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Handedness has traditionally been employed as a proxy of brain lateralization in research. Alzheimer's disease (AD) manifests as a neurodegenerative disorder characterized by impairments across various neuropsychological functions, including visuospatial and language, many of which exhibit lateralization in the human brain. While previous studies have investigated the relationship between AD and handedness, findings have been inconsistent. This article aims to provide an up-to-date overview of studies investigating hand preference in AD and the subtypes, specifically early- and late-onset AD. Through a synthesis of these studies, we conclude that handedness currently lacks utility as a diagnostic biomarker for AD and its subtypes, and this is further supported by the meta-analytic results based on data from over 10,000 AD patients. We emphasize the necessity for future research endeavors, particularly those leveraging advanced neuroimaging techniques to explore the role of brain asymmetry in AD. [ABSTRACT FROM AUTHOR]

[Display omitted] • Gyral size, which characterizes the average size of gyri, is essential for understanding gyrification. • Across mammals, gyral sizes are largely independent of brain size. • Gyral sizes are smaller for species facing a greater risk of head impact. • Sulci may protect the brain but also may impede neuronal connections. A study on primates has established that gyral size is largely independent of overall brain size. Building on this–and other research suggesting that brain gyrification may mitigate the effects of head impacts–our study aims to explore potential correlations between gyral size and the risk of head impact across a diverse range of mammalian species. Our findings corroborate the idea that gyral sizes are largely independent of brain sizes, especially among species with larger brains, thus extending this observation beyond primates. Preliminary evidence also suggests a correlation between an animal's gyral size and its lifestyle, particularly in terms of head-impact risk. For instance, goats, known for their headbutting behaviors, exhibit smaller gyral sizes. In contrast, species such as manatees and dugongs, which typically face lower risks of head impact, have lissencephalic brains. Additionally, we explore mechanisms that may explain how narrower gyral sizes could offer protective advantages against head impact. Finally, we discuss a possible trade-off associated with gyrencephaly. [ABSTRACT FROM AUTHOR]

Despite significant advances at the level of basic research, the characterization of higher-level processes in Rett and MECP2 Duplication syndrome remains understudied. In this pilot study, we assessed social-emotional information processing by testing whether children (ages 4–12 years) with Rett (n = 9) and MECP2 Duplication syndrome (n = 7) distinguished their own spoken name from other names. We hypothesized that own and familiar names would elicit more positive parietal P300 responses than unknown names, and that the groups would have different neural responses to these stimuli. The MECP2 Duplication group partially mirrored the parietal responses to own name observed in typically developing participants, and better name discrimination correlated with more adaptive behaviors. Conversely, participants with RTT did not resemble the typical group, and showed greater responses to close other names at frontal/central regions. These results may reflect the different consequences of too much ( MECP2 Duplication) vs. too little (RTT) MeCP2 protein. [ABSTRACT FROM AUTHOR]

The inferior longitudinal fascicle (ILF) is one of the major occipital-temporal association pathways. Several studies have mapped its hierarchical segmentation to specific functions. There is, however, no consensus regarding a detailed description of ILF fibre organisation. The aim of this study was to establish whether the ILF has a constant number of subcomponents. A secondary aim was to determine the quantitative diffusion proprieties of each subcomponent and assess their anatomical trajectories and connectivity patterns. A white matter dissection of 14 post-mortem normal human hemispheres was conducted to define the course of the ILF and its subcomponents. These anatomical results were then investigated in 24 right-handed, healthy volunteers using in vivo diffusion tensor imaging (DTI) and streamline tractography. Fractional anisotropy (FA), volume, fibre length and the symmetry coefficient of each fibre group were analysed. In order to show the connectivity pattern of the ILF, we also conducted an analysis of the cortical terminations of each segment. We confirmed that the main structure of the ILF is composed of three constant components reflecting the occipital terminations: the fusiform, the lingual and the dorsolateral-occipital. ILF volume was significantly lateralised to the right. The examined indices of ILF subcomponents did not show any significant difference in lateralisation. The connectivity pattern and the quantitative distribution of ILF subcomponents suggest a pivotal role for this bundle in integrating information from highly specialised modular visual areas with activity in anterior temporal territory, which has been previously shown to be important for memory and emotions. [ABSTRACT FROM AUTHOR]

The aims of this review are: 1) to describe which cholinergic neurons are affected in brain neurodegenerative diseases leading to dementia; 2) to discuss the possible causes of the degeneration of the cholinergic neurons, 3) to summarize the functional consequences of the cholinergic deficit. The brain cholinergic system is basically constituted by three populations of phenotypically similar neurons forming a series of basal forebrain nuclei, the midpontine nuclei and a large population of striatal interneurons. In Alzheimer’s disease there is an extensive loss of forebrain cholinergic neurons accompanied by a reduction of the cholinergic fiber network of the cortical mantel and hippocampus. The midpontine cholinergic nuclei are spared. The same situation occurs in the corticobasal syndrome and dementia following alcohol abuse and traumatic brain injury. Conversely, in Parkinson’s disease, the midpontine nuclei degenerate, together with the dopaminergic nuclei, reducing the cholinergic input to thalamus and forebrain whereas the forebrain cholinergic neurons are spared. In Parkinson’s disease with dementia, Lewis Body Dementia and Parkinsonian syndromes both groups of forebrain and midpontine cholinergic nuclei degenerate. In Huntington’s disease a dysfunction of the striatal cholinergic interneurons without cell loss takes place. The formation and accumulation of misfolded proteins such as β-amyloid oligomers and plaques, tau protein tangles and α-synuclein clumps, and aggregated mutated huntingtin play a crucial role in the neuronal degeneration by direct cellular toxicity of the misfolded proteins and through the toxic compounds resulting from an extensive inflammatory reaction. Evidences indicate that β-amyloid disrupts NGF metabolism causing the degeneration of the cholinergic neurons which depend on NGF for their survival, namely the forebrain cholinergic neurons, sparing the midpontine and striatal neurons which express no specific NGF receptors. It is feasible that the latter cholinergic neurons may be damaged by direct toxicity of tau, α-synuclein and inflammations products through mechanisms not fully understood. Attention and learning and memory impairment are the functional consequences of the forebrain cholinergic neuron dysfunction, whereas the loss of midpontine cholinergic neurons results primarily in motor and sleep disturbances. [ABSTRACT FROM AUTHOR]

