Antipsychotic drugs selectively decorrelate long-range interactions in deep cortical layers

GENERAL COMMENTARY article Front. Syst. Neurosci., 24 June 2013 | https://doi.org/10.3389/fnsys.2013.00025

K v channel interacting protein 3 expression and regulation by haloperidol in midbrain dopaminergic neurons

In the primary visual cortex, the development of orientation selectivity is influenced by patterns of neural activity. The introduction of artificially correlated activity into the visual pathway (through synchronous activation of retinal ganglion cell axons in the optic nerve) substantially weakens the orientation selectivity of neurons in superficial and deep cortical layers. This is consistent with activity having an instructive role in shaping cortical neuron receptive field tuning properties.

Migraine episodes are known to induce heightened photosensitivity. Neuroimaging investigations have revealed that the primary visual cortex exhibits abnormal activation patterns both during and between migraine attacks. Growing evidence suggests that altered cortical activity patterns may underlie the pathophysiology of neurological disorders. This study explored whether and how chronic migraine affects cortical activity patterns at single-cell resolution in the primary visual cortex during its progression. Longitudinal in vivo two-photon calcium imaging was performed in the primary visual cortex of a chronic migraine mouse model across multiple time points. Cortical circuit activity patterns and behavioral correlates were assessed through combined chemogenetic manipulation and pharmacological interventions, with a particular focus on primary visual cortex functional modulation. Following chronic migraine induction, spontaneous hyperactivation emerged in cortical activity patterns within the primary visual cortex. Layer II/III neurons appeared as major contributors to this neural dysregulation, with layer V neurons showing less pronounced involvement. Prophylactic topiramate treatment attenuated allodynia and light aversion behaviors while reducing pathological cortical hyperactivity. Chemogenetic inhibition of primary visual cortex layer II/III neurons ameliorated light aversion without attenuating pain sensitization, while modulating aberrant spontaneous cortical activity patterns. These findings provide preliminary evidence for dynamic alterations in spontaneous cortical neural signatures within the primary visual cortex throughout chronic migraine progression. Modulation of these neural adaptations appears to show the potential to alleviate associated light sensitivity, providing insight into potential pathophysiological mechanisms underlying light sensitivity in chronic migraine.

Layer 5 neurons in primary visual cortex make putative reciprocal feedback connections to the superficial layers. To test this hypothesis, we employed scanning laser photostimulation combined with intracellular dye injection to examine local functional excitatory inputs to and axonal projections from individual layer 5 neurons in brain slices from monkey V1. In contrast with previous studies of other V1 neurons, layer 5 neurons received significant input from nearly all of the cortical layers, suggesting individual layer 5 cells integrate information from a broad range of input sources. Nevertheless relative strengths of laminar inputs varied across neurons. Cluster analysis of relative strength of laminar inputs to individual layer 5 neurons revealed four discrete clusters representing recurring input patterns; each cluster included both excitatory and inhibitory neurons. Twenty-five of 40 layer 5 neurons fell into two clusters, both characterized by very strong input from superficial layers. These input patterns are consistent with layer 5 neurons providing feedback to superficial layers. The remaining 15 neurons received stronger input from deep layers. Differences in input from layer 4Calpha versus 4Cbeta also suggest specific associations of the magnocellular and parvocellular visual pathways, with populations receiving stronger input from deep versus superficial cortical layers.

The correlation between cortical neuron maturation and neurofilament phosphorylation: a developmental study of phosphorylated 200 kDa neurofilament protein in cat visual cortex

Segregation of Seizures and Spreading Depolarization Across Cortical Layers Zakharov A, Chernova K, Burkhanova G, Holmes GL, Khazipov R. Epilepsia. 2019;60(12):2386-2397. doi:10.1111/epi.16390.Objective:Cortical spreading depolarization (SD) and seizures are often co-occurring electrophysiological phenomena. However, the cross-layer dynamics of SD during seizures and the effect of SD on epileptic activity across cortical layers remain largely unknown.Methods:We explored the spatial–temporal dynamics of SD and epileptic activity across layers of the rat barrel cortex using direct current silicone probe recordings during flurothyl-induced seizures.Results:Spreading depolarization occurred in half of the flurothyl-evoked seizures. Spreading depolarization always started from the superficial layers and spread downward either through all cortical layers or stopping at the L4/L5 border. In cases without SD, seizures were characterized by synchronized population firing across all cortical layers throughout the entire seizure. However, when SD occurred, epileptic activity was transiently silenced in layers involved with SD but persisted in deeper layers. During partial SD, epileptiform activity persisted in deep layers throughout the entire seizure, with positive signals at the cortical surface reflecting passive sources of population spikes generated in deeper cortical layers. During full SD, the initial phase of SD propagation through the superficial layers was similar to partial SD, with suppression of activity at the superficial layers and segregation of seizures to deep layers. Further propagation of SD to deep layers resulted in a wave of transient suppression of epileptic activity through the entire cortical column. Thus, vertical propagation of SD through the cortical column creates dynamic network states during which epileptiform activity is restricted to layers without SD.Significance:Our results point to the importance of vertical SD spread in the SD-related depression of epileptiform activity across cortical layers.

