Neurophysiological Substrates Research Articles

Symposium Title: The Regulation of Affective and Social Behaviors: Neurophysiological Substrates

Symposium Title: The Regulation of Affective and Social Behaviors: Neurophysiological Substrates

Cortical excitability in migraine: Contributions of magnetic resonance imaging.

Migraine is characterized by symptoms related to cortical hyperexcitability such as photophobia, phonophobia, osmophobia and allodynia. One-third of migraineurs experience aura, whose neurophysiological substrate is thought to be cortical spreading depression (CSD). Functional magnetic resonance imaging (MRI) has shown the migraine aura to be characterized by cerebral hyperactivity/hyperperfusion followed by hypometabolism/hypoperfusion spreading along the occipital cortex with the same spatiotemporal organization as the experimentally triggered CSD. The link between migraine aura and headache remains undetermined. Neuroimaging studies have failed to show a leakage of the blood-brain barrier, which was suspected to occur during CSD and to cause the stimulation of trigeminal nociceptive receptors. However, recent studies have highlighted the involvement of neuroglial inflammation and other studies have suggested that a common central network plays a role in the link between CSD and migraine pain. Finally, MRI has made it possible to study the contribution of metabolites such as glutamic acid, γ-amino-butyric acid and sodium in the pathophysiology of hyperexcitability in migraine.

Aperiodic sleep networks promote memory consolidation.

Hierarchical synchronization of sleep oscillations establishes communication pathways to support memory reactivation, transfer, and consolidation. From an information-theoretical perspective, oscillations constitute highly structured network states that provide limited information-coding capacity. Recent findings indicate that sleep oscillations occur in transient bursts that are interleaved with aperiodic network states, which were previously considered to be random noise. We argue that aperiodic activity exhibits unique and variable spatiotemporal patterns, providing an ideal information-rich neurophysiological substrate for imprinting new mnemonic patterns onto existing circuits. We discuss novel avenues in conceptualizing and quantifying aperiodic network states during sleep to further understand their relevance and interplay with sleep oscillations in support of memory consolidation.

Low-Resolution Neurocognitive Aging and Cognition: An Embodied Perspective.

Consistent with embodied cognition, a growing evidence in young adults show that sensorimotor processing is at the core of cognition. Considering that this approach predicts direct interaction between sensorimotor processing and cognition, embodied cognition may thus be particularly relevant to study aging, since this population is characterized by concomitant changes in sensorimotor and cognitive processing. The present perspective aims at showing the value and interest to explore normal aging throughout embodiment by focusing on the neurophysiological and cognitive changes occurring in aging. To this end, we report some of the neurophysiological substrates underpinning the perceptual and memory interactions in older adults, from the low and high perceptual processing to the conjunction in the medial temporal lobe. We then explore how these changes could explain more broadly the cognitive changes associated with aging in terms of losses and gains.

Detection of functional and structural brain alterations in female schizophrenia using elastic net logistic regression

Neuroimaging technique is a powerful tool to characterize the abnormality of brain networks in schizophrenia. However, the neurophysiological substrate of schizophrenia is still unclear. Here we investigated the patterns of brain functional and structural changes in female patients with schizophrenia using elastic net logistic regression analysis of resting-state functional magnetic resonance imaging data. Data from 52 participants (25 female schizophrenia patients and 27 healthy controls) were obtained. Using an elastic net penalty, the brain regions most relevant to schizophrenia pathology were defined in the models using the amplitude of low-frequency fluctuations (ALFF) and gray matter, respectively. The receiver operating characteristic analysis showed reliable classification accuracy with 85.7% in ALFF analysis, and 77.1% in gray matter analysis. Notably, our results showed eight common regions between the ALFF and gray matter analyses, including the Frontal-Inf-Orb-R, Rolandic-Oper-R, Olfactory-R, Angular-L, Precuneus-L, Precuenus-R, Heschl-L, and Temporal-Pole-Mid-R. In addition, the severity of symptoms was found positively associated with the ALFF within the Rolandic-Oper-R and Frontal-Inf-Orb-R. Our findings indicated that elastic net logistic regression could be a useful tool to identify the characteristics of schizophrenia -related brain deterioration, which provides novel insights into schizophrenia diagnosis and prediction.

Psychophysiological Markers of Performance and Learning during Simulated Marksmanship in Immersive Virtual Reality.