Cerebellum undergoes degenerative changes in neurodegenerative diseases. Two main factors including oxidative stress and neuroinflammation mediate neurodegeneration. Neuregulin-1 (Nrg1) has been implicated in many neurodegenerative diseases, while the underlying mechanisms are unknown. We hypothesized that Nrg1 prevents oxidative stress and neuroinflammation in neurodegeneration. We found a positive correlation between Nrg1 protein levels and ErbB4 and ErbB2 receptor phosphorylation in microarrays of normal human cerebellar tissue. In addition, Nrg1 was also co-localized with pErbB4 and pErbB2. Primary mouse cerebellar granule neurons (CGNs) were treated with H 2 O 2 or LPS combined with recombinant Nrg1β (rNrg1β). Western blot analysis and immunofluorescence revealed that H 2 O 2 and LPS-induced neuronal toxicity down-regulated the activation of ErbB receptors and Akt1, and the ratio of Bcl2/Bax, which was reversed by rNrg1β. In vivo studies showed that LPS-induced neuroinflammation in mouse cerebellum down-regulated pErbB4, pErbB2, pAkt1/Akt1 and Bcl2/Bax levels, whereas rNrg1β treatment reversed the changes. Immunohistochemistry and Western blot analysis showed that rNrg1β alleviates neuroinflammation by reducing the number of microglial cells and astrocytes and the expression of IL1β. Our results indicate that Nrg1 protects against oxidative stress and neuroinflammation in mouse cerebellum, suggesting potential therapeutic application in neuroinflammation associated with neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Absence epileptic activity was analyzed during pregnancy, the postpartum period and after weaning to establish alterations of seizures throughout the reproductive cycle. Wistar Albino Glaxo Rijswijk (WAG/Rij) rats were used in the study as a model of absence epilepsy and because their seizures do not interfere with rearing offspring. The number of spike-wave discharges (SWDs) was gradually elevated from the 19th pregnancy day to delivery. Meanwhile, the characteristics of individual SWDs did not change suggesting that SWD generation remained the same. In the postpartum and postweaning periods, the number of SWDs was not increased in the absence of pups. However, returning the pups to mothers resulted in a markedly elevated number of SWDs for 1 h. If pups were taken away after 30 min, the number of SWDs dropped immediately suggesting that the presence of pups increased the SWD number. The time mothers spent with the litter and in kyphosis suckling posture were in correlation with their SWD number further suggesting the importance of interaction with pups in SWD induction. Suckling elevates prolactin levels but surprisingly, its intracerebroventricular injection markedly reduced SWD number in suckled WAG/Rij mothers suggesting that the SWD-inducing effect of suckling is not mediated by prolactin. Rather, the elevated prolactin level may provide some protection against pro-epileptic effects of suckling. In conclusion, we first identified periods within the reproductive cycle with increased absence epileptic activity, implying that more attention should be devoted to epileptic activity changes in mothers. [ABSTRACT FROM AUTHOR]

Multiple studies have found neurofunctional changes in normal aging in a context of selective attention. Furthermore, many articles report intrahemispheric alteration in functional networks. However, little is known about age-related changes within the Ventral Attention Network (VAN), which underlies selective attention. The aim of this study is to examine age-related changes within the VAN, focusing on connectivity between its regions. Here we report our findings on the analysis of 27 participants’ (13 younger and 14 older healthy adults) BOLD signals as well as their performance on a letter-matching task. We identified the VAN independently for both groups using spatial independent component analysis. Three main findings emerged: First, younger adults were faster and more accurate on the task. Second, older adults had greater connectivity among posterior regions (right temporoparietal junction, right superior parietal lobule, right middle temporal gyrus and left cerebellum crus I) than younger adults but lower connectivity among anterior regions (right anterior insula, right medial superior frontal gyrus and right middle frontal gyrus). Older adults also had more connectivity between anterior and posterior regions than younger adults. Finally, correlations between connectivity and response time on the task showed a trend toward connectivity in posterior regions for the older group and in anterior regions for the younger group. Thus, this study shows that intrahemispheric neurofunctional changes in aging also affect the VAN. The results suggest that, in contexts of selective attention, posterior regions increased in importance for older adults, while anterior regions had reduced centrality. [ABSTRACT FROM AUTHOR]

The balance of neural excitation and inhibition (E/I balance) is often hypothesised to be altered in autism spectrum disorder (ASD). One widely held view is that excitation levels are elevated relative to inhibition in ASD. Understanding whether, and how, E/I balance may be altered in ASD is important given the recent interest in trialling pharmacological interventions for ASD which target inhibitory neurotransmitter function. Here we provide a critical review of evidence for E/I balance in ASD. We conclude that data from a number of domains provides support for alteration in excitation and inhibitory neurotransmission in ASD, but when considered collectively, the available literature provide little evidence to support claims for either a net increase in excitation or a net increase in inhibition. Strengths and limitations of available techniques are considered, and directions for future research discussed. [ABSTRACT FROM AUTHOR]

Glutamatergic synapses are shown to mature during activity and development. In order to further explore how glutamate can change the excitability of noradrenergic neurons of locus coeruleus (LC) and to better understand the involvement of Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl- d -aspartate (NMDA) receptors complements across the LC, we investigated developmental changes in their activity during first postnatal weeks. Spontaneous and evoked excitatory postsynaptic currents (sEPSC and eEPSCs) were recorded in neurons of LC slices from 7, 14 and 21 days old rats using the whole cell patch clamp method. Also, the AMPA/NMDA current ratio (A/N) was measured. A pronounced AMPAR and NMDAR components mediated involvement in synaptic transmission were seen from the first postnatal week. Over this period of development, we have demonstrated that AMPA sEPSCs show an increase in frequency without major changes in their amplitude, while NMDA sEPSCs show an increase in frequency with a major change in amplitude. Neither the probability of release nor the AMPA/NMDA ratio was found to change significantly with age. It is concluded that NMDAR activity as well as AMPAR activity may be involved in coerulear excitability and modulatory effect during postnatal development. [ABSTRACT FROM AUTHOR]

The perception of beat within an auditory rhythm can be facilitated when accompanied by synchronised movements. Electrophysiological investigation shows that this facilitatory effect is associated with a larger P300 amplitude. It has remained unclear, however, which movement-related processes drive this P300 effect. To investigate whether vestibular signals play a role, we administered alternating, sub-sensory (mean=.3 mA) galvanic current to the vestibular nerves of participants while they counted the number of oddballs presented in a stream of tones played at a rate of 1 Hz. Consistent with a vestibular effect, the P300 elicited by the oddballs was increased during stimulation relative to a sham condition, but only when the frequency of the alternating current matched that at which the tones were played. This finding supports the general idea that the vestibular system is involved in audio-motor synchronisation and is the first to show by electrophysiological means that it influences cognitive processes involved in beat perception. [ABSTRACT FROM AUTHOR]

A partially informative cue presented before a stimulus can facilitate the production of the response. Prior information about an upcoming target can increase brain activity in both stimulus (c.f., Desimone and Duncan, 1995) and response (c.f., Leuthold et al., 1996) processing regions; however, it is unclear how the representation of the task might influence the recruitment of this network of task-relevant regions. In the current experiment, we employed an event-related fMRI design with a response cuing procedure to investigate whether S-R pairings jointly influence activity in stimulus- and response-specific processing areas during the presentation of a cue. Participants learned S-R mappings in which pictures of faces and places were paired with either left or right hand finger responses. On some trials, a cue provided partial information about the upcoming trial (e.g., that the trial would involve a face or place stimuli or a left or right hand response). Importantly, because different stimulus types were associated with each hand, any informative cue implicitly indicated both a stimulus type and response hand, allowing participants to represent the task as two distinct subtasks. Region-of-interest analyses at the cue event demonstrated a biasing of response processing regions for both stimulus- and response-related cues, as well as increased connectivity with the associated stimulus-processing regions. The results suggest that the cue results in the recruitment of just the task-relevant subnetwork on each trial. [ABSTRACT FROM AUTHOR]

