Prefrontal Research Articles

Measurement of craving among gamers with internet gaming disorder using repeated presentations of game videos: a resting-state electroencephalography study

BackgroundInternet gaming disorder (IGD) is receiving increasing attention owing to its effects on daily living and psychological function.MethodsIn this study, electroencephalography was used to compare neural activity triggered by repeated presentation of a stimulus in healthy controls (HCs) and those with IGD. A total of 42 adult men were categorized into two groups (IGD, n = 21) based on Y-IAT-K scores. Participants were required to watch repeated presentations of video games while wearing a head-mounted display, and the delta (D), theta (T), alpha (A), beta (B), and gamma (G) activities in the prefrontal (PF), central (C), and parieto-occipital (PO) regions were analyzed.ResultsThe IGD group exhibited higher absolute powers of DC, DPO, TC, TPO, BC, and BPO than HCs. Among the IGD classification models, a neural network achieves the highest average accuracy of 93% (5-fold cross validation) and 84% (test).ConclusionsThese findings may significantly contribute to a more comprehensive understanding of the neurological features associated with IGD and provide potential neurological markers that can be used to distinguish between individuals with IGD and HCs.

Do we understand the prefrontal cortex?

Many suggestions have been made as to the functions of the prefrontal (PF) cortex. However, they involve labelling areas using psychological terminology. But what we need to know is how the PF cortex operates. We argue that understanding this must start with describing the flow of information. We illustrate this argument by considering three PF areas. Each has a unique pattern of inputs and outputs, and we suggest that the implication is that each performs a unique transformation from the inputs to the outputs. The caudal PF cortex transforms input that is maintained by attention or short-term memory into the target of the appropriate eye movement. The mid-dorsal PF cortex transforms input concerning the order of objects or actions into the target of the appropriate eye and hand movements, thus supporting sequences of action. The ventral PF cortex transforms input concerning an object or sound into prospective activity that encodes the associated object or sound. However, it is important to appreciate that the mid-dorsal and ventral PF cortex are specialized for encoding abstract transformations, irrespective of the specific actions or objects. The advantage is that this enables generalization to novel problems that have the same underlying logic. We account for the difference between fast learning and slow learning in this way. The human brain has co-opted these mechanisms so as to support intelligence. Non-verbal tests of IQ typically use sequences of letters, numbers or designs. These test the ability to understand the abstract rules that apply. Here the activations lie in the mid-dorsal PF cortex. Verbal tests typically assess the ability to understand semantic associations. These can be presented either in pictorial or verbal form. Here the activations lie in the ventral PF cortex.

Cardiac-Brain Dynamics Depend on Context Familiarity and Their Interaction Predicts Experience of Emotional Arousal.

Our brain continuously interacts with the body as we engage with the world. Although we are mostly unaware of internal bodily processes, such as our heartbeats, they may be influenced by and in turn influence our perception and emotional feelings. Although there is a recent focus on understanding cardiac interoceptive activity and interaction with brain activity during emotion processing, the investigation of cardiac–brain interactions with more ecologically valid naturalistic emotional stimuli is still very limited. We also do not understand how an essential aspect of emotions, such as context familiarity, influences affective feelings and is linked to statistical interaction between cardiac and brain activity. Hence, to answer these questions, we designed an exploratory study by recording ECG and EEG signals for the emotional events while participants were watching emotional movie clips. Participants also rated their familiarity with the stimulus on the familiarity scale. Linear mixed effect modelling was performed in which the ECG power and familiarity were considered as predictors of EEG power. We focused on three brain regions, including prefrontal (PF), frontocentral (FC) and parietooccipital (PO). The analyses showed that the interaction between the power of cardiac activity in the mid-frequency range and the power in specific EEG bands is dependent on familiarity, such that the interaction is stronger with high familiarity. In addition, the results indicate that arousal is predicted by cardiac–brain interaction, which also depends on familiarity. The results support emotional theories that emphasize context dependency and interoception. Multimodal studies with more realistic stimuli would further enable us to understand and predict different aspects of emotional experience.

