Cortical Networks Research Articles

Human tripartite cortical network model for temporal assessment of alpha-synuclein aggregation and propagation in Parkinson’s Disease

Previous studies have shown that aggregated alpha-synuclein (α-s) protein, a key pathological marker of Parkinson’s disease (PD), can propagate between cells, thus participating in disease progression. This prion-like propagation has been widely studied using in vivo and in vitro models, including rodent and human cell cultures. In this study, our focus was on temporal assessment of functional changes during α-s aggregation and propagation in human induced pluripotent stem cell (hiPSC)-derived neuronal cultures and in engineered networks. Here, we report an engineered circular tripartite human neuronal network model in a microfluidic chip integrated with microelectrode arrays (MEAs) as a platform to study functional markers during α-s aggregation and propagation. We observed progressive aggregation of α-s in conventional neuronal cultures and in the exposed (proximal) compartments of circular tripartite networks following exposure to preformed α-s fibrils (PFF). Furthermore, aggregated forms propagated to distal compartments of the circular tripartite networks through axonal transport. We observed impacts of α-s aggregation on both the structure and function of neuronal cells, such as in presynaptic proteins, mitochondrial motility, calcium oscillations and neuronal activity. The model enabled an assessment of the early, middle, and late phases of α-s aggregation and its propagation during a 13-day follow-up period. While our temporal analysis suggested a complex interplay of structural and functional changes during the in vitro propagation of α-s aggregates, further investigation is required to elucidate the underlying mechanisms. Taken together, this study demonstrates the technical potential of our introduced model for conducting in-depth analyses for revealing such mechanisms.

Systematic cross-species comparison of prefrontal cortex functional networks targeted via transcranial magnetic stimulation

Abstract Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method that safely modulates neural activity in vivo. Its precision in targeting specific brain networks makes TMS invaluable in diverse clinical applications. For example, TMS is used to treat depression by targeting prefrontal brain networks and their connection to other brain regions. Despite its widespread use, however, the underlying neural mechanisms of TMS are not completely understood. Non-human primates (NHPs) offer an ideal model to study TMS mechanisms through invasive electrophysiological recordings. As such, bridging the gap between NHP experiments and human applications is imperative to ensure translational relevance. Here, we systematically compare the TMS-targeted functional networks in the prefrontal cortex in humans and NHPs. We combine TMS electric field modeling in humans and macaques with resting-state functional magnetic resonance imaging (fMRI) data to compare the functional networks targeted via TMS across species. Distinct stimulation zones in macaque and human models arose, each exhibiting differences in impacted networks (macaque: Frontoparietal Network, Somatomotor Network; human: Frontoparietal Network, Default Network). We identified differences in brain gyrification and functional organization across species as the underlying cause of found network differences. The TMS-network profiles we identified will allow researchers to establish consistency in network stimulation across species, aiding in the translational efforts to develop improved TMS functional network targeting approaches.

Mediodorsal thalamus and ventral pallidum contribute to subcortical regulation of the default mode network

Humans and other animals readily transition from externally to internally focused attention, and these transitions are accompanied by activation of the default mode network (DMN). The DMN was considered a cortical network, yet recent evidence suggests subcortical structures are also involved. We investigated the role of ventral pallidum (VP) and mediodorsal thalamus (MD) in DMN regulation in tree shrew, a close relative of primates. Electrophysiology and deep learning-based classification of behavioral states revealed gamma oscillations in VP and MD coordinated with gamma in anterior cingulate (AC) cortex during DMN states. Cross-frequency coupling between gamma and delta oscillations was higher during DMN than other behaviors, underscoring the engagement of MD, VP and AC. Our findings highlight the importance of VP and MD in DMN regulation, extend homologies in DMN regulation among mammals, and underline the importance of thalamus and basal forebrain to the regulation of DMN.

Speech and music recruit frequency-specific distributed and overlapping cortical networks

To what extent does speech and music processing rely on domain-specific and domain-general neural networks? Using whole-brain intracranial EEG recordings in 18 epilepsy patients listening to natural, continuous speech or music, we investigated the presence of frequency-specific and network-level brain activity. We combined it with a statistical approach in which a clear operational distinction is made between shared, preferred, and domain-selective neural responses. We show that the majority of focal and network-level neural activity is shared between speech and music processing. Our data also reveal an absence of anatomical regional selectivity. Instead, domain-selective neural responses are restricted to distributed and frequency-specific coherent oscillations, typical of spectral fingerprints. Our work highlights the importance of considering natural stimuli and brain dynamics in their full complexity to map cognitive and brain functions.

