Mapping Depression in Schizophrenia: A Functional Magnetic Resonance Imaging Study.

Depressive symptoms are common in schizophrenia, often left untreated, and associated with a high relapse rate, suicidal ideation, increased mortality, reduced social adjustment and poor quality of life. The neural mechanisms underlying depression in psychosis are poorly understood. Given reports of altered brain response to negative facial affect in depressive disorders, we examined brain response to emotive facial expressions in relation to levels of depression in people with psychosis. Seventy outpatients (final N= 63) and 20 healthy participants underwent functional magnetic resonance imaging during an implicit affect processing task involving presentation of facial expressions of fear, anger, happiness as well as neutral expressions and a (no face) control condition. All patients completed Beck Depression Inventory (BDI-II) and had their symptoms assessed on the Positive and Negative Syndrome Scale (PANSS). In patients, depression (BDI-II) scores associated positively with activation of the left thalamus, extending to the putamen-globus pallidus, insula, inferior-middle frontal and para-post-pre-central gyri during fearful expressions. Furthermore, patients with moderate-to-severe depression had significantly higher activity in these brain regions during fearful expressions relative to patients with no, minimal, or mild depression and healthy participants. The study provides first evidence of enhanced brain response to fearful facial expressions, which signal an uncertain source of threat in the environment, in patients with psychosis and a high level of self-reported depression.

Functional MRI of verbal self-monitoring in schizophrenia: performance and illness-specific effects.

Previous small-sample studies have shown altered frontotemporal activity in schizophrenia patients with auditory hallucinations and impaired monitoring of self-generated speech. We examined a large cohort of patients with schizophrenia (n = 63) and a representative group of healthy controls (n = 20) to disentangle performance, illness, and symptom-related effects in functional magnetic resonance imaging-detected brain abnormalities during monitoring of self- and externally generated speech in schizophrenia. Our results revealed activation of the thalamus (medial geniculate nucleus, MGN) and frontotemporal regions with accurate monitoring across all participants. Less activation of the thalamus (MGN, pulvinar) and superior-middle temporal and inferior frontal gyri occurred in poorly performing patients (1 standard deviation below controls' mean; n = 36), relative to the combined group of controls and well-performing patients. In patients, (1) greater deactivation of the ventral striatum and hypothalamus to own voice, combined with nonsignificant activation of the same regions to others' voice, associated positively with negative symptoms (blunted affect, emotional withdrawal, poor rapport, passive social avoidance) regardless of performance and (2) exaggerated activation of the right superior-middle temporal gyrus during undistorted, relative to distorted, feedback associated with both positive symptoms (hallucinations, persecution) and poor performance. A further thalamic abnormality characterized schizophrenia patients regardless of performance and symptoms. We conclude that hypoactivation of a neural network comprised of the thalamus and frontotemporal regions underlies impaired speech monitoring in schizophrenia. Positive symptoms and poor monitoring share a common activation abnormality in the right superior temporal gyrus during processing of degraded speech. Altered striatal and hypothalamic modulation to own and others' voice characterizes emotionally withdrawn and socially avoidant patients.

The hodology of hallucinations.

The hodotopic framework is a recent revision of Geschwind's disconnection paradigm incorporating advances in functional and white matter imaging. Its intention is to help clinico-pathological correlations across a range of neurological and psychiatric conditions and generate novel research questions. Here I consider hallucinations within this framework. The paper is divided into three parts. The first reviews the auditory and visual hallucination literature from the dual perspectives of dysfunction localised to specific brain regions (topological) and dysfunction related to connections between brain regions (hodological), combining evidence from tractography, functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) studies. Patients prone to hallucinations have complex, task-specific hodological abnormalities that persist between hallucination episodes. During hallucinations, topological increases in activity are found whose location defines hallucination content and modality. Whether these activity increases are accompanied by transient hodological change is unclear. The second part of the paper addresses this issue in EEG and fMRI studies of a 200-year-old paradigm. Photic stimulation within a specific frequency and luminance range induces hallucinations of geometrical patterns, colours and motion in normal subjects. By comparing hallucination-inducing with control stimulation, topological activity increases were identified in visual areas whose specialisations matched the induced hallucination contents. During hallucinations, fMRI connectivity between LGN and cortex changed from a positive to negative relationship while EEG connectivity between occipital and other brain regions increased. The complex and dynamic topological and hodological changes during induced hallucinations are consistent with a shift in thalamocortical circuitry from tonic to burst mode and may have direct relevance to the Charles Bonnet Syndrome. The third part of the paper considers the relevance of the finding to other disorders, examines the strengths and limitations of our current imaging approaches to connectivity and looks to future developments in the field.

PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans.

The ability to maintain adequate nutrient intake is critical for survival. Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour, from food-seeking to meal termination. The hypothalamus and brainstem are thought to be the principal homeostatic brain areas responsible for regulating body weight. However, in the current 'obesogenic' human environment food intake is largely determined by non-homeostatic factors including cognition, emotion and reward, which are primarily processed in corticolimbic and higher cortical brain regions. Although the pleasure of eating is modulated by satiety and food deprivation increases the reward value of food, there is currently no adequate neurobiological account of this interaction between homeostatic and higher centres in the regulation of food intake in humans. Here we show, using functional magnetic resonance imaging, that peptide YY3-36 (PYY), a physiological gut-derived satiety signal, modulates neural activity within both corticolimbic and higher-cortical areas as well as homeostatic brain regions. Under conditions of high plasma PYY concentrations, mimicking the fed state, changes in neural activity within the caudolateral orbital frontal cortex predict feeding behaviour independently of meal-related sensory experiences. In contrast, in conditions of low levels of PYY, hypothalamic activation predicts food intake. Thus, the presence of a postprandial satiety factor switches food intake regulation from a homeostatic to a hedonic, corticolimbic area. Our studies give insights into the neural networks in humans that respond to a specific satiety signal to regulate food intake. An increased understanding of how such homeostatic and higher brain functions are integrated may pave the way for the development of new treatment strategies for obesity.