Frontal Cortex Area Research Articles

Neuronal representation of task performance in the medial frontal cortex undergoes dynamic alterations dependent upon the demand for volitional control of action

Neural network contributing to forelimb task performance in the frontal cortex is dynamically reorganized by the necessity for volitional control of action. Neurons in the posterior medial prefrontal cortex (pmPFC) exhibit clear activity modulation when monkeys volitionally select the correct response tactic from multiple choices, but such activity disappears if selection of a tactic is unnecessary. Prompted by these results, we studied how the requirement to select an appropriate tactic affects the neural representation of action in downstream cortical areas. Two monkeys performed a spatial arm-reaching task with either left or right targets. The task required the monkeys to reach either toward (concordant trials) or away from (discordant trials) an illuminated target. Under the dual-tactic condition, concordant and discordant trials were randomly intermixed, requiring the selection of a response tactic. Under the single-tactic condition, only concordant trials were presented, allowing the monkeys to use the same tactic. Neurons in the pmPFC exhibited clear activity related to task performance under the former condition, but such activity disappeared under the latter condition. In contrast, neurons related to task performance were present under both conditions in supplementary motor area (SMA) and presupplementary motor area (pre-SMA). However, the efficacy of action representation by SMA but not pre-SMA neurons dramatically improved under the single-tactic condition. These results suggest that selection of the appropriate response tactic reorganizes neural circuits in specific motor areas in the medial frontal cortex, in addition to the pmPFC.

EEG Based BCI Using Visual Imagery Task for Robot Control

The aim of this study is to detect the brain activation on scalp by Electroencephalogram (EEG) task–based for brain computer interface (BCI) using wirelessly control robot. EEG was measured in 8 normal subjects for control and task conditions. The objective is to determine one scalp location which will give signals that can be used to control the wireless robot using BCI and EEG, using non invasive and without subject training. In control condition subjects were ask to relax but in task condition, subjects were asked to imagine a star rotating clockwise at position 45 degrees direction pointed by the wireless robot where at this angle the target is located. At position 0 and 90 degree angle subjects were asked to relax since there is no target on that direction. Using EEG spectral power analysis and normalization, the optimum location for this task has been detected at position F8 which is in frontal cortex area and the rhythm happened at alpha frequency band. At this position, the signals from the brain should be able to drive the robot to the required direction by giving correct and accurate signals to robot moving towards target.

