Restoration of hand function with long-term paired associative stimulation after chronic incomplete tetraplegia: a case study.

Introduction: This case study explores the gains in hand function in an individual with a chronic spinal cord injury (SCI). The intervention was long-term paired associative simulation (PAS). We aimed to provide PAS until full recovery of hand muscle strength occurred, or until improvements ceased. Case presentation: A 46-year-old man with traumatic C7 AIS B tetraplegia was administered PAS three times per week. After 24 weeks, PAS was combined with concomitant motor training of the remaining weak hand muscles. Outcome measures included the manual muscle test (MMT), motor-evoked potentials (MEPs), F-responses, hand functional tests, and the spinal cord independence measure (SCIM). Discussion: After 47 weeks of PAS the subject had improved self-care and indoor mobility and was able to perform complex motor tasks (SCIM score improved from 40 to 56). His left hand regained maximum MMT score (total 75; increase of score from baseline condition 19); the effect remained stable in the 32-week follow up. In the right-hand muscles, MMT scores of 4-5 were observed in follow up (total 71; increase from baseline 48). Improved values were also observed in other outcomes. This is the first demonstration of long-term PAS restoring muscle strength corresponding to MMT scores of 4-5 in an individual with chronic SCI. The effect persisted for several months, indicating that PAS induces stable plastic changes in the corticospinal pathway.

Auditory cortical responses in humans with profound unilateral sensorineural hearing loss from early childhood.

We recorded auditory evoked magnetic fields from five patients with profound unilateral sensorineural hearing loss from early childhood, using a 122-channel whole-scalp neuromagnetometer. The stimuli were 50-ms 1-kHz tone bursts delivered to the healthy ear at interstimulus intervals (ISI) of 1, 2, and 4 s. As the normal-hearing controls, four patients had shorter latencies of N100m, the 100-ms response, over the hemisphere contralateral to the stimulation than over the ipsilateral hemisphere. With 1-s ISI, three patients had, instead of N100m, a deflection of opposite polarity at about 100 ms (P100m) after the stimulus onset. A 10-year-old patient had a prominent P100m response, did not produce a clear N100m at any ISI, but had a clear N50m at the 4-s ISI. Four patients had bilateral N200m deflections peaking about 200 ms after the stimulus onset; the fifth patient showed N200m over the right hemisphere. N200m was also observed in the three youngest controls in both hemispheres. The ISI dependence of N100m amplitude and latency was similar in controls and patients. The amplitudes and latencies of N200m did not show any ISI dependence. In patients, the appearance of P100m-N200m deflections of auditory evoked fields, normally present in children, is more pronounced than in controls. The defect apparently delays the development of N100m, possibly by interfering with function of callosal connections.

Human auditory cortex is activated by omissions of auditory stimuli.

Cortical signals associated with infrequent tone omissions were recorded from 9 healthy adults with a whole-head 122 channel neuromagnetometer. The stimulus sequence consisted of monaural (left or right) 50-ms 1-kHz tones repeated every 0.2 or 0.5 s, with 7% of the tones randomly omitted. Tones elicited typical responses in the supratemporal auditory cortices. Omissions evoked strong responses over temporal and frontal areas, independently of the side of stimulation, with peak amplitudes at 145-195 ms. Response amplitudes were 60% weaker when the subject was not attending to the stimuli. Omission responses originated in supratemporal auditory cortices bilaterally, indicating that auditory cortex plays an important role in the brain's modelling of temporal characteristics of the auditory environment. Additional activity was observed in the posterolateral frontal cortex and in the superior temporal sulcus, more often in the right than in the left hemisphere.

Auditory evoked fields to illusory sound source movements.

Auditory motion can be simulated by presenting binaural sounds with time-varying interaural intensity differences. We studied the human cortical response to both the direction and the rate of illusory motion by recording the auditory evoked magnetic fields with a 122-channel whole-head neuromagnetometer. The illusion of motion from left to right, right to left, and towards and away from the subject was produced by varying a 6-dB intensity difference between the two ears in the middle of a 600-ms tone. Both the onset and the intensity transition within the stimulus elicited clear responses in auditory cortices of both hemispheres, with the strongest responses occurring about 100 ms after the stimulus and transition onsets. The transition responses were significantly earlier and larger for fast than slow shifts and larger in the hemisphere contralateral to the increase in stimulus intensity for azimuthal shifts. Transition response amplitude varied with the direction of the simulated motion, suggesting that these responses are mediated by directionally selective cells in auditory cortex.