Using prefrontal and midline right frontal EEG-derived theta cordance and depressive symptoms to predict the differential response or remission to antidepressant treatment in major depressive disorder

There is a growing need for optimizing treatment selection and response prediction in individuals with major depressive disorder (MDD). Prior investigations have shown that changes in electroencephalographic (EEG)-based measures precede symptom improvement and could serve as biomarkers of treatment outcome. One such method is cordance, a computation of regional brain activity based on a combination of absolute and relative resting EEG activity. Specifically, early reduction in prefrontal (PF) and midline right frontal (MRF) theta (4-8Hz) cordance has been shown to predict response to various antidepressants, though replication is required. Thus, this study examined early changes (baseline to week 1) in PF and MRF cordance in 47 MDD patients undergoing antidepressant treatment. Early changes in cordance and in Montgomery Åsberg Depression Rating Scale (MADRS) scores were assessed alone, and in combination, to predict eventual (by week 12) treatment response and remission. Models combining early changes in theta cordance (PF and MRF) and depressive symptoms were most predictive of response to treatment at week 12; remission models (cordance, MADRS, and their combination) were weaker, though provided modest prediction values. These results suggest that antidepressant response may be optimally predicted by combining both EEG and symptom-based measures after one week of treatment.

Context-Dependent Duration Signals in the Primate Prefrontal Cortex.

The activity of some prefrontal (PF) cortex neurons distinguishes short from long time intervals. Here, we examined whether this property reflected a general timing mechanism or one dependent on behavioral context. In one task, monkeys discriminated the relative duration of 2 stimuli; in the other, they discriminated the relative distance of 2 stimuli from a fixed reference point. Both tasks had a pre-cue period (interval 1) and a delay period (interval 2) with no discriminant stimulus. Interval 1 elapsed before the presentation of the first discriminant stimulus, and interval 2 began after that stimulus. Both intervals had durations of either 400 or 800 ms. Most PF neurons distinguished short from long durations in one task or interval, but not in the others. When neurons did signal something about duration for both intervals, they did so in an uncorrelated or weakly correlated manner. These results demonstrate a high degree of context dependency in PF time processing. The PF, therefore, does not appear to signal durations abstractedly, as would be expected of a general temporal encoder, but instead does so in a highly context-dependent manner, both within and between tasks.

Epigenetic regulations of immediate early genes expression involved in memory formation by the amyloid precursor protein of Alzheimer disease.

We previously demonstrated that APP epigenetically regulates Egr1 expression both in cultured neurons and in vivo. Since Egr1 is an immediate early gene involved in memory formation, we wondered whether other early genes involved in memory were regulated by APP and we studied molecular mechanisms involved. By comparing prefrontal (PF) cortex from wild type (APP+/+) and APP knockout mice (APP−/−), we observed that APP down regulates expression of four immediate early genes, Egr1, c-Fos, Bdnf and Arc. Down regulation of Egr1, c-Fos and Bdnf transcription resulted from a decreased enrichment of acetylated histone H4 on the corresponding gene promoter. Further characterization of H4 acetylation at Egr1 and c-Fos promoters revealed increased acetylation of H4K5 and H4K12 residues in APP−/− mice. Whereas APP affected Egr1 promoter activity by reducing access of the CREB transcription factor, its effect on c-Fos appeared to depend on increased recruitment of HDAC2 histone deacetylase to the gene promoter. The physiological relevance of the epigenetic regulation of Egr1 and c-Fos gene transcription by APP was further analyzed following exposure of mice to novelty. Although transcription of Egr1 and c-Fos was increased following exposure of APP+/+ mice to novelty, such an induction was not possible in APP−/− mice with a high basal level of expression of these immediate early genes. Altogether, these results demonstrate that APP-mediated regulation of c-Fos and Egr1 by different epigenetic mechanisms is needed for their induction during exposure to novelty.

