrome and inform preventive interventions.

Methods

I performed a signed differential mapping (SDM) voxel-wise meta-analysis of functional magnetic resonance imaging (fMRI) studies of patients at clinical high risk for psychosis.

Results

Ten studies were included in the analysis. Compared with controls, high-risk patients showed reduced neural activation in the left inferior frontal gyrus (Brodmann area [BA] 9) and in a cluster spanning the bilateral medial frontal gyrus (BA 8,6), bilateral superior frontal gyrus (BA 8,6) and the left anterior cingulate (BA 32). There was no publication bias. Heterogeneity across studies was low. Sensitivity analysis confirmed the robustness of the findings.

Limitations

The cross-sectional nature of the included studies prevented the comparison of high-risk patients who later experienced a psychotic episode with those who did not. Other caveats are reflected in methodologic heterogeneity across tasks employed by different individual imaging studies.

Conclusion

Reduced neurofunctional activation in prefrontal regions may represent a neurophysiologic correlate of increased vulnerability to psychosis.     

Cognitive behavioral therapy versus paroxetine in the treatment of hypochondriasis: An 18-month naturalistic follow-up

Background

The present maintenance study investigated whether the reduction in hypochondriacal complaints after initial treatment with CBT or paroxetine sustained during a follow-up period and whether psychiatric severity at pretest predicted the course of hypochondriacal symptoms.

Method

A naturalistic follow-up period of 18 months after a 16-week RCT consisting of 33 patients initially allocated to a CBT condition and 29 patients to a paroxetine condition. The main outcome measure was the Whiteley Index.

Results

The initial treatment effect of CBT and paroxetine sustained during the follow-up period. No significant differences between CBT and paroxetine were found. Treatment course could not be predicted by psychiatric comorbidity.

Conclusion

CBT and paroxetine are both effective treatments for hypochondriasis in the long term.     

An evoked auditory response fMRI study of the effects of rTMS on putative AVH pathways in healthy volunteers

Background

Auditory verbal hallucinations (AVH) are the most prevalent symptom in schizophrenia. They are associated with increased activation within the temporoparietal cortices and are refractory to pharmacological and psychological treatment in approximately 25% of patients. Low frequency repetitive transcranial magnetic stimulation (rTMS) over the temporoparietal cortex has been demonstrated to be effective in reducing AVH in some patients, although results have varied. The cortical mechanism by which rTMS exerts its effects remain unknown, although data from the motor system is suggestive of a local cortical inhibitory effect. We explored neuroimaging differences in healthy volunteers between application of a clinically utilized rTMS protocol and a sham rTMS equivalent when undertaking a prosodic auditory task.

Method

Single-blind placebo controlled fMRI study of 24 healthy volunteers undertaking an auditory temporoparietal activation task, who received either right temporoparietal rTMS or sham RTMS.

Results

The main effect of group was bilateral inferior parietal deactivation following real rTMS. An interaction of group and task type showed deactivation during real rTMS in the right superior temporal gyrus (STG), left thalamus, left postcentral gyrus and cerebellum. However, the left parietal lobe showed an increase in activation following right sided real rTMS, but this increase was specific to a non-linguistic, tone-sequence task.

Conclusion

rTMS does cause local inhibitory effects, not only in the underlying region of application, but also in functionally connected cortical regions. However, there is also a related, task dependent, increase in activation within selected cortical areas in the contralateral hemisphere; these are likely to reflect compensatory mechanisms, and such cortical activation may in some cases contribute to, or retard, some of the therapeutic effects seen with rTMS.     

Frontal dysconnectivity in 22q11.2 deletion syndrome: an atlas-based functional connectivity analysis

Background

22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental syndrome associated with deficits in cognitive and emotional processing. This syndrome represents one of the highest risk factors for the development of schizophrenia. Previous studies of functional connectivity (FC) in 22q11DS report aberrant connectivity patterns in large-scale networks that are associated with the development of psychotic symptoms.

Methods

In this study, we performed a functional connectivity analysis using the CONN toolbox to test for differential connectivity patterns between 54 individuals with 22q11DS and 30 healthy controls, between the ages of 17–25 years old. We mapped resting-state fMRI data onto 68 atlas-based regions of interest (ROIs) generated by the Desikan-Killany atlas in FreeSurfer, resulting in 2278 ROI-to-ROI connections for which we determined total linear temporal associations between each. Within the group with 22q11DS only, we further tested the association between prodromal symptoms of psychosis and FC.

