Subcortical Circuits Research Articles

Monosynaptic trans-collicular pathways link mouse whisker circuits to integrate somatosensory and motor cortical signals.

The superior colliculus (SC), a conserved midbrain node with extensive long-range connectivity throughout the brain, is a key structure for innate behaviors. Descending cortical pathways are increasingly recognized as central control points for SC-mediated behaviors, but how cortico-collicular pathways coordinate SC activity at the cellular level is poorly understood. Moreover, despite the known role of the SC as a multisensory integrator, the involvement of the SC in the somatosensory system is largely unexplored in comparison to its involvement in the visual and auditory systems. Here, we mapped the connectivity of the whisker-sensitive region of the SC in mice with trans-synaptic and intersectional tracing tools and in vivo electrophysiology. The results reveal a novel trans-collicular connectivity motif in which neurons in motor- and somatosensory cortices impinge onto the brainstem-SC-brainstem sensory-motor arc and onto SC-midbrain output pathways via only one synapse in the SC. Intersectional approaches and optogenetically assisted connectivity quantifications in vivo reveal convergence of motor and somatosensory cortical input on individual SC neurons, providing a new framework for sensory-motor integration in the SC. More than a third of the cortical recipient neurons in the whisker SC are GABAergic neurons, which include a hitherto unknown population of GABAergic projection neurons targeting thalamic nuclei and the zona incerta. These results pinpoint a whisker region in the SC of mice as a node for the integration of somatosensory and motor cortical signals via parallel excitatory and inhibitory trans-collicular pathways, which link cortical and subcortical whisker circuits for somato-motor integration.

Histamine Regulates Accumbens Microcircuits: An Arousing Finding for Addiction Research

The concept of “reward” is evolutionarily central as it is critical to reinforce behaviors that improve the chances of survival and reproduction and avoid behaviors that reduce fitness. Feelings of reward drive organisms to engage in behaviors like the consumption of calorie-dense foods or the pursuit of sexual reproduction, and some of the most crucial brain circuitry driving this reward is relatively well understood. One key reward region is the nucleus accumbens (NAc), which integrates information delivered by glutamatergic inputs from the hippocampus (providing information on previous experiences and context), the prefrontal cortex (conveying the organism’s current plan and goals), and the amygdala (affording emotional salience and relevance). The integration of all this information in the NAc is controlled by neuromodulatory neurotransmitters, the most well-studied being dopamine delivered by projections from the ventral tegmental area. Dopamine drives increased function of D1-type NAc medium spiny neurons (MSNs) comprising the direct pathway and reinforcing behavior, while the same dopamine drives down activity of D2-type NAc MSNs comprising the indirect pathway that prevent reinforcement. In more recent years, the understanding of other neuromodulatory signals and their effects on NAc function and outputs has emerged as a key goal, and histamine actions in the NAc is primary among these signals. SEE CORRESPONDING ARTICLE ON PAGE 1041 SEE CORRESPONDING ARTICLE ON PAGE 1041 Accumbal Histamine Signaling Engages Discrete Interneuron MicrocircuitsBiological PsychiatryVol. 93Issue 11PreviewCentral histamine (HA) signaling modulates diverse cortical and subcortical circuits throughout the brain, including the nucleus accumbens (NAc). The NAc, a key striatal subregion directing reward-related behavior, expresses diverse HA receptor subtypes that elicit cellular and synaptic plasticity. However, the neuromodulatory capacity of HA within interneuron microcircuits in the NAc remains unknown. Full-Text PDF

Dynamic synchronization between hippocampal representations and stepping

The hippocampus is a mammalian brain structure that expresses spatial representations1 and is crucial for navigation2,3. Navigation, in turn, intricately depends on locomotion; however, current accounts suggest a dissociation between hippocampal spatial representations and the details of locomotor processes. Specifically, the hippocampus is thought to represent mainly higher-order cognitive and locomotor variables such as position, speed and direction of movement4–7, whereas the limb movements that propel the animal can be computed and represented primarily in subcortical circuits, including the spinal cord, brainstem and cerebellum8–11. Whether hippocampal representations are actually decoupled from the detailed structure of locomotor processes remains unknown. To address this question, here we simultaneously monitored hippocampal spatial representations and ongoing limb movements underlying locomotion at fast timescales. We found that the forelimb stepping cycle in freely behaving rats is rhythmic and peaks at around 8 Hz during movement, matching the approximately 8 Hz modulation of hippocampal activity and spatial representations during locomotion12. We also discovered precisely timed coordination between the time at which the forelimbs touch the ground (‘plant’ times of the stepping cycle) and the hippocampal representation of space. Notably, plant times coincide with hippocampal representations that are closest to the actual position of the nose of the rat, whereas between these plant times, the hippocampal representation progresses towards possible future locations. This synchronization was specifically detectable when rats approached spatial decisions. Together, our results reveal a profound and dynamic coordination on a timescale of tens of milliseconds between central cognitive representations and peripheral motor processes. This coordination engages and disengages rapidly in association with cognitive demands and is well suited to support rapid information exchange between cognitive and sensory–motor circuits.

