Sensory Cortical Areas Research Articles

The Use of Botulinum Toxin for Treatment of the Dystonias.

Dystonias are characterized by involuntary muscle contractions, twisting movements, abnormal postures, and often tremor in various body regions. However, in the last decade several studies have demonstrated that dystonias are also characterized by sensory abnormalities. While botulinum toxin is the gold standard therapy for focal dystonia, exactly how it improves this disorder is not entirely understood. Neurophysiological studies in animals and humans have clearly demonstrated that botulinum toxin improves dystonic motor manifestations by inducing chemodenervation, therefore weakening the injected muscles. In addition, neurophysiological and neuroimaging evidence also suggests that botulinum toxin modulates the activity of various neural structures in the CNS distant from the injected site, particularly cortical motor and sensory areas. Concordantly, recent studies have shown that in patients with focal dystonias botulinum toxin ameliorates sensory disturbances, including reduced spatial discrimination acuity and pain. Overall, these observations suggest that in these patients botulinum toxin-induced effects encompass complex mechanisms beyond chemodenervation of the injected muscles.

Aberrant Somatosensory Processing and Connectivity in Mice Lacking Engrailed-2.

Overreactivity and defensive behaviors in response to tactile stimuli are common symptoms in autism spectrum disorder (ASD) patients. Similarly, somatosensory hypersensitivity has also been described in mice lacking ASD-associated genes such as Fmr1 (fragile X mental retardation protein 1). Fmr1 knock-out mice also show reduced functional connectivity between sensory cortical areas, which may represent an endogenous biomarker for their hypersensitivity. Here, we measured whole-brain functional connectivity in Engrailed-2 knock-out (En2-/-) adult mice, which show a lower expression of Fmr1 and anatomical defects common to Fmr1 knock-outs. MRI-based resting-state functional connectivity in adult En2-/- mice revealed significantly reduced synchronization in somatosensory-auditory/associative cortices and dorsal thalamus, suggesting the presence of aberrant somatosensory processing in these mutants. Accordingly, when tested in the whisker nuisance test, En2-/- but not WT mice of both sexes showed fear behavior in response to repeated whisker stimulation. En2-/- mice undergoing this test exhibited decreased c-Fos-positive neurons (a marker of neuronal activity) in layer IV of the primary somatosensory cortex and increased immunoreactive cells in the basolateral amygdala compared with WT littermates. Conversely, when tested in a sensory maze, En2-/- and WT mice spent a comparable time in whisker-guided exploration, indicating that whisker-mediated behaviors are otherwise preserved in En2 mutants. Therefore, fearful responses to somatosensory stimuli in En2-/- mice are accompanied by reduced basal connectivity of sensory regions, reduced activation of somatosensory cortex, and increased activation of the basolateral amygdala, suggesting that impaired somatosensory processing is a common feature in mice lacking ASD-related genes.SIGNIFICANCE STATEMENT Overreactivity to tactile stimuli is a common symptom in autism spectrum disorder (ASD) patients. Recent studies performed in mice bearing ASD-related mutations confirmed these findings. Here, we evaluated the behavioral response to whisker stimulation in mice lacking the ASD-related gene Engrailed-2 (En2-/- mice). Compared with WT controls, En2-/- mice showed reduced functional connectivity in the somatosensory cortex, which was paralleled by fear behavior, reduced activation of somatosensory cortex, and increased activation of the basolateral amygdala in response to repeated whisker stimulation. These results suggest that impaired somatosensory signal processing is a common feature in mice harboring ASD-related mutations.

The Caudal Part of Putamen Represents the Historical Object Value Information.

The basal ganglia, especially the circuits originating from the putamen, are essential for controlling normal body movements. Notably, the putamen receives inputs not only from motor cortical areas but also from multiple sensory cortices. However, how these sensory signals are processed in the putamen remains unclear. We recorded the activity of tentative medium spiny neurons in the caudal part of the putamen when the monkey viewed many fractal objects. We found many neurons that responded to these objects, mostly in the ventral region. We called this region "putamen tail" (PUTt), as it is dorsally adjacent to "caudate tail" (CDt). Although PUTt and CDt are mostly separated by a thin layer of white matter, their neurons shared several features. Almost all of them had receptive fields in the contralateral hemifield. Moreover, their responses were object selective (i.e., variable across objects). The object selectivity was higher in the ventral region (i.e., CDt > PUTt). Some neurons above PUTt, which we called the caudal-dorsal putamen (cdPUT), also responded to objects, but less selectively than PUTt. Next, we examined whether these visual neurons changed their responses based on the reward outcome. We found that many neurons encoded the values of many objects based on long-term memory, but not based on short-term memory. Such stable value responses were stronger in PUTt and CDt than in cdPUT. These results suggest that PUTt, together with CDt, controls saccade/attention among objects with different historical values, and may control other motor actions as well.SIGNIFICANCE STATEMENT Although the putamen receives inputs not only from motor cortical areas but also from sensory cortical areas, how these sensory signals are processed remains unclear. Here we found that neurons in the caudal-ventral part of the putamen (putamen tail) process visual information including spatial and object features. These neurons discriminate many objects, first by their visual features and later by their reward values as well. Importantly, the value discrimination was based on long-term memory, but not on short-term memory. These results suggest that the putamen tail controls saccade/attention among objects with different historical values and might control other motor actions as well.