Speech and music recruit frequency-specific distributed and overlapping cortical networks.

To what extent does speech and music processing rely on domain-specific and domain-general neural networks? Using whole-brain intracranial EEG recordings in 18 epilepsy patients listening to natural, continuous speech or music, we investigated the presence of frequency-specific and network-level brain activity. We combined it with a statistical approach in which a clear operational distinction is made between shared, preferred, and domain-selective neural responses. We show that the majority of focal and network-level neural activity is shared between speech and music processing. Our data also reveal an absence of anatomical regional selectivity. Instead, domain-selective neural responses are restricted to distributed and frequency-specific coherent oscillations, typical of spectral fingerprints. Our work highlights the importance of considering natural stimuli and brain dynamics in their full complexity to map cognitive and brain functions.

Interneuron-selective HCN channel knockdown in prelimbic cortex of female rats mimics effects of chronic ethanol exposure

Our laboratory has previously shown that chronic ethanol exposure elicits enhanced working memory performance in female, but not male, adult Sprague–Dawley rats, indicative of a fundamental sex difference in cortical plasticity. Recent studies have furthermore revealed that females display markedly reduced HCN-mediated channel activity in inhibitory Martinotti interneurons after chronic ethanol exposure that is similarly not observed in males. From these observations we hypothesized that alcohol induces facilitated working memory performance via down-regulation of these channels’ activity specifically within interneurons. To test this hypothesis, we employed a Pol-II compatible shRNA expression system to elicit targeted knockdown of HCN channel activity in these cells, and measured performance on a delayed Non-Match-to-Sample (NMS) T-maze test to gauge effects on working memory performance. A significant baseline enhancement of working memory performance with HCN channel knockdown was observed, indicative of a critical role for interneuron-expressed HCNs in maintaining optimal cortical network activity during cognitively-demanding tasks. Consistent with previous observations, ethanol exposure resulted in enhanced NMS T-maze performance, however elevated working memory performance was observed in both scram- and hcn-shRNA infected groups after alcohol administration. We therefore conclude that interneuron-expressed HCN channels, despite representing a minor population of total cortical HCN expression, contribute substantially to maintaining working memory processes. Downregulated HCN channel activity, though, does not alone appear sufficient to manifest alcohol-induced enhancement of working memory performance observed in female rats during acute withdrawal.

A brief history of somatostatin interneuron taxonomy or: how many somatostatin subtypes are there, really?

We provide a brief (and unabashedly biased) overview of the pre-transcriptomic history of somatostatin interneuron taxonomy, followed by a chronological summary of the large-scale, NIH-supported effort over the last ten years to generate a comprehensive, single-cell RNA-seq-based taxonomy of cortical neurons. Focusing on somatostatin interneurons, we present the perspective of experimental neuroscientists trying to incorporate the new classification schemes into their own research while struggling to keep up with the ever-increasing number of proposed cell types, which seems to double every two years. We suggest that for experimental analysis, the most useful taxonomic level is the subdivision of somatostatin interneurons into ten or so "supertypes," which closely agrees with their more traditional classification by morphological, electrophysiological and neurochemical features. We argue that finer subdivisions ("t-types" or "clusters"), based on slight variations in gene expression profiles but lacking clear phenotypic differences, are less useful to researchers and may actually defeat the purpose of classifying neurons to begin with. We end by stressing the need for generating novel tools (mouse lines, viral vectors) for genetically targeting distinct supertypes for expression of fluorescent reporters, calcium sensors and excitatory or inhibitory opsins, allowing neuroscientists to chart the input and output synaptic connections of each proposed subtype, reveal the position they occupy in the cortical network and examine experimentally their roles in sensorimotor behaviors and cognitive brain functions.