Music Therapy in the Treatment of Dementia: A Review Article.

The etiology of depression is the degeneration of the brain cells involved in cognitive function before the other brain cells.It is characterized by a neurological condition that causes a reduction in terms of physical, social, and cognitive impairment and has no cure presently. These nonpharmacological approaches, such as music therapy, enhance living outcomes for those dealing with dementia and also reduce behavioral incidence. Among these strategies is music therapy, and individual or gap-time psychological and educational counseling. Many scientists believe in the advantages of music for the brain. The brain is affected by music function and enhances some cognitive abilities, including the mechanism of speech, alteration, memory, and learning. Music can activate the limbic system, subcortical circuits, and emotionally related systems, inducing the sensation of well-being. The music itself is quite effective at increasing cerebral plasticity. Music therapy has powerful stimulation for neuroplastic alterations in the adult and developing brain. Dementiacan be cured by music therapy and music-based intervention (nonpharmacological intervention) rather than by medication. This study highlights dementia therapy utilizing the music therapy method.

Cell-type specific vulnerability in a subcortical limbic circuit node in Alzheimer's disease

Cell-type specific vulnerability in a subcortical limbic circuit node in Alzheimer's disease

Effects of trunk neuromuscular electrical stimulation on the motor circuits of able-bodied individuals

Upper- and lower-limb neuromuscular electrical stimulation (NMES) is known to modulate the excitability of the neural motor circuits. However, it remains unclear whether short-duration trunk muscle NMES could achieve similar neuromodulation effects. We assessed motor evoked potentials (MEPs) elicited through transcranial magnetic stimulation of the primary motor cortex representation of the trunk extensor muscles to evaluate corticospinal excitability. Moreover, cervicomedullary motor evoked potentials (CMEPs) were assessed through cervicomedullary junction magnetic stimulation to evaluate subcortical excitability. Twelve able-bodied individuals participated in the MEP study, and another twelve in the CMEP study. During the interventions, NMES was applied bilaterally to activate the erector spinae muscle and produce intermittent contractions (20 s ON/20 s OFF) for a total of 20 min while participants remained seated. Assessments were performed: (i) before; (ii) during (in brief periods when NMES was OFF); and (iii) immediately after the interventions to compare MEP or CMEP excitability. Our results showed that MEP responses were not affected by trunk NMES, while CMEP responses were facilitated for approximately 8 min during the intervention, and returned to baseline before the end of the 20 min stimulating period. Our findings therefore suggest that short-duration NMES of the trunk extensor muscles likely does not affect the corticospinal excitability, but it has a potential to facilitate subcortical neural circuits immediately after starting the intervention. These findings indicate that short-duration application of NEMS may be helpful in rehabilitation to enhance neuromodulation of the trunk subcortical neural motor circuits.

P-125 Consistent PSP-atrophy affects regions connecting the salience-network to subcortical circuits

P-125 Consistent PSP-atrophy affects regions connecting the salience-network to subcortical circuits

