Katherine M. Becker

Multimodal neuroimaging evidence of alterations in cortical structure and function in HIV-infected older adults.

Combination antiretroviral therapy transformed human immunodefiency virus (HIV)‐infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in frontoparietal networks of HIV‐infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high‐resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV‐related cognitive impairments. HIV‐infected adults and individually matched controls completed 3‐Tesla structural magnetic resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data were examined using advanced beamforming methods, and sMRI data were analyzed using the latest voxel‐based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV‐infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially coincident with abnormal MEG responses in HIV‐infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV‐associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV‐associated cognitive impairment, and may hold promise as a potential disease marker. Hum Brain Mapp 36:897–910, 2015.

Neurophysiological abnormalities in the sensorimotor cortices during the motor planning and movement execution stages of children with cerebral palsy.

This investigation used magnetoencephalography (MEG) to examine the neural oscillatory responses of the sensorimotor cortices during the motor planning and movement execution stages of children with typical development and children with cerebral palsy (CP).

Circadian modulation of motor-related beta oscillatory responses.

Previous electrophysiological investigations have evaluated movement-related beta (14-28 Hz) oscillatory activity in healthy participants. These studies have described an abrupt decrease in beta activity that starts before movement onset, and a sharp increase in beta power that peaks after movement termination. These neural responses have been respectively termed the event-related beta desynchronization or pre-movement beta ERD, and the post-movement beta rebound (PMBR). Previous studies have shown that a variety of movement parameters and demographic factors (e.g., age) modulate the amplitude of these oscillatory responses, and in the current study we evaluated whether the amplitudes follow a biological temporal rhythm (e.g., circadian), as it is known that spontaneous beta levels increase from morning to afternoon in some brain areas. To this end, we used magnetoencephalography (MEG) to evaluate oscillatory activity during a right hand finger-tapping task in four participants who were recorded at three different times (09:00, 12:00, 16:00) on three consecutive days (i.e., 36 total MEG sessions). All MEG data were corrected for head motion and examined in the time-frequency domain using beamforming methods. We found a significant linear increase in beta ERD amplitude from 09:00 to 16:00 h in the left precentral gyrus, left premotor cortices, left supplementary motor area (SMA), and right precentral and postcentral gyri. In contrast, the amplitude of the PMBR was very steady across the day in all brain regions except the left SMA, which exhibited a linear increase from morning to afternoon. Finally, beta levels during the baseline period also increased from 09:00 to 16:00 in most regions of the cortical sensorimotor network. These data show that both the pre-movement beta ERD and spontaneous beta levels strongly increase from morning to afternoon in the motor cortices, which may indicate that the amplitude of the beta ERD response is determined by the spontaneous beta level during the motor planning period.

Aberrant synchrony in the somatosensory cortices predicts motor performance errors in children with cerebral palsy

Cerebral palsy (CP) results from a perinatal brain injury that often results in sensory impairments and greater errors in motor performance. Although these impairments have been well catalogued, the relationship between sensory processing networks and errors in motor performance has not been well explored. Children with CP and typically developing age-matched controls participated in this investigation. We used high-density magnetoencephalography to measure event-related oscillatory changes in the somatosensory cortices following tactile stimulation to the bottom of the foot. In addition, we quantified the amount of variability or errors in the isometric ankle joint torques as these children attempted to match a target. Our results showed that neural populations in the somatosensory cortices of children with CP were desynchronized by the tactile stimulus, whereas those of typically developing children were clearly synchronized. Such desynchronization suggests that children with CP were unable to fully integrate the external stimulus into ongoing sensorimotor computations. Our results also indicated that children with CP had a greater amount of errors in their motor output when they attempted to match the target force, and this amount of error was negatively correlated with the degree of synchronization present in the somatosensory cortices. These results are the first to show that the motor performance errors of children with CP are linked with neural synchronization within the somatosensory cortices.