Objective A rarely occurring and highly relevant auditory stimulus occurring outside of the current focus of attention can cause a switching of attention. Such attention capture is often studied in oddball paradigms consisting of a frequently occurring “standard” stimulus which is changed at odd times to form a “deviant”. The deviant may result in the capturing of attention. An auditory ERP, the P3a, is often associated with this process. To collect a sufficient amount of data is however very time-consuming. A more multi-feature “optimal” paradigm has been proposed but it is not known if it is appropriate for the study of attention capture. Methods An optimal paradigm was run in which 6 different rare deviants (p=.08) were separated by a standard stimulus (p=.50) and compared to results when 4 oddball paradigms were also run. Results A large P3a was elicited by some of the deviants in the optimal paradigm but not by others. However, very similar results were observed when separate oddball paradigms were run. Conclusions & significance The present study indicates that the optimal paradigm provides a very time-saving method to study attention capture and the P3a. [ABSTRACT FROM AUTHOR]

The history, content and consequences of the highly-cited 1982 Brain Research paper by Halliwell and Adams are summarized. The paper pioneered the use of the single-electrode voltage clamp in mammalian brain slices, described 2 novel sub-threshold voltage-dependent ionic currents, I M and I Q / H , and suggested that cholinergic inputs “enabled” pyramidal cell firing in response to conventional synaptic input, the first example of central neuromodulation. The paper, published in Brain Research to give the first author appropriate importance, heralded an ongoing tidal wave of quantitative electrophysiology in mammalian central neurons. original article abstract Voltage-clamp analysis of muscarinic excitation in hippocampal neurons Pyramidal cells in the CA1 field of guinea pig hippocampal slices were voltage-clamped using a single microelectrode, at 23–30 °C. Small inwardly relaxing currents triggered by step hyperpolarizations from holding potentials of −80 to −40 mV were investigated. Inward relaxations occurring for negative steps between −40 mV and −70 mV resembled M-currents of sympathetic ganglion cells: they were abolished by addition of carbachol, muscarine or bethanechol, as well as by 1 mM barium; the relaxations appeared to invert at around −80 mV; they became faster at more negative potentials; and the inversion potential was shifted positively by raising external K + concentration. Inward relaxations triggered by steps negative to −80 mV, in contrast, appeared to reflect passage of another current species, which has been labeled I Q .Thus I Q did not invert negative to −80 mV, it was insensitive to muscarinic agonizts or to barium, and it was blocked by 0.5–3 mM cesium (which does not block I M ). Turn-on of I Q causes the well known droop in the hyperpolarizing electrotonic potential in these cells. The combined effects of I Q and I M make the steady-state current–voltage relation of CA1 cells slightly sigmoidal around rest potential. It is suggested that activation of cholinergic septal inputs to the hippocampus facilitates repetitive firing off pyramidal cells by turning off the M-conductance, without much change in the resting potential of the cell. © 1982. This article is part of a Special Issue entitled SI:50th Anniversary Issue . [ABSTRACT FROM AUTHOR]

The brainstem nucleus locus coeruleus (LC) is a major source of norepinephrine (NE) projections throughout the CNS. This important property was masked in very early studies by the inability to visualize endogenous monoamines. The development of monoamine histofluorescence methods by Swedish scientists led to a plethora of studies, including a paper published in Brain Research by Loizou in 1969. That paper was highly cited (making it a focal point for the 50th anniversary issue of this journal), and helped to spark a large and continuing set of investigations to further refine our understating of the LC-NE system and its contribution to brain function and behavior. This paper very briefly reviews the ensuing advances in anatomical, physiological and behavioral aspects of the LC-NE system. Although its projections are ubiquitously present throughout the CNS, recent studies find surprising specificity within the organizational and operational domains of LC neurons. These and other findings lead us to expect that future work will unmask additional features of the LC-NE system and its roles in normative and pathological brain and behavioral processes. This article is part of a Special Issue entitled SI:50th Anniversary Issue . [ABSTRACT FROM AUTHOR]

In the early 1980’s, the dispute on the existence of a multiplicity of receptors for neurotransmitter was at its height. Several subtypes of serotonin (5-HT) receptors were proposed on the basis of radioligand binding assays. In order to provide further support to the existence of these receptors we performed quantitative autoradiographic mapping of the binding of several ligands for the 5-HT 1 receptor labeling the subtypes 5-HT 1A , 5-HT 1B and 5-HT 1C , and characterized pharmacologically these different receptors. The results demonstrated differential localization of the subtypes of 5-HT 1 receptors indicating that they were expressed by different cell populations, probably neurons, in the brain and further supporting their reality. Shortly afterwards, the cloning of the genes coding for these 5-HT receptors, and many others, ended the dispute by demonstrating that they were different proteins. The advent of Molecular Biology provided new methodologies for the study of the chemical and molecular anatomy of 5-HT receptors in brain, by visualizing cells expressing their mRNA by in situ hybridization and showed that the family of mammalian 5-HT receptors has 14 members, a figure much larger than ever suspected at that time. Original article abstract: Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors The distribution of serotonin-1 (5-HT 1 ) receptors in the rat brain was studied by light microscopic quantitative autoradiography. Receptors were labeled with [ 3 H]serotonin (5-[ 3 H]HT), 8-hydroxy-2-[H-dipropylamino- 3 H]tetralin (8-OH-[ 3 H]DPAT), [ 3 H]LSD and [ 3 H]mesulergine, and the densities quantified by microdensitometry with the aid of a computer-assisted image-analysis system. Competition experiments for 5-[ 3 H]HT binding by several serotonin-1 agonizts led to the identification of brain areas enriched in each one of the three subtypes of 5-HT 1 recognition sites already described (5-HT 1A , 5-HT 1B , 5-HT 1C ). The existence of these׳selective׳ areas allowed a detailed pharmacological characterization of these sites to be made in a more precise manner than has been attained in membrane-binding studies. While 5-[ 3 H]HT labeled with nanomolar affinity all the 5-HT 1 subtypes, the other 3 H-labeled ligands labeled selectively 5-HT 1A (8-OH-[ 3 H]DPAT), 5-HT 1C ([ 3 H]mesulergine) and both of them ([ 3 H]LSD). Very high concentrations of 5-HT 1 receptors were localized in the choroid plexus, lateroseptal nucleus, globus pallidus and ventral pallidum, dentate gyrus, dorsal subiculum, olivary pretectal nucleus, substantia nigra, reticular and external layer of the entorhinal cortex. The different fields of the hippocampus (CA 1 –CA 4 ), some nuclei of the amygdaloid complex, the hypothalamic nuclei and the dorsal raphé, among others, also presented high concentrations of sites. Areas containing intermediate densities of 5-HT 1 receptors included the claustrum, olfactory tubercle, accumbens, central gray and lateral cerebellar nucleus. The nucleus caudate-putamen and the cortex, at the different levels studied, presented receptor densities ranging from intermediate to low. Finally, in other brain areas-pons, medulla, and spinal cord-only low or very low concentrations of 5-HT 1 receptors were found. From the areas strongly enriched in 5-HT 1 sites, dentate gyrus and septal nucleus contained 5-HT 1A sites, while globus pallidus, dorsal subiculum, substantia nigra and olivary pretectal nucleus were enriched in 5-HT 1B . The sites in the choroid plexus, which presented the highest density of receptors in the rat brain, were of the 5-HT 1C subtype. The distribution of 5-HT 1 receptors reported here is discussed in correlation with the distribution of serotoninergic neurons and fibers, the related anatomical pathways and the effects which appear to be mediated by these sites. © 1985. This article is part of a Special Issue entitled SI:50th Anniversary Issue . This article is part of a Special Issue entitled SI:50th Anniversary Issue . [ABSTRACT FROM AUTHOR]

