Real-Time Functional Magnetic Resonance Imaging Neurofeedback for the Relief of Distressing Auditory-Verbal Hallucinations: Methodological and Empirical Advances.

Auditory-verbal hallucinations (AVH) are often associated with high levels of distress and disability in individuals with schizophrenia-spectrum disorders. In around 30% of individuals with distressing AVH and diagnosed with schizophrenia, traditional antipsychotic drugs have little or no effect. Thus, it is important to develop mechanistic models of AVH to inform new treatments. Recently a small number of studies have begun to explore the use of real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) for the treatment of AVH in individuals with schizophrenia. rtfMRI-NF protocols have been developed to provide feedback about brain activation in real time to enable participants to progressively achieve voluntary control over their brain activity. We offer a conceptual review of the background and general features of neurofeedback procedures before summarizing and evaluating existing mechanistic models of AVH to identify feasible neural targets for the application of rtfMRI-NF as a potential treatment. We consider methodological issues, including the choice of localizers and practicalities in logistics when setting up neurofeedback procedures in a clinical setting. We discuss clinical considerations relating to the use of rtfMRI-NF for AVH in individuals distressed by their experiences and put forward a number of questions and recommendations about best practice. Lastly, we conclude by offering suggestions for new avenues for neurofeedback methodology and mechanistic targets in relation to the research and treatment of AVH.

Joint Multi-modal Parcellation of the Human Striatum: Functions and Clinical Relevance.

The human striatum is essential for both low- and high-level functions and has been implicated in the pathophysiology of various prevalent disorders, including Parkinson's disease (PD) and schizophrenia (SCZ). It is known to consist of structurally and functionally divergent subdivisions. However, previous parcellations are based on a single neuroimaging modality, leaving the extent of the multi-modal organization of the striatum unknown. Here, we investigated the organization of the striatum across three modalities-resting-state functional connectivity, probabilistic diffusion tractography, and structural covariance-to provide a holistic convergent view of its structure and function. We found convergent clusters in the dorsal, dorsolateral, rostral, ventral, and caudal striatum. Functional characterization revealed the anterior striatum to be mainly associated with cognitive and emotional functions, while the caudal striatum was related to action execution. Interestingly, significant structural atrophy in the rostral and ventral striatum was common to both PD and SCZ, but atrophy in the dorsolateral striatum was specifically attributable to PD. Our study revealed a cross-modal convergent organization of the striatum, representing a fundamental topographical model that can be useful for investigating structural and functional variability in aging and in clinical conditions.

A look into hallucinations: the relationship between visual imagery and hallucinations in Alzheimer's disease.

Introduction: We investigated the relationship between visual hallucinations and vividness of visual imagery in patients with Alzheimer's disease (AD). Method: We recruited 28 patients with AD and 30 healthy control participants, matched for age and education. We evaluated proneness towards hallucinations with the Launay-Slade Hallucinations Scale, which includes items assessing visual and auditory hallucinations. We also evaluated vividness of visual imagery with the Vividness of Visual Imagery Questionnaire on which participants had to imagine four images (i.e., imagining the face of a friend, the rising sun, a familiar shop-front, and a country scene) and report the vividness of the images they generated. Results: Analysis demonstrated significant positive correlations between visual hallucinations and vividness of visual imagery in AD patients, however, no significant correlations were observed between auditory hallucinations and vividness of visual imagery in these participants. No significant correlations were observed between hallucinations and vividness of visual imagery in healthy control participants, probably due to the lack of hallucinations in these participants. Discussion: These results demonstrate a selective relationship between the occurrence of visual (but not auditory) hallucinations and the ability to generate vivid visual images in AD.

Prediction of activation patterns preceding hallucinations in patients with schizophrenia using machine learning with structured sparsity.

