Impaired awareness: Why people with multiple sclerosis continue using cannabis despite evidence to the contrary.

BACKGROUND: With widespread moves toward legalization of cannabis, increasing numbers of people with multiple sclerosis (pwMS) are using the drug. Emerging MS-related data show that cannabis can cause or exacerbate cognitive dysfunction. OBJECTIVE: To understand why people with MS continue using cannabis despite adverse cognitive consequences. It was hypothesized that lack of awareness, a component of metacognition, could explain this decision, in part. METHOD: Forty pwMS who smoked cannabis almost daily were assigned by odd-even case number selection to either a cannabis continuation (CC) or cannabis withdrawal (CW) group. Both groups were followed for 28 days. All participants completed, at baseline and day 28, the brief repeatable battery of neuropsychological tests (BRNB) in MS for measures of processing speed, memory and executive function; Modified fatigue impact scale (mFIS) for self-report indices of cognitive functioning. RESULTS: No significant baseline differences between the groups on the BRNB and mFIS. At day 28, significant improvement within group was seen on all measures of the BRNB, but only in the CW group (p = .0001 for all indices). A repeat measure ANOVA did not find any significant group (CC vs. CW) × time (baseline and day 28) interactions for the self-report cognitive measures on the mFIS. Cannabis abstainers did report less ability to function away from home. All 19 participants in the CW group reverted to using cannabis on study completion despite being informed individually of their cognitive improvement. CONCLUSIONS AND RELEVANCE: The inability of pwMS to accurately appraise their memory and executive function can help explain, in part, why they continue to smoke cannabis despite objective evidence of the deleterious cognitive side effects of this behavior.

The influence of an acute bout of moderate-intensity cycling exercise on sensorimotor integration.

Acute cycling exercise can modulate motor cortical circuitry in the non-exercised upper-limb. Within the primary motor cortex, measures of intracortical inhibition are reduced and intracortical facilitation is enhanced following acute exercise. Further, acute cycling exercise decreases interhemispheric inhibition between the motor cortices and lowers cerebellar-to-motor cortex inhibition. Yet, investigations into the effects of acute exercise on sensorimotor integration, referring to the transfer of incoming afferent information from the primary somatosensory cortex to motor cortex, are lacking. The current work addresses this gap in knowledge with two experimental sessions. In the first session, we tested the exercise-induced changes in somatosensory and motor excitability by assessing somatosensory (SEP) and motor evoked potentials (MEPs). In the second session, we explored the effects of acute cycling exercise on short- (SAI) and long-latency afferent inhibition (LAI), and afferent facilitation. In both experimental sessions, neurophysiological measures were obtained from the non-exercised upper-limb muscle, tested at two time points pre-exercise separated by a 25-min period of rest. Next, a 25-min bout of moderate-intensity lower-limb cycling was performed with measures assessed at two time points post-exercise. Acute lower-limb cycling increased LAI, without modulation of SAI or afferent facilitation. Further, there were no exercise-induced changes to SEP or MEP amplitudes. Together, these results suggest that acute exercise has unique effects on sensorimotor integration, which are not accompanied by concurrent changes in somatosensory or motor cortical excitability.

A History of Concussion Affects Relevancy-Based Modulation of Cortical Responses to Tactile Stimuli.

Modulating cortical excitability based on a stimulus' relevance to the task at hand is a component of sensory gating, and serves to protect higher cortical centers from being overwhelmed with irrelevant information (McIlroy et al., 2003; Kumar et al., 2005; Wasaka et al., 2005). This study examined relevancy-based modulation of cortical excitability, and corresponding behavioral responses, in the face of distracting stimuli in participants with and without a history of concussion (mean age 22 ± 3 SD years; most recent concussion 39.1 ± 30 SD months). Participants were required to make a scaled motor response to the amplitudes of visual and tactile stimuli presented individually or concurrently. Task relevance was manipulated, and stimuli were occasionally presented with irrelevant distractors. Electroencephalography (EEG) and task accuracy data were collected from participants with and without a history of concussion. The somatosensory-evoked N70 event-related potential (ERP) was significantly modulated by task relevance in the control group but not in those with a history of concussion, and there was a significantly greater cost to task accuracy in the concussion history group when relevant stimuli were presented with an irrelevant distractor. This study demonstrated that relevancy-based modulation of electrophysiological responses and behavioral correlates of sensory gating differ in people with and without a history of concussion, even after patients were symptom-free and considered recovered from their injuries.

