Duration and reliability of the silent period in individuals with spinal cord injury.

DESIGN: Prospective cohort study. OBJECTIVES: We aim to better understand the silent period (SP), an inhibitory counterpart to the well-known motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS), in individuals with spinal cord injury (SCI). SETTING: Veterans Affairs Hospital in New York. METHODS: EMG responses were measured in the target abductor pollicis brevis at rest (TMS at 120% of resting motor threshold (RMT)) and during maximal effort (TMS at 110% of RMT). Participants with chronic cervical SCI (n = 9) and AB participants (n = 12) underwent between 3 and 7 sessions of testing on separate days. The primary outcomes were the magnitude and reliability of SP duration, resting and active MEP amplitudes, and RMT. RESULTS: SCI participants showed significantly lower MEP amplitudes compared to AB participants. SCI SP duration was not significantly different from AB SP duration. SP duration demonstrated reduced intra-participant variability within and across sessions compared with MEP amplitudes. SCI participants also demonstrated a higher prevalence of SP 'interruptions' compared to AB participants. CONCLUSIONS: In a small group of individuals with chronic cervical SCI, we confirmed the well-known findings that SCI individuals have lower TMS evoked potential amplitudes and a tendency toward higher TMS motor thresholds relative to able-bodied controls. We did not observe a significant difference in SP duration between individuals with versus without SCI. However, SP duration is a more reliable outcome within and across multiple sessions than MEP amplitude.

Top-down and Bottom-up Regulated Auditory Phantom Perception.

Auditory phantom percepts such as tinnitus are associated with auditory deafferentation. The idea is that auditory deafferentation limits the amount of information the brain can acquire to make sense of the world. Because of this, auditory deafferentation increases the uncertainty of the auditory environment. To minimize uncertainty, the deafferented brain will attempt to obtain or fill in the missing information. A proposed multiphase compensation model suggests two distinct types of bottom-up related tinnitus: an auditory cortex related tinnitus and a parahippocampal cortex related tinnitus. The weakness of this model is that it cannot explain why some people without hearing loss develop tinnitus, whereas conversely others with hearing loss do not develop tinnitus. In this human study, we provide evidence for a top-down type of tinnitus associated with a deficient noise-cancelling mechanism. A total of 72 participants (age: 40.96 ± 7.67 years; males: 48; females: 24) were recruited for this study. We demonstrate that top-down related tinnitus is related to a change in the pregenual anterior cingulate cortex that corresponds to increased activity in the auditory cortex. This is in accordance with the idea that tinnitus can have different generators as proposed in a recent model that suggests that different compensation mechanisms at a cortical level can be linked to phantom percepts.SIGNIFICANCE STATEMENT Chronic tinnitus affects 15% of the population worldwide. The term "tinnitus" however represents a highly heterogeneous condition, as evidenced by the fact that there are no effective treatments or even an adequate understanding of the underlying neural mechanisms. Consistent with this idea, our research shows that tinnitus indeed has different subtypes related to hearing loss. In a human study tightly controlled for hearing loss, we establish a tinnitus subtype associated with a deficient top-down noise-cancelling mechanism, which distinguishes it from bottom-up subtypes. We demonstrate that top-down related tinnitus relates to a change in the pregenual anterior cingulate cortex that corresponds to increased activity in the auditory cortex, whereas bottom-up tinnitus instead relates to changes in the parahippocampal cortex.

Transspinal stimulation decreases corticospinal excitability and alters the function of spinal locomotor networks.

Locomotion requires the continuous integration of descending motor commands and sensory inputs from the legs by spinal central pattern generator circuits. Modulation of spinal neural circuits by transspinal stimulation is well documented, but how transspinal stimulation affects corticospinal excitability during walking in humans remains elusive. We measured the motor evoked potentials (MEPs) at multiple phases of the step cycle conditioned with transspinal stimulation delivered at sub- and suprathreshold intensities of the spinally mediated transspinal evoked potential (TEP). Transspinal stimulation was delivered before or after transcranial magnetic stimulation during which summation between MEP and TEP responses in the surface EMG was absent or present. Relationships between MEP amplitude and background EMG activity, silent period duration, and phase-dependent EMG amplitude modulation during and after stimulation were also determined. Ankle flexor and extensor MEPs were depressed by suprathreshold transspinal stimulation when descending volleys were timed to interact with transspinal stimulation-induced motoneuron depolarization at the spinal cord. MEP depression coincided with decreased MEP gain, unaltered MEP threshold, and unaltered silent period duration. Locomotor EMG activity of bilateral knee and ankle muscles was significantly depressed during the step at which transspinal stimulation was delivered but fully recovered at the subsequent step. The results support a model in which MEP depression by transspinal stimulation occurs via subcortical or spinal mechanisms. Transspinal stimulation disrupts the locomotor output of flexor and extensor motoneurons initially, but the intact nervous system has the ability to rapidly overcome this pronounced locomotor adaptation. In conclusion, transspinal stimulation directly affects spinal locomotor centers in healthy humans.NEW & NOTEWORTHY Lumbar transspinal stimulation decreases ankle flexor and extensor motor evoked potentials (MEPs) during walking. The MEP depression coincides with decreased MEP gain, unaltered MEP threshold changes, and unaltered silent period duration. These findings indicate that MEP depression is subcortical or spinal in origin. Healthy subjects could rapidly overcome the pronounced depression of muscle activity during the step at which transspinal stimulation was delivered. Thus, transspinal stimulation directly affects the function of spinal locomotor networks in healthy humans.

The potential interruptive effect of tinnitus-related distress on attention.