A Sensorimotor Pathway via Higher-Order Thalamus.

We now know that sensory processing in cortex occurs not only via direct communication between primary to secondary areas, but also via their parallel cortico-thalamo-cortical (i.e., trans-thalamic) pathways. Both corticocortical and trans-thalamic pathways mainly signal through glutamatergic class 1 (driver) synapses, which have robust and efficient synaptic dynamics suited for the transfer of information such as receptive field properties, suggesting the importance of class 1 synapses in feedforward, hierarchical processing. However, such a parallel arrangement has only been identified in sensory cortical areas: visual, somatosensory, and auditory. To test the generality of trans-thalamic pathways, we sought to establish its presence beyond purely sensory cortices to determine whether there is a trans-thalamic pathway parallel to the established primary somatosensory (S1) to primary motor (M1) pathway. We used trans-synaptic viral tracing, optogenetics in slice preparations, and bouton size analysis in the mouse (both sexes) to document that a circuit exists from layer 5 of S1 through the posterior medial nucleus of the thalamus to M1 with glutamatergic class 1 properties. This represents a hitherto unknown, robust sensorimotor linkage and suggests that the arrangement of parallel direct and trans-thalamic corticocortical circuits may be present as a general feature of cortical functioning.SIGNIFICANCE STATEMENT During sensory processing, feedforward pathways carry information such as receptive field properties via glutamatergic class 1 synapses, which have robust and efficient synaptic dynamics. As expected, class 1 synapses subserve the feedforward projection from primary to secondary sensory cortex, but also a route through specific higher-order thalamic nuclei, creating a parallel feedforward trans-thalamic pathway. We now extend the concept of cortical areas being connected via parallel, direct, and trans-thalamic circuits from purely sensory cortices to a sensorimotor cortical circuit (i.e., primary sensory cortex to primary motor cortex). This suggests a generalized arrangement for corticocortical communication.

Reduced auditory cortical adaptation in autism spectrum disorder.

Adaptation is a fundamental property of cortical neurons and has been suggested to be altered in individuals with autism spectrum disorder (ASD). We used fMRI to measure adaptation induced by repeated audio-visual stimulation in early sensory cortical areas in individuals with ASD and neurotypical (NT) controls. The initial transient responses were equivalent between groups in both visual and auditory cortices and when stimulation occurred with fixed-interval and randomized-interval timing. However, in auditory but not visual cortex, the post-transient sustained response was greater in individuals with ASD than NT controls in the fixed-interval timing condition, reflecting reduced adaptation. Further, individual differences in the sustained response in auditory cortex correlated with ASD symptom severity. These findings are consistent with hypotheses that ASD is associated with increased neural responsiveness but that responsiveness differences only manifest after repeated stimulation, are specific to the temporal pattern of stimulation, and are confined to specific cortical regions.

The Interplay Between Cortical State and Perceptual Learning: A Focused Review.

Measurements of population activity in alert animals have demonstrated that the intrinsic response state of the cortex has profound effects on the neuronal representation of sensory inputs, raising the possibility that cortical state could influence the behavioral performance in perceptual learning (PL). PL is a process by which sensory experience leads to gradual and semi-permanent improvements in perceptual judgment, and it is generally agreed that these improvements are modulated by sensory cortical areas. Although the precise neural mechanisms underlying the improved perceptual judgment remain unclear, cortical state has been shown to impact the behavioral outcome of PL. We discuss several ways in which cortical state might influence PL based on the recent evidence for state-dependent modulation of sensory encoding. Conversely, training in a certain perceptual task feeds back to modulate cortical state, suggesting a bi-directional relationship between cortical state and behavioral outcomes of PL. We highlight the recent studies that shed light on the mechanism of the interplay between cortical state and PL.