Activity in Functional Cortical Networks Temporally Associated with Postural Instability.

Human bipedal balance control is proposed to be the integrated activity of distributed neural areas. There is growing understanding about the cortical involvement in this highly automated behavior. While evidence exists for cortical activity temporally linked to reactive balance control, little is known about the functional interaction of potential cortical regions. Here, we used functional connectivity and graph theoretical analysis to derive functional cortical networks during reactive balance control from an event-related potential evoked by external perturbation known as the perturbation-evoked potential N1 (PEP N1). Fourteen healthy young adults were subjected to temporally unpredictable postural perturbations using a custom-made lean and release cable system. Electroencephalographic signals were recorded using a 64-channel electrode cap and segmented around perturbation onset. Functional connectivity was analyzed in source-space and sensor-space using coherence measures and functional cortical networks were characterized using graph measures. The results suggest that there might exist a balance control cortical network while standing and rapid, transient, and frequency-specific reorganization occurs in this network during reactive balance control events. This reorganization was characterized by an increased number of short-range connections between neighboring areas and increased strength between connections in delta, theta, alpha, and beta frequency bands during PEP N1 compared to baseline. To our knowledge, this is the first study to report the existence of functional cortical networks during reactive balance control with potential implications on assessing impaired balance associated with various neural diseases.

Simultaneity and Temporal Order Judgments Are Coded Differently and Change With Age: An Event-Related Potential Study.

Multisensory integration is required for a number of daily living tasks where the inability to accurately identify simultaneity and temporality of multisensory events results in errors in judgment leading to poor decision-making and dangerous behavior. Previously, our lab discovered that older adults exhibited impaired timing of audiovisual events, particularly when making temporal order judgments (TOJs). Simultaneity judgments (SJs), however, were preserved across the lifespan. Here, we investigate the difference between the TOJ and SJ tasks in younger and older adults to assess neural processing differences between these two tasks and across the lifespan. Event-related potentials (ERPs) were studied to determine between-task and between-age differences. Results revealed task specific differences in perceiving simultaneity and temporal order, suggesting that each task may be subserved via different neural mechanisms. Here, auditory N1 and visual P1 ERP amplitudes confirmed that unisensory processing of audiovisual stimuli did not differ between the two tasks within both younger and older groups, indicating that performance differences between tasks arise either from multisensory integration or higher-level decision-making. Compared to younger adults, older adults showed a sustained higher auditory N1 ERP amplitude response across SOAs, suggestive of broader response properties from an extended temporal binding window. Our work provides compelling evidence that different neural mechanisms subserve the SJ and TOJ tasks and that simultaneity and temporal order perception are coded differently and change with age.

The neurocognitive mechanisms underlying food cravings and snack food consumption. A combined continuous theta burst stimulation (cTBS) and EEG study.