Early Attentional Modulation of the Neural Network Evoked with the Auditory Paired-click Paradigm: An MEG Study

Although numerous research studies have explored the functional attributes of the human duration perception, the spatio- temporal information on cortical networks underlying this process is still an open question. Moreover, the issue of possible differences in the nature of timing mechanisms responsible for perception of sub- and supra-second intervals requires the implementation of the functional brain imaging techniques with both high spatial and temporal resolution. Attention is very frequently used as a modulating factor for the perceived duration of a sensory stimulus. The non-attended stimuli appear to last shorter than the attended ones, increasing the perceived duration of a concurrent stimulus (Gorea, 2011). This study challenges the accepted model of early sensory responses, activated during the first 100ms after stimulus presentation, as preattentive, automatic processes which modulate the neural sensitivity to incoming stimuli (gating phenomena). We utilized Elekta Neuromag 306-channel whole-head system for magnetoencephalography (MEG) measurements and multi-dipole Calibrated Start Spatio Temporal (CSST) localization technique (Ranken et al., 2002) to investigate whether voluntary attention directed at the second tone of a pair in the standard paired-click paradigm could affect cortical networks underlying the gating out phenomenon. MEG recordings were obtained in a magnetically shielded room at the Biomagnetic Center in Jena, Germany. Two consecutive (ISI=500ms) identical short tonnes (S1 and S2; duration=20ms; f=1200Hz; ITI=8±1s) were used to evoke standard gating cortical responses in 19 healthy participants (21-38 years). In the second condition, the task was to direct attention toward the second tone and to respond to a rarely presented non-identical second tone of the pair (R=1300Hz, p(S1R)=0.3). MEG recordings showed transient early and middle latency responses with peak amplitudes over the temporo-parietal sensors followed by a peak of a sustained activity. Less prominent transient activity was recorded over the frontal sensors, accompanied with a more steady- state component from 100 until 400ms post-stimulus for both conditions. Preliminary results of the CSST spatio-temporal analyses revealed 4-6 brain regions activated during 20-500ms time interval including bilateral superior temporal gyrus (STG), bilateral and medial prefrontal (PF), bilateral parietal (PA) regions, and central motor cortex area. A cortical source underlying the steady-state component was identified in the left prefrontal region for S1 tone, and in central posterior regions (PA) for the repeated tone S2. During the standard paradigm the M50 gating suppression was observed only for bilateral STG sources while bilateral PF and PA sources did not show any reduction in the response during the first 100ms post-stimulus. Targeting the attention towards the second tone enhanced the M50 amplitude of the bilateral STG responses in respect to the repeated stimulus S2 and caused a change in the activated network evident by the emergence of a new generator in the medial PF area (orbitofrontal) instead of dorsolateral PF generators evoked in non-attended condition. These results demonstrate that voluntary attention can exert a topological and functional modulatory influence on the neural network even during early stages of auditory processing.

Excitatory Deep Repetitive Transcranial Magnetic Stimulation With H-coil as Add-on Treatment of Motor Symptoms in Parkinson's Disease: An Open Label, Pilot Study

BackgroundRepetitive transcranial magnetic stimulation (rTMS) has been proposed as a potential treatment for Parkinson's disease (PD). H-coils, inducing deeper and wider magnetic fields compared to traditional coils, may be potentially useful in PD, characterized by widespread, bilateral involvement of cortico-subcortical circuits. ObjectiveTo evaluate the safety of repetitive deep TMS (rDTMS) with H-coil as add-on treatment of motor symptoms in PD. MethodsTwenty-seven PD patients (aged 60.1 ± 6.8 y; PD-duration: 6.3 ± 2.8 y; motor-UPDRS: 39.6 ± 10.1) underwent 12 rDTMS sessions over 4 weeks at excitatory (10 Hz) frequency over primary motor (M1) and bilateral prefrontal (PF) regions. Motor UPDRS off therapy was assessed before and after the last rDTMS session, together with safety records at each treatment session. ResultsNo drop-outs or adverse events were recorded. Motor UPDRS significantly improved after rDTMS (10.8 points average reduction; P < 0.0001). ConclusionsHigh-frequency rDTMS might be a safe treatment for PD motor symptoms. Further placebo-controlled, randomized studies are warranted.