Dorsal temporal pole (dTP) is a cortical region at the rostral end of the superior temporal gyrus that forms part of the ventral auditory object processing pathway. Anatomical connections with frontal and medial temporal areas, as well as a recent single-unit recording study, suggest this area may be an important part of the network underlying auditory working memory (WM). To further elucidate the role of dTP in auditory WM, local field potentials (LFPs) were recorded from the left dTP region of two rhesus macaques during an auditory delayed matching-to-sample (DMS) task. Sample and test sounds were separated by a 5-s retention interval, and a behavioral response was required only if the sounds were identical (match trials). Sensitivity of auditory evoked responses in dTP to behavioral significance and context was further tested by passively presenting the sounds used as auditory WM memoranda both before and after the DMS task. Average evoked potentials (AEPs) for all cue types and phases of the experiment comprised two small-amplitude early onset components (N20, P40), followed by two broad, large-amplitude components occupying the remainder of the stimulus period (N120, P300), after which a final set of components were observed following stimulus offset (N80 OFF , P170 OFF ). During the DMS task, the peak amplitude and/or latency of several of these components depended on whether the sound was presented as the sample or test, and whether the test matched the sample. Significant differences were also observed among the DMS task and passive exposure conditions. Comparing memory-related effects in the LFP signal with those obtained in the spiking data raises the possibility some memory-related activity in dTP may be locally produced and actively generated. The results highlight the involvement of dTP in auditory stimulus identification and recognition and its sensitivity to the behavioral significance of sounds in different contexts. This article is part of a Special Issue entitled SI: Auditory working memory . [ABSTRACT FROM AUTHOR]

Auditory working memory (WM) is the cognitive faculty that allows us to actively hold and manipulate sounds in mind over short periods of time. We develop here a particular perspective on WM for non-verbal, auditory objects as well as for time based on the consideration of possible parallels to visual WM. In vision, there has been a vigorous debate on whether WM capacity is limited to a fixed number of items or whether it represents a limited resource that can be allocated flexibly across items. Resource allocation models predict that the precision with which an item is represented decreases as a function of total number of items maintained in WM because a limited resource is shared among stored objects. We consider here auditory work on sequentially presented objects of different pitch as well as time intervals from the perspective of dynamic resource allocation. We consider whether the working memory resource might be determined by perceptual features such as pitch or timbre, or bound objects comprising multiple features, and we speculate on brain substrates for these behavioural models. This article is part of a Special Issue entitled SI: Auditory working memory . [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is highly prevalent and occurs in a variety of populations. Because of the complexity of its sequelae, treatment strategies pose a challenge. Given this complexity, TBI provides a unique target of opportunity for complementary and alternative medicine (CAM) treatments. The present review describes and discusses current opportunitites and challenges associated with CAM research and clinical applications in civilian, veteran and military service populations. In addition to a brief overview of CAM, the translational capacity from basic to clinical research to clinical practice will be described. Finally, a systematic approach to developing an adoptable evidence base, with proof of effectiveness based on the literature will be discussed. Inherent in this discussion will be the methodological and ethical challenges associated with CAM research in those with TBI and associated comorbidities, specifically in terms of how these challenges relate to practice and policy issues, implementation and dissemination. This article is part of a Special Issue entitled SI:Brain injury and recovery . [ABSTRACT FROM AUTHOR]

A neuron׳s response to a sound can be suppressed by the presentation of a preceding sound. It has been suggested that this suppression is a direct correlate of the psychophysical phenomenon of forward masking, however, forward suppression, as measured in the responses of the auditory nerve, was insufficient to account for behavioural performance. In contrast the neural suppression seen in the inferior colliculus and auditory cortex was much closer to psychophysical performance. In anaesthetised guinea-pigs, using a physiological two-interval forced-choice threshold tracking algorithm to estimate suppressed (masked) thresholds, we examine whether the enhancement of suppression can occur at an earlier stage of the auditory pathway, the ventral cochlear nucleus (VCN). We also compare these responses with the responses from the central nucleus of the inferior colliculus (ICc) using the same preparation. In both nuclei, onset-type neurons showed the greatest amounts of suppression (16.9–33.5 dB) and, in the VCN, these recovered with the fastest time constants (14.1–19.9 ms). Neurons with sustained discharge demonstrated reduced masking (8.9–12.1 dB) and recovery time constants of 27.2–55.6 ms. In the VCN the decrease in growth of suppression with increasing suppressor level was largest for chopper units and smallest for onset-type units. The threshold elevations recorded for most unit types are insufficient to account for the magnitude of forward masking as measured behaviourally, however, onset responders, in both the cochlear nucleus and inferior colliculus demonstrate a wide dynamic range of suppression, similar to that observed in human psychophysics. [ABSTRACT FROM AUTHOR]

Orexinergic projections originating from the lateral hypothalamus (LH) have an important role in the acquisition of the LH-stimulation conditioned place preference (CPP). Among the brain areas associated with reward processing, LH orexinergic neurons send projections to the dentate gyrus (DG) region of the hippocampus, and it has been shown that orexin receptors are expressed in the DG. In this study, we investigated the role of intra-DG orexin-1 (OX1) and orexin-2 (OX2) receptors on acquisition, expression and extinction of CPP induced by stimulation of the LH. Rats were unilaterally implanted by two separate cannulae into the LH and DG. The CPP paradigm was done; conditioning scores and locomotor activities were recorded by Ethovision software. The results showed that intra-DG administration of SB334867, a selective OX1r antagonist, and TCS OX2 29, a selective OX2r antagonist, (0.5, 5, 12.5 and 50 nM/0.5 µl DMSO) before carbachol microinjection (250 nM; effective dose) during the 3-days conditioning phase, dose-dependently inhibited the development of LH stimulation-induced CPP in the rats. However, this reduction in OX1r antagonist treated groups was more than that in OX2r antagonist treated animals. In addition, these antagonists decreased the expression of LH-induced CPP. Moreover, OX1r but not OX2r antagonist could shorten the extinction duration of place preference. We conclude that the orexinergic projections from the LH to DG are involved in the development, expression and extinction of CPP induced by LH stimulation. [ABSTRACT FROM AUTHOR]

How do we know where we are, and how do we remember the places we visited? Since the discovery of place cells in 1971, our understanding of the brain׳s maps of external space has exploded. Yet the origin of the place-cell signal remained elusive. The discovery of grid cells in the medial entorhinal cortex (MEC) in 2005 put place cells in a context, since the existence of grid cells pointed to circuit mechanisms that might explain the formation of place cells. In this review, I shall review recent experimental and theoretical advances in the understanding of how space is mapped in the medial entorhinal cortex. I will also review recent studies of interactions between hippocampus and the lateral entorhinal cortex (LEC). Research on spatial mapping in the hippocampal-entorhinal system provides a fundament for future attempts to decipher some of the neural-circuit codes of the cortex. [ABSTRACT FROM AUTHOR]

