Lynn M. Rogers

Targeted enhancement of cortical-hippocampal brain networks and associative memory

Brain stimulation to improve human memory The hippocampus is a crucial brain area for certain types of memory. Working with humans, Wang et al. found that a specific type of non-invasive brain stimulation improved memory tests and enhanced information flow between the hippocampus and a number of other brain regions. This increased connectivity was highly specific for the individual target areas selected for each participant. Science, this issue p. 1054 Noninvasive stimulation of the brain can improve memories for episodes by boosting the connectivity between cortical regions. The influential notion that the hippocampus supports associative memory by interacting with functionally distinct and distributed brain regions has not been directly tested in humans. We therefore used targeted noninvasive electromagnetic stimulation to modulate human cortical-hippocampal networks and tested effects of this manipulation on memory. Multiple-session stimulation increased functional connectivity among distributed cortical-hippocampal network regions and concomitantly improved associative memory performance. These alterations involved localized long-term plasticity because increases were highly selective to the targeted brain regions, and enhancements of connectivity and associative memory persisted for ~24 hours after stimulation. Targeted cortical-hippocampal networks can thus be enhanced noninvasively, demonstrating their role in associative memory.

A paradox: After stroke, the non-lesioned lower limb motor cortex may be maladaptive

What are the neuroplastic mechanisms that allow some stroke patients to regain high‐quality control of their paretic leg, when others do not? One theory implicates ipsilateral corticospinal pathways projecting from the non‐lesioned hemisphere. We devised a new transcranial magnetic stimulation protocol to identify ipsilateral corticospinal tract conductivity from the non‐lesioned hemisphere to the paretic limb in chronic stroke patients. We also assessed corticospinal tract degeneration by diffusion tensor imaging, and used an ankle tracking task to assess lower limb motor control. We found greater tracking error during antiphase bilateral ankle movement for patients with strong conductivity from the non‐lesioned hemisphere to the paretic ankle than for those with weak or no conductivity. These findings suggest that, instead of assisting motor control, contributions to lower limb motor control from the non‐lesioned hemisphere of some stroke survivors may be maladaptive.

Foot force direction control during leg pushes against fixed and moving pedals in persons post-stroke.

The component of foot force generated by muscle action (F(m)) during pedaling in healthy humans has a nearly constant direction with increasing force magnitude. The present study investigated the effect of stroke on the control of foot force. Ten individuals with hemiparesis secondary to a cerebral vascular accident performed pushing efforts against translationally fixed and moving pedals on a custom stationary cycle ergometer. We found that while F(m) direction remained constant with increasing effort in both the fixed- and moving-crank conditions for both limbs, the orientation of that force component differed between limbs. The non-paretic limb produced the same F(m) orientation as seen previously in healthy humans. However, relative to the non-paretic limb, the paretic limb force line-of-action was shifted away from the hip and closer to the knee in the sagittal-plane for both pedal motion conditions. In the frontal plane, the paretic limb force line-of-action was shifted laterally, closer to parallel to the midline, for both pedal motion conditions. These shifts were consistent with previously reported lower limb muscle weakness and alterations in muscle activation observed during pedaling tasks following stroke. The finding of similar orientations for static and dynamic pushing efforts suggests that limb posture could be a trigger for relative muscle activation levels. The preservation of a constant direction in F(m) with increasing force magnitude post-stroke, despite an orientation shift, suggests that control of lower limb force may be organized by magnitude and direction and that these two aspects are differentially affected by stroke.

Associative Recognition Memory Awareness Improved by Theta-Burst Stimulation of Frontopolar Cortex

Neuroimaging and lesion studies have implicated specific prefrontal cortex locations in subjective memory awareness. Based on this evidence, a rostrocaudal organization has been proposed whereby increasingly anterior prefrontal regions are increasingly involved in memory awareness. We used theta-burst transcranial magnetic stimulation (TBS) to temporarily modulate dorsolateral versus frontopolar prefrontal cortex to test for distinct causal roles in memory awareness. In three sessions, participants received TBS bilaterally to frontopolar cortex, dorsolateral prefrontal cortex, or a control location prior to performing an associative-recognition task involving judgments of memory awareness. Objective memory performance (i.e., accuracy) did not differ based on stimulation location. In contrast, frontopolar stimulation significantly influenced several measures of memory awareness. During study, judgments of learning were more accurate such that lower ratings were given to items that were subsequently forgotten selectively following frontopolar TBS. Confidence ratings during test were also higher for correct trials following frontopolar TBS. Finally, trial-by-trial correspondence between overt performance and subjective awareness during study demonstrated a linear increase across control, dorsolateral, and frontopolar TBS locations, supporting a rostrocaudal hierarchy of prefrontal contributions to memory awareness. These findings indicate that frontopolar cortex contributes causally to memory awareness, which was improved selectively by anatomically targeted TBS.