Placebo Controlled Trial of Familiar Auditory Sensory Training for Acute Severe Traumatic Brain Injury

1.Participant will be able to explain that the Familiar Auditory Sensory Training (FAST) protocol is a passive auditory sensory stimulation intervention.2.Participant will be able to explain therapeutic effects of FAST protocol for severe TBI3.Participant will be able to explain changes in volumes of neural activation corresponding with FAST intervention and Placebo relative to heathy controls Double Blind Randomized Placebo Controlled Trial Community and Inpatient rehabilitation 15 subjects in vegetative (VS) or minimally conscious (MCS) states on average 70 days after TBI. Eight assigned to the experimental FAST and 7 to the Placebo. Placebo Silence or FAST, which is a passive familiar auditory sensory stimulation protocol comprised of familiar people telling stories about memorable events. All subjects received 168 doses of assigned interventions provided four times daily for six weeks. Coma-Near-Coma scale and volumetric activation measured with functional imaging according to pre-selected regions. Mixed-effects models indicate that FAST group had significantly quicker recovery and more functioning. Mean CNC weekly slope difference is -0.63 points (p = 0.0022) and endpoint CNC indicates 6 points of more functioning. All subjects had significant (p < 0.05) neural activation within Heschl's Region. Examination of significant changes (p < 0.05) in functional activation when listening to Familiar (FV) and Nonfamiliar (NFV) voices telling the same story indicate FAST subjects had significantly (p < 0.05) increased pre-frontal (PF) activation to FV with no changes to NFV. Placebo subjects had signficantly decreased PF activation to FV and NFV. FAST subjects had significantly decreased Heschl's Region activation to NFV. Placebo subjects activation did not change within Heschl's. FAST is associated with improved functioning for persons in VS or MCS after TBI. Completed activation analyses indicate increased PF activity to FV with decreased activity in Heschl's to NFV suggesting enhanced engagement and processing when listening to FV.

Abnormal Functioning of the Thalamocortical System Underlies the Conscious Awareness of the Phantom Limb Phenomenon

Phantom limb (PL), a phenomenon experienced by most patients after amputation, has mostly served as a paradigm to study experiences that appear to be associated with neural plasticity within the CNS. However, the subjective nature of PL experiences has had no definitive means of reliable assessment other than using patients' direct reports, nor was there a way to study the neural mechanisms involved in the conscious awareness of this mental phenomenon. Here we obtained patients' indirect responses to PL experiences for an objective evaluation using functional magnetic resonance imaging (fMRI). Six control subjects and six lower limb (LL) amputees participated in a motor imagery task for both the intact and the particular phantom toes. While all subjects shared neural processing of distinctive regional cerebral activations during motor imagery of the intact toes (prefrontal (PF), supplementary motor area (SMA), primary motor cortex (M1), superior temporal gyrus (STG)), it was only during motor imagery of the amputated toes in amputees that we observed an increased blood oxygen level-dependent (BOLD) signal in the contralateral basal ganglia at the medial globus pallidus (MGP), substantia nigra (SN), and thalamus. This increased BOLD signal in the basal ganglia-thalamus-cortex pathway during imaginary movement of the phantom toes may reflect an abnormal open loop functioning of the thalamocortical system underlying the conscious awareness of the phantom phenomenon. We suggest that the reduction in afferent information contributes to and coalesces with the higher-level reorganization resulting in the subjective conscious awareness of the phantom limb.