Stop! Stay tuned for more information

It is widely believed that the prefrontal cortex contributes to adap-tive control over prepotent or habitual behaviors. One of the proposedmeans of implementing control involves directed “top-down” inhibi-tion of actions. While this descriptive model is helpful, much work re-mains to be done to explain the distinct neural mechanisms by whichsuch top-down control alters action selection. In a recent report, Alegreet al. (2013) provide evidence that the cortex and subthalamic nucleus(STN) of the basal ganglia interact to both enable and inhibit behaviorby exchanging information across different oscillatory frequency bands.The STN are small subcortical nuclei that lie between the brainstemand the pallidum. Long considered a part of the cortico-striatal indirectpathway, they have been implicated as a part of an inhibitory systemthat prevents motor gating, acting in antagonism to the facilitatory di-rect pathway (Alexander and Crutcher, 1990; Mink, 1996). However,morerecenthistological (Nambuet al.,2002,2012), functionalconnec-tivity (Aron et al., 2007),and computational (Frank,2006) descriptionsof thecortico-basalganglia systemsuggestthat theSTNparticipate in athird extra-striatal information processing stream: the “hyperdirect”pathway. In this role, motor and premotor cortex project directly tothe STN (bypassing the striatum altogether), which projects to basalganglia output in order to act a global brake on striatal output. Thishyperdirect system is thus a compelling candidate “hold-your horses”mechanism by which high-level premotor areas of frontal cortex (suchasthemidcingulatecortexorpre-supplementalmotorarea)couldrapid-ly delay motor output due to signals of con flict between competing re-sponse options, buying time so the best decision can be made ( Frank,2006). While functional MRI studies show STN activation during re-sponse inhibition (e.g.,Aron et al., 2007), a better understanding ofthe detailed neuronal dynamics within the STN is needed to under-standhow this systemprocesses information andhowit cango awryin Parkinson's disease.Given the pathology of akinesia and bradykinesia in Parkinsonism,it should be apparent that removal of this STN brake on motor outputcan provide increased motor fluidity to patients, such that relativelyless amount of direct pathway activity is needed. Moreover, dopa-mine depletion can cause the STN to function aberrantly, increasingoscillatory coupling between the STN and globus pallidus and leadingtomotortremor(Bergman et al., 1998; Levy et al., 2000; Raz et al.,2000). Ameliorative treatment can be provided by interfering withSTN function via lesions (Bergman et al., 1990)ordeepbrainstimu-lation, which alters neuronal output and provides tremendous symp-tom relief including abolishment o f tremor. However, this procedurehas some unfortunate side effects in vulnerable individuals, where itcan increase impulsivity and induce poor decision making ( Frank et al.,2007;Halbigetal.,2009).Clearly,athoroughunderstandingofthisneu-ral system will not only have important implications for understandingbasic mechanisms of action selection, but also for optimizing treatmentfor Parkinsonism and other motor disorders.In their recent report, Alegre et al. (2013) capitalize on the abilityto record from the STN after implantation of deep brain stimulationelectrodes in Parkinsonian patients. In order to assess adaptive inhib-itory control, patients performed a stop signal task where a ‘go’ cueindicates the need for action, unless it is followed (at varying delays)by a ‘stop’ cue that indicates a need to cancel the action. Recordingswere supplemented by simultaneous scalp EEG over motor cortex, andwere performed both on and off dopaminergic medication. Given thatprevious reports have suggested that dorsal (motor) and ventral (cogni-tiveandaffective)areasoftheSTNmaydifferentiallycontributetoactionselection (Greenhouse et al., 2011; Hershey et al., 2010; Weinbergeret al., 2006), the spatial speci ficity of these recordings were considered,including the hemisphericlaterality of any potentialeffects.The findingsrevealed that different action selection processes were not only spatiallydistinct, but were also represented in different frequency bands in theEEG. Field oscillations at different frequencies allow neurons to ‘tune in’to different networks in order to communicate different types of infor-mation. In the case of EEG, Alegre et al. (2013) revealed that the theta(~4–6Hz),beta(~12–25 Hz)andgamma(~55–75 Hz)bandseachcon-tributedtodistinctaspectsofactionselectioninthecortico-STNnetwork.Neuronal activities in the beta band are thought to reflect a typeof active inhibition (e.g. “preserving the status quo”: Engel and Fries,2010). A diminishment in beta power during action readiness is thusobservedinbothcortexandSTN,possiblyduetodopaminergicin fluence(JenkinsonandBrown,2011).Dopaminedepletioncontributestoexces-sive synchronization of beta activities in STN ( Marceglia et al., 2011;Weinbergeretal.,2006),aswellaswithinnetworksincludingtheexter-nalglobuspallidus(Malletetal.,2008a),andcortex(Eusebioetal.,2009;Malletetal.,2008b),suggestingthatitenhancesthefunctionalroleofac-tive inhibition to a maladaptive degree. Conversely, activity in the thetaand gamma bands are thought to reflect active information processing(Fries,2009;Womelsdorfetal.,2010),whichsometimesinteracttogeth-er to facilitate information transfer across long distances or timescales(Canolty et al., 2006). The spectral width of each of these frequenciesalso appears to relate to the specificity of information content. Theta

Performance monitoring by presupplementary and supplementary motor area during an arm movement countermanding task

A key component of executive control and decision making is the ability to use the consequences of chosen actions to update and inform the process of future action selection. Evaluative signals, which monitor the outcomes of actions, are critical for this ability. Signals related to the evaluation of actions have been identified in eye movement-related areas of the medial frontal cortex. Here we examined whether such evaluative signals are also present in areas of the medial frontal cortex related to arm movements. To answer this question, we recorded from cells in the supplementary motor area (SMA) and pre-SMA, while monkeys performed an arm movement version of the countermanding paradigm. SMA and pre-SMA have been implicated in the higher-order control of movement selection and execution, although their precise role within the skeletomotor control circuit is unclear. We found evaluative signals that encode information about the expected outcome of the reward, the actual outcome, and the mismatch between actual and intended outcome. These findings suggest that signals that monitor and evaluate movement outcomes are represented throughout the medial frontal cortex, playing a general role across effector systems. These evaluation signals supervise the relationship between intentional motor behavior and reward expectation and could be used to adaptively shape future goal-directed behavior.