The fusion of immersive virtual reality, kinematic movement tracking, and EEG offers a powerful test bed for naturalistic neuroscience research. Here, we combined these elements to investigate the neuro-behavioral mechanisms underlying precision visual-motor control as 20 participants completed a three-visit, visual-motor, coincidence-anticipation task, modeled after Olympic Trap Shooting and performed in immersive and interactive virtual reality. Analyses of the kinematic metrics demonstrated learning of more efficient movements with significantly faster hand RTs, earlier trigger response times, and higher spatial precision, leading to an average of 13% improvement in shot scores across the visits. As revealed through spectral and time-locked analyses of the EEG beta band (13-30 Hz), power measured prior to target launch and visual-evoked potential amplitudes measured immediately after the target launch correlated with subsequent reactive kinematic performance in the shooting task. Moreover, both launch-locked and shot/feedback-locked visual-evoked potentials became earlier and more negative with practice, pointing to neural mechanisms that may contribute to the development of visual-motor proficiency. Collectively, these findings illustrate EEG and kinematic biomarkers of precision motor control and changes in the neurophysiological substrates that may underlie motor learning.

Neural correlates of citalopram and placebo response in acute bipolar depression: A randomized trial

While serotonin reuptake inhibitors are sometimes used in clinical practice to treat acute bipolar depression, the neurophysiological substrates underlying their efficacy are little studied. In the context of a larger clinical efficacy trial, the present study explored neural mechanisms associated with citalopram versus placebo treatment for bipolar depression. FDG-PET imaging examined whole-brain metabolic changes before and after treatment. Clinical efficacy was similar for citalopram versus placebo. Neuroimaging results demonstrated greater glucose metabolism in the left orbitofrontal cortex (OFC) before treatment (combined citalopram and placebo subjects) relative to after treatment, but did not correlate with clinical recovery. Glucose metabolism in the left OFC was also a predictor of depression severity when baseline scans were regressed with baseline MADRS scores. Despite of our small sample size and possibly underpowered whole-brain analysis approach, these preliminary results suggest the OFC, a key region involved in reward circuity, may be a neural substrate for depressive symptom improvement in bipolar depression, regardless of whether due to active treatment or placebo.

The Neurophysiological Basis of the Trial-Wise and Cumulative Ventriloquism Aftereffects.

Our senses often receive conflicting multisensory information, which our brain reconciles by adaptive recalibration. A classic example is the ventriloquism aftereffect, which emerges following both cumulative (long-term) and trial-wise exposure to spatially discrepant multisensory stimuli. Despite the importance of such adaptive mechanisms for interacting with environments that change over multiple timescales, it remains debated whether the ventriloquism aftereffects observed following trial-wise and cumulative exposure arise from the same neurophysiological substrate. We address this question by probing electroencephalography recordings from healthy humans (both sexes) for processes predictive of the aftereffect biases following the exposure to spatially offset audiovisual stimuli. Our results support the hypothesis that discrepant multisensory evidence shapes aftereffects on distinct timescales via common neurophysiological processes reflecting sensory inference and memory in parietal-occipital regions, while the cumulative exposure to consistent discrepancies additionally recruits prefrontal processes. During the subsequent unisensory trial, both trial-wise and cumulative exposure bias the encoding of the acoustic information, but do so distinctly. Our results posit a central role of parietal regions in shaping multisensory spatial recalibration, suggest that frontal regions consolidate the behavioral bias for persistent multisensory discrepancies, but also show that the trial-wise and cumulative exposure bias sound position encoding via distinct neurophysiological processes.SIGNIFICANCE STATEMENT Our brain easily reconciles conflicting multisensory information, such as seeing an actress on screen while hearing her voice over headphones. These adaptive mechanisms exert a persistent influence on the perception of subsequent unisensory stimuli, known as the ventriloquism aftereffect. While this aftereffect emerges following trial-wise or cumulative exposure to multisensory discrepancies, it remained unclear whether both arise from a common neural substrate. We here rephrase this hypothesis using human electroencephalography recordings. Our data suggest that parietal regions involved in multisensory and spatial memory mediate the aftereffect following both trial-wise and cumulative adaptation, but also show that additional and distinct processes are involved in consolidating and implementing the aftereffect following prolonged exposure.

Rehabilitation of cortically induced visual field loss.