P3a and P3b of event-related potentials in persons with Asperger disorder

Although numerous research studies have explored the functional attributes of the human duration perception, the spatio- temporal information on cortical networks underlying this process is still an open question. Moreover, the issue of possible differences in the nature of timing mechanisms responsible for perception of sub- and supra-second intervals requires the implementation of the functional brain imaging techniques with both high spatial and temporal resolution. Attention is very frequently used as a modulating factor for the perceived duration of a sensory stimulus. The non-attended stimuli appear to last shorter than the attended ones, increasing the perceived duration of a concurrent stimulus (Gorea, 2011). This study challenges the accepted model of early sensory responses, activated during the first 100 ms after stimulus presentation, as preattentive, automatic processes which modulate the neural sensitivity to incoming stimuli (gating phenomena). We utilized Elekta Neuromag 306-channel whole-head system for magnetoencephalography (MEG) measurements and multi-dipole Calibrated Start Spatio Temporal (CSST) localization technique (Ranken et al., 2002) to investigate whether voluntary attention directed at the second tone of a pair in the standard paired-click paradigm could affect cortical networks underlying the gating out phenomenon. MEG recordings were obtained in a magnetically shielded room at the Biomagnetic Center in Jena, Germany. Two consecutive (ISI=500 ms) identical short tonnes (S1 and S2; duration=20ms; f=1200 Hz; ITI=8±1s) were used to evoke standard gating cortical responses in 19 healthy participants (21-38 years). In the second condition, the task was to direct attention toward the second tone and to respond to a rarely presented non-identical second tone of the pair (R=1300 Hz, p(S1R)=0.3). MEG recordings showed transient early and middle latency responses with peak amplitudes over the temporo-parietal sensors followed by a peak of a sustained activity. Less prominent transient activity was recorded over the frontal sensors, accompanied with a more steady- state component from 100 until 400 ms post-stimulus for both conditions. Preliminary results of the CSST spatio-temporal analyses revealed 4-6 brain regions activated during 20-500 ms time interval including bilateral superior temporal gyrus (STG), bilateral and medial prefrontal (PF), bilateral parietal (PA) regions, and central motor cortex area. A cortical source underlying the steady-state component was identified in the left prefrontal region for S1 tone, and in central posterior regions (PA) for the repeated tone S2. During the standard paradigm the M50 gating suppression was observed only for bilateral STG sources while bilateral PF and PA sources did not show any reduction in the response during the first 100 ms post-stimulus. Targeting the attention towards the second tone enhanced the M50 amplitude of the bilateral STG responses in respect to the repeated stimulus S2 and caused a change in the activated network evident by the emergence of a new generator in the medial PF area (orbitofrontal) instead of dorsolateral PF generators evoked in non-attended condition. These results demonstrate that voluntary attention can exert a topological and functional modulatory influence on the neural network even during early stages of auditory processing.

907 GERD Alters the Functional Brain Connectivity Models Associated with Acid Stimulation

Previous fMRI studies have documented in healthy controls and GERD patients activation of sensory/motor (SM), prefrontal (PF), anterior (AC) and posterior (PC) cingulate and insula (I) brain regions associated with esophageal acid perfusion. GERD was found to significantly amplify the volume and intensity of fMRI signals compared to controls. (Kern M, Am J Physiol 2004; 286(1):G174-81) The effects of GERD on the connectivity of cortical networks have not been studied. Aim: To compare the functional connectivity models of brain regions showing fMRI activation during esophageal acid perfusion in GERD patients and healthy controls. Methods: Structural Equation Modeling (SEM) was used to generate partial regression coefficients representing the covariance among regional fMRI signals activated by esophageal acid perfusion. We studied 7 GERD patients (4 female, age range: 20-62 years) and 8 controls (4 female, age range: 22-40 years), during high spatial resolution fMRI scanning sequences. Brain images were acquired during alternating intervals of 0.1N HCl and saline perfusion of the distal esophagus. Grouped data was used in the SEM to yield maps showing significant (p<0.05, goodness-of-fit test) connectivity paths from a general network based on known anatomical connections among the brain regions. Results: There were substantial differences in the connectivity maps associated with esophageal acid perfusion in GERD compared to controls. As seen (Figure), arrows between regions show the direction of significant covariance. Partial regression coefficients for these paths represent a measure of the degree of correlation between the regions. For all network models, GERD connectivity was different than that of the controls. These differences were characterized by decreased connectivity between limbic and para-limbic structures like the AC and I as well as altered patterns of connectivity between PF, I and AC in GERD compared to controls. Conclusions: Models of brain connectivity associated with esophageal acid perfusion differ when comparing patients and controls suggesting alteration of the cerebral cortical networks associated with processing visceral sensory input in GERD.