Magnetic resonance imaging of amyloid plaques using hollow manganese oxide nanoparticles conjugated with antibody aβ1–40 in a transgenic mouse model

In this study, we have shown the feasibility of hollow manganese oxide nanoparticles (HMON) conjugated with an antibody of Aβ1-40 peptide (abAβ40) (HMON-abAβ40) for MRI of amyloid plaques in APP/PS1 transgenic mice. MR brain images in APP/PS1 transgenic mice and their nontransgenic littermates were acquired using a 7.0 T MRI system before, and 24 and 72 h after an injection of HMON-abAβ40. After the injection of HMON-abAβ40, we found hyperenhanced spots in the frontal cortex area on T1-weighted MR images for transgenic mice, which corresponded qualitatively to amyloid plaques detected by thioflavin-S staining. For quantitative analysis, percent MR signal changes in six brain regions (olfactory cortex, frontal cortex, cerebral cortex, thalamus, hippocampus, and cerebellar cortex) were compared between transgenic and wild-type mice. We found significant increases in the percent MR signal changes in the olfactory cortex, frontal cortex, cerebral cortex, and hippocampus, but there were no significant differences in the thalamus and cerebellar cortex for transgenic mice compared with wild-type mice. This unique strategy allowed us to detect brain regions subjected to amyloid plaque deposition in Alzheimer's disease transgenic mouse models and has a potential to be developed for human applications, which has a current utility in preclinical research, particularly in monitoring therapeutic response for drug development in Alzheimer's disease.

Behavioral effects during the local activation and blockade of serotonin and dopamine receptors in the frontal cortex in cats in the model with a choice of reinforcements of different value

In the model with a choice of reinforcements of different value animals were able to "impulsive" and "self-controlled" behavior with an equal probability. Five adult cats were tested. A local application of agonists of 5-HT(1A) and 5-HT(2A/C) receptors (8-OH-DPAT, DOI) in the frontal cortex have resulted in a significant decrease of the "impulsive" reactions and an increase of omissions. The administration of antagonists of 5-HT(2A/C) receptors (ketanserin) and D1/D2 receptors (SCH 23390, raclopride) have impaired the "impulsive" behavior. However the combined administration of agonists/antagonists of 5-HT(2A/C) receptors and antagonists of D1/D2 receptors have not shown the significant changes in behavior as compared with control experiments. The data showed the realization of the optimal behavior with the "impulsive" and "self-controled" reactions in ambivalent animals requires the involvement of both dopaminergic and serotoninergic systems for the regulation of the activity of neurons in frontal cortex areas.

Neurobiology of human language and its evolution: primate and non-primate perspectives

The evolution of human language has been discussed for centuries from different perspectives. Linguistic theory has proposed grammar as a core part of human language that has to be considered in this context. Recent advances in neurosciences have allowed us to take a new neurobiological look on the similarities and dissimilarities of cognitive capacities and their neural basis across both closely and distantly related species. A couple of decades ago, the comparisons were mainly drawn between human and non-human primates, investigating the cytoarchitecture of particular brain areas and their structural connectivity. Moreover, comparative studies were conducted with respect to their ability to process grammars of different complexity. So far the available data suggest that non-human primates are able to learn simple probabilistic grammars, but not hierarchically structured complex grammars. The human brain, which easily learns both grammars, differs from the non-human brain (among others) in how two language-relevant brain regions (Broca's area in the inferior frontal cortex and the superior temporal cortex) are connected structurally by fiber tracts which run dorsally and ventrally in the primate brain. Whether the more dominant dorsal pathway in humans compared to non-human primates is causally related to this behavioral difference is an issue of current debate. Ontogenetic findings suggest at least a correlation between the maturation of the dorsal pathway and the behavior to process syntactically complex structures, although the ultimate causal prove is still not available. Thus, the neural basis of complex grammar processing in humans remains to be defined. More recently it has been reported that songbirds are also able to distinguish between sound sequences reflecting complex grammar. Interestingly, songbirds learn to sing by imitating adult song in a process not unlike language development in children. Moreover, the neural circuits supporting this behavior in songbirds bear anatomical and functional similarities to those in humans. In adult humans the fiber tract connecting the auditory cortex and motor cortex dorsally is known to be involved in the repetition of spoken language. This pathway is present already at birth and is taken to play a major role during language acquisition. In songbirds, detailed information exist concerning the interaction of auditory, motor, and cortical-basal ganglia processing during song learning, and present a rich substrate for comparative studies. The scope of the Research Topic was to bring together contributions of researchers from different fields, who investigate grammar processing in humans, non-human primates, and songbirds with the aim to find answers to the question of what constitutes the neurobiological basis of language and language learning. A number of contributions discuss the ventral and dorsal pathways in human and non-human primates considering their functional roles in speech and language. Some of these take an evolutionary perspective comparing non-human and human primates (Rauschecker, 2012; Rilling et al., 2012), whereas other takes an ontogenetic perspective (Friederici, 2012). The functional roles of the ventral and dorsal pathways in language and other modalities in particular action including articulatory and hand gestures are discussed in further articles (Fitch, 2011; Aboitiz, 2012; Rijntjes et al., 2012). Two articles consider the language system at the interface of two other human specific abilities, namely number processing (Heim et al., 2012) and reading (Lachmann et al., 2012). A couple of contributions take the evolutionary perspective even further by including song birds into their comparative approach (Berwick et al., 2012; Kiggins et al., 2012; Petkov and Jarvis, 2012). The selection of the articles provides a picture of the current views on the evolutionary and neurobiological basis of the language and language learning.