Homonymous visual field defects are a common sequela of stroke, and are assumed to be permanent within a few weeks of the event. Because consensus about the efficacy of rehabilitation is lacking, visual therapy is rarely prescribed. Here, we review current rehabilitation options and strategies in the translational pipeline that could change these perspectives. The mainstays of available therapy for homonymous visual defects are compensation training and substitution, which allow patients to better use their spared vision. However, early clinical studies suggest that vision can partially recover following intensive training inside the blind field. Research into the relative efficacy of different restorative approaches continues, providing insights into neurophysiologic substrates of recovery and its limitations. This, in turn, has led to new work examining the possible benefits of earlier intervention, advanced training procedures, noninvasive brain stimulation, and pharmacological adjuvants, all of which remain to be vetted through properly powered, randomized, clinical trials. Research has uncovered substantial visual plasticity after occipital strokes, suggesting that rehabilitative strategies for this condition should be more aggressive. For maximal benefit, poststroke vision-restorative interventions should begin early, and in parallel with strategies that optimize everyday use of an expanding field of view.

Differential effects of motor skill acquisition on the primary motor and sensory cortices in healthy humans

We explored the large variability in motor skill acquisition-related effects on the primary and sensory cortices. Namely, we tested whether this variability depends on interindividual variance or the type of motor task investigated. We compared different motor-learning tasks, i.e. model-free vs. model-based learning tasks, and their possible differential effects on the primary motor and sensory cortices by using transcranial magnetic stimulation techniques. The model-free learning task induced an increase in corticospinal excitability and a reduction in the amplitude of somatosensory-evoked potentials. Conversely, the model-based learning tasks induced a decrease in intracortical inhibition. No correlations were found between neurophysiological changes and motor performance, indicating that this differential modulation may be secondary to the motor skill acquisition. The study results suggest differential motor skill acquisition-related effects on cortical parameters, possibly due to the engagement of specific neurophysiological substrates. A large variability in learning-related neurophysiological changes in the primary motor and sensory cortices has been observed. It is unclear whether these differential effects are due to the different tasks investigated or to interindividual variance. Only a few studies have assessed different motor-learning tasks and their effects on neurophysiological features within the same group of participants, and several issues are unclear. Here, we compared the effects of different tasks within each individual. We investigated the effects on motor and sensory cortex parameters after a model-free learning task, i.e. a ballistic motor task, compared with model-based learning tasks, i.e. visuomotor-learning tasks. Motor- and sensory-evoked potentials, intracortical excitability as assessed by short-interval intracortical inhibition, and sensorimotor interaction, i.e. short-latency afferent inhibition, were recorded from 15 healthy subjects before and after the tasks. The ballistic motor task induced an increase in corticospinal excitability but did not change motor cortex intracortical inhibition or sensorimotor integration. In addition, it decreased the amplitude of cortical components of the somatosensory-evoked potentials. The visuomotor-learning tasks induced a reduction in motor cortex intracortical inhibition but did not modulate corticospinal and sensory cortex excitability or sensorimotor integration. This differential modulation is likely to be secondary to the motor skill acquisition, since no correlation was observed between neurophysiological changes and motor performance. Our results demonstrate differential motor skill acquisition-related effects on cortical parameters, possibly reflecting the engagement of specific neurophysiological substrates, and contribute in-depth knowledge of the mechanisms involved in different types of motor skill acquisition in humans.

Bradykinesia in Alzheimer’s disease and its neurophysiological substrates

ObjectiveAlzheimer’s disease is primarily characterized by cognitive decline; recent studies, however, emphasize the occurrence of motor impairment in this condition. Here, we investigate whether motor impairment, objectively evaluated with kinematic techniques, correlates with neurophysiological measures of the primary motor cortex in Alzheimer’s disease. MethodsTwenty patients and 20 healthy subjects were enrolled. Repetitive finger tapping was assessed by means of a motion analysis system. Primary motor cortex excitability was assessed by recording the input/output curve of the motor-evoked potentials and using a conditioning-test paradigm for the assessment of short-interval intracortical inhibition and short-latency afferent inhibition. Plasticity-like mechanisms were indexed according to changes in motor-evoked potential amplitude induced by the intermittent theta-burst stimulation. ResultsPatients displayed slowness and altered rhythm during finger tapping. Movement slowness correlated with reduced short-latency afferent inhibition in patients, thus suggesting that degeneration of the cholinergic system may also be involved in motor impairment in Alzheimer’s disease. Moreover, altered movement rhythm in patients correlated with worse scores in the Frontal Assessment Battery. ConclusionThis study provides new information on the pathophysiology of altered voluntary movements in Alzheimer’s disease. SignificanceThe study results suggest that a cortical cholinergic deficit may underlie movement slowness in Alzheimer’s disease.

