Prefrontal cortical plasticity during learning of cognitive tasks

Training in working memory tasks is associated with lasting changes in prefrontal cortical activity. To assess the neural activity changes induced by training, we recorded single units, multi-unit activity (MUA) and local field potentials (LFP) with chronic electrode arrays implanted in the prefrontal cortex of two monkeys, throughout the period they were trained to perform cognitive tasks. Mastering different task phases was associated with distinct changes in neural activity, which included recruitment of larger numbers of neurons, increases or decreases of their firing rate, changes in the correlation structure between neurons, and redistribution of power across LFP frequency bands. In every training phase, changes induced by the actively learned task were also observed in a control task, which remained the same across the training period. Our results reveal how learning to perform cognitive tasks induces plasticity of prefrontal cortical activity, and how activity changes may generalize between tasks.

Comparison of Electrophysiological Indices of Children With Attention Deficit Hyperactivity Disorder (ADHD) Comorbid With and Without Reading Disorder (ADHD & RD)

BackgroundAttention Deficit Hyperactivity Disorder (ADHD) is a neuropsychiatric disorder. Most children and adolescents with ADHD have at least some developmental or mental disorders identified from the early years of elementary school. The most common of these are educational and learning problems in these children, which are probably due to the attention deficits of these children. Therefore, it is expected that the cortical activity pattern of ADHD children is different from ADHD comorbid with learning disabilities, which we have examined in this study.MethodsThis study evaluated the pattern of cortical activity in children 6 to 12 years old with ADHD comorbid with and without the reading disorder (ADHD & RD) using 21-channel electroencephalography. Multivariate analysis of variance with repeated measures in a 2 * 3 * 7 design and T-test was used for statistical analysis.ResultsThe results show that in ADHD children, the activity of different bands increases compared to ADHD comorbid with RD children. In the ADHD group compared to the ADHD comorbid with RD group, the theta/beta ratio in all three regions, especially the anterior region, is higher than the theta/alpha activity in those areas, and this group has significantly higher activity in all three brain regions, especially the anterior region, compared to ADHD comorbid with RD patients.ConclusionsFunctional changes in the left parietal cortex, which is part of the frontoparietal attention network and involved in phonological processing, reading, and calculation, are evident in children with ADHD comorbid with and without the reading disorder (ADHD & RD). However, ADHD without reading disorder shows more activation of the frontoparietal network than ADHD comorbid with reading disorder, and therefore it can be said that ADHD without reading disorder exerts more cognitive control. Therefore, it is likely to be possible to prevent educational problems in these children by using neurofeedback or prescribing drugs that increase the activity of the areas involved in attention.

Cochlear implantation restores cortical processing for spatial hearing in asymmetric hearing loss

In asymmetric hearing loss (AHL), the normal pattern of contralateral hemispheric dominance for monaural stimulation is modified, with a shift towards the hemisphere ipsilateral to the better ear. The extent of this shift has been shown to relate to sound localisation deficits. In this study, we examined whether cochlear implantation to treat AHL can restore the normal functional pattern of auditory cortical activity and whether this relates to improved sound localisation. We recruited 10 subjects with a cochlear implant for AHL (AHL-CI) and 10 normally-hearing controls. The participants performed a voice/non-voice discrimination task with binaural and monaural presentation of the sounds, and the cortical activity was measured using positron emission tomography (PET) brain imaging with a H215O tracer. The auditory cortical activity was found to be lower in the AHL-CI participants for all of the conditions. A cortical asymmetry index was calculated and showed that a normal contralateral dominance was restored in the AHL-CI patients for the non-implanted ear, but not for the ear with the cochlear implant. It was found that the contralateral dominance for the non-implanted ear strongly correlated with sound localisation performance (rho = 0.8, p < 0.05). We conclude that the restoration of binaural mechanisms in AHL-CI subjects reverses the abnormal lateralisation pattern induced by the deafness, and that this leads to improved spatial hearing. Our results suggest that cochlear implantation fosters the rehabilitation of binaural excitatory/inhibitory cortical interactions, which could enable the reconstruction of the auditory spatial selectivity needed for sound localisation.