Layer 2/3 Pyramidal Neurons Control the Gain of Cortical Output

Initial anatomical and physiological studies suggested that sensory information relayed from the periphery by the thalamus is serially processed in primary sensory cortical areas. It is thought to propagate from layer 4 (L4) up to L2/3 and down to L5, which constitutes the main output of the cortex. However, more recent experiments point toward the existence of a direct processing of thalamic input by L5 neurons. Therefore, the role of L2/3 neurons in the sensory processing operated by L5 neurons is now highly debated. Using cell type-specific and reversible optogenetic manipulations in the somatosensory cortex of both anesthetized and awake mice, we demonstrate that L2/3 pyramidal neurons play a major role in amplifying sensory-evoked responses in L5 neurons. The amplification effect scales with the velocity of the sensory stimulus, indicating that L2/3 pyramidal neurons implement gain control in deep-layer neurons.

Basal Forebrain Nuclei Display Distinct Projecting Pathways and Functional Circuits to Sensory Primary and Prefrontal Cortices in the Rat.

Recent evidence supports that specific projections between different basal forebrain (BF) nuclei and their cortical targets are necessary to modulate cognitive functions in the cortex. We tested the hypothesis of the existence of specific neuronal populations in the BF linking with specific sensory, motor, and prefrontal cortices in rats. Neuronal tracing techniques were performed using retrograde tracers injected in the primary somatosensory (S1), auditory (A1), and visual (V1) cortical areas, in the medial prefrontal cortex (mPFC) as well as in BF nuclei. Results indicate that the vertical and horizontal diagonal band of Broca (VDB/HDB) nuclei target specific sensory cortical areas and maintains reciprocal projections with the prelimbic/infralimbic (PL/IL) area of the mPFC. The basal magnocellular nucleus (B nucleus) has more widespread targets in the sensory-motor cortex and does not project to the PL/IL cortex. Optogenetic stimulation was used to establish if BF neurons modulate whisker responses recorded in S1 and PL/IL cortices. We drove the expression of high levels of channelrhodopsin-2, tagged with a fluorescent protein (ChR2-eYFP) by injection of a virus in HDB or B nuclei. Blue-light pulses were delivered to the BF through a thin optic fiber to stimulate these neurons. Blue-light stimulation directed toward the HDB facilitated whisker responses in S1 cortex through activation of muscarinic receptors. The same optogenetic stimulation of HDB induced an inhibition of whisker responses in mPFC by activation of nicotinic receptors. Blue-light stimulation directed toward the B nucleus had lower effects than HDB stimulation. Our findings pointed the presence of specific neuronal networks between the BF and the cortex that may play different roles in the control of cortical activity.

Differential inhibition of pyramidal cells and inhibitory interneurons along the rostrocaudal axis of anterior piriform cortex

The spatial representation of stimuli in sensory neocortices provides a scaffold for elucidating circuit mechanisms underlying sensory processing. However, the anterior piriform cortex (APC) lacks topology for odor identity as well as afferent and intracortical excitation. Consequently, olfactory processing is considered homogenous along the APC rostral-caudal (RC) axis. We recorded excitatory and inhibitory neurons in APC while optogenetically activating GABAergic interneurons along the RC axis. In contrast to excitation, we find opposing, spatially asymmetric inhibition onto pyramidal cells (PCs) and interneurons. PCs are strongly inhibited by caudal stimulation sites, whereas interneurons are strongly inhibited by rostral sites. At least two mechanisms underlie spatial asymmetries. Enhanced caudal inhibition of PCs is due to increased synaptic strength, whereas rostrally biased inhibition of interneurons is mediated by increased somatostatin-interneuron density. Altogether, we show differences in rostral and caudal inhibitory circuits in APC that may underlie spatial variation in odor processing along the RC axis.