Diffusion tensor imaging (DTI) and tractography of the cerebellar projections to prefrontal and posterior parietal cortices: A study at 3T

Objectives Previous diffusion tensor imaging (DTI) studies have identified cerebellar pathways and supratentorial connections, but none of them have isolated cerebellar projections to prefrontal and posterior parietal cortices using tractography. The aim of our study was to identify and visualize on 3D projections, as well as on 2D cross-sectional images, the cerebellar projections to prefrontal (PF) and posterior parietal (PP) cortices. Material and methods The study included 10 healthy volunteers, four males and six females aged 25 to 45 years (mean age 31 years). A DTI sequence was applied at 3 Tesla using diffusion sensitizing gradients in 32 directions. White matter tracts were reconstructed by applying a multiple ROI (region of interest) tractography technique. Results PF projections were obtained in all subjects. PP projections were obtained in six over 10 subjects. On 2D cross-sectional images, the tracts showed the same anatomical location in each ROI in all subjects. Conclusion This DTI study at 3T resulted in a selective and full visualization of cerebellar projections to PF and PP cortices for the first time and is introductive for further optimized and quantitative DTI study of these tracts.

T2 measurement and quantification of glutamate in human brain in vivo

The proton NMR transverse relaxation time T(2) of glutamate (Glu) in human brain was measured by means of spectrally selective refocusing at 3.0 T in vivo. An 81.4-ms-long dual-band Gaussian 180 degrees RF pulse, designed for refocusing at 2.35 and 3.03 ppm, was employed within point-resolved spectroscopy (PRESS) to generate the Glu C4-proton target multiplet and the total creatine (tCr) singlet. Six optimal echo times (TEs) between 128 and 380 ms were selected from numerical analysis of the filtering performance for effective detection of the Glu signal with minimal contamination from glutamine (Gln), N-acetylaspartate (NAA), and glutathione (GSH). The magnetization of Glu and tCr was extracted from spectral fitting of experimental and calculated spectra. Apparent T(2) values of Glu and tCr were estimated as 201 +/- 18 and 164 +/- 12 ms for the medial prefrontal (PF) cortex, and 198 +/- 22 and 169 +/- 15 ms (mean +/- SD, N = 5) for the left frontal (LF) cortex, respectively. With water segmentation data, the magnetization values of Glu and tCr of the two adjacent voxels, calculated from the T(2) values and spectra following the thermal equilibrium magnetization, were combined to give the Glu and tCr concentrations as 10.37 +/- 1.06 and 8.87 +/- 0.56 mM for gray matter (GM), and 5.06 +/- 0.57 and 5.16 +/- 0.45 mM (mean +/- SD, N = 5) for white matter (WM), respectively.