Considerable progress has been made in the understanding of molecular and cellular mechanisms controlling the development of the mammalian cortex. The proliferative and neurogenic properties of cortical progenitors located in the ventricular germinal zone start being understood. Little is known however on the cis -regulatory control that finely tunes gene expression in these progenitors. Here, we undertook an in silico-based approach to address this question, followed by some functional validation. Using the Eurexpress database, we established a list of 30 genes specifically expressed in the cortical germinal zone, we selected mouse/human conserved non-coding elements (CNEs) around these genes and we performed motif-enrichment search in these CNEs. We found an over-representation of motifs corresponding to binding sites for Pax, Sox, and Lhx transcription factors, often found as pairs and located within 100 bp windows. A small subset of CNEs ( n =7) was tested for enhancer activity, by ex-vivo and in utero electroporation assays. Two showed strong enhancer activity in the germinal zone progenitors. Mutagenesis experiments on a selected CNE showed the functional importance of the Pax, Sox, and Lhx TFBS for conferring enhancer activity to the CNE. Overall, from a cis- regulatory viewpoint, our data suggest an input from Pax, Sox and Lhx transcription factors to orchestrate corticogenesis. These results are discussed with regards to the known functional roles of Pax6, Sox2 and Lhx2 in cortical development. [ABSTRACT FROM AUTHOR]

The Parvafox-nucleus in the lateral hypothalamus is characterized by the presence of two distinct neural populations, the Parvalbumin (Parv) and the Foxb1-expressing ones. Foxb1-neurons are born at day 10 in the subventricular zone of the mouse mammillary region. It would be interesting to know if the subpopulation of Parv- neurons develop independently at different times and then meet the Foxb1- expressing neurons in the lateral hypothalamus, their final settling place. The aim of this study was to define the period of birth of the Parv-positive neurons using an in-vivo Bromodeoxyuridine-based method in rats. Parv-neurons are generated from embryonic day 10 to day 13, with a peak at day 12. Thus, it appears that the birthdates of the two subpopulations in these two species is similar, perhaps suggesting that they are born from the same neuroepithelial region. [ABSTRACT FROM AUTHOR]

The insular cortex (IC) has been related to various reinforcing behavioral processes. This study examined the effect of electrical stimulation of the posterior agranular IC on concurrent place preferences. Two groups of animals and their respective controls underwent rewarding brain stimulation every day or on alternate days. While the rats stimulated every other day maintained their preference for the place associated with brain stimulation, those stimulated every day evidenced a reduction in their place preference, suggesting tolerance to the stimulation׳s rewarding effect. A 15% increase in the current intensity produced a recovery of the preferences of the daily-stimulated rats but had no effect on those stimulated on alternate days. These results are discussed in terms of the rewarding effects induced by different electrical and chemical rewarding agents. [ABSTRACT FROM AUTHOR]

Objective To investigate whether high performance on college preparedness tests at 18 years of age can be predicted from brain activation patterns during narrative comprehension at 5–7 years of age. Methods In this longitudinal study, functional MRI data during an auditory narrative-comprehension task were acquired from 15 children (5–7 years of age) who also provided their American College Testing (ACT) scores at the age of 18 years. Active voxels during the narrative-comprehension task were correlated with both composite ACT scores and the reading-comprehension component of the exam. Results Higher composite ACT scores and behavioral scores for reading comprehension were positively correlated with greater activation in frontal and anterior brain regions during the narrative-comprehension task. Conclusions Our results suggest that neural circuits supporting higher ACT performance are predictable from a narrative-comprehension task at the age of 5–7 years. This supports a critical role for the anterior cingulate cortex, which is a part of the cingulo-opercular cognitive-control network early in development, as a facilitator for better ACT scores. This study highlights that shared neural circuits that support overall ACT performance and neural circuits that support reading comprehension both rely on neural circuits related to narrative comprehension in childhood, suggesting that interventions involving narrative comprehension should be considered for individuals with reading and other academic difficulties. [ABSTRACT FROM AUTHOR]

Searching a target was shown to be facilitated when embedded in a homogeneous compared to a heterogeneous context. This study investigated extended attention deployment after visual search for a target that observers had to discriminate in contexts of varying heterogeneity. Results showed more efficient attention deployment towards targets in homogeneous contexts as evident in higher accuracy and larger N2pc amplitudes than in random contexts. RTs to subsequently presented probes were shorter and a larger posterior positivity was observed in the ERP when probes were presented at the target location compared to other locations. This on-target advantage was larger for homogeneous contexts at ISIs of 90 ms, but not for shorter (30 ms) or longer (150 ms) ISIs. These results show that visual search tasks induce an accelerated attention deployment after homogeneous contexts, however with a delay after target discrimination compared to less demanding target detection. [ABSTRACT FROM AUTHOR]

A substantial body of ERP research investigating the processing of syntactic long-distance dependencies has shown that, across languages and construction types, the second element in such configurations typically elicits phasic left anterior negativity (LAN). We hypothesized that these effects are not specific to syntactic dependencies, but rather index a more general cognitive operation in which the second (dependent) element in sentence-level linguistic long-distance relationships triggers a process of association with the first element. We tested this hypothesis with straightforward referential dependencies, comparing pronouns with proper name antecedents to those without, and proper names with and without preceding co-referring pronouns. We predicted phasic LAN effects in response to the second referential element in both comparisons, but observed them only in response to pronouns with antecedents; no differences were observed between responses to proper names with and without preceding co-referring pronouns. We argue that LAN effects observed at the pronoun index the cognitive operations necessary for the association of a pronoun with its antecedent, on which it depends for its reference. Similar but non-identical responses were elicited by the main clause verb following the gap position in object relative clause constructions compared to coordinate clause controls in an orthogonal manipulation. LAN effects were thus elicited by the second dependent element in both construction types, suggesting that long-distance syntactic and referential dependencies pose similar processing challenges. These findings help to clarify the cognitive processes indexed by anterior negative responses to associated dependent elements in a variety of language contexts. [ABSTRACT FROM AUTHOR]

Drug addiction is characterized by persistent relapse vulnerability during abstinence. In abstinent drug users, relapse is often precipitated by re-exposure to environmental contexts that were previously associated with drug use. This clinical scenario is modeled in preclinical studies using the context-induced reinstatement procedure, which is based on the ABA renewal procedure. In these studies, context-induced reinstatement of drug seeking is reliably observed in laboratory animals that were trained to self-administer drugs abused by humans. In this review, we summarize neurobiological findings from preclinical studies that have focused on the role of corticostriatal circuits in context-induced reinstatement of heroin, cocaine, and alcohol seeking. We also discuss neurobiological similarities and differences in the corticostriatal mechanisms of context-induced reinstatement across these drug classes. We conclude by briefly discussing future directions in the study of context-induced relapse to drug seeking in rat models. Our main conclusion from the studies reviewed is that there are both similarities (accumbens shell, ventral hippocampus, and basolateral amygdala) and differences (medial prefrontal cortex and its projections to accumbens) in the neural mechanisms of context-induced reinstatement of cocaine, heroin, and alcohol seeking. This article is part of a Special Issue entitled SI:Addiction circuits . [ABSTRACT FROM AUTHOR]

A number of previous studies have suggested segregated networks of brain areas for top-down controlled and bottom-up triggered orienting of visual attention. However, the corresponding networks involved in auditory attention remain less studied. Our participants attended selectively to a tone stream with either a lower pitch or higher pitch in order to respond to infrequent changes in duration of attended tones. The participants were also required to shift their attention from one stream to the other when guided by a visual arrow cue. In addition to these top-down controlled cued attention shifts, infrequent task-irrelevant louder tones occurred in both streams to trigger attention in a bottom-up manner. Both cued shifts and louder tones were associated with enhanced activity in the superior temporal gyrus and sulcus, temporo-parietal junction, superior parietal lobule, inferior and middle frontal gyri, frontal eye field, supplementary motor area, and anterior cingulate gyrus. Thus, the present findings suggest that in the auditory modality, unlike in vision, top-down controlled and bottom-up triggered attention activate largely the same cortical networks. Comparison of the present results with our previous results from a similar experiment on spatial auditory attention suggests that fronto-parietal networks of attention to location or pitch overlap substantially. However, the auditory areas in the anterior superior temporal cortex might have a more important role in attention to the pitch than location of sounds. This article is part of a Special Issue entitled SI: Prediction and Attention . [ABSTRACT FROM AUTHOR]

