Rationale The prepulse inhibition (PPI) of the startle reflex is the best-established index of sensorimotor gating. We documented that the neurosteroid allopregnanolone (AP) is necessary to reduce ...PPI in response to D.sub.1 dopamine receptor agonists. Since Sprague-Dawley (SD) rats are poorly sensitive to the PPI-disrupting effects of these drugs, we hypothesized that AP might increase this susceptibility. Objectives We tested whether AP is sufficient to increase the vulnerability of SD rats to PPI deficits in response to the D.sub.1 receptor full agonist SKF82958. Methods SD rats were tested for PPI after treatment with SKF82958 (0.05-0.3 mg/kg, SC) in combination with either intraperitoneal (1-10 mg/kg) or intracerebral (0.5 mug/mul/side) AP administration into the medial prefrontal cortex (mPFC) or nucleus accumbens shell. To rule out potential confounds, we measured whether SKF82958 affected the endogenous mPFC levels of AP. Results SD rats exhibited marked PPI deficits in response to the combination of systemic and intra-mPFC AP with SKF82958 but not with the D.sub.2 receptor agonist quinpirole (0.3-0.6 mg/kg, SC). SKF82958 did not elevate mPFC levels of AP but enhanced the content of its precursor progesterone. The PPI deficits caused by SKF82958 in combination with AP were opposed by the AP antagonist isoallopregnanolone (10 mg/kg, IP) and the glutamate NMDA receptor positive modulator CIQ (5 mg/kg, IP). Conclusion These results suggest that AP enables the detrimental effects of D.sub.1 receptor activation on sensorimotor gating. AP antagonism or glutamatergic modulation counters these effects and may have therapeutic potential for neuropsychiatric disorders characterized by gating deficits.
Human movement synchronisation with moving objects strongly relies on visual input. However, auditory information also plays an important role, since real environments are intrinsically multimodal. ...We used electroencephalography (EEG) frequency tagging to investigate the selective neural processing and integration of visual and auditory information during motor tracking and tested the effects of spatial and temporal congruency between audiovisual modalities. EEG was recorded while participants tracked with their index finger a red flickering (rate f.sub.V = 15 Hz) dot oscillating horizontally on a screen. The simultaneous auditory stimulus was modulated in pitch (rate f.sub.A = 32 Hz) and lateralised between left and right audio channels to induce perception of a periodic displacement of the sound source. Audiovisual congruency was manipulated in terms of space in Experiment 1 (no motion, same direction or opposite direction), and timing in Experiment 2 (no delay, medium delay or large delay). For both experiments, significant EEG responses were elicited at f.sub.V and f.sub.A tagging frequencies. It was also hypothesised that intermodulation products corresponding to the nonlinear integration of visual and auditory stimuli at frequencies f.sub.V ± f.sub.A would be elicited, due to audiovisual integration, especially in Congruent conditions.sub.. However, these components were not observed. Moreover, synchronisation and EEG results were not influenced by congruency manipulations, which invites further exploration of the conditions which may modulate audiovisual processing and the motor tracking of moving objects.
Working memory (WM) is a capacity- and duration-limited system that forms a temporal bridge between fleeting sensory phenomena and possible actions. But how are the contents of WM used to guide ...behavior? A recent high-profile study reported evidence for simultaneous access to WM content and linked motor plans during WM-guided behavior, challenging serial models where task-relevant WM content is first selected and then mapped on to a task-relevant motor response. However, the task used in that study was not optimized to distinguish the selection of spatial versus nonspatial visual information stored in memory, nor to distinguish whether or how the chronometry of selecting nonspatial visual information stored in memory might differ from the selection of linked motor plans. Here, we revisited the chronometry of spatial, feature, and motor selection during WM-guided behavior using a task optimized to disentangle these processes. Concurrent EEG and eye position recordings revealed clear evidence for temporally dissociable spatial, feature, and motor selection during this task. Thus, our data reveal the existence of multiple WM selection mechanisms that belie conceptualizations of WM-guided behavior based on purely serial or parallel visuomotor processing.
Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data ...analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.
•Afferent stimulation elicited a greater corticospinal drive to lumbar multifidus muscles in CLBP in comparison to controls.•Afferent stimulation alone elicited a larger reduction in paravertebral ...muscles activity compared to controls.•These results suggest an alteration of sensorimotor integration in our sample of participants with chronic low back pain.
