Improved naming after TMS treatments in a chronic,global aphasia patient – case report

We report improved ability to name pictures at 2 and 8 months after repetitive transcranial magnetic stimulation (rTMS) treatments to the pars triangularis portion of right Broca’s homologue in a 57 year-old woman with severe nonfluent/global aphasia (6.5 years post left basal ganglia bleed, subcortical lesion). TMS was applied at 1 Hz, 20 minutes a day, 10 days, over a two-week period. She received no speech therapy during the study. One year after her TMS treatments, she entered speech therapy with continued improvement. TMS may have modulated activity in the remaining left and right hemisphere neural network for naming.     

Task-dependent modulation of functional connectivity between hand motor cortices and neuronal networks underlying language and music: a transcranial magnetic stimulation study in humans

Although language functions are, in general, attributed to the left hemisphere, it is still a matter of debate to what extent the cognitive functions underlying the processing of music are lateralized in the human brain. To investigate hemispheric specialization we evaluated the effect of different overt musical and linguistic tasks on the excitability of both left and right hand motor cortices using transcranial magnetic stimulation (TMS). Task-dependent changes of the size of the TMS-elicited motor evoked potentials were recorded in 12 right-handed, musically naive subjects during and after overt speech, singing and humming, i.e. the production of melody without word articulation. The articulation of meaningless syllables served as control condition. We found reciprocal lateralized effects of overt speech and musical tasks on motor cortex excitability. During overt speech, the corticospinal projection of the left (i.e. dominant) hemisphere to the right hand was facilitated. In contrast, excitability of the right motor cortex increased during both overt singing and humming, whereas no effect was observed on the left hemisphere. Although the traditional concept of hemispheric lateralization of music has been challenged by recent neuroimaging studies, our findings demonstrate that right-hemisphere preponderance of music is nevertheless present. We discuss our results in terms of the recent concepts on evolution of language and gesture, which hypothesize that cerebral networks mediating hand movement and those subserving language processing are functionally linked. TMS may constitute a useful tool to further investigate the relationship between cortical representations of motor functions, music and language using comparative approaches.     

The right posterior inferior frontal gyrus contributes to phonological word decisions in the healthy brain: Evidence from dual-site TMS

There is consensus that the left hemisphere plays a dominant role in language processing, but functional imaging studies have shown that the right as well as the left posterior inferior frontal gyri (pIFG) are activated when healthy right-handed individuals make phonological word decisions. Here we used online transcranial magnetic stimulation (TMS) to examine the functional relevance of the right pIFG for auditory and visual phonological decisions. Healthy right-handed individuals made phonological or semantic word judgements on the same set of auditorily and visually presented words while they received stereotactically guided TMS over the left, right or bilateral pIFG (n = 14) or the anterior left, right or bilateral IFG (n = 14). TMS started 100 ms after word onset and consisted of four stimuli given at a rate of 10 Hz and intensity of 90% of active motor threshold. Compared to TMS of aIFG, TMS of pIFG impaired reaction times and accuracy of phonological but not semantic decisions for visually and auditorily presented words. TMS over left, right or bilateral pIFG disrupted phonological processing to a similar degree. In a follow-up experiment, the intensity threshold for delaying phonological judgements was identical for unilateral TMS of left and right pIFG. These findings indicate that an intact function of right pIFG is necessary for accurate and efficient phonological decisions in the healthy brain with no evidence that the left and right pIFG can compensate for one another during online TMS. Our findings motivate detailed studies of phonological processing in patients with acute and chronic damage of the right pIFG.     