Periodic synchronous dischargeを呈しCreutzfeldt-Jakob病との鑑別を要した橋本脳症の1例

Here, we report a case of Hashimoto's encephalopathy (HE) mimicking Creutzfeldt-Jakob disease (CJD). A 57-year-old man was admitted to our hospital for status epilepticus. He had gradually presented personality change over the last two years. On admission, he was in state of akinetic mutism. He exhibited seizures on the left side of his body, including the face, and intermittent myoclonic movement. Routine laboratory tests showed no abnormalities, including thyroid functions. An EEG study showed typical periodic synchronous discharge (PSD). Brain MRI showed high-intensity areas in the bilateral frontal cortex, thalamus, and right insula on diffusion-weighted imaging (DWI). So, initially, sporadic CJD was suspected. However, there were no abnormalities in the caudate or putamen on MRI. Anti-TG and anti-TPO antibodies, as well as anti-NAE antibody were all positive. He was administered methylpredonisolone pulse therapy. Subsequently, his consciousness levels and EEG and MRI findings markedly improved. So, he was finally diagnosed with HE. HE should be considered in patients with PSD on EEG, even if the patients have typical MRI abnormalities of CJD. Anti-thyroid antibodies should be examined in such patients.

Neurobiological Mechanisms of Addictive Behavior

Regular consumption of psychoactive substances leads to many unfavorable sequelae, the most serious of which is the development of addictive behavior, with the compulsive desire to consume a psychoactive substance despite its serious consequences displacing all other activities. Addiction is characterized by an extremely high risk of renewed substance abuse even after prolonged periods of abstinence. It is suggested that addiction is based on the pathological usurpation of the processes of reinforcement, memory, and motivatory regulation, along with dysfunctions of the frontal areas of the cerebral cortex, which in normal conditions regulates decision-taking processes. The key role in the development of these changes belongs to the mesocortical-limbic dopaminergic system. Types of addictive behavior based on agents other than psychoactive substances are linked with similar changes in the nervous system. Addiction results from the interaction of genetic factors and environmental factors. It is characterized by phenotypic and genotypic heterogeneity and a high level of interaction between genes and the environment. Apart from genes, a wide spectrum of external conditions lead to the development of both resistance and susceptibility to disorders associated with the consumption of psychoactive substances.

Rostral–caudal gradients of abstraction revealed by multi-variate pattern analysis of working memory

The lateral frontal cortex (LFC) is thought to represent contextual and rule-based information that allows adaptive behavior according to circumstance. Recent progress has suggested that the representations of the LFC vary along its rostral-caudal axis with more abstract, higher level representations associated with rostral areas of the LFC and more concrete, lower level representations associated with caudal areas of the LFC. Here, we investigated this proposal. Subjects responded to stimuli based upon a nested series of contextual cues stored in working memory (WM) while being scanned with fMRI. Higher level context cues denoted an abstract rule set while lower level context cues provided more concrete information. Using multi-variate pattern analysis (MVPA), we found varying forms of representation along the rostral-caudal axis of the LFC depending on the type of information stored in WM. Rostral areas of frontal cortex in the lateral orbitofrontal cortex (OFC) represented the higher level context, but not more concrete information, and only when more concrete information was unavailable. Mid-level areas in the mid-dorsolateral prefrontal cortex (DLPFC) and inferior frontal junction (IFJ) represented more concrete rules, but only when the forthcoming response could not be anticipated. By contrast, the dorsal premotor cortex (PMd) and primary motor cortex (M1) represented contextual and response information when the forthcoming response could be anticipated on the basis of context. Collectively, these data indicate that representations dedicated to higher levels of abstraction become less discriminating when more concrete information becomes available. These patterns are consistent with rostral-caudal abstraction proposals of the LFC.