Prediction and attention are fundamental brain functions in the service of perception and action. Theories on prediction relate to neural (mental) models inferring about (present or future) sensory or action-related information, whereas theories of attention are about the control of information flow underlying perception and action. Both concepts are related and not always clearly distinguishable. The special issue includes current research on prediction and attention in various subfields of perception and action. It especially considers interactions between predictive and attentive processes, which constitute a newly emerging and highly interesting field of research. As outlined in this editorial, the contributions in this special issue allow specifying as well as bridging concepts on prediction and attention. The joint consideration of prediction and attention also reveals common functional principles of perception and action. [ABSTRACT FROM AUTHOR]

The visual mismatch negativity (vMMN) component is regarded as a prediction error signal elicited by events violating the sequential regularities of environmental stimulation. The aim of the study was to investigate the effect of familiarity on the vMMN. Stimuli were patterns comprised of familiar (N) or unfamiliar (И) letters. In a passive oddball paradigm, letters (N and И) were presented as either standard or deviant in separate conditions. VMMNs emerged in both conditions; peak latency of vMMN was shorter to the И deviant compared to the vMMN elicited by the N deviant. To test the orientation-specific effect of the oblique lines on the vMMN, we introduced a control experiment. In the control experiment, the patterns were constructed solely from oblique lines, identical to the oblique lines of the N and И stimuli. Contrary to the first experiment, there was no significant difference between the vMNNs elicited by the two orientations. Therefore, the differences in vMMNs to И and N deviants are not attributable to the physical difference between the И and N stimuli. Consequently, the vMMN is sensitive to the familiarity of the stimuli. This article is part of a Special Issue entitled SI: Prediction and Attention . [ABSTRACT FROM AUTHOR]

The dynamic attending theory as originally proposed by Jones, 1976. Psychol. Rev. 83(5), 323–355 posits that tone sequences presented at a regular rhythm entrain attentional oscillations and thereby facilitate the processing of sounds presented in phase with this rhythm. The increased interest in neural correlates of dynamic attending requires robust behavioral indicators of the phenomenon. Here we aimed to replicate and complement the most prominent experimental implementation of dynamic attending (Jones et al., 2002. Psychol. Sci. 13(4), 313–319). The paradigm uses a pitch comparison task in which two tones, the initial and the last of a longer series, have to be compared. In-between the two, distractor tones with variable pitch are presented, at a regular pace. A comparison tone presented in phase with the entrained rhythm is hypothesized to lead to better behavioral performance. Aiming for a conceptual replication, four different variations of the original paradigm were created which were followed by an exact replication attempt. Across all five experiments, only 40 of the 140 tested participants showed the hypothesized pattern of an inverted U-shaped profile in task accuracy, and the group average effects did not replicate the pattern reported by Jones et al., 2002. Psychol. Sci. 13(4), 313–319 in any of the five experiments. However, clear evidence for a relationship between musicality and overall behavioral performance was found. This study casts doubt on the suitability of the pitch comparison task for demonstrating auditory dynamic attending. We discuss alternative tasks that have been shown to support dynamic attending theory, thus lending themselves more readily to studying its neural correlates. This article is part of a Special Issue entitled SI: Prediction and Attention . [ABSTRACT FROM AUTHOR]

The notion of predictive coding is a common feature of many theories of auditory information processing. Experimental demonstrations of predictive auditory processing often rest on omitting predictable input in order to uncover the prediction made by the brain. Findings show that auditory cortical activity elicited by the omission of a predictable tone resembles the activity elicited by the actual tone. Here we attempted to extend this approach towards using noises instead of omissions in order to capture a more prevalent case of degraded sensory input. By applying a subtraction approach to remove ERP effects of the noise itself, auditory cortical activity elicited “behind” the noise was uncovered. We hypothesized that ERPs elicited behind noise stimuli covering predictable tones should be more similar to ERPs elicited by the actual tones than when the same comparison is made for unpredictable tones. ERP results during passive listening partly confirm this hypothesis, but also point towards some methodological caveats in this particular approach towards studying neural correlates of predictive auditory processing due to contributions from predictability-unrelated factors. A follow-up active listening condition indicated that participants were not more likely to perceive the tone sequence as continuous when a predictable tone was covered with noise than when this pertained to an unpredictable tone. Overall, the noise-based paradigm in its present form was not shown to be successful in revealing predictive processing in perceptual judgments or early neural correlates of sound processing. We discuss these findings in the contexts of predictive processing and illusory auditory continuity. This article is part of a Special Issue entitled SI: Prediction and Attention . [ABSTRACT FROM AUTHOR]

Scientific research from the last two decades has provided a vast amount of evidence that brain oscillations reflect physiological activity enabling diverse cognitive processes. The goal of this review is to give a broad empirical and conceptual overview of how ongoing oscillatory activity may support attention processes. Keeping in mind that definitions of cognitive constructs like attention are prone to being blurry and ambiguous, the present review focuses mainly on the neural correlates of ‘top-down’ attention deployment. In particular, we will discuss modulations of (ongoing) oscillatory activity during spatial, temporal, selective, and internal attention. Across these seemingly distinct attentional domains, we will summarize studies showing the involvement of two oscillatory processes observed during attention deployment: power modulations mainly in the alpha band, and phase modulations in lower frequency bands. This article is part of a Special Issue entitled SI: Prediction and Attention . [ABSTRACT FROM AUTHOR]

Rare changes in a stream of otherwise repeated task-irrelevant sounds break through selective attention and disrupt performance in an unrelated visual task. This deviance distraction effect emerges because deviant sounds violate the cognitive system’s predictions. In this study we sought to examine whether predictability also mediate the so-called semantic effect whereby behavioral performance suffers from the clash between the involuntary semantic evaluation of irrelevant sounds and the voluntary processing of visual targets (e.g., when participants must categorize a right visual arrow following the presentation of the deviant sound “left”). By manipulating the conditional probabilities of the congruent and incongruent deviant sounds in a left/right arrow categorization task, we elicited implicit predictions about the upcoming target and related response. We observed a linear increase of the semantic effect with the proportion of congruent deviant trials (i.e., as deviant sounds increasingly predicted congruent targets). We conclude that deviant sounds affect response times based on a combination of crosstalk interference and two types of prediction violations: stimulus violations (violations of predictions regarding the identity of upcoming irrelevant sounds) and semantic violations (violations of predictions regarding the target afforded by deviant sounds). We report a three-parameter model that captures all key features of the observed RTs. Overall, our results fit with the view that the brain builds forward models of the environment in order to optimize cognitive processing and that control of one’s attention and actions is called upon when predictions are violated. This article is part of a Special Issue entitled SI: Prediction and Attention . [ABSTRACT FROM AUTHOR]