FORENSIC NEUROFEEDBACK AND PREFRONTAL WORKOUT, A SURVEY

IntroductionThe logic behind the neuropsychological rehabilitation of the impulsive criminal is to treat the behavioral manifestations of these individuals as the product of a real pre-frontal syndrome, capable of causing deficits in the planning of behavior, in self-regulation, in the inhibition of impulsiveness and more generally in social and interpersonal skills. With the term prefrontal workout, literally “prefrontal workout” Eagleman (2011) refers to a real form of rehabilitation intended for subjects characterized by strong impulsive tendencies. Neurofeedback is used in prefrontal training. This technique mainly uses electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) as indicators of brain function.ObjectivesThe premise of prefrontal training is that through rehabilitation, and therefore repeated practice, the frontal areas of our brain can be trained in order to improve the “control” of subcortical circuits and limbic areas responsible for impulsive and potentially destructive behavioral forces. Although this rehabilitation proposal does not specifically concern deviant individuals, it is intended for subjects with impulsive tendencies and difficulty in repressing a stimulus-seeking behavior, skills that fall within the category of frontal functions.MethodsIt is possible that similar strategies can also be used effectively against deviant individuals, working to improve their ability to inhibit a behavioral tendency and reinforcing everything with real-time feedback. There is a very high incidence of attention deficit, hyperactivity disorder and related symptoms among people convicted of crimes, and a great many criminal acts involve impulsive behavior or loss of emotional control such as anger. Better control of behavior and emotions are among the most commonly reported outcomes of neurotherapeutic treatment.ResultsResearch and clinical experience also demonstrate the positive effects of neurofeedback with alcohol and drug abuse and depression, both common accompaniments of criminal behavior ( Fielenbach S. 2019; Margarita R. 2016; Konicar L. 2015).ConclusionsCertainly, research in this field is at a preliminary stage, and the limitations of these techniques are numerous. There are, for example, several doubts about which is the best strategy for the patient to use to control mental activity and inhibit, for example, the search for the substance to which one is addicted. Although promising, the literature highlights sometimes conflicting results: in this regard, see the meta-analysis by Cortese and colleagues (2016) and the document published by Youcha and colleagues (2008).Disclosure of InterestNone Declared

Effects of focused ultrasound pulse duration on stimulating cortical and subcortical motor circuits in awake sheep.

Low-intensity transcranial focused ultrasound (tFUS) offers new functional neuromodulation opportunities, enabling stimulation of cortical as well as deep brain areas with high spatial resolution. Brain stimulation of awake sheep, in the absence of the confounding effects of anesthesia on brain function, provides translational insight into potential human applications with safety information supplemented by histological analyses. We examined the effects of tFUS pulsing parameters, particularly regarding pulse durations (PDs), on stimulating the cortical motor area (M1) and its thalamic projection in unanesthetized, awake sheep (n = 8). A wearable tFUS headgear, custom-made for individual sheep, enabled experiments to be conducted without using anesthesia. FUS stimuli, each 200 ms long, were delivered to the M1 and the thalamus using three different PDs (0.5, 1, and 2 ms) with the pulse repetition frequency (PRF) adjusted to maintain a 70% duty cycle at a derated in situ spatial-peak temporal-average intensity (Ispta) of 3.6 W/cm2. Efferent electromyography (EMG) responses to stimulation were quantified from both hind limbs. Group-averaged EMG responses from each of the hind limbs across the experimental conditions revealed selective responses from the hind limb contralateral to sonication. The use of 0.5 and 1 ms PDs generated higher EMG signal amplitudes compared to those obtained using a 2 ms PD. Faster efferent response was also observed from thalamic stimulation than that from stimulating the M1. Post-sonication behavioral observation and histological assessment performed 24 h and 1 month after sonication were not indicative of any abnormalities. The results suggest the presence of pulsing scheme-dependent effects of tFUS on brain stimulation and attest its safety in awake large animals.

Going down to go up: understanding human auditory cognition by investigating cortical-subcortical interactions.

Human auditory cognition spans everything from detecting a creaking door in the night to enjoying beautiful music. Neurofunctional models of these processes tend to focus on cortical networks, but how do subcortical circuits contribute to auditory cognition? Answering this question will lead to a richer understanding of how we process the complex auditory world.

Modulation of striatal glutamatergic, dopaminergic and cholinergic neurotransmission pathways concomitant with motor disturbance in rats with kaolin-induced hydrocephalus