Reactivated Spatial Context Guides Episodic Recall

The medial temporal lobe (MTL) is known as the locus of spatial coding and episodic memory, but the interaction between these cognitive domains as well as the extent to which they rely on common neurophysiological mechanisms is poorly understood. Here, we use intracranial electroencephalography and a hybrid spatial-episodic memory task (29 subjects, 15 female) to determine how spatial information is dynamically reactivated in subregions of the human MTL and how this reactivation guides recall of episodic information. Our results implicate theta oscillations across the MTL as a common neurophysiological substrate for spatial coding in navigation and episodic recall. We further show that our index of retrieved spatial context is high in the hippocampus (HC) in an early time window preceding recall. Closer to recall, it decreases in the HC and increases in the parahippocampal gyrus. Finally, we demonstrate that hippocampal theta phase modulates parahippocampal gamma amplitude during retrieval of spatial context, suggesting a role for cross-frequency coupling in coding and transmitting retrieved spatial information.SIGNIFICANCE STATEMENT By recording from the human medial temporal lobe (MTL) while subjects recall items experienced in a virtual environment, we establish a direct relation between the strength of theta activity during memory search and the extent to which memories are organized by their spatial locations. We thereby pinpoint a role for theta oscillations in accessing the "cognitive map" during episodic retrieval and further highlight the dynamic interplay of hippocampus and extrahippocampal MTL in representing retrieved spatial context. Our results provide an important step toward a unified theory of MTL function encompassing its role in spatial navigation and episodic memory.

The Neurophysiological Substrate of the Decision-Making Process in Depressed Patients

Background: The neural circuits involved in the decision-making process and social emotion participate in the same circuits seen in major depressive disorder. This study aimed to investigate in depressed patients, the decision making process in risk/reward situations using neurophysiological methods for a better assessment of functional aspects related to decision making deficit that are seen in major depression. Methods: Forty patients were studied, 20 with depression and 20 without. After applied the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and Hamilton Depression scale (HAM-D), the Iowa Gambling Task (IGT) was applied to analyze the risk/ reward decision-making behavior. The Skin Conductance Response (SCR) was recorded to analyze the emotional anticipatory learning effect during the IGT. Besides, an EEG was recorded to measure the Frontal Alpha Asymmetry Index (FAAI). Results: Depressed patients presented a lower Net score and a deficit in anticipatory learning effect in the IGT. Furthermore, the FAAI revealed more frontal right activation as have described in previous studies. Conclusion: Patients with major depression have a dysfunction in the circuits that modulate cognitive, emotional and social behavior, and also, impairment in cognitive fluidity for evaluating strategies for risk-reward. The EEG helps to confirm that asymmetry in frontal areas and oscillation of alpha frequencies participate in the regulation of emotion in depressed patients.

Neurophysiological substrates of configural face perception in schizotypy

Face perception is a highly developed function of the human visual system. Previous studies of event-related potentials (ERPs) have identified a face-selective ERP component (negative peak at about 170 ms after stimulus onset, N170) in healthy participants. In contrast, patients with schizophrenia exhibit reduced amplitude of the N170, which may represent a pathological deficit in the neurophysiology of face perception. Interestingly, healthy humans with schizophrenia-like experiences (schizotypy) also exhibit abnormal processing of face perception. Yet, it has remained unknown how schizotypy in healthy humans is associated with the neurophysiological substrates of face perception. Here, we recruited 35 healthy participants and assessed their schizotypy by the magical ideation rating scale. We used high-density electroencephalography to obtain ERPs elicited by a set of Mooney faces (face and non-face visual stimuli). We investigated median and mean reaction times and visual ERP components in response to the stimuli. We observed a significant difference in N170 amplitude between the two face-stimulus conditions and found that the measured schizotypy scores were significantly correlated with both reaction times and N170 amplitude in response to the face stimuli across all participants. Our results thus support the model of schizotypy as a manifestation of a continuum between healthy individuals and patients with schizophrenia, where the N170 impairment serves as a biomarker for the degree of pathology along this continuum.