The magnitude of the somatosensory cortical activity is related to the mobility and strength impairments seen in children with cerebral palsy

The noted disruption of thalamocortical connections and abnormalities in tactile sensory function has resulted in a new definition of cerebral palsy (CP) that recognizes the sensorimotor integration process as central to the motor impairments seen in these children. Despite this updated definition, the connection between a childs motor impairments and somatosensory processing remains almost entirely unknown. In this investigation, we explored the relationship between the magnitude of neural activity within the somatosensory cortices, the strength of the ankle plantarflexors, and the gait spatiotemporal kinematics of a group of children with CP and a typically developing matched cohort. Our results revealed that the magnitude of somatosensory cortical activity in children with CP had a strong positive relationship with the ankle strength, step length, and walking speed. These results suggest that stronger activity within the somatosensory cortices in response to foot somatosensations was related to enhanced ankle plantarflexor strength and improved mobility in the children with CP. These results provide further support for the notion that children with CP exhibit, not only musculoskeletal deficits, but also somatosensory deficits that potentially contribute to their overall functional mobility and strength limitations.

Children with cerebral palsy have uncharacteristic somatosensory cortical oscillations after stimulation of the hand mechanoreceptors.

Numerous clinical investigations have reported that children with cerebral palsy (CP) have tactile discrimination deficits that likely limit their ability to plan and manipulate objects. Despite this clinical awareness, we still have a substantial knowledge gap in our understanding of the neurological basis for these tactile discrimination deficits. Previously, we have shown that children with CP have aberrant theta-alpha (4-14 Hz) oscillations in the somatosensory cortices following tactile stimulation of the foot. In this investigation, we evaluated if these aberrant theta-alpha oscillations also extend to the hand. Magnetoencephalography was used to evaluate event-related changes in the theta-alpha and beta (18-34 Hz) somatosensory cortical oscillations in groups of children with CP and typically developing (TD) children following tactile stimulation of their hands. Our results showed that the somatosensory theta-alpha oscillations were relatively intact in children with CP, which is in contrast to our previous results for foot tactile stimulations. We suspect that these inter-study differences may be related to the higher probability that the neural tracts serving the lower extremities are damaged in children with CP, compared to those serving the upper extremities. This inference is plausible since the participating children with CP had Manual Ability Classification System (MACS) levels between I and II. In contrast to the theta-alpha results, children with CP did exhibit a sharp increase in beta activity during the same time period, which was not observed in TD children. This suggests that children with CP still have deficits in the computational aspect of somatosensory processing.

Magnetic Resonance Spectroscopy Studies of Glutamate and GABA in Autism: Implications for Excitation-Inhibition Imbalance Theory

One popular major theory of neurotransmitter dysfunction is an imbalance in excitation and inhibition (EI theory).The EI imbalance theory is thought to impact widely across neural circuits mediating language, social, and cognitive functions, and could potentially explain some aspects of the autism phenotype. Evidence from genetic and molecular studies provide support for abnormal suppression of γ-aminobutyric acid (GABA) function and an overabundance of glutamatergic transmission as potential mechanisms of this hyperexcitability. Proton magnetic resonance spectroscopy (1H-MRS) is a potentially exciting neuroimaging tool allowing in vivo estimation of glutamate and GABA neurotransmitters in people with autism spectrum disorder (ASD). We reviewed all available published studies of ASD reporting 1H-MRS measurement of glutamate, GABA, or both neurotransmitters. Glutamate results across studies are equivocal, with nearly equal numbers of studies reporting increases or decreases in autism. However, the age of the individuals studied appears to relate to the direction of the findings, suggesting that future longitudinal studies of glutamate should be conducted. Although fewer GABA-specific studies have been published, all have reported decreases in autism. Overall, from 1H-MRS studies alone, support for the glutamate side of the EI imbalance theory is tenuous, but this is an indication of serious limitations in the 1H-MRS literature. For GABA dysfunction, the GABA findings to date are consistent for reduced concentration in autism; however, there are only a few published 1H-MRS studies of GABA in autism, all from studies with a small number of subjects. More studies, particularly longitudinal developmental studies across both child and adult development, are needed.