BackgroundHydrocephalus is characterized by abnormal accumulation of cerebrospinal fluid in the cerebral ventricles and causes motor impairments. The mechanisms underlying the motor changes remain elusive. Enlargement of ventricles compresses the striatum of the basal ganglia, a group of nuclei involved in the subcortical motor circuit. Here, we used a kaolin-injection juvenile rat model to explore the effects of acute and chronic hydrocephalus, 1 and 5 weeks post-treatment, respectively on the three major neurotransmission pathways (glutamatergic, dopaminergic and cholinergic) in the striatum.MethodsRats were evaluated for motor impairments. Expressions of presynaptic and postsynaptic protein markers related to the glutamatergic, dopaminergic, and cholinergic connections in the striatum were evaluated. Combined intracellular dye injection and substance P immunohistochemistry were used to distinguish between direct and indirect pathway striatal medium spiny neurons (d and i-MSNs) for the analysis of their dendritic spine density changes.ResultsHydrocephalic rats showed compromised open-field gait behavior. However, male but not female rats displayed stereotypic movements and compromised rotarod performance. Morphologically, the increase in lateral ventricle sizes was greater in the chronic than acute hydrocephalus conditions. Biochemically, hydrocephalic rats had significantly decreased striatal levels of synaptophysin, vesicular glutamate transporter 1, and glutamatergic postsynaptic density protein 95, suggesting a reduction of corticostriatal excitation. The expression of GluR2/3 was also reduced suggesting glutamate receptor compositional changes. The densities of dendritic spines, morphological correlates of excitatory synaptic foci, on both d and i-MSNs were also reduced. Hydrocephalus altered type 1 (DR1) and 2 (DR2) dopamine receptor expressions without affecting tyrosine hydroxylase level. DR1 was decreased in acute and chronic hydrocephalus, while DR2 only started to decrease later during chronic hydrocephalus. Since dopamine excites d-MSNs through DR1 and inhibits i-MSNs via DR2, our findings suggest that hydrocephalus downregulated the direct basal ganglia neural pathway persistently and disinhibited the indirect pathway late during chronic hydrocephalus. Hydrocephalus also persistently reduced the striatal choline acetyltransferase level, suggesting a reduction of cholinergic modulation.ConclusionsHydrocephalus altered striatal glutamatergic, dopaminergic, and cholinergic neurotransmission pathways and tipped the balance between the direct and indirect basal ganglia circuits, which could have contributed to the motor impairments in hydrocephalus.

Stimulation of the ventromedial prefrontal cortex blocks the return of subcortically mediated fear responses

The ventromedial prefrontal cortex (vmPFC) mediates the inhibition of defensive responses upon encounters of cues, that had lost their attribute as a threat signal via previous extinction learning. Here, we investigated whether such fear extinction recall can be facilitated by anodal transcranial direct current stimulation (tDCS). Extinction recall was tested twenty-four hours after previously acquired fear was extinguished. Either anodal tDCS or sham stimulation targeting the vmPFC was applied during this test. After stimulation ceased, we examined return of fear after subjects had been re-exposed to aversive events. Fear was assessed by reports of threat expectancy and modulations of autonomic (skin conductance, heart rate) and protective reflex (startle potentiation) measures, the latter of which are mediated by subcortical defense circuits. While tDCS did not affect initial extinction recall, it abolished the return of startle potentiation and autonomic components of the fear response. Results suggest hierarchical multi-level vmPFC functions in human fear inhibition and indicate, that its stimulation might immunize against relapses into pathological subcortically mediated defensive activation.

The tyrosine capsid mutations on retrograde adeno-associated virus accelerates gene transduction efficiency

Adeno-associated virus (AAV) vector is a critical tool for gene delivery through its durable transgene expression and safety profile. Among many serotypes, AAV2-retro is typically utilized for dissecting neural circuits with its retrograde functionality. However, this vector requires a relatively long-term incubation period (over 2 weeks) to obtain enough gene expression levels presumably due to low efficiency in gene transduction. Here, we aimed to enhance transgene expression efficiency of AAV2-retro vectors by substituting multiple tyrosine residues with phenylalanines (YF mutations) in the virus capsid, which is previously reported to improve the transduction efficiency of AAV2-infected cells by evading host cell responses. We found that AAV2-retro with YF mutations (AAV2-retroYF)-mediated transgene expression was significantly enhanced in the primary culture of murine cortical neurons at 1 week after application, comparable to that of the conventional AAV2-retro at 2 week after application. Moreover, transgene expressions in the retrogradely labeled neurons mediated by AAV2-retroYF were significantly increased both in the cortico-cortical circuits and in the subcortical circuits in vivo, while the retrograde functionality of AAV2-retroYF was equally effective as that of AAV2-retro. Our data indicate that YF mutations boost AAV2-retro-mediated retrograde gene transduction in vivo and suggest that the AAV2-retroYF should be useful for efficient targeting of the projection-defined neurons, which is suited to applications for dissecting neural circuits during development as well as future clinical applications.