The mechanism through which tinnitus affects attention is unclear. This study examines whether distress mediates the relationship(s) between tinnitus and sustained, selective and executive attentions as well as response inhibition. Eighteen participants with tinnitus and fifteen controls completed the Counting Stroop, Vigilance and Stop Signal tasks. Tinnitus distress was assessed using the Tinnitus Questionnaire (TQ), severity of depressive mood states examined using the Beck Depression Inventory-II, and general distress assessed using the Hospital Anxiety and Depression Scale. Tinnitus participants had significantly slower reactions during the Vigilance task (F = 4.86, p = .035), and incongruent trials of the Cognitive Counting task (F = 3.45, p = .045) compared to controls. Tinnitus-related distress significantly mediated the effect of tinnitus in incongruent trials (TQ: Sobel test t = 1.73, p = .042) of the Cognitive Counting Task. Complaints of distress and concentration difficulties are common amongst tinnitus patients in clinical settings and these afflictions have been shown to negatively impact an individual's quality of life. If confirmed in future studies, results suggest that distress may be an important factor in the causal mechanism between tinnitus and attention.

COMT and the neurogenetic architecture of hearing loss induced tinnitus.

As the COMT polymorphism is especially prominent in the prefrontal cortex and has been associated with auditory gating, we hypothesize that tinnitus patients with this polymorphism have altered activity in the ventromedial prefrontal/anterior cingulate areas that modulates the tinnitus percept. To test this, we recruited a total of 40 tinnitus subjects and 20 healthy controls for an EEG study. A comparison between tinnitus subjects and healthy controls and their frequency of being Val/Val genotype or Met carriers (including Val/Met and Met/Met genotype) shows no significant effect, suggesting that the distributions for the tinnitus and healthy groups are similar. Our results show that an interaction between the amount of hearing loss and the COMT Val158Met polymorphism can increase susceptibility to the clinical manifestation of tinnitus. We further demonstrate that the parahippocampus becomes involved in tinnitus in patients with hearing loss that are Met carriers. In these patients, the parahippocampus sends more tinnitus information to the pregenual anterior cingulate cortex and auditory cortex that is specifically related with increased loudness. At the same time, the pregenual anterior cingulate cortex, which normally functions as a gatekeeper, is not cancelling this auditory information, ultimately leading to increased tinnitus loudness.

Misophonia and Potential Underlying Mechanisms: A Perspective.

There is a growing research interest in the diagnosis rate of misophonia, a condition characterized by a negative emotional/autonomic reaction to specific everyday sounds. Diagnosis of misophonia requires a thorough case history and audiological test procedures. Associative and non-associative learning models for understanding the underlying mechanisms of misophonia have been presented. Currently, there is no cure or pharmaceutical agent for misophonia; however, therapy programs addressing misophonia and its characteristics do exist. Investigation of comorbid conditions and other psychological therapy strategies might help to reveal more about the underlying mechanisms and potentially lead to a successful treatment method.

Salivary Stress-Related Responses in Tinnitus: A Preliminary Study in Young Male Subjects with Tinnitus.

OBJECTIVE: This preliminary study examined if baseline measures of stress-related biomarkers as measured by salivary secretions of specific autonomic [measured by salivary α-amylase (sAA)], endocrine (measured by salivary cortisol), and immune (measured by salivary neopterin) responses are greater in male subjects with tinnitus in response to an induced-stress task. METHOD: Twenty male subjects with no significant hearing loss, 10 with tinnitus, and 10 without tinnitus were enrolled in this study.Salivary secretions were collected before and after the induced stress task at four different time intervals. RESULTS: sAA levels were lower in the tinnitus group in comparison to subjects without tinnitus, suggesting impaired sympathetic activity in the subjects with tinnitus although these levels remained stable throughout the stress experiment.While no significant effects could be obtained for salivary cortisol or neopterin, salivary neopterin levels were trending toward significance over all measurements. Behavioral measures of stress were found to correlate negatively with measures of sAA and salivary neopterin. CONCLUSION: The results of this study suggest impaired stress-related sAA mechanisms in male subjects with tinnitus, as evidenced by the different stress reactions induced in the endocrine system (as measured by salivary cortisol) and the immune system (as measured by salivary neopterin).

The Neural Correlates of Chronic Symptoms of Vertigo Proneness in Humans.

Vestibular signals are of significant importance for variable functions including gaze stabilization, spatial perception, navigation, cognition, and bodily self-consciousness. The vestibular network governs functions that might be impaired in patients affected with vestibular dysfunction. It is currently unclear how different brain regions/networks process vestibular information and integrate the information into a unified spatial percept related to somatosensory awareness and whether people with recurrent balance complaints have a neural signature as a trait affecting their development of chronic symptoms of vertigo. Pivotal evidence points to a vestibular-related brain network in humans that is widely distributed in nature. By using resting state source localized electroencephalography in non-vertiginous state, electrophysiological changes in activity and functional connectivity of 23 patients with balance complaints where chronic symptoms of vertigo and dizziness are among the most common reported complaints are analyzed and compared to healthy subjects. The analyses showed increased alpha2 activity within the posterior cingulate cortex and the precuneues/cuneus and reduced beta3 and gamma activity within the pregenual and subgenual anterior cingulate cortex for the subjects with balance complaints. These electrophysiological variations were correlated with reported chronic symptoms of vertigo intensity. A region of interest analysis found reduced functional connectivity for gamma activity within the vestibular cortex, precuneus, frontal eye field, intra-parietal sulcus, orbitofrontal cortex, and the dorsal anterior cingulate cortex. In addition, there was a positive correlation between chronic symptoms of vertigo intensity and increased alpha-gamma nesting in the left frontal eye field. When compared to healthy subjects, there is evidence of electrophysiological changes in the brain of patients with balance complaints even outside chronic symptoms of vertigo episodes. This suggests that these patients have a neural signature or trait that makes them prone to developing chronic balance problems.