1. The laminar and temporal distribution of synaptic activity supplied by forward and feedback connections between different areas of rat visual cortex was determined with the use of current source density (CSD) analysis in in vitro slices. In forward connections, synaptic potentials were evoked by electrically stimulating area 17 and recording in the extrastriate area LM (lateromedial), that ranks at the second hierarchical level, one step above primary visual cortex. For activating feedback connections, the location of stimulating and recording electrodes was reversed. 2. The synaptic interactions in reciprocal intracortical circuits are excitatory, and they are mediated through glutamate receptors that are blocked by kynurenic acid. 3. Forward connections from area 17 to area LM provide input to all layers including a strong input to layer 4. In contrast, feedback input to layer 4 is weak and is mainly directed to superficial and deep layers. This laminar distribution closely resembles that seen anatomically. 4. Both forward and feedback connections evoke distinct temporal patterns of synaptic activation in different layers. Although onset and peak latencies are slightly shorter in the forward than in the feedback pathway, the difference is not statistically significant. 5. The spatiotemporal distribution of synaptic activation by forward connections resembles the pattern evoked by geniculocortical inputs. Feedback connections show greater similarities to long-range connections within area 17, although they are not identical. Our results support the notion derived from anatomic and in vivo physiological studies that forward and feedback pathways belong to functionally distinct cortical circuits.

Cochlear implant electrode configuration effects on activation threshold and tonotopic selectivity

Background Sustained attention is essential for effective learning, especially in virtual reality (VR) environments with a high degree of operational freedom. Electroencephalogram (EEG) feedback has proven effective in terms of monitoring and regulating students' attentional states. However, EEG feedback faces implementation challenges in VR environments. Auditory feedback may interfere with voice‐based learning content, while visual feedback can exacerbate the cognitive load in visually rich environments. Objective The aim was to explore methods that would help students maintain attention in the VR learning environment (including voice learning or voice guidance from virtual characters), thereby enhancing learning effectiveness. Method This study proposed and integrated a vibration‐based EEG feedback mechanism into a VR learning system. Grounded in the Cognitive Theory of Multimedia Learning, this approach leverages tactile prompts to avoid sensory conflict. A quasi‐experiment involving 64 university students was subsequently conducted in an English for Geography course. Of the participants, 32 were exposed to a VR environment incorporating the vibration‐based EEG feedback, while the other 32 used the same VR environment without the feedback. The data collection included students' attention levels, performance, and learning behaviours. Systematic records and interviews were used to retrace the students' states when the vibration feedback was triggered. Results and Conclusions Results showed that students in the VR learning system with vibration‐based EEG feedback exhibited higher attention levels, improved vocabulary memory and retention, and more structured behaviour patterns such as review and evaluation, planned learning and refocusing after EEG feedback. This study innovates EEG feedback in VR environments, providing a design reference to promote VR‐based learning. In addition, the results of identified scenarios and subjective reasons for inattention will help in the design of future language VR environments and learning activities.

Objective To analyze the clinical and histology characteristics of a patient with frontal lobe epilepsy diagnosed with mild malformation of cortical development with oligodendroglial hyperplasia, and to recognize the new neuropathological entity. Methods Clinical history, seizure types, neuroimaging, electroencephalography as well as macroscope, histology and immunohistochemistry characteristics were collected from a frontal lobe epilepsy patient and were compared with cases from literature. Results It was a female patient aged 16 years with 12 years history of epilepsy. The seizures manifested as episodes of conscious loss with automatism including grope and voice lasting for seconds. About 10 episodes a day were found and sometimes with secondary generalized tonic-clonic seizures. MRI showed blurring of grey-white matter interface in left orbital frontal cortex. Video-encephalography revealed left frontal lobe origin of seizures. So left prefrontal lobe was removed. Histology showed almost normal cortex neuropil and neurons. Blurring of grey-white interface in some area with patches of proliferation of oligodendrocytes in the corresponding sub-cortical white matter was found. The density of oligodendrocytes was significantly higher in sub-cortical than in deep white matter both shown in HE and Oligo-2 staining. Obvious oligodendrocytes increase and satellite phenomenon in deep cortical layer as well as increased ectopic neurons in sub-cortical white matter were found in the lesion. In proliferation area, there were some nuclei stained with Ki-67, but not as high as tumor. Subsequent follow up for two years proved the operation efficacy and benign prognosis. Conclusions There are special and undiscovered histopathological entities in epilepsy etiology. Although known as grey matter disease, white matter pathology plays an important role in epilepsy pathophysiology which needs further research. Key words: Epilepsy, frontal lobe; Oligodendroglia; Malformation of cortical development

