Relationships between serotonin availability and frontolimbic response to fearful and threatening faces.

Serotonin is a critical neurotransmitter in the regulation of emotional behavior. Although emotion processing is known to engage a corticolimbic circuit, including the amygdala and prefrontal cortex, exactly how this brain system is modulated by serotonin remains unclear. Here, we hypothesized that serotonin modulates variability in excitability and functional connectivity within this circuit. We tested whether this modulation contributes to inter-individual differences in emotion processing. Using a multimodal neuroimaging approach with a simultaneous PET-3T fMRI scanner, we simultaneously acquired BOLD signal while participants viewed emotional faces depicting fear and anger, while also measuring serotonin transporter (SERT) levels, regulating serotonin functions. Individuals with higher activity of the medial amygdala BOLD in response to fearful or angry facial expressions, who were temperamentally more anxious, also exhibited lower SERT availability in the dorsal raphe nucleus (DRN). Moreover, higher connectivity of the medial amygdala with the left dorsolateral prefrontal and the anterior cingulate cortex was associated with lower levels of SERT availability in the DRN. These results demonstrate the association between the serotonin transporter level and emotion processing through changes in functional interactions between the amygdala and the prefrontal areas in healthy humans.

A review of the impact of hormone therapy on prefrontal structure and function at menopause.

The menopause transition arises mainly from a decline in ovarian function characterized by a decrease in levels of ovarian estrogens (estradiol) and progesterone in women. Menopausal hormone therapy (MHT) has been used to counteract menopause-associated symptoms in postmenopausal women. With the development of advanced brain imaging methods, understanding MHT-related effects on brain structures and functions could help advance our understanding of the biological consequence of MHT-related effects on behavior, thereby contributing to developing new strategies for optimizing brain health during the menopause transition. This review focuses on the human research related to the impact of MHT on structural and functional organization of the prefrontal cortex in postmenopausal women. Although such MHT-related effects on brain structures and functions have only begun to be understood, it may be useful to examine present findings to identify areas for future research.

Cognitive and hormonal regulation of appetite for food presented in the olfactory and visual modalities.

The ability to regulate appetite is essential to avoid food over-consumption. The desire for a particular food can be triggered by its odor before it is even seen. Using fMRI, we identify the neural systems modulated by cognitive regulation when experiencing appetizing food stimuli presented in both olfactory and visual modalities, while being hungry. Regulatory instruction modulated bids for food items and inhalation patterns. Distinct brain regions were observed for up and down appetite-regulation, respectively the dorsomedial prefrontal cortex (dmPFC) and dorsolateral PFC. Food valuation engaged the ventromedial PFC and bilateral striatum. Furthermore, we identified a neurobiological marker for successful appetite upregulation. Individuals with higher blood levels of ghrelin were better at exercising up-regulation, and engaged the dmPFC more. These findings characterize the neural circuitry regulating food consumption within the healthy population and highlight how cognitive regulation modulates olfactomotor measures of olfaction.

Shifted risk preferences in pathological gambling.

BACKGROUND: Pathological gambling (PG) is an impulse control disorder characterized by excessive monetary risk seeking in the face of negative consequences. We used tools from the field of behavioral economics to refine our description of risk-taking behavior in pathological gamblers. This theoretical framework allowed us to confront two hypotheses: (1) pathological gamblers distort winning probabilities more than controls; and (2) pathological gamblers merely overweight the whole probability range. Method Eighteen pathological gamblers and 20 matched healthy participants performed a decision-making task involving choices between safe amounts of money and risky gambles. The online adjustment of safe amounts, depending on participants' decisions, allowed us to compute 'certainty equivalents' reflecting the subjective probability weight associated with each gamble. The behavioral data were then fitted with a mathematical function known as the 'probability weighting function', allowing us to disentangle our two hypotheses. RESULTS: The results favored the second hypothesis, suggesting that pathological gamblers' behavior reflects economic preferences globally shifted towards risk, rather than excessively distorted probability weighting. A mathematical parameter (elevation parameter) estimated by our fitting procedure was found to correlate with gambling severity among pathological gamblers, and with gambling affinity among controls. CONCLUSIONS: PG is associated with a specific pattern of economic preferences, characterized by a global (i.e. probability independent) shift towards risky options. The observed correlation with gambling severity suggests that the present 'certainty equivalent' task may be relevant for clinical use.