Transformations of neural representations in a social behaviour network.

Mating and aggression are innate social behaviours that are controlled by subcortical circuits in the extended amygdala and hypothalamus1-4. The bed nucleus of the stria terminalis (BNSTpr) is a node that receives input encoding sex-specific olfactory cues from the medial amygdala5,6, and which in turn projects to hypothalamic nuclei that control mating7-9 (medial preoptic area (MPOA)) and aggression9-14 (ventromedial hypothalamus, ventrolateral subdivision (VMHvl)), respectively15. Previous studies have demonstrated that male aromatase-positive BNSTpr neurons are required for mounting and attack, and may identify conspecific sex according to their overall level of activity16. However, neural representations in BNSTpr, their function and their transformations in the hypothalamus have not been characterized. Here we performed calcium imaging17,18 of male BNSTprEsr1 neurons during social behaviours. We identify distinct populations of female- versus male-tuned neurons in BNSTpr, with the former outnumbering the latter by around two to one, similar to the medial amygdala and MPOA but opposite to VMHvl, in which male-tuned neurons predominate6,9,19. Chemogenetic silencing of BNSTprEsr1 neurons while imaging MPOAEsr1 or VMHvlEsr1 neurons in behaving animals showed, unexpectedly, that the male-dominant sex-tuning bias in VMHvl was inverted to female-dominant whereas a switch from sniff- to mount-selective neurons during mating was attenuated in MPOA. Our data also indicate that BNSTprEsr1 neurons are not essential for conspecific sex identification. Rather, they control the transition from appetitive to consummatory phases of male social behaviours by shaping sex- and behaviour-specific neural representations in the hypothalamus.

Association of Genetic Variant Linked to Hemochromatosis With Brain Magnetic Resonance Imaging Measures of Iron and Movement Disorders

Hereditary hemochromatosis (HH) is an autosomal recessive genetic disorder that leads to iron overload. Conflicting results from previous research has led some to believe the brain is spared the toxic effects of iron in HH. To test the association of the strongest genetic risk variant for HH on brainwide measures sensitive to iron deposition and the rates of movement disorders in a substantially larger sample than previous studies of its kind. This cross-sectional retrospective study included participants from the UK Biobank, a population-based sample. Genotype, health record, and neuroimaging data were collected from January 2006 to May 2021. Data analysis was conducted from January 2021 to April 2022. Disorders tested included movement disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10], codes G20-G26), abnormalities of gait and mobility (ICD-10 codes R26), and other disorders of the nervous system (ICD-10 codes G90-G99). Homozygosity for p.C282Y, the largest known genetic risk factor for HH. T2-weighted and T2* signal intensity from brain magnetic resonance imaging scans, measures sensitive to iron deposition, and clinical diagnosis of neurological disorders. The total cohort consisted of 488 288 individuals (264 719 female; ages 49-87 years, largely northern European ancestry), 2889 of whom were p.C282Y homozygotes. The neuroimaging analysis consisted of 836 individuals: 165 p.C282Y homozygotes (99 female) and 671 matched controls (399 female). A total of 206 individuals were excluded from analysis due to withdrawal of consent. Neuroimaging analysis showed that p.C282Y homozygosity was associated with decreased T2-weighted and T2* signal intensity in subcortical motor structures (basal ganglia, thalamus, red nucleus, and cerebellum; Cohen d >1) consistent with substantial iron deposition. Across the whole UK Biobank (2889 p.C282Y homozygotes, 485 399 controls), we found a significantly increased prevalence for movement disorders in male homozygotes (OR, 1.80; 95% CI, 1.28-2.55; P = .001) but not female individuals (OR, 1.09; 95% CI, 0.70-1.73; P = .69). Among the 31 p.C282Y male homozygotes with a movement disorder, only 10 had a concurrent HH diagnosis. These findings indicate increased iron deposition in subcortical motor circuits in p.C282Y homozygotes and confirm an increased association with movement disorders in male homozygotes. Early treatment in HH effectively prevents the negative consequences of iron overload in the liver and heart. Our work suggests that screening for p.C282Y homozygosity in high-risk individuals also has the potential to reduce brain iron accumulation and to reduce the risk of movement disorders among male individuals who are homozygous for this mutation.