Despite significant progress in the field, the detection of fMRI signal changes during hallucinatory events remains difficult and time-consuming. This article first proposes a machine-learning algorithm to automatically identify resting-state fMRI periods that precede hallucinations versus periods that do not. When applied to whole-brain fMRI data, state-of-the-art classification methods, such as support vector machines (SVM), yield dense solutions that are difficult to interpret. We proposed to extend the existing sparse classification methods by taking the spatial structure of brain images into account with structured sparsity using the total variation penalty. Based on this approach, we obtained reliable classifying performances associated with interpretable predictive patterns, composed of two clearly identifiable clusters in speech-related brain regions. The variation in transition-to-hallucination functional patterns not only from one patient to another but also from one occurrence to the next (e.g., also depending on the sensory modalities involved) appeared to be the major difficulty when developing effective classifiers. Consequently, second, this article aimed to characterize the variability within the prehallucination patterns using an extension of principal component analysis with spatial constraints. The principal components (PCs) and the associated basis patterns shed light on the intrinsic structures of the variability present in the dataset. Such results are promising in the scope of innovative fMRI-guided therapy for drug-resistant hallucinations, such as fMRI-based neurofeedback.

Current Issues in the Use of fMRI-Based Neurofeedback to Relieve Psychiatric Symptoms.

fMRI-based neurofeedback (fMRI-NF) is a non-invasive technique that allows participants to achieve control of their own brain activity using the real-time feedback of the activity (measured indirectly based on the BOLD signal) of a particular brain region or network. The feasibility of fMRI-NF in healthy subjects has been documented for a variety of brain areas and neural systems, and this technique has also been proposed for the treatment of psychiatric disorders in recent years. Through a systematic review of the scientific literature this paper probes the rationale and expected applications of fMRI-NF in psychiatry, discusses issues that must be addressed in the use of this technique to treat mental disorders. Six relevant references and five ongoing studies were identified according to our inclusion criteria. These studies show that in most psychiatric disorders (major depressive disorder, schizophrenia, personality disorders, addiction), patients are able to learn voluntary control of the neuronal activity of the targeted brain region(s). Interestingly, in some cases, this learning is associated with clinical improvement, showing that fMRI-NF can potentially be developed into a therapeutic tool. However, only low-level evidence is available to support the use of this relatively new technique in clinical practice. Notably, no randomized, controlled trial is currently available in this field of research. Finally, methodological issues and clinical perspectives (especially the potential use of pattern recognition in fMRI-NF protocols) are discussed.

Aripiprazole for treating cannabis-induced psychotic symptoms in ultrahigh-risk individuals.

Cannabis-induced psychotic symptoms (CIPSs) have both similarities and differences with positive symptoms of schizophrenia, and it remains unclear whether CIPSs result from dopaminergic mechanisms and can be treated with antipsychotics. We report the case of a 22-year-old male patient with ultrahigh risk criteria for psychosis, who reported cannabis addiction and recurrent CIPSs. Aripiprazole 10 mg/d could totally and durably suppress CIPSs in the patient, but had no effect on the smoking level. Treating CIPSs in ultrahigh risk individuals who cannot stop or refuse stopping cannabis might fit a harm-reduction strategy by preventing transition into psychosis.

Therapeutic prospects of PPARs in psychiatric disorders: a comprehensive review.

Peroxisome Proliferator-Activated Receptors (PPARs) are a family of nuclear receptors whose activation modulates the gene expression that underlies both the glucid-lipid and the inflammation pathways. While many PPARs agonists have been used for years as medication for metabolic disorders, an increasing attention is being currently dedicated to these drugs for inflammation-related pathologies. Within the psychiatric field, it has recently appeared that inflammatory processes are highly suspected in the pathophysiology of several important disorders, such as schizophrenia and mood disorders. By their anti-inflammatory properties, PPARs might have a disease-modifying action that could help in improving the outcome of patients. Furthermore, recent data suggest that PPARs could also modulate the expression of some neurotransmission factors. Therefore, PPARs may directly modify the information processing, and have a potential symptomatic action on several psychiatric disorders. At last, PPARs action of metabolic regulation could have a role on corrective or even preventive strategies against the metabolic adverse events that are commonly observed with some current psychiatric medications, notably antipsychotics. This triple potential action profile of PPARs modulators is investigated in this article, successively for schizophrenia spectrum disorders and mood disorders. Theoretical involvements of PPARs are also discussed for the treatment of Post- Traumatic Stress Disorder and Personality Disorders. At the time of the emerging concept of psychoneuroimmunology, PPARs open original therapeutic prospects for the psychiatric research.