Corticomotor excitability of arm muscles modulates according to static position and orientation of the upper limb

OBJECTIVE We investigated how multi-joint changes in static upper limb posture impact the corticomotor excitability of the posterior deltoid (PD) and biceps brachii (BIC), and evaluated whether postural variations in excitability related directly to changes in target muscle length. METHODS The amplitude of individual motor evoked potentials (MEPs) was evaluated in each of thirteen different static postures. Four functional postures were investigated that varied in shoulder and elbow angle, while the forearm was positioned in each of three orientations. Posture-related changes in muscle lengths were assessed using a biomechanical arm model. Additionally, M-waves were evoked in the BIC in each of three forearm orientations to assess the impact of posture on recorded signal characteristics. RESULTS BIC-MEP amplitudes were altered by shoulder and elbow posture, and demonstrated robust changes according to forearm orientation. Observed changes in BIC-MEP amplitudes exceeded those of the M-waves. PD-MEP amplitudes changed predominantly with shoulder posture, but were not completely independent of influence from forearm orientation. CONCLUSIONS Results provide evidence that overall corticomotor excitability can be modulated according to multi-joint upper limb posture. SIGNIFICANCE The ability to alter motor pathway excitability using static limb posture suggests the importance of posture selection during rehabilitation aimed at retraining individual muscle recruitment and/or overall coordination patterns.

The effects of paired associative stimulation on knee extensor motor excitability of individuals post-stroke: A pilot study

OBJECTIVE Paired associative stimulation (PAS) modulates bilateral distal lower limb motor pathways during walking. We assessed the effects of inhibitory PAS applied to the vastus medialis (VM) motor pathways of chronic stroke patients. METHODS PAS consisted of 120 electrical stimuli applied to the femoral nerve paired with transcranial magnetic stimulation (TMS) of the lower limb primary motor cortex so that the estimated arrival of the afferent volley occurred 8 ms after delivery of the magnetic stimulus. Stimulus pairs were delivered to the non-paretic VM motor system of 11 chronic stroke patients and the right limb motor system of 11 non-impaired subjects at 0.19 Hz. The effects of PAS on VM motor pathway excitability and muscle activity were assessed during pedaling. TMS-induced motor evoked potential (MEP) amplitudes and the percent of VM activity in the flexion phase of active pedaling (% FLEXVM) was examined before and after PAS. RESULTS Inhibitory PAS reduced VM MEP amplitudes in the target limb (p<0.05) of both groups, while post-PAS paretic VM MEP amplitudes increased for some patients and decreased for others. Group mean paretic limb % FLEXVM was not altered by inhibitory PAS. CONCLUSIONS These results indicate PAS can be used to manipulate motor cortical excitability in proximal lower limb representations, however the sign of induced modulation was unpredictable and cyclic muscle activity was not modified. SIGNIFICANCE The study has important implications for the development of therapies involving non-invasive brain stimulation to modify abnormal motor behavior following stroke.

Transcranial direct current stimulation and aphasia: the case of mr. C.

Abstract Purpose: To illustrate the ethical challenges that arose from investigating a novel treatment procedure, transcranial direct current stimulation (tDCS), in a research participant with aphasia. Method: We review the current evidence supporting the use of tDCS in aphasia research, highlighting methodological gaps in our knowledge of tDCS. Then, we examine the case of Mr. C, a person with chronic aphasia who participated in a research protocol investigating the impact of tDCS on aphasia treatment. We describe the procedures that he underwent and the resulting behavioral and neurophysiological outcomes. Finally, we share the steps that were taken to balance beneficence and nonmaleficence and to ensure Mr. C’s autonomy. Results: The objective data show that while Mr. C may not have benefitted from participating in the research, neither did he experience any harm. Conclusion: Researchers must consider not only the scientific integrity of their studies, but also potential ethical issues and consequences to the research participants.