Effects of intensity variation on human auditory evoked magnetic fields.

We recorded auditory evoked magnetic fields from 6 healthy subjects with a 122-channel whole-head neuromagnetometer. The stimuli were 200-ms 1-kHz tones delivered at 4 different intensities (40, 50, 60, and 65 dB HL). The tones were given once every second, binaurally in the first session, and monaurally to each ear in the second one. The four intensities were presented randomly and equiprobably within a single sequence. In both stimulus conditions, the 100-ms response (N100m) decreased in latency and increased in amplitude as a function of intensity in both hemispheres. No systematic dependence was found between stimulus intensity and the N100m source location in the auditory cortex. Our study illustrates a noninvasive method to examine the functional properties of human auditory cortex, allowing simultaneous comparison between signals arising from both hemispheres.

Auditory pathway plasticity in adult humans after unilateral idiopathic sudden sensorineural hearing loss.

We recorded auditory evoked magnetic fields from 8 patients with unilateral, idiopathic, sudden, sensorineural hearing loss and from 8 healthy controls, using a 122-channel whole-scalp neuromagnetometer. The stimuli were 50-ms l-kHz tone bursts, delivered to the healthy ear at interstimulus intervals (ISIs) of 1, 2, 4, 8, and 16 s. On average, as in normal-hearing controls, the dipole moments and the latencies of N100m, the 100-ms response, increased as a function of ISI over both hemispheres to left- and right-ear stimulation. Four patients had shorter response latencies and 4 had stronger dipole moments over the hemisphere ipsilateral to the stimulation. In 3 patients, one additional source was observed over the anterolateral right hemisphere and another near head midline. These findings suggest that unilateral sensorineural hearing loss may modify information processing in the central auditory pathways.

Effect of interaural time differences on middle-latency and late auditory evoked magnetic fields.

To determine if interaural time differences (ITDs) in binaural stimuli affect the middle-latency auditory evoked fields (AEFs) in the same manner as they affect the N100m deflection, neuromagnetic responses were recorded over the whole head using a 122-channel SQUID magnetometer. Binaural stimuli were lateralized to three positions, left, midline, and right, on the basis of ITDs. The N100m was significantly larger to stimuli with contralaterally-leading ITDs than to stimuli with no, or with ipsilaterally-leading ITDs. Neither the P30m nor the P50m deflections of the middle-latency response were significantly affected by ITD, although the P30m showed a tendency, similar to but smaller than that of N100m, to be larger to stimuli with contralaterally-leading ITDs. In some subjects, the source location of the P50m was anterior and inferior to the sources of the P30m and N100m, which are generated in the superior surface of the temporal lobe. Sound-related muscular artifacts were seen in the posterior recording channels of one subject, and the contribution of this activity to the signals over the temporal area was determined.

Modification of neuromagnetic responses of the human auditory cortex by masking sounds.

We have studied the effects of masking sounds on auditory evoked magnetic fields (AEFs) of healthy humans. The AEFs were elicited by 25-ms tones presented randomly to the left or to the right ear, and the responses were recorded over the right auditory cortex. Without masking, the 100-ms deflection (N100m) was of somewhat higher amplitude and of shorter latency for contra- than ipsilateral stimuli. Continuous speech, music, or intermittent noise, delivered to the left ear, dampened N100m to stimulation of both ears without correlated changes in sensation. Intermittent noise had a weaker effect on N100m than speech or music. Continuous noise fed to the left ear dampened both the sensation of and the responses to the left-ear stimuli, with no significant effect on the responses to the right-ear stimuli. The results suggest that the masking effects of continuous noise, seen at the auditory cortex, derive mainly from the periphery whereas the effects of sounds with intensity and frequency modulations take place at more central auditory pathways.

Neuromagnetic responses to frequency modulation of a continuous tone.

Neuromagnetic responses to frequency modulation of a continuous tone were studied in nine subjects. The latencies of the transient responses increased and the amplitudes decreased with decreasing speed of modulation. The equivalent dipoles for modulation of a 1,000 Hz tone were slightly but statistically significantly anterior to the dipoles activated by modulation of a 500 Hz tone. The generation mechanisms of N100m are discussed.