Unexpected Terrain Induced Changes in Cortical Activity in Bipedal-Walking Rats

Humans and other animals can quickly respond to unexpected terrains during walking, but little is known about the cortical dynamics in this process. To study the impact of unexpected terrains on brain activity, we allowed rats with blocked vision to walk on a treadmill in a bipedal posture and then walk on an uneven area at a random position on the treadmill belt. Whole brain EEG signals and hind limb kinematics of bipedal-walking rats were recorded. After encountering unexpected terrain, the θ band power of the bilateral M1, the γ band power of the left S1, and the θ to γ band power of the RSP significantly decreased compared with normal walking. Furthermore, when the rats left uneven terrain, the β band power of the bilateral M1 and the α band power of the right M1 decreased, while the γ band power of the left M1 significantly increased compared with normal walking. Compared with the flat terrain, the θ to low β (3–20 Hz) band power of the bilateral S1 increased after the rats contacted the uneven terrain and then decreased in the single- or double- support phase. These results support the hypothesis that unexpected terrains induced changes in cortical activity.

Excess interictal activity marks seizure prone cortical areas and mice in a genetic epilepsy model

Genetic epilepsies are often caused by variants in widely expressed genes, potentially impacting numerous brain regions and functions. For instance, gain-of-function (GOF) variants in the widely expressed Na+-activated K+ channel gene KCNT1 alter basic neurophysiological and synaptic properties of cortical neurons, leading to developmental epileptic encephalopathy. Yet, aside from causing seizures, little is known about how such variants reshape interictal brain activity, and how this relates to epileptic activity and other disease symptoms. To address this knowledge gap, we monitored neural activity across the dorsal cortex in a mouse model of human KCNT1-related epilepsy using in vivo, awake widefield Ca2+ imaging. We observed 52 spontaneous seizures and 1700 interictal epileptiform discharges (IEDs) in homozygous mutant (Kcnt1m/m) mice, allowing us to map their appearance and spread at high spatial resolution. Outside of seizures and IEDs, we detected ~46,000 events, representing interictal cortical activity, in both Kcnt1m/m and wild-type (WT) mice, and we classified them according to their spatial profiles. Spontaneous seizures and IEDs emerged within a consistent set of susceptible cortical areas, and seizures propagated both contiguously and non-contiguously within these areas in a manner influenced, but not fully determined, by underlying synaptic connectivity. Seizure emergence was predicted by a progressive concentration of total cortical activity within the impending seizure emergence zone. Outside of seizures and IEDs, similar events were detected in WT and Kcnt1m/m mice, suggesting that the spatial structure of interictal activity was largely preserved. Several features of these events, however, were altered in Kcnt1m/m mice. Most event types were briefer, and their intensity more variable, across Kcnt1m/m mice; mice showing more intense activity spent more time in seizure. Furthermore, the rate of events whose spatial profile overlapped with where seizures and IEDs emerged was increased in Kcnt1m/m mice. Taken together, these results demonstrate that an epilepsy-causing K+ channel variant broadly alters physiology. Yet, outside of seizures and IEDs, it acts not to produce novel types of cortical activity, but rather to modulate its amount. The areas where seizures and IEDs emerge show excessively frequent and intense interictal activity and the mean intensity of an individual's cortical activity predicts its seizure burden. These findings provide critical guidance for targeting future research and therapy development.

Sensory cortical dynamics during optical microstimulation training

Primary sensory cortex is a key locus of plasticity during learning. Exposure to novel stimuli often alters cortical activity, but isolating cortex-specific dynamics is challenging due to extensive pre-cortical processing. Here, we employ optical microstimulation of pyramidal neurons in layer (L) 2/3 of mouse primary vibrissal somatosensory cortex (vS1) to study cortical dynamics as mice learn to discriminate microstimulation intensity. Tracking activity over weeks using two-photon calcium imaging, we observe a rapid sparsification of the photoresponsive population, with the most responsive neurons exhibiting the largest declines in responsiveness. Following sparsification, the photoresponsive population attains a stable rate of neuronal turnover. At the same time, the photoresponsive population increasingly overlaps with populations encoding whisker movement and touch. Finally, we find that mice with larger declines in responsiveness learn the task more slowly than mice with smaller declines. Our results reveal that microstimulation-evoked cortical activity undergoes extensive reorganization during task learning and that the dynamics of this reorganization impact perception.

