Exercise promotes neuroplasticity in both healthy and depressed brains: an fMRI pilot study

Memory impairments are a frequently reported cognitive symptom in people suffering from major depressive disorder (MDD) and often persist despite antidepressant therapy. Neuroimaging studies have identified abnormal hippocampal activity during memory processes in MDD. Exercise as an ad-on treatment for MDD is a promising therapeutic strategy shown to improve mood, cognitive function, and neural structure and function. To advance our understanding of how exercise impacts neural function in MDD, we must also understand how exercise impacts healthy individuals without MDD. This pilot study used a subsequent memory paradigm to investigate the effects of an eight-week exercise intervention on hippocampal function in low-active healthy (n=8) and low-active MDD (n=8) individuals. Results showed a marked improvement in depression scores for the MDD group (p0.05). Functional imaging results showed a marginally significant decrease in hippocampal activity in both groups following the exercise intervention. Our whole brain analysis collapsed across groups revealed a similar deactivation pattern across several memory-associated regions. These results suggest that exercise may enhance neural efficiency in low-fit individuals while still resulting in a substantially greater mood effect for those suffering from MDD. This trial is registered with clinical trials.gov NCT03191994

Sensorimotor integration and motor learning during a novel force-matching task in young adults with attention-deficit/hyperactivity disorder

IntroductionAttention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that exhibits unique neurological and behavioral characteristics. Those with ADHD often have noted impairments in motor performance and coordination, including during tasks that require force modulation. The present study provides insight into the role of altered neural processing and SMI in response to a motor learning paradigm requiring force modulation and proprioception, that previous literature has suggested to be altered in those with ADHD, which can also inform our understanding of the neurophysiology underlying sensorimotor integration (SMI) in the general population.MethodsAdults with ADHD (n = 15) and neurotypical controls (n = 15) performed a novel force-matching task, where participants used their right-thumb to match a trace template that varied from 2–12% of their Abductor Pollicis Brevis maximum voluntary contraction. This motor task was completed in pre, acquisition, and post blocks. Participants also completed a retention test 24 h later. Median nerve somatosensory-evoked potentials (SEPs) were collected pre and post motor acquisition. SEPs were stimulated at two frequencies, 2.47 Hz and 4.98 Hz, and 1,000 sweeps were recorded using 64-electrode electroencephalography (EEG) at 2,048 Hz. SEP amplitude changes were normalized to each participant’s baseline values for that peak.ResultsBoth groups improved at post measures (ADHD: 0.85 ± 0.09; Controls: 0.85 ± 0.10), with improvements maintained at retention (ADHD: 0.82 ± 0.11; Controls: 0.82 ± 0.11). The ADHD group had a decreased N18 post-acquisition (0.87 ± 0.48), while the control N18 increased (1.91 ± 1.43). The N30 increased in both groups, with a small increase in the ADHD group (1.03 ± 0.21) and a more pronounced increase in controls (1.15 ± 0.27).DiscussionUnique neural differences between groups were found after the acquisition of a novel force-matching motor paradigm, particularly relating to the N18 peak. The N18 differences suggest that those with ADHD have reduced olivary-cerebellar-M1 inhibition when learning a novel motor task dependent on force-modulation, potentially due to difficulties integrating the afferent feedback necessary to perform the task. The results of this work provide evidence that young adults with ADHD have altered proprioceptive processing when learning a novel motor task when compared to neurotypical controls

Audiovisual Multisensory Integration and Evoked Potentials in Young Adults With and Without Attention-Deficit/Hyperactivity Disorder