Descending control to the nonparetic limb degrades the cyclic activity of paretic leg muscles

During anti-phased locomotor tasks such as cycling or walking, hemiparetic phasing of muscle activity is characterized by inappropriate early onset of activity for some paretic muscles and prolonged activity in others. Pedaling with the paretic limb alone reduces inappropriate prolonged activity, suggesting a combined influence of contralesional voluntary commands and movement-related sensory feedback. Five different non-target leg movement state conditions were performed by 15 subjects post-stroke and 15 nonimpaired controls while they pedaled with the target leg and EMG was recorded bilaterally. Voluntary engagement of the non-lesioned motor system increased prolonged paretic vastus medialis (VM) activity and increased phase-advanced rectus femoris (RF) activity. We suggest bilateral descending commands are primarily responsible for the inappropriate activity in the paretic VM during anti-phase pedaling, and contribute to the dysfunctional motor output in the paretic RF. Findings from controls suggest that even an undamaged motor system can contribute to this phenomenon.

Posture-Dependent Corticomotor Excitability Differs between the Transferred Biceps in Individuals with Tetraplegia and the Biceps of Nonimpaired Individuals

Background. Following biceps transfer to enable elbow extension in individuals with tetraplegia, motor re-education may be facilitated by greater corticomotor excitability. Arm posture modulates corticomotor excitability of the nonimpaired biceps. If arm posture also modulates excitability of the transferred biceps, posture may aid in motor re-education. Objective. Our objective was to determine whether multi-joint arm posture affects corticomotor excitability of the transferred biceps similar to the nonimpaired biceps. We also aimed to determine whether corticomotor excitability of the transferred biceps is related to elbow extension strength and muscle length. Methods. Corticomotor excitability was assessed in 7 arms of individuals with tetraplegia and biceps transfer using transcranial magnetic stimulation and compared to biceps excitability of nonimpaired individuals. Single-pulse transcranial magnetic stimulation was delivered to the motor cortex with the arm in functional postures at rest. Motor-evoked potential amplitude was recorded via surface electromyography. Elbow moment was recorded during maximum isometric extension trials, and muscle length was estimated using a biomechanical model. Results. Arm posture modulated corticomotor excitability of the transferred biceps differently than the nonimpaired biceps. Elbow extension strength was positively related and muscle length was unrelated, respectively, to motor-evoked potential amplitude across the arms with biceps transfer. Conclusions. Corticomotor excitability of the transferred biceps is modulated by arm posture and may contribute to strength outcomes after tendon transfer. Future work should determine whether modulating corticomotor excitability via posture promotes motor re-education during the rehabilitative period following surgery.

Reciprocal inhibition becomes facilitation after spinal cord injury: clinical application of a system identification approach.

Alteration in spinal inputs from descending pathways following spinal cord injury (SCI) affects different mechanisms including reciprocal Ia inhibition. However, whether there is a consistent pattern of change in reciprocal inhibition following SCI is uncertain. Typical attempts to evaluate reciprocal inhibition have been restricted to electrophysiological measurements, which may have limited translation to function. Our objective was to address the uncertainty regarding changes in reciprocal inhibition after SCI by quantitatively evaluating reciprocal inhibition of ankle extensors from ankle flexors using our novel, more functionally relevant system identification approach. To evaluate reciprocal inhibition using the system identification technique, a series of small-amplitude PseudoRandom Binary Sequence (PRBS) perturbations were applied to the ankle when subjects contracted their dorsiflexors. Depression of reflex stiffness with tibialis anterior (TA) activation was evaluated as reciprocal inhibition. Our results showed that reflex stiffness decreased continuously as dorsiflexor torque increased in the healthy control subjects whereas it remained almost unchanged in the SCI subjects, indicating the absence of reciprocal inhibition in patients. This pattern was consistent with the results obtained from electrophysiological measures in a exploratory control experiment revealing depression of the control H-reflex but no change to the SCI H-reflex. These findings suggest that our system identification mechanical technique is a reliable and valid approach for evaluating reciprocal inhibition. Furthermore, our results demonstrate that reciprocal inhibition can diminish or change to reciprocal facilitation after SCI, which in turn can result in reflex hyperexcitability and unwanted activity of ankle extensors triggered by TA activity. This suggests that reciprocal facilitation may play a major role in pathophysiology of spasticity and impaired function.