Homologous mechanisms of visuospatial working memory maintenance in macaque and human: Properties and sources

Although areas of frontal cortex are thought to be critical for maintaining information in visuospatial working memory, the event-related potential (ERP) index of maintenance is found over posterior cortex in humans. In the present study, we reconcile these seemingly contradictory findings. Here, we show that macaque monkeys and humans exhibit the same posterior ERP signature of working memory maintenance that predicts the precision of the memory-based behavioral responses. In addition, we show that the specific pattern of rhythmic oscillations in the alpha band, recently demonstrated to underlie the human visual working memory ERP component, is also present in monkeys. Next, we concurrently recorded intracranial local field potentials from two prefrontal and another frontal cortical area to determine their contribution to the surface potential indexing maintenance. The local fields in the two prefrontal areas, but not the cortex immediately posterior, exhibited amplitude modulations, timing, and relationships to behavior indicating that they contribute to the generation of the surface ERP component measured from the distal posterior electrodes. Rhythmic neural activity in the theta and gamma bands during maintenance provided converging support for the engagement of the same brain regions. These findings demonstrate that nonhuman primates have homologous electrophysiological signatures of visuospatial working memory to those of humans and that a distributed neural network, including frontal areas, underlies the posterior ERP index of visuospatial working memory maintenance.

Pride Diaries: Sex, Brain Size and Sociality in the African Lion (Panthera leo) and Cougar (Puma concolor)

The purpose of this study was to examine if differences in social life histories correspond to intraspecific variation in total or regional brain volumes in the African lion (Panthera leo) and cougar (Puma concolor). African lions live in gregarious prides usually consisting of related adult females, their dependent offspring, and a coalition of immigrant males. Upon reaching maturity, male lions enter a nomadic and often, solitary phase in their lives, whereas females are mainly philopatric and highly social throughout their lives. In contrast, the social life history does not differ between male and female cougars; both are solitary. Three-dimensional virtual endocasts were created using computed tomography from the skulls of 14 adult African lions (8 male, 6 female) and 14 cougars (7 male, 7 female). Endocranial volume and basal skull length were highly correlated in African lions (r = 0.59, p < 0.05) and in cougars (r = 0.67, p < 0.01). Analyses of total endocranial volume relative to skull length revealed no sex differences in either African lions or cougars. However, relative anterior cerebrum volume comprised primarily of frontal cortex and surface area was significantly greater in female African lions than males, while relative posterior cerebrum volume and surface area was greater in males than females. These differences were specific to the neocortex and were not found in the solitary cougar, suggesting that social life history is linked to sex-specific neocortical patterns in these species. We further hypothesize that increased frontal cortical volume in female lions is related to the need for greater inhibitory control in the presence of a dominant male aggressor.

Homologous Mechanisms of Visuospatial Working Memory Maintenance in Macaque and Human: Properties and Sources

Although areas of frontal cortex are thought to be critical for maintaining information in visuospatial working memory, the event-related potential (ERP) index of maintenance is found over posterior cortex in humans. In the present study, we reconcile these seemingly contradictory findings. Here, we show that macaque monkeys and humans exhibit the same posterior ERP signature of working memory maintenance that predicts the precision of the memory-based behavioral responses. In addition, we show that the specific pattern of rhythmic oscillations in the alpha band, recently demonstrated to underlie the human visual working memory ERP component, is also present in monkeys. Next, we concurrently recorded intracranial local field potentials from two prefrontal and another frontal cortical area to determine their contribution to the surface potential indexing maintenance. The local fields in the two prefrontal areas, but not the cortex immediately posterior, exhibited amplitude modulations, timing, and relationships to behavior indicating that they contribute to the generation of the surface ERP component measured from the distal posterior electrodes. Rhythmic neural activity in the theta and gamma bands during maintenance provided converging support for the engagement of the same brain regions. These findings demonstrate that nonhuman primates have homologous electrophysiological signatures of visuospatial working memory to those of humans and that a distributed neural network, including frontal areas, underlies the posterior ERP index of visuospatial working memory maintenance.