Out of focus – Brain attention control deficits in adult ADHD

Modern environments are full of information, and place high demands on the attention control mechanisms that allow the selection of information from one (focused attention) or multiple (divided attention) sources, react to changes in a given situation (stimulus-driven attention), and allocate effort according to demands (task-positive and task-negative activity). We aimed to reveal how attention deficit hyperactivity disorder (ADHD) affects the brain functions associated with these attention control processes in constantly demanding tasks. Sixteen adults with ADHD and 17 controls performed adaptive visual and auditory discrimination tasks during functional magnetic resonance imaging (fMRI). Overlapping brain activity in frontoparietal saliency and default-mode networks, as well as in the somato-motor, cerebellar, and striatal areas were observed in all participants. In the ADHD participants, we observed exclusive activity enhancement in the brain areas typically considered to be primarily involved in other attention control functions: During auditory-focused attention, we observed higher activation in the sensory cortical areas of irrelevant modality and the default-mode network (DMN). DMN activity also increased during divided attention in the ADHD group, in turn decreasing during a simple button-press task. Adding irrelevant stimulation resulted in enhanced activity in the salience network. Finally, the irrelevant distractors that capture attention in a stimulus-driven manner activated dorsal attention networks and the cerebellum. Our findings suggest that attention control deficits involve the activation of irrelevant sensory modality, problems in regulating the level of attention on demand, and may encumber top-down processing in cases of irrelevant information.

Multiple sclerosis–related fatigue: Altered resting-state functional connectivity of the ventral striatum and dorsolateral prefrontal cortex

Objective: Since recent studies suggested a role of the striatum and prefrontal cortex for multiple sclerosis (MS)-related fatigue, we investigated resting-state functional connectivity alterations of striatal subdivisions and the dorsolateral prefrontal cortex (dlPFC). Methods: Resting-state functional magnetic resonance imaging was acquired in 77 relapsing–remitting MS patients (38 fatigued (F-MS), 39 non-fatigued (NF-MS)) and 41 matched healthy controls (HC). Fatigue severity was assessed using the fatigue severity scale. Seed-based connectivity analyses were performed using subregions of the striatum and the dlPFC as regions of interest applying non-parametric permutation testing. Results: Compared to HC and NF-MS patients, F-MS patients showed reduced caudate nucleus and ventral striatum functional connectivity with the sensorimotor cortex (SMC) and frontal, parietal, and temporal cortex regions. Fatigue severity correlated negatively with functional connectivity of the caudate nucleus and ventral striatum with the SMC and positively with functional connectivity of the dlPFC with the rostral inferior parietal gyrus and SMC. Conclusion: MS-related fatigue is associated with reduced functional connectivity between the striatum and sensorimotor as well as attention and reward networks, in which the ventral striatum might be a key integration hub. Together with increased connectivity between the dlPFC and sensory cortical areas, these connectivity alterations shed light on the mechanisms of MS-related fatigue.

Indices of repetitive behaviour are correlated with patterns of intrinsic functional connectivity in youth with autism spectrum disorder

The purpose of the current study was to examine how repetitive behaviour in Autism Spectrum Disorder (ASD) is related to intrinsic functional connectivity patterns in a number of large-scale, neural networks. Resting-state fMRI scans from thirty subjects with ASD and thirty-two age-matched, typically developing control subjects were analysed. Seed-to-voxel and ROI-to-ROI functional connectivity analyses were used to examine resting-state connectivity in a number of cortical and subcortical neural networks. Bivariate correlation analysis was performed to examine the relationship between repetitive behaviour scores from the Repetitive Behaviour Scale – Revised and intrinsic functional connectivity in ASD subjects. Compared to control subjects, ASD subjects displayed marked over-connectivity of the thalamus with several cortical sensory processing areas, as well as over-connectivity of the basal ganglia with somatosensory and motor cortices. Within the ASD group, significant correlations were found between functional connectivity patterns and total RBS-R scores as well as one principal component analysis-derived score from the RBS-R. These results suggest that thalamocortical resting-state connectivity is altered in individuals with ASD, and that resting-state functional connectivity is associated with ASD symptomatology.

Connectivity-based characterisation of subcortical grey matter pathology in frontotemporal dementia and ALS: a multimodal neuroimaging study.