The purpose of this study was to assess how young adults with attention-deficit/hyperactivity disorder (ADHD) process audiovisual (AV) multisensory stimuli using behavioral and neurological measures. Adults with a clinical diagnosis of ADHD (n = 10) and neurotypical controls (n = 11) completed a simple response time task, consisting of auditory, visual, and AV multisensory conditions. Continuous 64-electrode electroencephalography (EEG) was collected to assess neurological responses to each condition. The AV multisensory condition resulted in the shortest response times for both populations. Analysis using the race model (Miller, 1982) demonstrated that those with ADHD had violation of the race model earlier in the response, which may be a marker for impulsivity. EEG analysis revealed that both groups had early multisensory integration (MSI) occur following multisensory stimulus onset. There were also significant group differences in event-related potentials (ERPs) in frontal, parietal, and occipital brain regions, which are regions reported to be altered in those with ADHD. This study presents results examining multisensory processing in the population of adults with ADHD, and can be used as a foundation for future ADHD research using developmental research designs as well as the development of novel technological supports

Exercise leads to better clinical outcomes in those receiving medication plus cognitive behavioral therapy for major depressive disorder

Objective: The aim of this study is to investigate the effects of exercise as an add-on therapy with antidepressant medication and cognitive behavioral group therapy (CBGT) on treatment outcomes in low-active major depressive disorder (MDD) patients. We also explored whether exercise reduces the residual symptoms of depression, notably cognitive impairment and poor sleep quality, and aimed to identify putative biochemical markers related to treatment response.Methods: Sixteen low-active MDD patients were recruited from a mental health day treatment program at a local hospital. Eight medicated patients performed an 8-week exercise intervention in addition to CBGT, and eight medicated patients attended the CBGT only. Twenty-two low-active, healthy participants with no history of mental health illness were also recruited to provide normal healthy values for comparison.Results: Results showed that exercise resulted in greater reduction in depression symptoms (p = 0.007, d = 2.06), with 75% of the patients showing either a therapeutic response or a complete remission of symptoms vs. 25% of those who did not exercise. In addition, exercise was associated with greater improvements in sleep quality (p = 0.046, d = 1.28) and cognitive function (p = 0.046, d = 1.08). The exercise group also had a significant increase in plasma brain-derived neurotrophic factor (BDNF), p = 0.003, d = 6.46, that was associated with improvements in depression scores (p = 0.002, R2 = 0.50) and sleep quality (p = 0.011, R2 = 0.38).Conclusion: We provide evidence that exercise as an add-on to conventional antidepressant therapies improved the efficacy of standard treatment interventions. Our results suggest that plasma BDNF levels and sleep quality appear to be good indicators of treatment response and potential biomarkers associated with the clinical recovery of MDD

Subclinical recurrent neck pain and its treatment impacts motor training-induced plasticity of the cerebellum and motor cortex

The cerebellum processes pain inputs and is important for motor learning. Yet, how the cerebellum interacts with the motor cortex in individuals with recurrent pain is not clear. Functional connectivity between the cerebellum and motor cortex can be measured by a twin coil transcranial magnetic stimulation technique in which stimulation is applied to the cerebellum prior to stimulation over the motor cortex, which inhibits motor evoked potentials (MEPs) produced by motor cortex stimulation alone, called cerebellar inhibition (CBI). Healthy individuals without pain have been shown to demonstrate reduced CBI following motor acquisition. We hypothesized that CBI would not reduce to the same extent in those with mild-recurrent neck pain following the same motor acquisition task. We further hypothesized that a common treatment for neck pain (spinal manipulation) would restore reduced CBI following motor acquisition. Motor acquisition involved typing an eight-letter sequence of the letters Z,P,D,F with the right index finger. Twenty-seven neck pain participants received spinal manipulation (14 participants, 18-27 years) or sham control (13 participants, 19-24 years). Twelve healthy controls (20-27 years) also participated. Participants had CBI measured; they completed manipulation or sham control followed by motor acquisition; and then had CBI re-measured. Following motor acquisition, neck pain sham controls remained inhibited (58 ± 33% of test MEP) vs. healthy controls who disinhibited (98 ± 49% of test MEP, P<0.001), while the spinal manipulation group facilitated (146 ± 95% of test MEP, P<0.001). Greater inhibition in neck pain sham vs. healthy control groups suggests that neck pain may change cerebellar-motor cortex interaction. The change to facilitation suggests that spinal manipulation may reverse inhibitory effects of neck pain

Manipulation of dysfunctional spinal joints affects sensorimotor integration in the prefrontal cortex: a brain source localization study