Determining brain regions in which neuroleptic drugs of different types produce similar effects, especially where these effects are not shared with drugs lacking antipsychotic efficacy, provides evidence as to how and where the clinical effects of neuroleptic drugs are mediated. For this study, the pattern of expression of the protein Fos, a marker of cellular activation, was compared after administration of the typical neuroleptic haloperidol, the antipsychotic drug clozapine, and the atypical neuroleptic olanzapine, as well as the sedative drug diphenhydramine and the anxiolytic lorazepam. Animals (Sprague-Dawley rats, three per cohort) received intraperitoneal injections of haloperidol (1 mg/kg), clozapine (20 mg/kg), olanzapine (5 mg/kg), diphenhydramine hydrochloride (1 mg/kg), lorazepam (5 mg/kg) or vehicle (2% lactic acid, 1 ml/kg). Two hours after drug administration, animals were killed. Patterns of activated cells were observed by immunohistochemistry for Fos-like antibodies in regions previously suggested as responding to all antipsychotic drugs, including nucleus accumbens, central amygdala, and central medial thalamus. Cells staining for Fos were counted by semi-automated methods. RESULTS. A very similar pattern and number of Fos positive cells in nucleus accumbens, central amygdala, and central medial thalamus followed administration of each antipsychotic drug. The numbers of apparently activated cells were much greater following antipsychotic drug administration than after vehicle, with differences between each drug and vehicle being highly statistically significant in each region. Lorazepam produced apparent activation of cells of the central amygdala similar in degree and location but not identical in distribution to that of antipsychotic drugs. Diphenhydramine produced no apparent activation of cells in any of the sites tested. Typical and atypical antipsychotic drugs shared a distinctive pattern of robust activation of cells in nucleus accumbens, central medial thalamus, and central amygdala. Antipsychotic drug-induced activation of amygdala was shared by lorazepam, but activation of thalamus and nucleus accumbens was much greater following antipsychotic drugs than following lorazepam. The pattern of activated cells may be relevant to the therapeutic actions of antipsychotic drugs.

Human aging is characterized by reductions in the ability to remember associations between items, despite intact memory for single items. Older adults also show less selectivity in task-related brain activity, such that patterns of activation become less distinct across multiple experimental tasks. This reduced selectivity or dedifferentiation has been found for episodic memory, which is often reduced in older adults, but not for semantic memory, which is maintained with age. We used fMRI to investigate whether there is a specific reduction in selectivity of brain activity during associative encoding in older adults, but not during item encoding, and whether this reduction predicts associative memory performance. Healthy young and older adults were scanned while performing an incidental encoding task for pictures of objects and houses under item or associative instructions. An old/new recognition test was administered outside the scanner. We used agnostic canonical variates analysis and split-half resampling to detect whole-brain patterns of activation that predicted item versus associative encoding for stimuli that were later correctly recognized. Older adults had poorer memory for associations than did younger adults, whereas item memory was comparable across groups. Associative encoding trials, but not item encoding trials, were predicted less successfully in older compared with young adults, indicating less distinct patterns of associative-related activity in the older group. Importantly, higher probability of predicting associative encoding trials was related to better associative memory after accounting for age and performance on a battery of neuropsychological tests. These results provide evidence that neural distinctiveness at encoding supports associative memory and that a specific reduction of selectivity in neural recruitment underlies age differences in associative memory.

Meditation has been shown to improve creativity in some situation. However, little is known about the brain systems underling insight into a problem when the person fails to solve the problem. Here, we examined the neural correlation using Chinese Remote Association Test, as a measure of creativity. We provide a solution following the failure of the participant to provide one. We examine how meditation in comparison with relaxation influences the reaction of the participant to a correct solution. The event-related functional magnetic resonance imaging showed greater activity, mainly distributed in the right cingulate gyrus (CG), insula, putamen, inferior frontal gyrus (IFG), and the bilateral middle frontal gyrus (MFG), the inferior parietal lobule (IPL) and the superior temporal gyrus (STG). This pattern of activation was greater following 5 h of meditation training than the same amount of relaxation. Based on prior research, we speculate on the function of this pattern of brain activity: (i) CG may be involved in detecting conflict and breaking mental set, (ii) MFG/IFG may play an important role in restructuring of the problem representation, (iii) insula, IPL and STG may be associated with error detection, problem understanding or general attentive control and (iv) putamen may be activated by 'Aha' feeling.

The purpose of functional brain mapping is to localize patterns of neuronal activity associated with sensory, motor, and cognitive functions, or with disease processes. To be complete, an imaging modality needs near millimeter precision in localizing regions of activated tissue and sub-second temporal precision for characterizing changes in patterns of activation over time. Increasingly fine anatomical resolution is available with functional magnetic resonance imaging (fMRI). However, fMRI is an indirect measure of neuronal electrical activity whose temporal resolution is too gross to resolve the rapidly shifting patterns of activity that are characteristic of actual neurophysiological processes. In contrast, electroencephalography (EEG) and event-related potential (ERP) methods have a temporal resolution typically in the one to five millisecond range, depending on the AID rate. For simplicity the term EEG is used here in a general sense to refer both to recordings of brain electrical activity and, except where noted, to recordings of brain magnetic activity called magnetoencephalograms or MEGs. The nature of MEG recording technology and the relative strengths and weaknesses of EEG versus MEG approaches have been reviewed elsewhere (Cohen & Cuffin, 1991; Leahy et al., 1998; Williamson & Kaufman, 1987). From a broad perspective that considers all neuroimaging modalities, the differences between EEG and MEG are slight relative to their similarities.