Decreased somatosensory activity to non-threatening touch in combat veterans with posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a severe psychiatric disorder prevalent in combat veterans. Previous neuroimaging studies have demonstrated that patients with PTSD exhibit abnormal responses to non-threatening visual and auditory stimuli, but have not examined somatosensory processing. Thirty male combat veterans, 16 with PTSD and 14 without, completed a tactile stimulation task during a 306-sensor magnetoencephalography (MEG) recording. Significant oscillatory neural responses were imaged using a beamforming approach. Participants also completed clinical assessments of PTSD, combat exposure, and depression. We found that veterans with PTSD exhibited significantly reduced activity during early (0-125 ms) tactile processing compared with combat controls. Specifically, veterans with PTSD had weaker activity in the left postcentral gyrus, left superior parietal area, and right prefrontal cortex in response to nonthreatening tactile stimulation relative to veterans without PTSD. The magnitude of activity in these brain regions was inversely correlated with symptom severity, indicating that those with the most severe PTSD had the most abnormal neural responses. Our findings are consistent with a resource allocation view of perceptual processing in PTSD, which directs attention away from nonthreatening sensory information.

Developmental Trajectory of Beta Cortical Oscillatory Activity During a Knee Motor Task

There is currently a void in the scientific literature on the cortical beta oscillatory activity that is associated with the production of leg motor actions. In addition, we have limited data on how these cortical oscillations may progressively change as a function of development. This study began to fill this vast knowledge gap by using high-density magnetoencephalography to quantify the beta cortical oscillatory activity over a cross-section of typically developing children as they performed an isometric knee target matching task. Advanced beamforming methods were used to identify the spatiotemporal changes in beta oscillatory activity during the motor planning and motor action time frames. Our results showed that a widespread beta event-related desynchronization (ERD) was present across the pre/postcentral gyri, supplementary motor area, and the parietal cortices during the motor planning stage. The strength of this beta ERD sharply diminished across this fronto-parietal network as the children initiated the isometric force needed to match the target. Rank order correlations indicated that the older children were more likely to initiate their force production sooner, took less time to match the targets, and tended to have a weaker beta ERD during the motor planning stage. Lastly, we determined that there was a relationship between the child’s age and the strength of the beta ERD within the parietal cortices during isometric force production. Altogether our results suggest that there are notable maturational changes during childhood and adolescence in beta cortical oscillatory activity that are associated with the planning and execution of leg motor actions.

Resting-state neurophysiological abnormalities in posttraumatic stress disorder: A magnetoencephalography study

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric condition that is common in veterans returning from combat operations. While the symptoms of PTSD have been extensively characterized, the neural mechanisms that underlie PTSD are only vaguely understood. In this study, we examined the neurophysiology of PTSD using magnetoencephalography (MEG) in a sample of veterans with and without PTSD. Our primary hypothesis was that veterans with PTSD would exhibit aberrant activity across multiple brain networks, especially those involving medial temporal and frontal regions. To this end, we examined a total of 51 USA combat veterans with a battery of clinical interviews and tests. Thirty-one of the combat veterans met diagnostic criteria for PTSD and the remaining 20 did not have PTSD. All participants then underwent high-density MEG during an eyes-closed resting-state task, and the resulting data were analyzed using a Bayesian image reconstruction method. Our results indicated that veterans with PTSD had significantly stronger neural activity in prefrontal, sensorimotor and temporal areas compared to those without PTSD. Veterans with PTSD also exhibited significantly stronger activity in the bilateral amygdalae, parahippocampal and hippocampal regions. Conversely, healthy veterans had stronger neural activity in the bilateral occipital cortices relative to veterans with PTSD. In conclusion, these data suggest that veterans with PTSD exhibit aberrant neural activation in multiple cortical areas, as well as medial temporal structures implicated in affective processing.