Silence is golden: transient neural deactivation in the prefrontal cortex during attentive reading.

It is becoming increasingly clear that attention-demanding tasks engage not only activation of specific cortical regions but also deactivation of other regions that could interfere with the task at hand. At the same time, electrophysiological studies in animals and humans have found that the participation of cortical regions to cognitive processes translates into local synchronization of rhythmic neural activity at frequencies above 40 Hz (so-called gamma-band synchronization). Such synchronization is seen as a potential facilitator of neural communication and synaptic plasticity. We found evidence that cognitive processes can also involve the disruption of gamma-band activity in high-order brain regions. Intracerebral electroencephalograms were recorded in 3 epileptic patients during 2 reading tasks. Visual presentation of words induced a strong deactivation in a broad (20-150 Hz) frequency range in the left ventral lateral prefrontal cortex, in parallel with gamma-band activations within the reading network, including Broca's area. The observed energy decrease in neural signals was reproducible across patients. It peaked around 500 ms after stimulus onset and appeared subject to attention-modulated amplification. Our results suggest that cognition might be mediated by a coordinated interaction between regional gamma-band synchronizations and desynchronizations, possibly reflecting enhanced versus reduced local neural communication.

Temporal order and spatial memory in schizophrenia: a parametric study.

Spatial working memory has been shown to be impaired in schizophrenia. In contrast, memory for temporal order has been poorly studied in patients with schizophrenia. The aim of this study was to compare and to further characterize spatial working memory and sequence reproduction deficits in patients with schizophrenia under stable medication by manipulating cues (pattern versus sequence), delay, set-size and response type in various recall and recognition tasks. This allowed us to dissociate processes as encoding, retention and retrieval and to compare the performance of patients with schizophrenia to the performance of patients with prefrontal lesions, who have been previously tested in the same tasks. Our results show that increase of the set-size and of the delay decreased performance of both groups, and that these factors had larger detrimental effects in patients with schizophrenia than in controls. Furthermore, comparison between tasks revealed retention and retrieval deficits in schizophrenia. Finally, patients with schizophrenia showed impairments not only in recall but also in sequence recognition tasks with delay. This is in contrast to patients with prefrontal lesions, who have previously been shown to have intact recognition of sequences after a delay. These results suggest that the working memory deficit in schizophrenia cannot be restricted to a prefrontal dysfunction.

Planning dysfunction in schizophrenia: impairment of potentials preceding fixed/free and single/sequence of self-initiated finger movements.

To test the hypothesis of a planning dysfunction in schizophrenia using a precise temporal definition, the readiness potential (RP), a negative cortical wave preceding self-initiated movements and reflecting motor preparation processes, was studied in patients under stable medication and in controls. The supplementary motor area (SMA), known to be involved in the generation of the RP, has also been implicated in movement selection (fixed versus free) and complexity (single versus sequence). This is the first study using RP for the assessment of the influence of these factors on motor preparation in schizophrenics. Our results show that schizophrenics' RP amplitude is significantly lower than in controls at central and contralateral electrodes. However, RP amplitude increases with task difficulty in both groups, offering important new insight into classical SMA hypoactivation in schizophrenics performing motor tasks. Topographic analysis shows that RP amplitude is, for both groups, significantly higher in sequence than in single movements at fronto-central sites and higher for free than for fixed movements at centro-parietal sites. Finally, RP onset occurs significantly later in schizophrenics than in controls. These results support the view of a motor-preparation and decision-making dysfunction in schizophrenia. They are interpreted within the framework of a fronto-striatal disorder in this disease.