Regulation of food cravings is thought to be critical for modulating eating behavior, yet we do not fully understand the mechanisms by which cognitive control operates in the eating context. The current study combined rTMS and EEG paradigms to examine the causal role of the left dorsolateral prefrontal cortex (dlPFC) in modulating visceral and behavioral responses to high calorie foods, and the mediational mechanisms underlying this relation. 28 right-handed female participants received both active and sham continuous theta burst stimulation (cTBS; a rTMS variant used to decrease cortical activity) targeting the left dlPFC in a counterbalanced order. Prior to and following each stimulation session participants completed a flanker and food-cue presentation (high and low calorie food) task. Following cTBS participants had the opportunity to consume both high and low calorie foods during a taste test. Findings revealed a reliable effect of cTBS on food consumption, such that participants selectively ingested significantly more calories from appetitive calorie dense snack foods following active relative to sham cTBS; this effect did not translate to control (low calorie) food consumption. In addition, attenuation of dlPFC activity resulted in the significant increase in N2 amplitude and P3b latency to incongruent flanker trials, and the selective significant increase in the P3a amplitude to and P3a amplitude bias for high calorie food stimuli. Results from the parallel mediation analysis revealed that only the indirect effect of flanker task performance was significant; the indirect effects of stimulation induced changes in the P3 bias for high calorie foods, the urge to consume high calorie foods, and the general liking ratings for high calorie foods were not significant. These findings confirm the causal role of the left dlPFC in the modulation of calorie dense food consumption via inhibitory control capacity.

Frontal alpha asymmetry and aerobic exercise: are changes due to cardiovascular demand or bilateral rhythmic movement?

The left and right prefrontal cortices are linked to networks that control approach and withdrawal motivation, respectively. The relationship between activity in the left and right prefrontal activity is used to assess brain states and specifically their link to motivational behaviours and tendencies. The most common measure used in this context is called the frontal alpha asymmetry (FAA), which compares alpha (8-13Hz) power at each region. Interestingly, research shows that FAA is influenced by aerobic exercise by increasing relative left prefrontal cortex activity. In turn this effect may be beneficial for individuals with mood disorders that are associated with abnormal motivational tendencies. However, it is unknown whether changes in FAA after exercise are due to cardiovascular demands of activity or simply the movement required for the exercise. Therefore, this study aimed to investigate the influence of aerobic exercise and 'no intensity' bilateral movement cycling on FAA in young healthy adults. Results showed aerobic exercise caused a significant increase in FAA scores 22-38min after exercise. However, movement did not lead to a significant change in FAA. This suggests there is an intensity required for physical activity to evoke a change in FAA.

The medium latency muscle response to a vestibular perturbation is increased after depression of the cerebellar vermis.

INTRODUCTION: Galvanic vestibular stimulation (GVS) is able to evoke distinct responses in the muscles used for balance. These reflexes, termed the short (SL) and medium latency (ML) responses, can be altered by sensory input; decreasing in size when additional sensory cues are available. Although much is known about these responses, the origin and role of the responses are still not fully understood. It has been suggested that the cerebellum, a structure that is involved in postural control and sensory integration, may play a role in the modulation of these reflexes. METHODS: The cerebellar vermis was temporarily depressed using continuous theta burst stimulation and SL, ML and overall vestibular electromyographic and force plate shear response amplitudes were compared before and after cerebellar depression. RESULTS: There were no changes in force plate shear amplitude and a non-significant increase for the SL muscle response (p = .071), however, we did find significant increases in the ML and overall vestibular muscle response amplitudes after cerebellar depression (p = .026 and p = .016, respectively). No changes were evoked when a SHAM stimulus was used. DISCUSSION: These results suggest that the cerebellar vermis plays a role in the modulation of vestibular muscle reflex responses to GVS.

Effects of Moderate Exercise on Cortical Resilience: A Transcranial Magnetic Stimulation Study Targeting the Dorsolateral Prefrontal Cortex.