Unveiling altered connectivity between cognitive networks and cerebellum in schizophrenia

Cognitive functioning is a crucial aspect in schizophrenia (SZ), and when altered it has devastating effects on patients' quality of life and treatment outcomes. Several studies suggested that they could result from altered communication between the cortex and cerebellum. However, the neural correlates underlying these impairments have not been identified. In this study, we investigated resting state functional connectivity (rsFC) in SZ patients, by considering the interactions between cortical networks supporting cognition and cerebellum. In addition, we investigated the relationship between SZ patients' rsFC and their symptoms.We used fMRI data from 74 SZ patients and 74 matched healthy controls (HC) downloaded from the publicly available database SchizConnect. We implemented a seed-based connectivity approach to identify altered functional connections between specific cortical networks and cerebellum. We considered ten commonly studied resting state networks, whose functioning encompasses specific cognitive functions, and the cerebellum, whose involvement in supporting cognition has been recently identified. We then explored the relationship between altered rsFC values and Positive and Negative Syndrome Scale (PANSS) scores.The SZ group showed increased connectivity values compared with HC group for cortical networks involved in attentive processes, which were also linked to PANSS items describing attention and language-related processing. We also showed decreased connectivity between cerebellar regions, and increased connectivity between them and attentive networks, suggesting the contribution of cerebellum to attentive and affective deficits.In conclusion, our findings highlighted the link between negative symptoms in SZ and altered connectivity within the cerebellum and between the same and cortical networks supporting cognition.

Developmental dynamics of the prefrontal cortical SST and PV interneuron networks: Insights from the monkey highlight human-specific features.

The primate prefrontal cortex (PFC) is a quintessential hub of cognitive functions. Amidst its intricate neural architecture, the interplay of distinct neuronal subtypes, notably parvalbumin (PV) and somatostatin (SST) interneurons (INs), emerge as a cornerstone in sculpting cortical circuitry and governing cognitive processes. While considerable strides have been made in elucidating the developmental trajectory of these neurons in rodent models, our understanding of their postmigration developmental dynamics in primates still needs to be studied. Disruptions to this developmental trajectory can compromise IN function, impairing signal gating and circuit modulation within cortical networks. This study examined the expression patterns of PV and SST, ion transporter KCC2, and ion channel subtypes Kv3.1b, and Nav1.1 - associated with morphophysiological stages of development in the postnatal marmoset monkey in different frontal cortical regions (granular areas 8aD, 8aV, 9, 46; agranular areas 11, 47L). Our results demonstrate that the maturation of PV+ INs extends into adolescence, characterized by discrete epochs associated with specific expression dynamics of ion channel subtypes. Interestingly, we observed a postnatal decrease in SST interneurons, contrasting with studies in rodents. This endeavor broadens our comprehension of primate cortical development and furnishes invaluable insights into the etiology and pathophysiology of neurodevelopmental disorders characterized by perturbations in PV and SST IN function.

Human-Induced Pluripotent Stem Cell (iPSC)-Derived GABAergic Neuron Differentiation in Bipolar Disorder.

Bipolar disorder (BP) is a recurring psychiatric condition characterized by alternating episodes of low energy (depressions) followed by manias (high energy). Cortical network activity produced by GABAergic interneurons may be critical in maintaining the balance in excitatory/inhibitory activity in the brain during development. Initially, GABAergic signaling is excitatory; with maturation, these cells undergo a functional switch that converts GABAA channels from depolarizing (excitatory) to hyperpolarizing (inhibitory), which is controlled by the intracellular concentration of two chloride transporters. The earliest, NKCC1, promotes chloride entry into the cell and depolarization, while the second (KCC2) stimulates movement of chloride from the neuron, hyperpolarizing it. Perturbations in the timing or expression of NKCC1/KCC2 may affect essential morphogenetic events including cell proliferation, migration, synaptogenesis and plasticity, and thereby the structure and function of the cortex. We derived induced pluripotent stem cells (iPSC) from BP patients and undiagnosed control (C) individuals, then modified a differentiation protocol to form GABAergic interneurons, harvesting cells at sequential stages of differentiation. qRT-PCR and RNA sequencing indicated that after six weeks of differentiation, controls transiently expressed high levels of NKCC1. Using multi-electrode array (MEA) analysis, we observed that BP neurons exhibit increased firing, network bursting and decreased synchrony compared to C. Understanding GABA signaling in differentiation may identify novel approaches and new targets for treatment of neuropsychiatric disorders such as BP.