Frontotemporal dementia (FTD) phenotypes have distinctive and well-established cortical signatures, but their subcortical grey matter profiles are poorly characterised. The comprehensive characterisation of striatal and thalamic pathology along the ALS-FTD spectrum is particularly timely, as dysfunction of frontostriatal and cortico-thalamic networks contribute to phenotype-defining cognitive, behavioral, and motor deficits. Ten patients with behavioral-variant FTD, 11 patients with non-fluent-variant primary progressive aphasia, 5 patients with semantic-variant primary progressive aphasia, 14 ALS-FTD patients with C9orf72 hexanucleotide expansions, 12 ALS-FTD patients without hexanucleotide repeats, 36 ALS patients without cognitive impairment and 50 healthy controls were included in a prospective neuroimaging study. Striatal, thalamic, hippocampal and amygdala pathology was evaluated using volume measurements, density analyses and connectivity-based segmentation. Significant volume reductions were identified in the thalamus and putamen of non-fluent-variant PPA patients. Marked nucleus accumbens and hippocampal atrophy was observed in the behavioral-variant FTD cohort. Semantic-variant PPA patients only exhibited volumetric changes in the left hippocampus. C9-positive ALS-FTD patients showed preferential density reductions in thalamic sub-regions connected to motor and sensory cortical areas. C9-negative ALS-FTD patients exhibited striatal pathology in sub-regions projecting to rostral-motor and executive cortical areas. The bulk of striatal and thalamic pathology in non-fluent-variant PPA patients was identified in foci projecting to motor areas. Subcortical density alterations in svPPA patients were limited to basal ganglia regions with parietal projections. Striatal and thalamic changes in FTD exhibit selective, network-defined vulnerability patterns mirroring cortical pathology. Multi-modal cortico-basal imaging analyses confirm that the subcortical grey matter profiles of FTD phenotypes are just as distinct as their cortical signatures. Our findings support emerging concepts of network-wise degeneration, preferential circuit vulnerability and disease propagation along connectivity patterns.

Association of sleep impairments and gastrointestinal disorders in the context ofthevisceral theory of sleep.

It was noticed long ago that sleep disorders or interruptions to the normal sleep pattern were associated with various gastrointestinal disorders. We review the studies which established the causal link between these disorders and sleep impairment. However, the mechanism of interactions between the quality of sleep and gastrointestinal pathophysiology remained unclear. Recently, the visceral theory of sleep was formulated. This theory proposes that the same brain structures, and particularly the same cortical sensory areas, which in wakefulness are involved in processing of the exteroceptive information, switch during sleep to the processing of information coming from various visceral systems. We review the studies which demonstrated that neurons of the various cortical areas (occipital, parietal, frontal) during sleep began to fire in response to activation coming from the stomach and small intestine. These data demonstrate that, during sleep, the computational power of the central nervous system, including all cortical areas, is engaged in restoration of visceral systems. Thus, the general mechanism of the interaction between quality of sleep and health became clear.

Bilateral Pathways from the Basal Forebrain to Sensory Cortices May Contribute to Synchronous Sensory Processing.

Sensory processing in the cortex should integrate inputs arriving from receptive fields located on both sides of the body. This role could be played by the corpus callosum through precise projections between both hemispheres. However, different studies suggest that cholinergic projections from the basal forebrain (BF) could also contribute to the synchronization and integration of cortical activities. Using tracer injections and optogenetic techniques in transgenic mice, we investigated whether the BF cells project bilaterally to sensory cortical areas, and have provided anatomical evidence to support a modulatory role for the cholinergic projections in sensory integration. Application of the retrograde tracer Fluor-Gold or Fast Blue in both hemispheres of the primary somatosensory (S1), auditory or visual cortical areas showed labeled neurons in the ipsi- and contralateral areas of the diagonal band of Broca and substantia innominata. The nucleus basalis magnocellularis only showed ipsilateral projections to the cortex. Optogenetic stimulation of the horizontal limb of the diagonal band of Broca facilitated whisker responses in the S1 cortex of both hemispheres through activation of muscarinic cholinergic receptors and this effect was diminished by atropine injection. In conclusion, our findings have revealed that specific areas of the BF project bilaterally to sensory cortices and may contribute to the coordination of neuronal activity on both hemispheres.

The neurology timeline: Of demon holes, sacred pathways and great triumphs

The first chapter in neurology was composed in the prescience era. Chiseled with flint stones, grisly in nature, it was a narrative where men trephined human skull to treat such maladies as head injury, epilepsy, and disturbed mind. The ungodly practice survived from the late Stone Age until the renaissance. The first written reference to brain is found in the Edwin Smith surgical papyri. Written around 3000 BCE in Egypt, the papyri describe certain cognitive defects of head injuries. The first sapient exploration into the functions and diseases of brain opened in the sixth to fourth century BCE. It began with the Alexandrian anatomists and Hippocratic doctors, gathered steam in the classical era of science with Galen in the first century, and reached its peak with Vesalius during renaissance. Modern neurology, particularly the localization of brain functions, began with German physician Franz Joseph Gall's work on phrenology in the late 18th century and, over the next hundred years, was followed by the discovery of language, motor, and sensory cortical areas. The idea that the nervous system is made up of discrete nerve cells was born out of the neuroanatomical work of Camillo Golgi and a Spanish doctor, Santiago Ramon y Cajal, at the end of 19th century. Major 20th-century developments include advances in understanding of the frontal lobes, the role of visual cortex in perception, the function of hippocampus in memory, lateralization of cortical function, and the introduction of all revealing cross-sectional and functional imaging. While practitioners of medicine across the world unraveled the secrets of maladies that strike the seat of senses and intellect, other accomplished players struck sweet melodies of life by discovering potent molecules, devices, and surgical techniques which could work a remedy and cure.