Symbolic cues enhance express visuomotor responses in human arm muscles at the motor planning rather than the visuospatial processing stage.

Humans can produce "express" (∼100 ms) arm muscle responses that are inflexibly locked in time and space to visual target presentations, consistent with subcortical visuomotor transformations via the tecto-reticulo-spinal pathway. These express visuomotor responses are sensitive to explicit cue-driven expectations, but it is unclear at what stage of sensory-to-motor transformation such modulation occurs. Here, we recorded electromyographic activity from shoulder muscles as participants reached toward one of four virtual targets whose physical location was partially predictable from a symbolic cue. In an experiment in which targets could be veridically reached, express responses were inclusive of the biomechanical requirements for reaching the cued locations and not systematically modulated by cue validity. In a second experiment, movements were restricted to the horizontal plane so that the participants could perform only rightward or leftward reaches, irrespective of target position on the vertical axis. Express muscle responses were almost identical for targets that were validly cued in the horizontal direction, regardless of cue validity in the vertical dimension. Together, these findings suggest that the cue-induced enhancements of express responses are dominated by effects at the level of motor plans and not solely via facilitation of early visuospatial target processing. Notably, direct corticotectal and corticoreticular projections exist that are well-placed to modulate prestimulus motor preparation state in subcortical circuits. Our results could reflect a neural mechanism by which contextually relevant motor responses to compatible visual inputs are rapidly released via subcortical circuits that are sufficiently along the sensory-to-motor continuum.NEW & NOTEWORTHY Express arm muscle responses to suddenly appearing visual targets for reaching rapid have been attributed to the tecto-reticulo-spinal pathway in humans. We demonstrate that symbolic cues before target presentation can modulate such express arm muscle responses compatibly with the biomechanics of the cued reaching direction and the cue validity. This implies cortically mediated modulation of one or more sensorimotor transformation nodes of the subcortical express pathway.

Orexin neurons inhibit sleep to promote arousal

Humans and animals lacking orexin neurons exhibit daytime sleepiness, sleep attacks, and state instability. While the circuit basis by which orexin neurons contribute to consolidated wakefulness remains unclear, existing models posit that orexin neurons provide their wake-stabilizing influence by exerting excitatory tone on other brain arousal nodes. Here we show using in vivo optogenetics, in vitro optogenetic-based circuit mapping, and single-cell transcriptomics that orexin neurons also contribute to arousal maintenance through indirect inhibition of sleep-promoting neurons of the ventrolateral preoptic nucleus. Activation of this subcortical circuit rapidly drives wakefulness from sleep by differentially modulating the activity of ventrolateral preoptic neurons. We further identify and characterize a feedforward circuit through which orexin (and co-released glutamate) acts to indirectly target and inhibit sleep-promoting ventrolateral preoptic neurons to produce arousal. This revealed circuitry provides an alternate framework for understanding how orexin neurons contribute to the maintenance of consolidated wakefulness and stabilize behavioral state.

Structural brain network measures in elderly patients with cerebral small vessel disease and depressive symptoms

ObjectivesTo investigate the relationship between diffusion tensor imaging (DTI) indicators and cerebral small vessel disease (CSVD) with depressive states, and to explore the underlying mechanisms of white matter damage in CSVD with depression.MethodA total of 115 elderly subjects were consecutively recruited from the neurology clinic, including 36 CSVD patients with depressive state (CSVD+D), 34 CSVD patients without depressive state (CSVD-D), and 45 controls. A detailed neuropsychological assessment and multimodal magnetic resonance imaging (MRI) were performed. Based on tract-based spatial statistics (TBSS) analysis and structural network analysis, differences between groups were compared, including white matter fiber indicators (fractional anisotropy and mean diffusivity) and structural brain network indicators (global efficiency, local efficiency and network strength), in order to explore the differences and correlations of DTI parameters among the three groups.ResultsThere were no significant differences in terms of CSVD burden scores and conventional imaging findings between the CSVD-D and CSVD+D groups. Group differences were found in DTI indicators (p < 0.05), after adjusting for age, gender, education level, and vascular risk factors (VRF), there were significant correlations between TBSS analysis indicators and depression, including: fractional anisotropy (FA) (r = − 0.291, p < 0.05), mean diffusivity (MD) (r = 0.297, p < 0.05), at the same time, between structural network indicators and depression also show significant correlations, including: local efficiency (ELocal) (r = − 0.278, p < 0.01) and network strength (r = − 0.403, p < 0.001).ConclusionsChanges in FA, MD values and structural network indicators in DTI parameters can predict the depressive state of CSVD to a certain extent, providing a more direct structural basis for the hypothesis of abnormal neural circuits in the pathogenesis of vascular-related depression. In addition, abnormal white matter alterations in subcortical neural circuits probably affect the microstructural function of brain connections, which may be a mechanism for the concomitant depressive symptoms in CSVD patients.