Thyroid hormone T4 mitigates traumatic brain injury in mice by dynamically remodeling cell type specific genes, pathways, and networks in hippocampus and frontal cortex

The complex pathology of mild traumatic brain injury (mTBI) is a main contributor to the difficulties in achieving a successful therapeutic regimen. Thyroxine (T4) administration has been shown to prevent the cognitive impairments induced by mTBI in mice but the mechanism is poorly understood. To understand the underlying mechanism, we carried out a single cell transcriptomic study to investigate the spatiotemporal effects of T4 on individual cell types in the hippocampus and frontal cortex at three post-injury stages in a mouse model of mTBI. We found that T4 treatment altered the proportions and transcriptomes of numerous cell types across tissues and timepoints, particularly oligodendrocytes, astrocytes, and microglia, which are crucial for injury repair. T4 also reversed the expression of mTBI-affected genes such as Ttr, mt-Rnr2, Ggn12, Malat1, Gnaq, and Myo3a, as well as numerous pathways such as cell/energy/iron metabolism, immune response, nervous system, and cytoskeleton-related pathways. Cell-type specific network modeling revealed that T4 mitigated select mTBI-perturbed dynamic shifts in subnetworks related to cell cycle, stress response, and RNA processing in oligodendrocytes. Cross cell-type ligand-receptor networks revealed the roles of App, Hmgb1, Fn1, and Tnf in mTBI, with the latter two ligands having been previously identified as TBI network hubs. mTBI and/or T4 signature genes were enriched for human genome-wide association study (GWAS) candidate genes for cognitive, psychiatric and neurodegenerative disorders related to mTBI. Our systems-level single cell analysis elucidated the temporal and spatial dynamic reprogramming of cell-type specific genes, pathways, and networks, as well as cell-cell communications as the mechanisms through which T4 mitigates cognitive dysfunction induced by mTBI.

Expression of activity-regulated transcripts in pyramidal neurons across the cortical visuospatial working memory network in unaffected comparison individuals and individuals with schizophrenia

Visuospatial working memory (vsWM), which is impaired in schizophrenia (SZ), is mediated by multiple cortical regions including the primary (V1) and association (V2) visual, posterior parietal (PPC) and dorsolateral prefrontal (DLPFC) cortices. In these regions, parvalbumin (PV) or somatostatin (SST) GABA neurons are altered in SZ as reflected in lower levels of activity-regulated transcripts. As PV and SST neurons receive excitatory inputs from neighboring pyramidal neurons, we hypothesized that levels of activity-regulated transcripts are also lower in pyramidal neurons in these regions. Thus, we quantified levels of four activity-regulated, pyramidal neuron-selective transcripts, namely adenylate cyclase-activating polypeptide-1 (ADCYAP1), brain-derived neurotrophic factor (BDNF), neuronal pentraxin-2 (NPTX2) and neuritin-1 (NRN1) mRNAs, in V1, V2, PPC and DLPFC from unaffected comparison and SZ individuals. In SZ, BDNF and NPTX2 mRNA levels were lower across all four regions, whereas ADCYAP1 and NRN1 mRNA levels were lower in V1 and V2. The regional pattern of deficits in BDNF and NPTX2 mRNAs was similar to that in transcripts in PV and SST neurons in SZ. These findings suggest that lower activity of pyramidal neurons expressing BDNF and/or NPTX2 mRNAs might contribute to alterations in PV and SST neurons across the vsWM network in SZ.

Intentional binding for noninvasive BCI control.

Noninvasive brain-computer interfaces (BCIs) allow to interact with the external environment by naturally bypassing the musculoskeletal system.
Making BCIs efficient and accurate is paramount to improve the reliability of real-life and clinical applications, from open-loop device control to closed-loop neurorehabilitation. By promoting sense of agency and embodiment, realistic setups including multimodal channels of communication, such as eye-gaze, and robotic prostheses aim to improve BCI performance. However, how the mental imagery command should be integrated in those hybrid systems so as to ensure the best interaction is still poorly understood.
To address this question, we performed a hybrid EEG-based BCI training involving healthy volunteers enrolled in a reach-and-grasp action operated by a robotic arm. Main results showed that the hand grasping motor imagery timing significantly affects the BCI accuracy evolution as well as the spatiotemporal brain dynamics. Larger accuracy improvement was obtained when motor imagery is performed just after the robot reaching, as compared to before or during the movement. The proximity with the subsequent robot grasping favored intentional binding, led to stronger motor-related brain activity, and primed the ability of sensorimotor areas to integrate information from regions implicated in higher-order cognitive functions.
Taken together, these findings provided fresh evidence about the effects of intentional binding on human behavior and cortical network dynamics that can be exploited to design a new generation of efficient brain-machine interfaces.