Impact of midwives' training on postnatal depression screening in the first week post delivery: a quality improvement report.

BACKGROUND: postnatal depression (PND) is a major public health problem. The objective of this study was to improve early PND screening by midwives in a maternity unit. Professional screening techniques were evaluated and compared with reference screening techniques [Edinburgh Postnatal Depression Scale (EPDS), Mini International Neuropsychiatric Interview (MINI-DSM-IV)]. METHODS: the evaluation took place before and after the midwife training in order to determine the effectiveness of specific clinical recommendations for two successive 10-week inclusion periods (from November 2004 to September 2005). A short training course and posters were used to convey the recommendations, agreed by obstetricians, paediatricians and psychiatrists. RESULTS: a total of 463 postpartum women were included in the two phases of the study. Quantitative and qualitative PND screening by midwives improved significantly following training (Z=2.07, p=0.04; Z=2.62, p=0.008, respectively). Early detection of major depressive episodes increased by 37.7% (95% confidence interval 25.7-49.7) following training. A combination of midwives' perception of poor emotional well-being and the EPDS led to a significant improvement in early detection of PND (Q=8.00, p=0.04). DISCUSSION: targeted recommendations given to the midwives led to an improvement in the early detection of PND. Suitable programmes need to be offered to reduce the number of cases of PND. Perinatal psychiatrists should be seen to be meticulous and available for such prevention action.

Fetal cortical activation to sound at 33 weeks of gestation: a functional MRI study.

Hearing already functions before birth, but little is known about the neural basis of fetal life experiences. Recent imaging studies have validated the use of functional magnetic resonance imaging (fMRI) in pregnant women at 38-weeks of gestation. The aim of the present study was to examine fetal brain activation to sound, using fMRI at the beginning of the third trimester of pregnancy. 6 pregnant women between 28- and 34-weeks of gestation were scanned using a magnetic strength of 1.5 T, with an auditory stimulus applied to their abdomen. 3 fetuses with a gestational age of 33 weeks, showed significant activation to sound in the left temporal lobe, measured using a new data-driven approach (Independent Component Analysis for fMRI time series). Only 2 of these fetuses showed left temporal activation, when the standard voxel-wise analysis method was used (p=0.007; p=0.001). Moreover, motion parameters added as predictors of the General Linear Model confirmed that motion cannot account for the signal variance in the fetal temporal cortex (p=0.01). Comparison between the statistical maps obtained from MRI scans of the fetuses with those obtained from adults, made it possible to confirm our hypothesis, that there is brain activation in the primary auditory cortex in response to sound. Measurement of the fetal hemodynamic response revealed an average fMRI signal change of +3.5%. This study shows that it is possible to use fMRI to detect early fetal brain function, but also confirms that sound processing occurs beyond the reflexive sub-cortical level, at the beginning of the third trimester of pregnancy.

Self awareness and speech processing: an fMRI study.

Language production and perception imply motor system recruitment. Therefore, language should obey the theory of shared motor representation between self and other, by means of mirror-like systems. These mirror-like systems (referring to single-unit recordings in animals) show the property to be recruited both when accomplishing and when perceiving a goal-directed action, whatever the sensory modality may be. This hypothesis supposes that a neural network for self-awareness is involved to distinguish speech production from speech listening. We used fMRI to test this assumption in 12 healthy subjects, who performed two different block-design experiments. The first experiment showed involvement of a lateral mirror-like network in speech listening, including ventral premotor cortex, superior temporal sulcus and the inferior parietal lobule (IPL). The activity of this mirror-like network is associated with the perception of an intelligible speech. The second experiment looked at a self-awareness network. It showed involvement of a medial resting-state network, including the medial parietal and medial prefrontal cortices, during the 'self-generated voice' condition, as opposed to passive speech listening. Our results support the fact that deactivation of this medial network, in association with modulation of the activity of the IPL (part of the mirror-like network previously described), is linked to self-awareness in speech processing. Overall, these results support the idea that self-awareness is present when distinguishing between speech production and speech listening situations, and may depend on these two different parieto-frontal networks.