The role of cortical areas hMT/V5+ and TPJ on the magnitude of representational momentum and representational gravity: a transcranial magnetic stimulation study.

The perceived vanishing location of a moving target is systematically displaced forward, in the direction of motion-representational momentum-, and downward, in the direction of gravity-representational gravity. Despite a wealth of research on the factors that modulate these phenomena, little is known regarding their neurophysiological substrates. The present experiment aims to explore which role is played by cortical areas hMT/V5+, linked to the processing of visual motion, and TPJ, thought to support the functioning of an internal model of gravity, in modulating both effects. Participants were required to perform a standard spatial localization task while the activity of the right hMT/V5+ or TPJ sites was selectively disrupted with an offline continuous theta-burst stimulation (cTBS) protocol, interspersed with control blocks with no stimulation. Eye movements were recorded during all spatial localizations. Results revealed an increase in representational gravity contingent on the disruption of the activity of hMT/V5+ and, conversely, some evidence suggested a bigger representational momentum when TPJ was stimulated. Furthermore, stimulation of hMT/V5+ led to a decreased ocular overshoot and to a time-dependent downward drift of gaze location. These outcomes suggest that a reciprocal balance between perceived kinematics and anticipated dynamics might modulate these spatial localization responses, compatible with a push-pull mechanism.

Electroencephalographic (EEG) alterations in young women with high subclinical eating pathology levels: a quantitative EEG study.

To explore electroencephalographic (EEG) alterations in young women with different eating disorder (ED) psychopathology levels. Thirty-seven young women completed general and ED psychopathology (i.e., the ED Examination Questionnaire; EDE-Q) measures. EEG power spectra data were investigated in two conditions: (a) 5 min of resting state (RS) and (b) 5 min of RS after a single taste of a milkshake (ML-RS). EEG analyses were performed using exact Low-Resolution Electromagnetic Tomography software (eLORETA). Cluster analysis performed on the EDE-Q responses revealed a group of 17 women with high levels of ED pathology falling into the subclinical (i.e., sub-threshold) EDs category and a group of 20 women with low levels of ED pathology (controls). In the RS conditions, no significant modifications were observed between groups. Compared to controls, women with subclinical EDs showed an increase in theta activity in the parieto-occipital areas in the ML-RS condition. After controlling for body mass index and general psychopathology, theta activity in these brain structures was positively associated with EDE-Q global and subscale (restraint, shape and weight concern) scores. Our results may reflect the neurophysiological substrate of ED psychopathology core features like shape/weight concerns. Previous brain imaging and qEEG studies with full-syndrome ED patients also underscored the involvement of parieto-occipital areas in ED pathophysiology. These studies also found brain alterations in the RS condition, not observed here. This is notable given that full-syndrome and subclinical EDs are considered as different manifestations of the same disease along a severity spectrum. Level V, cross-sectional, electroencephalographic, descriptive study.

Fine-Grained Parcellation of the Macaque Nucleus Accumbens by High-Resolution Diffusion Tensor Tractography

Limited in part by the spatial resolution of typical in vivo magnetic resonance imaging (MRI) data, recent neuroimaging studies have only identified a connectivity-based shell-core-like partitioning of the nucleus accumbens (Acb) in humans. This has hindered the process of making a more refined description of the Acb using non-invasive neuroimaging technologies and approaches. In this study, high-resolution ex vivo macaque brain diffusion MRI data were acquired to investigate the tractography-based parcellation of the Acb. Our results identified a shell-core-like partitioning in macaques that is similar to that in humans as well as an alternative solution that subdivided the Acb into four parcels, the medial shell, the lateral shell, the ventral core, and the dorsal core. Furthermore, we characterized the specific anatomical and functional connectivity profiles of these Acb subregions and generalized their specialized functions to establish a fine-grained macaque Acb brainnetome atlas. This atlas should be helpful in neuroimaging, stereotactic surgery, and comparative neuroimaging studies to reveal the neurophysiological substrates of various diseases and cognitive functions associated with the Acb.