Challenging sleep in aging: the effects of 200 mg of caffeine during the evening in young and middle‐aged moderate caffeine consumers

The aim of this study was to evaluate the effects of a 200-mg administration of caffeine on polysomnographic sleep variables and quantitative sleep electroencephalography (EEG) in 12 young (20-30 years) and 12 middle-aged (40-60 years) moderate caffeine consumers (one to three cups of coffee per day). All subjects were submitted to both a caffeine (200 mg) and placebo (lactose) condition in a double-blind cross-over design. The conditions were separated by 1 week. Compared with the placebo condition, the evening ingestion of caffeine lengthened sleep latency, reduced sleep efficiency, and decreased sleep duration and amount of stage 2 sleep in both age groups. Caffeine also reduced spectral power in delta frequencies in frontal, central and parietal brain areas, but not in prefrontal (PF) and occipital regions. Moreover, caffeine increased spectral power in beta frequencies in frontal and central brain areas in both age groups. A suppression of spectral power in the PF area in low delta frequencies (0.5-1.00 Hz) and a rise in spectral power in the parietal region in high alpha (10.00-12.00 Hz) and beta frequencies (17.00-21.00, 23.00-25.00, 27.00-29.00 Hz) occurred solely in middle-aged subjects. No such changes were noticeable in young subjects. Generally, caffeine produced similar effects in young and middle-aged subjects. Only a few frequency bins showed more effects of caffeine in middle-aged subjects compared with young subjects. Furthermore, sleep EEG results do not entirely support the hypothesis that caffeine fully mimics the effects of a reduction of homeostatic sleep propensity when following a normal sleep-wake cycle.

Shape changes in prefrontal, but not parieto-occipital regions: brains of schizophrenic patients come closer to a circle in coronal and sagittal view

There is some evidence for prefrontal (PF) lobe changes in schizophrenia while the parieto-occipital (PO) region seems to be unaffected. This magnetic resonance imaging (MRI) study was performed to examine shape differences as part of the spectrum of structural abnormalities in schizophrenia. The measurements were done on families affected with schizophrenia to identify the influence of genetic and environmental factors on these changes. The sample under study consisted of 164 subjects including 45 family members (FM) suffering from schizophrenia, 27 FM with other psychiatric disorders and 51 FM without psychiatric disorders based on ICD-10 criteria. In addition, 41 nonpsychiatric control subjects were included in the study. On defined planes at the corpus callosum boundary of the PF and the PO, brain width, height and length were measured on coronal slices. Ratios of these linear measurements were also calculated based on the idea that a plane can be approximated by a circle if the concerning ratio comes close to 1. It was hypothesized that these relative brain shape parameters, especially the PF ratio width/height, would show differences between schizophrenic patients and control subjects. For all members from families with schizophrenia compared with control subjects, there were significant differences in the PF, but not in the PO region. PF height was increased. PF ratios of width/height and height/(2×length) were closer to 1 in affected families than in control subjects. The results can be interpreted as an indication for PF brain shape changes in subjects with a disposition for schizophrenia. On coronal and sagittal planes situated at the corpus callosum, their PF could be approximated by a circle better than in control subjects. As the frontal lobe takes shape late in brain development, underlying genetic mechanisms may be dysregulated in schizophrenic patients and subjects at risk to develop the disorder.

Prefrontal atrophy in first episodes of schizophrenia associated with limbic metabolic hyperactivity

Reduced volume and activity of the prefrontal (PF) cortical gray matter (GM) and hippocampal hypermetabolism are repeated findings in schizophrenia. There is still an information deficit about the significance of reduction of PF GM in schizophrenia, and a simultaneous study of PF anatomy and activity and limbic metabolism can contribute to fill that deficit. In order to do so, we used positron emission tomography (PET) with 18-fluoro-deoxyy-glucose (FDG) during an attention task and magnetic resonance imaging (MRI) to study a sample of first episodes of pscyhosis. We included 21 first episodes (FE) of psychosis and 16 healthy controls. A diagnosis of schizophrenia was confirmed in the follow-up in eleven of these patients and ruled out in the remaining 10 cases. Volumes of PF GM were determined and also activity in the same region and in the hippocampus. Residual GM was estimated in the PF region as a quantitative measurement of the degree of atrophy in each individual, using age and intracranial volume data from a set of 45 healthy controls and linear regression.Patients with schizophrenia had lower PF metabolic activation and greater hippocampal activity than controls. FE patients without schizophrenia were no different in any parameter as compared to controls. Patients with schizophrenia presented an inverse and significant association between GM deficit and hippocampal activity that was not observed in controls or in patients without schizophrenia. The same association was previously described by our group using PET in the resting state in recent-onset and chronic patients with schizophrenia. These findings support a loss in PF inhibitory capacity as a possible link between anatomical and functional alterations in schizophrenia.