Evidence of semantic processing impairments in behavioural variant frontotemporal dementia and Parkinson's disease.

Category-specific impairments caused by brain damage can provide important insights into how semantic concepts are organized in the brain. Recent research has demonstrated that disease to sensory and motor cortices can impair perceptual feature knowledge important to the representation of semantic concepts. This evidence supports the grounded cognition theory of semantics, the view that lexical knowledge is partially grounded in perceptual experience and that sensory and motor regions support semantic representations. Less well understood, however, is how heteromodal semantic hubs work to integrate and process semantic information. Although the majority of semantic research to date has focused on how sensory cortical areas are important for the representation of semantic features, new research explores how semantic memory is affected by neurodegeneration in regions important for semantic processing. Here, we review studies that demonstrate impairments to abstract noun knowledge in behavioural variant frontotemporal degeneration (bvFTD) and to action verb knowledge in Parkinson's disease, and discuss how these deficits relate to disease of the semantic selection network. Findings demonstrate that semantic selection processes are supported by the left inferior frontal gyrus (LIFG) and basal ganglia, and that disease to these regions in bvFTD and Parkinson's disease can lead to categorical impairments for abstract nouns and action verbs, respectively.

Shaping somatosensory responses in awake rats: cortical modulation of thalamic neurons.

Massive corticothalamic afferents originating from layer 6a of primary sensory cortical areas modulate sensory responsiveness of thalamocortical neurons and are pivotal for shifting neuronal firing between burst and tonic modes. The influence of the corticothalamic pathways on the firing mode and sensory gain of thalamic neurons has only been extensively examined in anesthetized animals, but has yet to be established in the awake state. We made lesions of the rat barrel cortex and on the following day recorded responses of single thalamocortical and thalamic reticular neurons to a single vibrissal deflection in the somatosensory system during wakefulness. Our results showed that the cortical lesions shifted the response of thalamic neurons towards bursting, elevated the response probability and the gain of thalamocortical neurons, predominantly of recurring responses. In addition, after the lesions, the spontaneous activities of the vibrissa-responsive thalamic neurons, but not those of vibrissa-unresponsive cells, were typified by waxing-and-waning spindle-like rhythmic spiking with frequent bursting. In awake rats with intact cortex, identified layer 6a corticothalamic neurons responded to a single vibrissal deflection with short latencies that matched those of layer 4 neurons, strongly suggesting the existence of an immediate corticothalamic feedback. The present results show the importance of corticothalamic neurons in shaping thalamic activities during wakefulness.

Higher-Order Areas of the Mouse Visual Cortex.

The brain has evolved to transform sensory information in the environment into neural representations that can be used for perception and action. Higher-order sensory cortical areas, with their increasingly complex receptive fields and integrative properties, are thought to be critical nodes for this function. This is especially true in the primate visual cortex, in which functionally specialized areas are engaged in parallel streams to support diverse computations. Recent anatomical and physiological studies of the mouse visual cortex have revealed a similarly complex network of specialized higher-order areas. This structure provides a useful model for determining the synaptic and circuit mechanisms through which information is transformed across distinct processing stages. In this review, we summarize the current knowledge on the layout, connectivity, and functional properties of the higher visual areas in the mouse. In addition, we speculate on the contribution of these areas to perception and action, and how knowledge of the mouse visual system can inform us about the principles that govern information processing in integrated networks.

The brain behaves as a muscle?

It is known that lactate accumulates in the skeletal muscle during intense anaerobic exercise but is rapidly cleared from the muscles when they resume aerobic metabolism; however, at least some lactate reaches the blood stream. It has been observed that during maximal exercise, blood lactate increases with transport of the blood to the brain. This could be interpreted as a mechanism to protect against possible "central fatigue" in times of maximal activity during the course of which the lactate would preserve the functionality of the primary cortical motor and sensory areas, even at the expense of the efficiency of the other structures. In this way, the role of lactate, both at the muscular level and in the CNS, appears to shift from being responsible for fatigue to protector from fatigue, which represents a real transition similar to that of how the image of Mr. Hyde changes to that of Dr. Jekyll.