Recent empirical research suggests that understanding a counterfactual event (e.g. ‘If Josie had revised, she would have passed her exams’) activates mental representations of both the factual and counterfactual versions of events. However, it remains unclear when readers switch between these models during comprehension, and whether representing multiple ‘worlds’ is cognitively effortful. This paper reports two ERP studies where participants read contexts that set up a factual or counterfactual scenario, followed by a second sentence describing a consequence of this event. Critically, this sentence included a noun that was either consistent or inconsistent with the preceding context, and either included a modal verb to indicate reference to the counterfactual-world or not (thus referring to the factual-world). Experiment 2 used adapted versions of the materials used in Experiment 1 to examine the degree to which representing multiple versions of a counterfactual situation makes heavy demands on cognitive resources by measuring individuals’ working memory capacity. Results showed that when reference to the counterfactual-world was maintained by the ongoing discourse, readers correctly interpreted events according to the counterfactual-world (i.e. showed larger N400 for inconsistent than consistent words). In contrast, when cues referred back to the factual-world, readers showed no difference between consistent and inconsistent critical words, suggesting that they simultaneously compared information against both possible worlds. These results support previous dual-representation accounts for counterfactuals, and provide new evidence that linguistic cues can guide the reader in selecting which world model to evaluate incoming information against. Crucially, we reveal evidence that maintaining and updating a hypothetical model over time relies upon the availability of cognitive resources. [ABSTRACT FROM AUTHOR]

Recent research suggested a link between the prediction mechanism and depressive symptoms. While healthy people tend to maintain unrealistic optimism in the face of reality challenging their beliefs, depressed people show systematic pessimism. However, it remains unclear at which stage these individual differences in optimism/pessimism arise in the brain. In the current study we designed a simple gambling task with two difficulty levels, the easy game and the hard game. Participants were required to press one of four keys to gain a bonus signalled by a sinusoidal tone. For three of the four keys, the probability of getting a large bonus was 80% in the easy game and 8% in the hard game. In both games, the fourth key, randomly determined in each trial, yielded a large bonus with a probability of 100%. This arrangement allowed us to observe less/more depressed participants׳ optimistic/pessimistic expectations about hitting the key that guarantees a large bonus. The opposite expectation patterns of less/more depressed participants were reflected on the N1 amplitude. Meanwhile, all participants were well aware of the true probability of obtaining certain bonus in each game as reflected on the P3 amplitude. The results suggest that the subjective system (tracking subjective beliefs) and the objective system (tracking objective evidence) are dissociable in the human brain, with the former feeding information into sensory areas and the latter representing prediction errors on a higher level. Moreover, individual differences arise from variability in the former rather than the latter. [ABSTRACT FROM AUTHOR]

This fMRI study investigated the functional mechanisms related to mental simulation of abstract- and action-related words and measured the effect of the type of stimulus (Abstract vs. action verbs) and the type of task (imagery vs. control task) to explore how conceptual representations interact with processing demands. A significant task by stimuli interaction showed that action-related words activated the left sensorimotor cortex during explicit imagery (as compared to the control task), whereas abstract-related verbs did not automatically activate this area. Rather, as we made sure that Abstract verbs were not associated with motor states (as tested in a rating study of our stimulus list), imagery elicited by abstract verb processing (as compared to Action verbs, and controlled for letter detection) differentially activated a right hemisphere neural network including the right supramarginal (SMG) gyrus and the precuneus which might be related to mental imagery of emotion-related scenes and not to the semantics of the stimuli per se. Our results confirmed the view that the activation of the sensorimotor cortex during language processing of abstract- and action-related words is strategy-dependent. [ABSTRACT FROM AUTHOR]

Previous M/EEG studies on visuospatial attention have shown that attending to one hemifield, while ignoring the other, leads to a decrease in occipito-parietal alpha power contralateral to the target and a concurrent ipsilateral alpha increase. Here, we tested whether this alpha modulation facilitates the processing of attended faces in the presence of distracters. Face processing was tested in a match-to-sample task, in which participants matched a target face in a cued hemifield to a previously seen sample face. The target faces in the cued hemifield were presented together with a distracter face (intact or scrambled faces) in the other hemifield. The behavioral data indicated a larger impairment of matching performance when the distracter was another face, rather than a scrambled face. We hypothesized that enhanced alpha power contralateral to the distracter would enhance target matching by decreasing the interference from similar distracters. We found this effect, but only in the left hemisphere. Moreover, we found that with targets contralateral from the left hemisphere, a down-regulation of relative alpha power in the left hemisphere also correlated with increased target matching performance. Hence, the left hemisphere could protect the target from distracter interference either by decreasing alpha power in response to a contralateral target, or increasing alpha power to a contralateral distracter. Remarkably, alpha power in the right hemisphere was not predictive for matching performance. These findings support the hypothesis that alpha modulations contribute to the suppression of task-irrelevant information, but suggest a dominant role herein of the left hemisphere during face matching in the presence of distracters. [ABSTRACT FROM AUTHOR]

Layer 1 of the dorsal cortex of the inferior colliculus (DCIC) is distinguished from other layers by its cytoarchitecture and fiber connections. However, the information of the sound types represented in layer 1 of the DCIC remains unclear because placing electrodes on such thin structures is challenging. In this study, we utilized in vivo calcium imaging to assess auditory-evoked activities in multiple cells in layer 1 of DCIC and to characterize sound stimuli producing strong activity. Most cells examined showed strong responses to broad-band noise and low-frequency tone bursts of high sound intensity. In some cases, we successfully obtained frequency response areas, which are receptive fields to tone frequencies and intensities, and ~30% of these showed V-shape tunings. This is the first systematic study to record auditory responses of cells in layer 1 of DCIC. These results indicate that cells in this area are selective to tones with low frequency, implying the importance of such auditory information in the neural circuitry of layer 1 of DCIC. [ABSTRACT FROM AUTHOR]

Chronic pain is often intractable to analgesics, and in animals it involves a conditioned nociceptive response (CR) – learned pain. The neural pathways of nociception and olfactory function in the brain overlap. The influence of olfactory stimuli on acute pain has been studied in some depth in animal and human models, but the influence of olfactory stimuli on learned pain has not been understood. We examined the effects of analgesic drugs and olfactory stimulants (preferred or repellent odor) on acute pain, the unconditioned nociceptive response (UCR) and the CR in mice. The CR was provoked by repeated injection of formalin into the hind-paw in animals in the same context, which elicited the typical pain behaviors of paw licking (including biting). The analgesic drugs acetaminophen, fentanyl, gabapentin and fluvoxamine diminished the UCR but did not affect the CR. In contrast, the preferred odor reduced both the UCR and the CR. Our findings suggest that, like chronic pain, the CR is resistant to analgesic drugs and that preferred odor suppress the neural pathways that mediate the CR of pain perception. [ABSTRACT FROM AUTHOR]

We explored implicit motor simulation processes in Parkinson's Disease (PD) patients with ON-OFF subthalamic deep brain stimulation (DBS) of the sub-thalamic nucleus (STN). Participants made lexical decisions about hand action-related verbs, abstract verbs, and pseudowords presented either within a positive (e.g., "Do …") or a negative (e.g., "Don't …") sentence context. Healthy controls showed significantly slower responses for hand-action verbs (vs. abstract verbs) in the negative (vs. positive) context, which suggests that negative contexts may suppress motor simulation or preparation processes. The STN-DBS improves cortical motor functions, thus patients are expected to perform at the same level as unimpaired subjects in the ON condition. By contrast, the 50% reduced DBS is expected to result in a reduced activation for motor information, which in turn might cause a reduced, if not absent, context modulation. PD patients exhibited the same pattern as controls when their DBS was at 100% ON; however, reducing the DBS to 50% had a deleterious outcome on the positive faster than negative context effect, suggesting that the altered inhibition mechanism in PD could be responsible for the missed effect. In addition, our results confirm the view that implicit motor simulation mechanisms behind action-related verb processing are flexible and context-dependent. [ABSTRACT FROM AUTHOR]