Addressing the sources of inter-subject variability in E-field parameters in anodal tDCS stimulation over motor cortical network

Objetive: . Although transcranial direct current stimulation constitutes a non-invasive neuromodulation technique with promising results in a great variety of applications, its clinical implementation is compromised by the high inter-subject variability reported. This study aims to analyze the inter-subject variability in electric fields (E-fields) over regions of the cortical motor network under two electrode montages: the classical C3Fp2 and an alternative P3F3, which confines more the E-field over this region. Approach. Computational models of the head of 98 healthy subjects were developed to simulate the E-field under both montages. E-field parameters such as magnitude, focality and orientation were calculated over three regions of interest (ROI): M1S1, supplementary motor area (SMA) and preSMA. The role of anatomical characteristics as a source of inter-subject variability on E-field parameters and individualized stimulation intensity were addressed using linear mixed-effect models.Main results. P3F3 showed a more confined E-field distribution over M1S1 than C3Fp2; the latter elicited higher E-fields over supplementary motor areas. Both montages showed high inter-subject variability, especially for the normal component over C3Fp2. Skin, bone and CSF ROI volumes showed a negative association with E-field magnitude irrespective of montage. Grey matter volume and montage were the main sources of variability for focality. The curvature of gyri was found to be significantly associated with the variability of normal E-fields.Significance. Computational modeling proves useful in the assessment of E-field variability. Our simulations predict significant differences in E-field magnitude and focality for C3Fp2 and P3F3. However, anatomical characteristics were also found to be significant sources of E-field variability irrespective of electrode montage. The normal E-field component better captured the individual variability and low rate of responder subjects observed in experimental studies.

Could Accelerated Long-Term Forgetting Be a Feature of the Higher Rate of Memory Complaints Associated with Subjective Cognitive Decline? An Exploratory Study.

Recently, subjective cognitive decline (SCD) was proposed as an early risk factor for future Alzheimer's disease (AD). In this study, we investigated whether accelerated long-term forgetting (ALF), assessed with extended testing intervals than those adopted in clinical practice, might be a cognitive feature of SCD. Using an explorative MRI analysis of the SCD sample, we attempted to investigate the areas most likely involved in the ALF pattern. We recruited 31 individuals with SCD from our memory clinic and subdivided them based on their rate of memory complaints into mild SCDs (n = 18) and severe SCDs (n = 13). A long-term forgetting procedure, involving the recall of verbal and visuo-spatial material at four testing delays (i.e., immediate, 30 min, 24 h, and 7 days post-encoding) was used to compare the two sub-groups of SCDs with a healthy control group (HC; n = 16). No significant between-group difference was found on the standard neuropsychological tests, nor in the immediate and 30 min recall of the experimental procedure. By contrast, on the verbal test severe SCDs forgot significantly more than HCs in the prolonged intervals (i.e., 24 h and 7 days), with the greatest decline between 30 min and 24 h. Finally, in the whole SCD sample, we found significant associations between functional connectivity values within some cortical networks involved in memory (default mode network, salience network, and fronto-parietal network) and verbal long-term measures. Our preliminary findings suggest that long-term forgetting procedures could be a sensitive neuropsychological tool for detecting memory concerns in SCDs, contributing to early AD detection.

Arginine vasopressin activates serotonergic neurons in the dorsal raphe nucleus during neonatal development in vitro and in vivo

Birth stress is a risk factor for psychiatric disorders and associated with exaggerated release of the stress hormone arginine vasopressin (AVP) into circulation and in the brain. In perinatal hippocampus, AVP activates GABAergic interneurons which leads to suppression of spontaneous network events and suggests a protective function of AVP on cortical networks during birth. However, the role of AVP in developing subcortical networks is not known. Here we tested the effect of AVP on the dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT, serotonin) system in male and female neonatal rats, since early 5-HT homeostasis is critical for the development of cortical brain regions and emotional behaviors. We show that AVP is strongly excitatory in neonatal DRN: it increases excitatory synaptic inputs of 5-HT neurons via V1A receptors in vitro and promotes their action potential firing through a combination of its effect on glutamatergic synaptic transmission and a direct effect on the excitability of these neurons. Furthermore, we identified two major firing patterns of neonatal 5-HT neurons in vivo, tonic regular firing and low frequency oscillations of regular spike trains and confirmed that these neurons are also activated by AVP in vivo. Finally, we show that the sparse vasopressinergic innervation in neonatal DRN originates exclusively from cell groups in medial amygdala and bed nucleus of stria terminalis. Hyperactivation of the neonatal 5-HT system by AVP during birth stress may impact its own functional development and affect the maturation of cortical target regions, which may increase the risk for psychiatric conditions later on.