Kernohan's notch phenomenon demonstrated by diffusion tensor imaging and transcranial magnetic stimulation

Kernohan's notch phenomenon is the ipsilateral hemiplegia caused by compression of the contralateral cerebral peduncle against the tentorial edge by a supratentorial mass. Diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS) could be useful for exploring the state of the corticospinal tract (CST). This report attempts to demonstrate Kernohan's notch phenomenon in a patient with subdural haematoma by using DTI and TMS. One patient and six normal control subjects were recruited. The patient showed severe right hemiplegia even though the subdural haematoma was located in the right hemisphere. Brain CT at the time of onset showed right transtentorial herniation, and T2 weighted images at 6 weeks after onset showed a leucomalacic lesion on the left cerebral peduncle. DTI and TMS were performed at 6 weeks after onset. The fractional anisotrophy value of the left midbrain and medulla of the patient was found to be decreased in comparison with that of the control subjects. On fibre tractography for the CST, an interruption was observed in the left midbrain and medulla. The motor evoked potential obtained from the right hand muscle showed delayed latency, low amplitude and a higher excitatory threshold, thus indicating that the CST of the left hemisphere had been damaged. It seems that the CST had been damaged at the left midbrain, although subdural haematoma and transtentorial herniation had occurred in the right hemisphere in this patient. This report demonstrates Kernohan's notch phenomenon in this patient using DTI and TMS.     

The right hemisphere is not unitary in its role in aphasia recovery

Neurologists and aphasiologists have debated for over a century whether right hemisphere recruitment facilitates or impedes recovery from aphasia. Here we present a well-characterized patient with sequential left and right hemisphere strokes whose case substantially informs this debate. A 72-year-old woman with chronic nonfluent aphasia was enrolled in a trial of transcranial magnetic stimulation (TMS). She underwent 10 daily sessions of inhibitory TMS to the right pars triangularis. Brain activity was measured during picture naming using functional magnetic resonance imaging (fMRI) prior to TMS exposure and before and after TMS on the first day of treatment. Language and cognition were tested behaviorally three times prior to treatment, and at 2 and 6 months afterward. Inhibitory TMS to the right pars triangularis induced immediate improvement in naming, which was sustained 2 months later. fMRI confirmed a local reduction in activity at the TMS target, without expected increased activity in corresponding left hemisphere areas. Three months after TMS, the patient suffered a right hemisphere ischemic stroke, resulting in worsening of aphasia without other clinical deficits. Behavioral testing 3 months later confirmed that language function was impacted more than other cognitive domains. The paradoxical effects of inhibitory TMS and the stroke to the right hemisphere demonstrate that even within a single patient, involvement of some right hemisphere areas may support recovery, while others interfere. The behavioral evidence confirms that compensatory reorganization occurred within the right hemisphere after the original stroke. No support is found for interhemispheric inhibition, the theoretical framework on which most therapeutic brain stimulation protocols for aphasia are based.     

Changing cortical excitability with low-frequency transcranial magnetic stimulation can induce sustained disruption of tactile perception.

Transcranial magnetic stimulation (TMS) is promising as a therapeutic tool, and TMS of the motor system has served as a model for regionally specific modulations of cortical excitability. It is unclear, however, to what extent response characteristics of the motor cortex are representative of other brain systems. We wanted to determine whether TMS could induce a sustained disruption of somatosensory processing beyond the stimulation duration, similar to observations in the motor system. We applied 1-Hz TMS at 110% of subjects' motor thresholds for a variable duration over the right and left somatosensory cortex before subjects performed a tactile frequency discrimination task with the left hand. Tactile discrimination was impaired only after TMS over the right somatosensory cortex (analysis of variance: p <.01). The duration of this impairment correlated with the duration of the preceding TMS; the effect lasted approximately 2 min after 5 min of TMS, 4 min after 10 min of TMS, and 8 min after 20 min of TMS. Two conclusions arise: 1) low-frequency TMS can interfere with tactile perception in a robust and sustained way, and 2) TMS dosing parameters effective in the motor system are also effective in the somatosensory system and may reflect a modality-independent response characteristic of the cerebral cortex.     

Language laterality assessed by unilateral ECT and dichotic monitoring

A dichotic monitoring test for the lateralisation of speech dominance was compared with testing for dysphasia after unilateral electroconvulsive therapy to each side of the head in 31 patients, and the intracarotid amylobarbitone test in four epileptic patients. Twenty-eight patients shown to be left speech dominant also showed right ear advantages in the dichotic test. Four of the five right speech dominant patients showed left ear advantages. Two patients with bilateral speech representation showed nonsignificant ear asymmetries. The noninvasive dichotic monitoring task is quick and simple and produces large mean ear advantages (14 to 25%) in normal subjects as well as patients.     