OBJECTIVE: The beneficial effects of exercise on the brain regions that support cognitive control and memory are well documented. However, examination of the capacity of acute exercise to promote cortical resilience-the ability to recover from temporary pertubation-has been largely unexplored. The present study sought to determine whether single session of moderate-intensity aerobic exercise can accelerate recovery of inhibitory control centers in the dorsolateral prefrontal cortex after transient perturbation via continuous theta burst stimulation (cTBS). METHODS: In a within-participants experimental design, 28 female participants aged 18 to 26 years (mean [standard deviation] = 20.32 [1.79] years) completed a session each of moderate-intensity and very light-intensity exercise, in a randomized order. Before each exercise session, participants received active cTBS to the left dorsolateral prefrontal cortex. A Stroop task was used to quantify both the initial perturbation and subsequent recovery effects on inhibitory control. RESULTS: Results revealed a significant exercise condition (moderate-intensity exercise, very light-intensity exercise) by time (prestimulation, poststimulation, postexercise) interaction (F(2,52) = 5.93, p = .005, d = 0.38). Specifically, the proportion of the cTBS-induced decrement in inhibition restored at 40 minutes postexercise was significantly higher after a bout of moderate-intensity exercise (101.26%) compared with very light-intensity exercise (18.36%; t(27) = -2.17, p = .039, d = -.57, 95% confidence interval = -161.40 to -4.40). CONCLUSION: These findings support the hypothesis that exercise promotes cortical resilience, specifically in relation to the brain regions that support inhibitory control. The resilience-promoting effects of exercise have empirical and theoretical implications for how we conceptualize the neuroprotective effects of exercise.

Multiple sclerosis, cannabis, and cognition: A structural MRI study.

OBJECTIVE: A subset of patients with multiple sclerosis (MS) smoke cannabis to relieve symptoms including spasticity and pain. Recent evidence suggests that smoking cannabis further impairs cognition in people with MS and is linked to impaired functional brain changes. No such association, however, has been reported between cannabis use and structural brain changes, hence the focus of the present study. METHODS: Twenty patients with MS who smoke cannabis for symptom relief, and 19 matched non-cannabis-smoking MS patients were given the Brief Repeatable Neuropsychological Battery and structural MRI scans. Images were segmented into gray matter and white matter, and subsequently analysed with Partial Least Squares, a data-driven multivariate technique that explores brain-behaviour associations. RESULTS: In both groups, the Partial Least Squares analysis yielded significant correlations between cognitive scores and both gray matter (33% variance, p < .0001) and white matter (17% variance, p < .05) volume. Gray matter volume in the thalamus, basal ganglia, medial temporal, and medial prefrontal regions, and white matter volume in the fornix correlated with cognitive deficits. Crucially, the analysis indicated that brain volume reductions were associated with more extensive cognitive impairment in the cannabis versus the non-cannabis MS group. INTERPRETATION: These results suggest that cannabis use in MS results in more widespread cognitive deficits, which correlate with tissue volume in subcortical, medial temporal, and prefrontal regions. These are the first findings demonstrating an association between cannabis use, cognitive impairment and structural brain changes in MS patients.

The effects of continuous theta burst stimulation to the left dorsolateral prefrontal cortex on executive function, food cravings, and snack food consumption.

OBJECTIVES: Prior research has demonstrated that executive function (EF) strength is positively associated with dietary self-control. As such, the differential operation of the brain centers underlying EFs (i.e., dorsolateral prefrontal cortex [DLPFC]) may explain controlled aspects of dietary self-control. The present study was designed to examine the causal relationship between DLPFC function and two aspects of dietary self-control: visceral cravings and actual consumptive behaviors. METHODS: The research was conducted using a within-participant design. A sample of 21 healthy female young adults aged 19 to 26 years (mean [M; standard deviation] = 21.10 [1.86] years) received both active and sham continuous theta burst stimulation (cTBS) to the left DLPFC. Before and after each session, subjective food cravings were assessed using the Food Craving Questionnaire-State. After each stimulation session, participants competed three measures of EF (Stroop, Go/No-Go, and Stop-Signal) and a bogus taste test. RESULTS: Participants reported larger increases in snack food cravings after active stimulation (M = 9.98% change, standard error [SE] = 0.45) than after sham stimulation (M = -3.46, SE = 0.39, p = .012) on the reinforcement anticipation dimension of Food Craving Questionnaire-State. Likewise, participants consumed significantly more snack foods after active stimulation (M = 70.62 grams, SE = 5.17) than after sham stimulation (M = 61.33, SE = 3.56, p = .006). Finally, performance on the Stroop task was reduced more after active (M = 71.56 milliseconds, SE = 25.18) than after sham stimulation (M = 20.16, SE = 13.32, p = .033); reduction in Stroop performance mediated the effect of active stimulation on increased appetitive food consumption. CONCLUSION: These results support the contention that EF strength, as modulated by DLPFC activity, is causally associated with effective dietary self-control.