Fibroblast Growth Factor 8 Organizes the Neocortical Area Map and Regulates Sensory Map Topography

The concept of an "organizer" is basic to embryology. An organizer is a portion of the embryo producing signals that lead to the creation of a patterned mature structure from an embryonic primordium. Fibroblast growth factor 8 (FGF8) is a morphogen that disperses from a rostromedial source in the neocortical primordium (NP), forms a rostral-to-caudal (R/C) gradient, and regulates embryonic and neonatal R/C patterns of gene expression in neocortex. Whether FGF8 also has organizer activity that generates the postnatal neocortical area map is uncertain. To test this possibility, new sources of FGF8 were introduced into the mouse NP with in utero microelectroporation at embryonic day 10.5, close to the estimated peak of area patterning. Results differed depending on the position of ectopic FGF8. Ectopic FGF8 in the caudalmost NP could duplicate somatosensory cortex (S1) and primary visual cortex (V1). FGF8 delivered to the midlateral NP generated a sulcus separating rostral and caudal portions of the NP, in effect creating duplicate NPs. In the caudal NP, ectopic FGF8 induced a second, inclusive area map, containing frontal cortex, S1, V1, and primary auditory areas. Moreover, duplicate S1 showed plasticity to sensory deprivation, and duplicate V1 responded to visual stimuli. Our findings implicate FGF8 as an organizer signal, and its source in the rostromedial telencephalon as an organizer of the neocortical area map.

Assessment of Cholinergic and Cognitive Function in Healthy Young Adults Using Pharmacologic ASL Perfusion MRI (S29.003)

Objective: To examine the cholinergic system in vivo using pharmacologic arterial spin-labeling (ASL) perfusion MRI. Background In vivo imaging of cholinergic function has the potential of advancing our understanding of the important role it plays in cognition. Pharmacologic MRI, by examining changes in cerebral blood flow (CBF) following drug administration, can elucidate physiological effects with high anatomic resolution in vivo and thereby link the cognitive effects of cholinergic modulation to specific anatomical structures. Design/Methods: Healthy young adults participated in a randomized, placebo-controlled crossover study (n=15). Each underwent four pharmacologic conditions (placebo, mecamylamine, scopolamine, mecamylamine+scopolamine) on four separate days. ASL scans were obtained at the time of peak drug concentration, and cognitive performance was assessed with a neuropsychological battery. SPM was used to identify regions of significantly altered CBF in clusters of at least 1800 voxels. Cognitive performance was analyzed with repeated measures ANOVA. Results: With scopolamine, CBF was decreased bilaterally in thalamus, frontal cortex, and supplementary motor area and increased in occipital cortex, postcentral gyrus, insula, hippocampus, and superior temporal pole (corrected p-value Conclusions: These results confirm previous findings of decreased frontal and thalamic perfusion and cognitive deficits with scopolamine and reveal other areas implicated in cognition with cholinergically modulated blood flow, suggesting that ASL may be more sensitive to the perfusion changes under study. The cognitive impairments with cholinergic antagonism, including impaired attention and encoding, are consistent with disruption of the attention network (eg. frontal cortex, supplementary motor area, thalamus, basal ganglia). Likewise memory deficits could result from disruptions of known memory structures (eg. hippocampus) or decreased activity of inhibitory thalamic projections to cortical structures. Supported by: This project was funded by the American Federation for Aging Research Medical Student Training in Aging Research (MSTAR) Program, NIH/NIA grants T35AG038027, T32AG023480, K23AG031320, the Doris Duke Charitable Foundation Clinical Research Fellowship at Harvard Medical School, and the American Academy of Neurology Medical Student Summer Research Scholarship. Disclosure: Dr. Huang has nothing to disclose. Dr. Dai has nothing to disclose. Dr. Alsop has nothing to disclose. Dr. Waterston has nothing to disclose. Dr. Inouye has nothing to disclose. Dr. Fong has nothing to disclose.