Bi-Anodal Transcranial Direct Current Stimulation Combined With Treadmill Walking Decreases Motor Cortical Activity in Young and Older Adults

Background: Walking in the “real world” involves motor and cognitive processes. In relation to this, declines in both motor function and cognition contribute to age-related gait dysfunction. Transcranial direct current stimulation (tDCS) and treadmill walking (STW) have potential to improve gait, particularly during dual-task walking (DTW); walking whilst performing a cognitive task. Our aims were to analyze effects of combined anodal tDCS + STW intervention on cortical activity and gait during DTW.Methods: Twenty-three young adults (YA) and 21 older adults (OA) were randomly allocated to active or sham tDCS stimulation groups. Participants performed 5-min of mixed treadmill walking (alternating 30 s bouts of STW and DTW) before and after a 20-min intervention of active or sham tDCS + STW. Anodal electrodes were placed over the left prefrontal cortex (PFC) and the vertex (Cz) using 9 cm2 electrodes at 0.6 mA. Cortical activity of the PFC, primary motor cortex (M1), premotor cortex (PMC), and supplementary motor area (SMA) bilaterally were recorded using a functional near-infrared spectroscopy (fNIRS) system. Oxygenated hemoglobin (HbO2) levels were analyzed as indicators of cortical activity. An accelerometer measured gait parameters. We calculated the difference between DTW and STW for HbO2 and gait parameters. We applied linear mixed effects models which included age group (YA vs. OA), stimulation condition (sham vs. active), and time (pre- vs. post-intervention) as fixed effects. Treadmill belt speed was a covariate. Partial correlation tests were also performed.Results: A main effect of age group was observed. OA displayed higher activity bilaterally in the PFC and M1, unilaterally in the right PMC and higher gait variability than YA. M1 activity decreased in both YA and OA following active tDCS + STW. There was no overall effect of tDCS + STW on PFC activity or gait parameters. However, negative correlations were observed between changes in left PFC and stride length variability following active tDCS + STW intervention.Conclusion: Increased activity in multiple cortical areas during DTW in OA may act as a compensatory mechanism. Reduction in M1 activity following active tDCS + STW with no observed gait changes suggests improved neural efficiency.

Regional difference in prefrontal oxygenation prior to and during overground walking in humans: A wearable multi-channel NIRS study

Using wireless multi-channel near-infrared spectroscopy, regional difference in cortical activity over the prefrontal cortex (PFC) was examined prior to and during overground walking, and in response to changes in speed and cognitive demand. Oxygenated-hemoglobin concentration (Oxy-Hb) as index of cortical activity in ventrolateral PFC (VLPFC), dorsolateral PFC (DLPFC), and frontopolar cortex (FPC) was measured in 14 subjects, while heart rate was measured as estimation of exercise intensity in 6 subjects. The impact of mental imagery on prefrontal Oxy-Hb was also explored. On both sides, Oxy-Hb in VLPFC, DLPFC, and lateral FPC was increased prior to the onset of normal speed walking, whereas Oxy-Hb in medial FPC did not respond prior to walking onset. During the walking, Oxy-Hb further increased in bilateral VLPFC, whereas Oxy-Hb was decreased in DLPFC and lateral and medial FPC. Increasing walking speed did not alter the increase in Oxy-Hb in VLPFC but counteracted the decrease in Oxy-Hb in DLPFC (but not in lateral and medial FPC). Treadmill running evoked a greater Oxy-Hb increase in DLPFC (n = 5 subjects). Furthermore, increasing cognitive demand during walking, by deprivation of visual feedback, counteracted the decrease in Oxy-Hb in DLPFC and lateral and medial FPC, but it did not affect the increase in Oxy-Hb in VLPFC. Taken together, the profound and localized Oxy-Hb increase is a unique response for the VLPFC. The regional heterogeneity of the prefrontal Oxy-Hb responses to natural overground walking was accentuated by increasing walking speed or cognitive demand, suggesting functional distinction within the PFC.