Frequency characteristics of cortical activity associated with perturbations to upright stability.

Cortical evoked potentials are evident in the control of whole-body balance reactions in response to transient instability. The focus of this work is to continue to advance understanding of the potential cortical contributions to bipedal balance control. Temporally unpredictable postural perturbations evoke a negative potential (N1), which has drawn parallels to error-related negativity (ERN) as well as visual and auditory evoked N1 responses. The mechanism underlying the generation of event-related potentials (ERPs) has been a matter of debate for the past few decades. While the evoked model proposes that ERPs are generated by the addition of fixed latency and fixed polarity responses, the phase reorganization model suggests that ERPs are the result of stimulus-induced phase reorganization of the ongoing oscillations. Previous studies have suggested phase reorganization as a possible mechanism in auditory N1, visual N1 and error-related negativity (ERN). The purpose of the current study was to explore the frequency characteristics of the cortical responses to whole-body balance perturbations. Perturbations were evoked using a lean and release protocol. The results revealed a significant power increase and phase-locking of delta, theta, alpha, and beta band activity during perturbation-evoked N1. This may suggest that the stimulus-induced phase reorganization of the ongoing electroencephalographic (EEG) activity could account for the features of cortical ERPs in response to perturbation of upright stability.

Localizing evoked cortical activity associated with balance reactions: does the anterior cingulate play a role?

The ability to correct balance disturbances is essential for the maintenance of upright stability. Although information about how the central nervous system controls balance reactions in humans remains limited, recent literature highlights a potentially important role for the cerebral cortex. The objective of this study was to determine the neural source of the well-reported balance-evoked N1 response. It was hypothesized that the N1 is associated with an "error-detection" event in response to the induced perturbation and therefore may be associated with activity within the anterior cingulate cortex (ACC). The localized source of the N1 evoked by perturbations to standing balance was compared, within each participant, to the location of an error-related negativity (ERN) known to occur within the ACC while performing a flanker task. In contrast to the main hypotheses, the results revealed that the location of the N1 was not within the ACC. The mean Talairach coordinates for the ERN were (6.47, -4.41, 41.17) mm, corresponding to the cingulate gyrus [Brodmann area (BA) 24], as expected. However, coordinates for the N1 dipole were (5.74, -11.81, 53.73) mm, corresponding to the medial frontal gyrus (BA 6), specifically the supplementary motor area. This may suggest the N1 is linked to the planning and execution of elements of the evoked balance reactions rather than being associated with error or event detection. Alternatively, it is possible that the N1 is associated with variation in the cortical representation due to task-specific differences in the activation of a distributed network of error-related processing. Subsequent work should focus on disentangling these two possible explanations as they relate to the cortical processing linked to reactive balance control.

The relationship between frontal somatosensory-evoked potentials and motor planning.

Performance of efficient and precise movement requires the proper planning of motor parameters as well as the integration of sensory feedback. This study tests the hypothesis that the frontal components of the median nerve somatosensory-evoked potentials are differentially modulated, depending on (i) the stage of motor preparation and (ii) the moving limb. Participants were instructed to make intermittent voluntary contractions with either their right or left hands while receiving median nerve stimulation to the right wrist only. The results indicate that the frontal N30 demonstrated a significant increase in amplitude during the execution, but not the preparation, of a movement contralateral to median nerve stimulation. These data have implications for interhemispheric control of sensory information within the primary and premotor cortices.