Optical and computational dissection of emergent prefrontal rewiring to encode fear memory

The prefrontal cortex regulates various emotional behaviors and memories, and prefrontal dysfunction can trigger psychiatric disorders. While untangling the internal network may provide clues to the neural architecture underlying such disorders, it is technically difficult due to the complexity and heterogeneity of the network. Here we propose an optical and computational dissection of the internal prefrontal network based on chronic two-photon imaging and a sparse modeling algorithm, which enabled the discrimination of newly emerged neuronal ensembles specifically encoding conditioned fear responses. Further graphical modeling revealed that neurons responding to the unconditioned stimulus during fear conditioning became a core of the ensembles with an enhanced capability for pattern completion, demonstrating the activity dependent rewiring upon the associative learning.

Impulsivity-Compulsivity Axis: Evidence of Its Clinical Validity to Individually Classify Subjects on the Use/Abuse of Information and Communication Technologies

The compulsive habit model proposed by Everitt and Robbins has accumulated important empirical evidence. One of their proposals is the existence of an axis, on which each a person with a particular addiction can be located depending on the evolutionary moment of his/her addictive process. The objective of the present study is to contribute in addressing the identification of such axis, as few studies related to it have been published to date. To do so, the use/abuse of Information and Communication Technologies (ICT) was quantified on an initial sample of 807 subjects. Questionnaires were also delivered to measure impulsivity, compulsivity and symptoms of prefrontal dysfunction. Evidence of the existence of the proposed axis was obtained by means of Machine Learning techniques, thus allowing the classification of each subject along the continuum. The present study provides preliminary evidence of the existence of the Impulsivity-Compulsivity axis, as well as an IT tool so that each patient that starts getting treatment for an addiction can be statistically classified as “impulsive” or “compulsive.” This would allow the matching of each person with the most appropriate treatment depending on his/her moment in the addiction/abuse process, thus facilitating the individualized design of each therapeutic process and a possible improvement of the results of the treatment.

Corticostriatal stimulation compensates for medial frontal inactivation during interval timing

Prefrontal dysfunction is a common feature of brain diseases such as schizophrenia and contributes to deficits in executive functions, including working memory, attention, flexibility, inhibitory control, and timing of behaviors. Currently, few interventions improve prefrontal function. Here, we tested whether stimulating the axons of prefrontal neurons in the striatum could compensate for deficits in temporal processing related to prefrontal dysfunction. We used an interval-timing task that requires working memory for temporal rules and attention to the passage of time. Our previous work showed that inactivation of the medial frontal cortex (MFC) impairs interval timing and attenuates ramping activity, a key form of temporal processing in the dorsomedial striatum (DMS). We found that 20-Hz optogenetic stimulation of MFC axon terminals increased curvature of time-response histograms and improved interval-timing behavior. Furthermore, optogenetic stimulation of terminals modulated time-related ramping of medium spiny neurons in the striatum. These data suggest that corticostriatal stimulation can compensate for deficits caused by MFC inactivation and they imply that frontostriatal projections are sufficient for controlling responses in time.

Corticostriatal stimulation compensates for medial frontal inactivation during interval timing

Prefrontal dysfunction is a common feature of brain diseases such as schizophrenia and contributes to deficits in executive functions, including working memory, attention, flexibility, inhibitory control, and timing of behaviors. Currently, few interventions can compensate for impaired prefrontal function. Here, we tested whether stimulating the axons of prefrontal neurons in the striatum could compensate for deficits in temporal processing related to prefrontal dysfunction. We used an interval-timing task that requires working memory for temporal rules and attention to the passage of time. Our previous work showed that inactivation of the medial frontal cortex (MFC) impairs interval timing and attenuates ramping activity, a key form of temporal processing in the dorsomedial striatum (DMS). We found that 20-Hz optogenetic stimulation of MFC axon terminals in the DMS shifted response times and improved interval-timing behavior. Furthermore, optogenetic stimulation of terminals modulated time-related ramping of medium spiny neurons in the striatum. These data suggest that corticostriatal stimulation can compensate for deficits caused by MFC inactivation and they imply that frontostriatal projections are sufficient for controlling responses in time.

Progressive Frontal Dysconnectivity During Working Memory in eos Patients: A Longitudinal Functional MRI Study

Working memory (WM) dysfunction is considered a cardinal feature of schizophrenia. Typically developing adolescents show significant gains in WM performance, which have been attributed to increased “frontalisation” within the fronto-cingulate-parietal network that underpins WM. We used functional magnetic resonance imaging and psycho-physiological interaction to measure blood oxygenation level–dependent signal and functional connectivity in response to the 2-back WM task from 25 youths with EOS and 25 yoked healthy adolescents that were assessed twice with a mean interval of 4 years between assessments. Patients showed reduced prefrontal connectivity at baseline and the magnitude of this effect increased over the follow-up period. Our results suggest on-going functional connectivity abnormalities in EOS patients’ post-disease onset that are linked to prefrontal dysfunction and contribute to worsening WM despite anti–psychotic treatment.Disclosure of interestThe authors have not supplied their declaration of competing interest.