Lower prefrontal gray matter volume in schizophrenia in chronic but not in first episode schizophrenia patients

Although a lower volume of prefrontal (PF) gray matter (GM) in patients with schizophrenia than in normal control subjects is a replicated finding, it is not yet clear whether this finding is present at the onset of illness. Clinical and imaging data suggest that the reduction in PF GM becomes apparent only some years following the onset of illness. To test this hypothesis, we used magnetic resonance imaging to study PF GM and sulcal cerebrospinal fluid (CSF) volumes in 81 schizophrenic patients. A Talairach-based tool was used for segmentation. Subjects included 44 healthy controls, 22 first-episode (FE), treatment-naı̈ve patients with duration of illness of less than 1 year; 29 short-term chronic (SC) patients with durations of illness between 1.5 and 6 years; and 30 long-term chronic (LC) patients with duration of illness of more than 6 years. The data from healthy controls were used to calculate volume residuals in the patients, defined as deviations from the expected values given individual age and intracranial volume. The FE group did not show significant differences in GM or in CSF volumes compared with controls. However, both the SC and the LC patients showed the expected pattern of lower values for PF GM and an excess of PF sulcal CSF compared with controls. There were no significant differences between SC and LC patients in any of these measurements. There was a significant and inverse association between duration of illness and GM residuals. That association fit a nonlinear rather than a linear model, which was consistent with a decrease of GM volume during the first years following illness onset. No significant differences were found between those receiving atypical and typical antipsychotic drugs during the previous year.

Timecourse of object-related neural activity in the primate prefrontal cortex during a short-term memory task.

We studied the timecourse of neural activity in the primate (Macacca mulatta) prefrontal (PF) cortex during an object delayed-matching-to-sample (DMS) task. To assess the effects of experience on this timecourse, we conducted the task using both novel and highly familiar objects. In addition, noise patterns containing no task-relevant information were used as samples on some trials. Comparison of average PF ensemble activity relative to baseline activity generated by objects and noise patterns revealed three distinct activity periods. (i) Sample onset elicited a transient sensory visual response. In this sensory period, novel objects elicited stronger average ensemble activity than both familiar objects and noise patterns. (ii) An intermediate period of elevated activity followed, which began before sample offset, and continued well into the delay period. In the intermediate period, activity was elevated for noise patterns and novel objects, but near baseline for familiar objects. (iii) Finally, after average ensemble activity reached baseline activity at the end of the intermediate period, a reactivation period occurred late in the delay. Experience had little effect during reactivation, where activity was elevated for both novel and familiar objects compared to noise patterns. We show that the ensemble average resembles the activity timecourse of many single prefrontal neurons. These results suggest that PF delay activity does not merely maintain recent sensory input, but is subject to more complex experience-dependent dynamics. This has implications for how delay activity is generated and maintained.

Search target selection in monkey prefrontal cortex.

To explore a visual scene, the brain must detect an object of interest and direct the eyes to it. To investigate the brain's mechanism of saccade target selection, we trained monkeys to perform a visual search task with a response delay and recorded neuronal activity in the prefrontal (PF) cortex. Even though the monkey was not allowed to express its choice until after a delay, the response field of a class of PF neurons was able to differentiate between target and distractors from the very beginning of their response (135 ms). Strong responses were obtained only when the target was presented at the field. Neurons responded much less during a nonsearch task in which saccade target was presented alone in this response field. These results suggest that the PF cortex may be involved in the decision-making process and the focal attention for saccade target selection.