Stimulus type shapes the topology of cellular functional networks in mouse visual cortex

On the timescale of sensory processing, neuronal networks have relatively fixed anatomical connectivity, while functional interactions between neurons can vary depending on the ongoing activity of the neurons within the network. We thus hypothesized that different types of stimuli could lead those networks to display stimulus-dependent functional connectivity patterns. To test this hypothesis, we analyzed single-cell resolution electrophysiological data from the Allen Institute, with simultaneous recordings of stimulus-evoked activity from neurons across 6 different regions of mouse visual cortex. Comparing the functional connectivity patterns during different stimulus types, we made several nontrivial observations: (1) while the frequencies of different functional motifs were preserved across stimuli, the identities of the neurons within those motifs changed; (2) the degree to which functional modules are contained within a single brain region increases with stimulus complexity. Altogether, our work reveals unexpected stimulus-dependence to the way groups of neurons interact to process incoming sensory information.

A dendritic substrate for temporal diversity of cortical inhibition.

In the mammalian neocortex, GABAergic interneurons (INs) inhibit cortical networks in profoundly different ways. The extent to which this depends on how different INs process excitatory signals along their dendrites is poorly understood. Here, we reveal that the functional specialization of two major populations of cortical INs is determined by the unique association of different dendritic integration modes with distinct synaptic organization motifs. We found that somatostatin (SST)-INs exhibit NMDAR-dependent dendritic integration and uniform synapse density along the dendritic tree. In contrast, dendrites of parvalbumin (PV)-INs exhibit passive synaptic integration coupled with proximally enriched synaptic distributions. Theoretical analysis shows that these two dendritic configurations result in different strategies to optimize synaptic efficacy in thin dendritic structures. Yet, the two configurations lead to distinct temporal engagement of each IN during network activity. We confirmed these predictions with in vivo recordings of IN activity in the visual cortex of awake mice, revealing a rapid and linear recruitment of PV-INs as opposed to a long-lasting integrative activation of SST-INs. Our work reveals the existence of distinct dendritic strategies that confer distinct temporal representations for the two major classes of neocortical INs and thus dynamics of inhibition.

Callousness, exploitativeness, and tracking of cooperation incentives in the human default network

Human cognitive capacities that enable flexible cooperation may have evolved in parallel with the expansion of frontoparietal cortical networks, particularly the default network. Conversely, human antisocial behavior and trait antagonism are broadly associated with reduced activity, impaired connectivity, and altered structure of the default network. Yet, behaviors like interpersonal manipulation and exploitation may require intact or even superior social cognition. Using a reinforcement learning model of decision-making on a modified trust game, we examined how individuals adjusted their cooperation rate based on a counterpart's cooperation and social reputation. We observed that learning signals in the default network updated the predicted utility of cooperation or defection and scaled with reciprocal cooperation. These signals were weaker in callous (vs. compassionate) individuals but stronger in those who were more exploitative (vs. honest and humble). Further, they accounted for associations between exploitativeness, callousness, and reciprocal cooperation. Separately, behavioral sensitivity to prior reputation was reduced in callous but not exploitative individuals and selectively scaled with responses of the medial temporal subsystem of the default network. Overall, callousness was characterized by blunted behavioral and default network sensitivity to cooperation incentives. Exploitativeness predicted heightened sensitivity to others' cooperation but not social reputation. We speculate that both compassion and exploitativeness may reflect cognitive adaptations to social living, enabled by expansion of the default network in anthropogenesis.

Controlling Alzheimer’s disease by deep brain stimulation based on a data-driven cortical network model

Controlling Alzheimer’s disease by deep brain stimulation based on a data-driven cortical network model