Results

We observed that relative to controls, individuals with 22q11DS displayed increased FC in lobar networks involving the frontal–frontal, frontal–parietal, and frontal–occipital ROIs. In contrast, FC between ROIs in the parietal–temporal and occipital lobes was reduced in the 22q11DS group relative to healthy controls. Moreover, positive psychotic symptoms were positively associated with increased functional connections between the left precuneus and right superior frontal gyrus, as well as reduced functional connectivity between the bilateral pericalcarine. Positive symptoms were negatively associated with increased functional connectivity between the right pericalcarine and right postcentral gyrus.

Conclusions

Our results suggest that functional organization may be altered in 22q11DS, leading to disruption in connectivity between frontal and other lobar substructures, and potentially increasing risk for prodromal psychosis.

     

Neuroanatomical markers of genetic liability to psychosis and first episode psychosis: A voxelwise meta-analytical comparison

Objectives. To address at a meta-analytical level the neuroanatomical markers of genetic liability to psychosis and a of first episode of psychosis. Methods. Fifteen voxel-based morphometry (VBM) studies of antipsychotic-naive subjects at genetic high-risk (HR) for psychosis or with a first-episode psychosis (FEP) were included in a Signed Differential Mapping (SDM) meta-analysis. Publication bias was assessed with funnel plots and Egger's intercept. Heterogeneity was assessed with Q statistics and I ² index. Results. The database comprised 458 HR and 206 antipsychotic-naïve FEP subjects, matched with controls. Gray matter (GM) reductions as compared to controls, were observed in the left parahippocampal gyrus and in the bilateral anterior cingulate gyrus in the HR group, and in the right superior temporal gyrus, in the left insula and in the left cerebellum in the FEP group. Further GM decreases were observed in the FEP group as compared to the HR group in the left anterior cingulate, in the right precuneus, in the left cerebellum and in the right superior temporal gyrus. Limitations. The cross-sectional nature of the included studies prevented the comparison of high risk subjects who later did or did not develop a psychotic episode. Other caveats are based on the methodological heterogeneity across individual imaging studies. Conclusions. GM reductions in the anterior cingulate are markers of genetic liability to psychosis while reductions in the superior temporal gyrus and cerebellum can be interpreted as markers of a first onset of the illness.     

Effects of methylphenidate on olfaction and frontal and temporal brain oxygenation in children with ADHD

Objective

Olfaction and attention-deficit-/hyperactivity disorder (ADHD) are mediated by dopamine metabolism and fronto-temporal functioning converging in recent findings of increased olfactory sensitivity in children with ADHD modulated by methylphenidate (MPH) and altered frontal and temporal oxygenation in adults with ADHD.

Method

We investigated olfactory sensitivity, discrimination, and identification (Sniffin’ Sticks) in 27 children and adolescents with ADHD under chronic MPH medication and after a wash-out period of at least 14 half-lives in balanced order and 22 controls comparable for handedness, age, and intelligence. In addition, inferior frontal and temporal oxygenation was measured by means of functional near-infrared spectroscopy (fNIRS) during the presentation of 2-phenylethanol. Group differences in regard to sex distribution were statistically controlled for by analysis of covariance.

Results

Patients did not differ from controls in any olfactory domain under treatment with MPH. Cessation of medication led to a significant increase in olfactory discrimination. Controls displayed typical inferior frontal and temporal brain activity in response to passive olfactory stimulation, while brain oxygenation was diminished in the patient group when assessed without medication. Under medication ADHD patients showed a trend for a normalisation of brain activity in the temporal cortex.

Conclusions

The here reported effects of MPH cessation on olfactory discrimination and frontal and temporal oxygenation along with previous findings of increased olfactory sensitivity in medication-naïve ADHD children and its normalisation under chronic MPH treatment lead to the conclusion that MPH exerts differential chronic effects vs. acute cessation effects on altered olfactory function in ADHD. These effects are most probably mediated by modulation of the dopaminergic system.