Objectives. Studies have shown decreases in N30 somatosensory evoked potential (SEP) peak amplitudes following spinal manipulation (SM) of dysfunctional segments in subclinical pain (SCP) populations. This study sought to verify these findings and to investigate underlying brain sources that may be responsible for such changes. Methods. Nineteen SCP volunteers attended two experimental sessions, SM and control in random order. SEPs from 62-channel EEG cap were recorded following median nerve stimulation (1000 stimuli at 2.3 Hz) before and after either intervention. Peak-to-peak amplitude and latency analysis was completedfor different SEPs peak. Dipolar models of underlying brain sources were built by using the brain electrical source analysis. Twoway repeated measures ANOVA was used to assessed differences in N30 amplitudes, dipole locations, and dipole strengths. Results. SM decreased the N30 amplitude by 16.9 ± 31.3% (P = 0.02), while no differences were seen following the control intervention (P = 0.4). Brain source modeling revealed a 4-source model but only the prefrontal source showed reduced activity by 20.2 ± 12.2% (P = 0.03) following SM. Conclusion. A single session of spinal manipulation of dysfunctional segments in subclinical pain patients alters somatosensory processing at the cortical level, particularly within the prefrontal cortex

The Interactive Effect of Tonic Pain and Motor Learning on Corticospinal Excitability

Prior work showed differential alterations in early somatosensory evoked potentials (SEPs) and improved motor learning while in acute tonic pain. The aim of the current study was to determine the interactive effect of acute tonic pain and early motor learning on corticospinal excitability as measured by transcranial magnetic stimulation (TMS). Two groups of twelve participants (n = 24) were randomly assigned to a control (inert lotion) or capsaicin (capsaicin cream) group. TMS input–output (IO) curves were performed at baseline, post-application, and following motor learning acquisition. Following the application of the creams, participants in both groups completed a motor tracing task (pre-test and an acquisition test) followed by a retention test (completed without capsaicin) within 24–48 h. Following an acquisition phase, there was a significant increase in the slope of the TMS IO curves for the control group (p < 0.05), and no significant change for the capsaicin group (p = 0.57). Both groups improved in accuracy following an acquisition phase (p < 0.001). The capsaicin group outperformed the control group at pre-test (p < 0.005), following an acquisition phase (p < 0.005), and following a retention test (p < 0.005). When data was normalized to the pre-test values, the learning effects were similar for both groups post-acquisition and at retention (p < 0.005), with no interactive effect of group. The acute tonic pain in this study was shown to negate the increase in IO slope observed for the control group despite the fact that motor performance improved similarly to the control group following acquisition and retention. This study highlights the need to better understand the implications of neural changes accompanying early motor learning, particularly while in pain

Does Location of Tonic Pain Differentially Impact Motor Learning and Sensorimotor Integration?

Recent work found that experimental pain appeared to negate alterations in cortical somatosensory evoked potentials (SEPs) that occurred in response to motor learning acquisition of a novel tracing task. The goal of this experiment was to further investigate the interactive effects of pain stimulus location on motor learning acquisition, retention, and sensorimotor processing. Three groups of twelve participants (n = 36) were randomly assigned to either a local capsaicin group, remote capsaicin group or contralateral capsaicin group. SEPs were collected at baseline, post-application of capsaicin cream, and following a motor learning task. Participants performed a motor tracing acquisition task followed by a pain-free retention task 24–48 h later while accuracy data was recorded. The P25 (p < 0.001) SEP peak significantly decreased following capsaicin application for all groups. Following motor learning acquisition, the N18 SEP peak decreased for the remote capsaicin group (p = 0.02) while the N30 (p = 0.002) SEP peaks increased significantly following motor learning acquisition for all groups. The local, remote and contralateral capsaicin groups improved in accuracy following motor learning (p < 0.001) with no significant differences between the groups. Early SEP alterations are markers of the neuroplasticity that accompanies acute pain and motor learning acquisition. Improved motor learning while in acute pain may be due to an increase in arousal, as opposed to increased attention to the limb performing the task