Brain-derived neurotrophic factor expression after acute administration of ethanol

Earlier findings suggest that, in addition to its well-known neurotrophic role, brain-derived neurotrophic factor (BDNF) is also involved in the rewarding and reinforcing effects of drugs of abuse. The purpose of the present study was to examine the effects of acute administration of ethanol (1.25 or 2.5g/kg i.p.) on the expression profile of BDNF in the rat brain by determining the BDNF mRNA expression in the frontal cortex, nucleus accumbens, amygdala, hippocampus, and ventral tegmental area. Ethanol decreased BDNF mRNA levels dose-dependently in the hippocampus, and after the higher ethanol dose in the frontal cortex, nucleus accumbens and amygdala, while increasing them in the ventral tegmental area. Furthermore, BDNF mRNA expression was found to be regulated in a temporally different manner in all investigated brain areas. These data suggest that BDNF is involved in the acute effects of ethanol, but separate brain areas may be differentially engaged in the mediation of these effects.

Endogenous Opioid Release in the Human Brain Reward System Induced by Acute Amphetamine Administration

We aimed to demonstrate a pharmacologically stimulated endogenous opioid release in the living human brain by evaluating the effects of amphetamine administration on [(11)C]carfentanil binding with positron emission tomography (PET). Twelve healthy male volunteers underwent [(11)C]carfentanil PET before and 3 hours after a single oral dose of d-amphetamine (either a "high" dose, .5 mg/kg, or a sub-pharmacological "ultra-low" dose, 1.25 mg total dose or approximately .017 mg/kg). Reductions in [(11)C]carfentanil binding from baseline to post-amphetamine scans (ΔBP(ND)) after the "high" and "ultra-low" amphetamine doses were assessed in 10 regions of interest. [(11)C]carfentanil binding was reduced after the "high" but not the "ultra-low" amphetamine dose in the frontal cortex, putamen, caudate, thalamus, anterior cingulate, and insula. Our findings indicate that oral amphetamine administration induces endogenous opioid release in different areas of human brain, including basal ganglia, frontal cortex areas, and thalamus. The combination of an amphetamine challenge and [(11)C]carfentanil PET is a practical and robust method to probe the opioid system in the living human brain.

The neural circuitry of conversion disorder and its recovery.

Little is understood about neural networks associated with conversion disorders. This case study reports the first investigation of the neural circuitry associated with the recovery of chronic conversion disorder. A patient with a four year history of hysterical mutism was assessed with functional MRI (fMRI) during a vocalization task, and then provided psychotherapy that attempted to reduce motivational factors that maintained mutism. The patient resumed full speech, and was readministered the fMRI vocalization task. Vocalization during mutism and following recovery of speech resulted in increases in speech-related networks, including the inferior frontal gyrus (IFG), middle frontal, and supplementary motor area of the frontal cortex, temporal and parietal cortices, and also in the primary and sensory motor regions. Following speech recovery but not during mutism, the IFG was correlated positively with the anterior cingulate cortex and negatively with the amygdala. This pattern suggests that during the conversion disorder there was impaired connectivity between speech networks and networks that regulate anxiety.

Normative database of judgment of complexity task with functional near infrared spectroscopy—Application for TBI

The ability to assess frontal lobe function in a rapid, objective, and standardized way, without the need for expertise in cognitive test administration might be particularly helpful in mild traumatic brain injury (TBI), where objective measures are needed. Functional near infrared spectroscopy (fNIRS) is a reliable technique to noninvasively measure local hemodynamic changes in brain areas near the head surface. In this paper, we are combining fNIRS and frameless stereotaxy which allowed us to co-register the functional images with previously acquired anatomical MRI volumes. In our experiment, the subjects were asked to perform a task, evaluating the complexity of daily life activities, previously shown with fMRI to activate areas of the anterior frontal cortex. We reconstructed averaged oxyhemoglobin and deoxyhemoglobin data from 20 healthy subjects in a spherical coordinate. The spherical coordinate is a natural representation of surface brain activation projection. Our results show surface activation projected from the medial frontopolar cortex which is consistent with previous fMRI results. With this original technique, we will construct a normative database for a simple cognitive test which can be useful in evaluating cognitive disability such as mild traumatic brain injury.

Mechanisms of Selective Attention: Response Enhancement, Noise Reduction, and Efficient Pooling of Sensory Responses

In this issue of Neuron, Pestilli and coworkers provide evidence that response gain and noise reduction are insufficient to account for attention-induced changes in perception. Instead, selection may critically depend on the biased pooling of sensory signals during decision making.