The midbrain dopaminergic perikarya are differentially affected in Parkinson's disease (PD). This study compared the effects of a partial unilateral intrastriatal 6-hydroxydopamine (6-OHDA) lesion model of PD on the number, morphology, and nucleolar volume of dopaminergic cells in the substantia nigra pars compacta (SNpc), ventral tegmental area (VTA), and retrorubral field (RRF). Adult, male rats (n=10) underwent unilateral intrastriatal infusion of 6-OHDA (12.5 µg). Lesions were verified by amphetamine-stimulated rotation 7 days post-infusion. Rats were euthanized 14 days after treatment with 6-OHDA and brains were stained with a tyrosine hydroxylase-silver nucleolar (TH-AgNOR) stain. Dopaminergic cell number and morphology in the lesioned and intact hemispheres were quantified using stereological methods. The magnitude of decrease in planimetric volume, neuronal number, cell density, and neuronal volume resulting from 6-OHDA lesion differed between regions, with the SNpc exhibiting the greatest loss of neurons (46%), but the smallest decrease in neuronal volume (13%). The lesion also resulted in a decrease in nucleolar volume that was similar in all three regions (22-26%). These findings indicate that intrastriatal 6-OHDA lesion differentially affects dopaminergic neurons in the SNpc, VTA, and RRF; however, the resulting changes in nucleolar morphology suggest a similar cellular response to the toxin in all three cell populations. [ABSTRACT FROM AUTHOR]

After traumatic brain injury (TBI), proteolysis of Alpha II Spectrin by Calpain 1 produces 145 Spectrin breakdown products (SBDPs) while proteolysis by Caspase 3 produces 120 SBDPs. 145 and 120 SBDP immunoblotting reflects the relative importance of caspase-dependent apoptosis or calpain-dependent excitotoxic/necrotoxic cell death in brain regions over time. In the adult rat, controlled cortical impact (CCI) increased 120 SBDPs in the first hours, lasting a few days, and increased 145 SBDPs within the first few days lasting up to 14 days after injury. Little is known about SBDPs in the immature brain after TBI. Since development affects susceptibility to apoptosis after TBI, we hypothesized that CCI would increase 145 and 120 SBDPs in the immature rat brain relative to SHAM during the first 3 and 5 days, respectively. SBDPs were measured in hippocampi and cortices at post injury days (PID) 1, 2, 3, 5, 7 and 14 after CCI or SHAM surgery in the 17 day old Sprague Dawley rat. 145 SBDPs increased in both brain tissues ipsilateral to injury during the first 3 days, while changes in contralateral tissues were limited to PID2 cortex. 145 SBDPs elevations were more marked and enduring in hippocampus than in cortex. Against expectations, 120 SBDPs only increased in PID1 hippocampus and PID2 cortex. 145 SBDPs elevations occurred early after CCI, similar to previous studies in the adult rat, but resolved more quickly. The minimal changes in 120 SBDPs suggest that calpain-dependent, but not caspase-dependent, cell death predominates in the 17 day old rat after CCI. [ABSTRACT FROM AUTHOR]

Abstract: Alterations of auditory feedback during piano performance can be profoundly disruptive. Furthermore, different alterations can yield different types of disruptive effects. Whereas alterations of feedback synchrony disrupt performed timing, alterations of feedback pitch contents can disrupt accuracy. The current research tested whether these behavioral dissociations correlate with differences in brain activity. Twenty pianists performed simple piano keyboard melodies while being scanned in a 3-T magnetic resonance imaging (MRI) scanner. In different conditions they experienced normal auditory feedback, altered auditory feedback (asynchronous delays or altered pitches), or control conditions that excluded movement or sound. Behavioral results replicated past findings. Neuroimaging data suggested that asynchronous delays led to increased activity in Broca׳s area and its right homologue, whereas disruptive alterations of pitch elevated activations in the cerebellum, area Spt, inferior parietal lobule, and the anterior cingulate cortex. Both disruptive conditions increased activations in the supplementary motor area. These results provide the first evidence of neural responses associated with perception/action mismatch during keyboard production. [Copyright &y& Elsevier]

Abstract: This article reviews the contributions of Ivan Michailovich Sechenov [1829–1905] to the neurophysiological concept of central inhibition. He first studied this concept in the frog and on himself. Later his trainees extended the study of central inhibition to other mammalian species. Outside his own country, Sechenov is better known for his prescient contributions to physiological psychology. In Russia, however, he is also revered as “the father of Russian physiology,” because of his contributions to neurophysiology and other aspects of physiology including blood gases and respiration, the physiology and biomechanics of movement, and general physiology concepts that appeared in his textbooks and later works he helped translate from largely German sources. After graduation from Moscow University Medical School in 1856 he spent 3½ years in Germany and Austria where he attended lectures and conducted research under the direction of several prominent physiologists and biochemists. In his subsequent academic career he held positions at universities in St. Petersburg (1860–1870; 1876–1888), Odessa (1871–1876) and Moscow (1890–1905). From 1860 onwards he was acclaimed as a physiologist in academic circles. He was also well known in Russian society for his public lectures on physiology and his views on physiological psychology. The latter resulted in him being branded “politically unreliable” by the tsarist bureaucracy from 1863 onwards. Sechenov's first (1862) study on central inhibition remains his most memorable. He delayed the withdrawal of a frog's foot from a weak acid solution by chemical or electrical stimulation of selected parts of the central nervous system. He also noted similar effects on his own hand during co-activation of other sensory inputs by tickling or teeth gnashing. [Copyright &y& Elsevier]

Abstract: The use of psychotropic drugs in clinical and translational brain research continues to grow, and the need for novel experimental models and screens is becoming widely recognized. Mounting evidence supports the utility of zebrafish (Danio rerio) for studying various pharmacological manipulations, as an alternative model complementing the existing rodent paradigms in this field. Here, we explore the effects of acute 20-min exposure to two commonly abused psychotropic compounds, Δ9-tetrahydrocannabinol (THC) and heroin, on adult zebrafish behavior in the novel tank test. Overall, THC administration (30 and 50mg/L) produces an anxiogenic-like reduction of top swimming, paralleled with a slower, continuous bottom swimming. In contrast, heroin exposure (15 and 25mg/L) evoked a hyperlocomotor response (with rapid bouts of bottom swimming and frequent ‘bouncing’ motions) without altering anxiety-sensitive top/bottom endpoints. The behavioral effects of these two compounds in zebrafish seem to parallel the respective rodent and human findings. Collectively, this emphasizes the growing significance of novel emerging aquatic models in translational drug abuse research and small molecule screening. [Copyright &y& Elsevier]

Abstract: The brain plays a major role in regulating physical activity behavior and exercise performance. Regular physical activity may also play a key role in the prevention and treatment of various neurological conditions, such as Parkinson's disease, Alzheimer's disease, depression, and cognitive function. This implies that not only does the brain (or the nervous system) regulate aspects of physical activity, but also that physical activity may potentially influence brain-related function and outcomes. This review details this bi-directional relationship and addresses its implications for improving physical activity, exercise performance, and brain-related function and outcomes. [Copyright &y& Elsevier]