Gamma tACS over the temporal lobe increases the occurrence of Eureka! moments

The solution to a problem might manifest itself as a burst of unexpected, unpredictable clarity. Such Eureka! events, or Insight moments, are among the most fascinating mysteries of human cognition, whose neurophysiological substrate seems to include a role for oscillatory activity within the α and γ bands in the right parietal and temporal brain regions. We tested this hypothesis on thirty-one healthy participants using transcranial Alternating Current Stimulation (tACS) to externally amplify α (10 Hz) and γ (40 Hz) activity in the right parietal and temporal lobes, respectively. During γ-tACS over the right temporal lobe, we observed an increase in accuracy on a verbal insight task. Furthermore, electroencephalography (EEG) data revealed an increase in γ spectral power over bilateral temporal lobes after stimulation. Additionally, resting-state functional MRI data acquired before the stimulation session suggested a correlation between behavioral response to right temporal lobe tACS and functional connectivity of bilateral temporal lobes, in line with the bilateral increase in γ band revealed by EEG. Overall, results suggest the possibility of enhancing the probability of generating Eureka! moments in humans by means of frequency-specific noninvasive brain stimulation.

Нейроэнергетические корреляты психоэмоциональных феноменов (проявлений) климактерического синдрома

Introduction. Studying psychoneurophysiological correlates in perimenopausal women is of great theoretical and practical importance, since it may help in identifying common and gender-specific patterns of aging. The menopausal syndrome and the neurophysiological substrate underlying the phenomena of psychological maladjustment in menopausal women merit special attention. This study reveals previously unknown neuro-energetic correlates of psycho-emotional characteristics of the climacteric syndrome.
 Methods. This study involved menopausal women with and without manifestations of the menopausal syndrome and reproductive-age women with the normal menstrual cycle. Using the questioning method the authors examined the respondents’ personality traits. After averaging over groups, these personality characteristics were compared with the constant potential level (CPL) in frontal, central, occipital, right and left temporal regions of the cortex, which was registered by the Neuro-energo-cartograph NEC-5 hardware/software complex. The CPL was assessed by means of a special embedded math program. This helped to distinguish the local and the average CPLs, CPL gradients between unipolar values and to map the obtained data on the computer screen.
 Results. The findings of the study indicated a positive correlation between the expression of situational anxiety and unmotivated aggressiveness and the increased CPL in the occipital and temporal cortex in women with the climacteric syndrome.
 Discussion. For the first time in the study of the female climacterium, the use of registration and neuro-energetic mapping of the CPLs in various regions of the cerebral cortex and their correlations with psycho-emotional characteristics helped to identify the intensity and topography of energy metabolism in the brain, which is an integral neurophysiological substrate for psycho-emotional manifestations of the climacteric syndrome. The registration of the CPLs enabled authors to correlate the intensity and topography of energy metabolism in various regions of the cortex with psycho-emotional characteristics of the climacteric syndrome.

The Firing Rate Speed Code of Entorhinal Speed Cells Differs across Behaviorally Relevant Time Scales and Does Not Depend on Medial Septum Inputs.

The firing rate of speed cells, a dedicated subpopulation of neurons in the medial entorhinal cortex (MEC), is correlated with running speed. This correlation has been interpreted as a speed code used in various computational models for path integration. These models consider firing rate to be linearly tuned by running speed in real-time. However, estimation of firing rates requires integration of spiking events over time, setting constraints on the temporal accuracy of the proposed speed code. We therefore tested whether the proposed speed code by firing rate is accurate at short time scales using data obtained from open-field recordings in male rats and mice. We applied a novel filtering approach differentiating between speed codes at multiple time scales ranging from deciseconds to minutes. In addition, we determined the optimal integration time window for firing-rate estimation using a general likelihood framework and calculated the integration time window that maximizes the correlation between firing rate and running speed. Data show that these time windows are on the order of seconds, setting constraints on real-time speed coding by firing rate. We further show that optogenetic inhibition of either cholinergic, GABAergic, or glutamatergic neurons in the medial septum/diagonal band of Broca does not affect modulation of firing rates by running speed at each time scale tested. These results are relevant for models of path integration and for our understanding of how behavioral activity states may modulate firing rates and likely information processing in the MEC.SIGNIFICANCE STATEMENT Path integration is the most basic form of navigation relying on self-motion cues. Models of path integration use medial septum/diagonal band of Broca (MSDB)-dependent MEC grid-cell firing patterns as the neurophysiological substrate of path integration. These models use a linear speed code by firing rate, but do not consider temporal constraints of integration over time for firing-rate estimation. We show that firing-rate estimation for speed cells requires integration over seconds. Using optogenetics, we show that modulation of firing rates by running speed is independent of MSDB inputs. These results enhance our understanding of path integration mechanisms and the role of the MSDB for information processing in the MEC.