Cortical-subcortical interactions in goal-directed behavior.

Flexibly selecting appropriate actions in response to complex, ever-changing environments requires both cortical and subcortical regions, which are typically described as participating in a strict hierarchy. In this traditional view, highly specialized subcortical circuits allow for efficient responses to salient stimuli, at the cost of adaptability and context specificity, which are attributed to the neocortex. Their interactions are often described as the cortex providing top-down command signals for subcortical structures to implement; however, as available technologies develop, studies increasingly demonstrate that behavior is represented by brainwide activity and that even subcortical structures contain early signals of choice, suggesting that behavioral functions emerge as a result of different regions interacting as truly collaborative networks. In this review, we discuss the field's evolving understanding of how cortical and subcortical regions in placental mammals interact cooperatively, not only via top-down cortical-subcortical inputs but through bottom-up interactions, especially via the thalamus. We describe our current understanding of the circuitry of both the cortex and two exemplar subcortical structures, the superior colliculus and striatum, to identify which information is prioritized by which regions. We then describe the functional circuits these regions form with one another, and the thalamus, to create parallel loops and complex networks for brainwide information flow. Finally, we challenge the classic view that functional modules are contained within specific brain regions; instead, we propose that certain regions prioritize specific types of information over others, but the subnetworks they form, defined by their anatomical connections and functional dynamics, are the basis of true specialization.

Evidence of Intact Corticostriatal and Altered Subcortical-striatal Resting-state Functional Connectivity in Chronic Pain

Highly relevant to both pain and reward, corticostriatal circuits are important for understanding chronic pain. Previous research has demonstrated importance of the nucleus accumbens (NAcc) - medial prefrontal cortex (MPFC) circuit in predicting localized pain chronification in chronic back pain (CBP). The aims of our study were to extend prior evidence of brain reward/value circuit alterations to new cohorts of chronic pain patients and further evaluate activity within reward/value networks in chronic pain. As outlined in our pre-registered plan on the Open Science Framework (OSF, https://osf.io/cj9u8), we hypothesized that resting-state brain reward circuits (i.e., fMRI-indicated NAcc-MPFC resting-state functional connectivity [rsFC] measurements) are altered in patients with fibromyalgia (FM). In a first study, we examined corticostriatal rsFC strength of the NAcc-MPFC circuit in patients with FM (N=17) compared to healthy controls (HC, N=17). Robust NAcc-MPFC functional connectivity was found among patients with FM and HCs, but no significant group differences were observed, indicating intact NAcc-MPFC rsFC in FM. Because previous resting-state studies in patients with CBP involved a pain-monitoring/rating task, in a second study, we compared our results from FM and HC cohorts to a separate cohort of patients with CBP (publicly available dataset, N=31) during resting-state fMRI with no rating task. We again found no significant group differences in NAcc-MPFC rsFC. In a third study, we conducted an expanded analysis of NAcc rsFC to mesolimbic (i.e., subcortical) circuit regions in chronic pain. We found reduced rsFC of the right NAcc with mesolimbic circuit regions (putamen, thalamus, and ventral pallidum) in FM vs. HC, and additional NAcc-mesolimbic alterations across FM and CBP vs. HC groups. Together, our results expand upon prior observed alterations in brain reward circuits, providing novel evidence of intact corticostriatal but altered subcortical-striatal circuits in chronic pain. This project was funded by the National Institutes of Health, National Institute of Drug Abuse (NIDA), K99/R00 DA040154 (awarded to K.T.M.), K24 NS126781 (awarded to S.C.M.), and the Redlich Pain Research Endowment (S.C.M.). Data used in this project from the Open Pain Project (OPP; Principal Investigator: A. Vania Apkarian, PhD, Northwestern University) was funded by the National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Drug Abuse (NIDA).