Chronic low back pain (CLBP) impacts on spine movement. Altered sensorimotor integration can be involved. Afferents from the lumbo-pelvic area might be processed differently in CLBP and impact on descending motor control. This study aimed to determine whether afferents influence the corticomotor control of paravertebral muscles in CLBP.
Fourteen individuals with CLBP (11 females) and 13 pain-free controls (8 females) were tested with transcranial magnetic stimulation (TMS) to measure the motor-evoked potential MEP amplitude of paravertebral muscles. Noxious and non-noxious electrical stimulation, and magnetic stimulation in the lumbo-sacral area were used as afferent stimuli and triggered 20 to 200 ms prior to TMS. EMG modulation elicited by afferent stimulation alone was measured to control net motoneuron excitability. MEP/EMG ratio was used as a measure of corticospinal excitability with control of net motoneuron excitability. MEP/ EMG ratio was larger at 60, 80 and 100-ms intervals in CLBP compared to controls, and afferent stimulations alone reduced EMG amplitude greater in CLBP than controls at 100 ms. Our results suggest alteration in sensorimotor integration in CLBP highlighted by a greater facilitation of the descending corticospinal input to paravertebral muscles. Our results can help to optimise interventions by better targeting mechanisms.
Our past anecdotal evidence prompted that a longer response window (RW) in the Trivector test (Cambridge Colour Test) improved mature observers' estimates of chromatic discrimination. Here, we ...systematically explored whether RW variation affects chromatic discrimination thresholds measured by the length of Protan, Deutan and Tritan vectors. We employed the Trivector test with three RWs: 3 s, 5 s, and 8 s. Data of 30 healthy normal trichromats were stratified as age groups: 'young' (20-29 years), 'middle-aged' (31-48 years), and 'mature' (57-64 years). We found that for the 'young' and 'middle-aged', the thresholds were comparable at all tested RWs. However, the RW effect was apparent for the 'mature' observers: their Protan and Tritan thresholds decreased at 8-s RW compared to 3-s RW; moreover, their Tritan threshold decreased at 5-s RW compared to 3-s RW. Elevated discrimination thresholds at shorter RWs imply that for accurate performance, older observers require longer stimulus exposure and are indicative of ageing effects manifested by an increase in critical processing duration. Acknowledging low numbers in our 'middle-aged' and 'mature' samples, we consider our study as pilot. Nonetheless, our findings encourage us to advocate a RW extension in the Trivector protocol for testing mature observers, to ensure veridical measures of their chromatic discrimination by disentangling these from other ageing effects-slowing down of both motor responses and visual processing.
Neuronal populations in sensory cortex produce variable responses to sensory stimuli and exhibit intricate spontaneous activity even without external sensory input. Cortical variability and ...spontaneous activity have been variously proposed to represent random noise, recall of prior experience, or encoding of ongoing behavioral and cognitive variables. Recording more than 10,000 neurons in mouse visual cortex, we observed that spontaneous activity reliably encoded a high-dimensional latent state, which was partially related to the mouse's ongoing behavior and was represented not just in visual cortex but also across the forebrain. Sensory inputs did not interrupt this ongoing signal but added onto it a representation of external stimuli in orthogonal dimensions. Thus, visual cortical population activity, despite its apparently noisy structure, reliably encodes an orthogonal fusion of sensory and multidimensional behavioral information.
Timing is critical to most forms of learning, behavior, and sensory-motor processing. Converging evidence supports the notion that, precisely because of its importance across a wide range of brain ...functions, timing relies on intrinsic and general properties of neurons and neural circuits; that is, the brain uses its natural cellular and network dynamics to solve a diversity of temporal computations. Many circuits have been shown to encode elapsed time in dynamically changing patterns of neural activity—so-called population clocks. But temporal processing encompasses a wide range of different computations, and just as there are different circuits and mechanisms underlying computations about space, there are a multitude of circuits and mechanisms underlying the ability to tell time and generate temporal patterns.
Temporal processing is among the most fundamental computations the brain performs. Paton and Buonomano review recent experimental and theoretical advances in the field and conclude that timing relies in part on the natural dynamics of neurons and neural circuits.
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