Regional cerebral blood flow changes after low-frequency transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in treatment-resistant depression

Several studies have proved that low-frequency transcranial magnetic stimulation (TMS) of the right dorsolateral prefrontal cortex (DLPFC) showed an antidepressant effect, although its mechanism is still not completely elucidated. The aim of the present study was to clarify the alteration in neuroanatomical function elicited by low-frequency TMS of the right DLPFC in treatment-resistant depression and to detect the difference between responders and nonresponders to TMS. Single-photon emission computed tomography with (99m)Tc-ethyl cysteinate dimer was performed in 14 right-handed male patients with treatment-resistant unipolar depression before and after low-frequency TMS of the right DLPFC. Five 60-second 1-Hz trains were applied and 12 treatment sessions were administered within a 3-week period (total pulses, 3,600). The Hamilton Rating Scale for Depression was administered and the regional cerebral blood flow (rCBF) was analyzed using statistical parametric mapping (SPM2). After TMS treatment in 14 patients, the score on the Hamilton Rating Scale for Depression decreased significantly, and considerable decreases in rCBF were seen in the bilateral prefrontal, orbitofrontal, anterior insula, right subgenual cingulate, and left parietal cortex, but no significant increase in rCBF occurred. Additionally, as compared with 8 nonresponders, 6 responders showed significant increases in rCBF at baseline in the left hemisphere including the prefrontal and limbic-paralimbic regions. These results suggest that the antidepressant effect of low-frequency TMS of the right DLPFC is associated with a decrease in rCBF in the limbic-paralimbic regions via the ipsilateral subgenual cingulate, and increased rCBF at baseline in the left hemisphere may be involved in the response to low-frequency TMS treatment.     

Right prefrontal TMS versus sham treatment of mania: a controlled study

Objective:  Left prefrontal transcranial magnetic stimulation (TMS) has been reported to have ECT-like effects in depression and we therefore planned a study of TMS in mania. Sixteen patients completed trial of right versus left prefrontal TMS at 20 Hz, 2-sec duration per train, 20 trains per day for 10 treatment days. Mania was evaluated using the Mania Scale, the Brief Psychiatric Rating Scale and the Clinical Global Impression. Significantly more improvement was observed in patients treated with right prefrontal TMS than with left prefrontal. We now report a follow-up study of right active TMS versus right sham TMS with the same indications and parameters.
Methods:  Twenty-five patients entered and 19 completed right TMS versus sham right TMS.
Results:  Right TMS was no more effective than sham TMS.
Conclusions:  It is possible that the previous results were due to an effect of left TMS to worsen mania. Alternatively, it is noted that the present patient group had much more psychosis than the previous study of TMS in mania, and depression studies have reported that psychosis is a poor prognostic sign for TMS response.     

Musical training-induced functional reorganization of the adult brain: functional magnetic resonance imaging and transcranial magnetic stimulation study on amateur string players

We used the combined technique of functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to observe changes that occur in adult brains after the practice of stringed musical instruments. We carried out fMRI on eight volunteers (aged 20-22 years): five novices and three individuals who had discontinued practice for more than 5 years. The motor paradigm contained a repetitive lift-abduction/fall-adduction movement of the left/right little finger, carried out with maximum efforts without pacing. The sensory paradigm was to stimulate the same little finger using a string. In parallel to the fMRI acquisition, TMS motor maps for the little finger were obtained using a frameless stereotactic neuronavigation system. After the baseline study, each participant began to learn a stringed instrument. Newly developed fMRI activations for the left little finger were observed 6 months after practice at multiple brain regions including inferior parietal lobule, premotor area (PMA), left precuneus, right anterior superior temporal gyrus, and posterior middle temporal gyrus. In contrast, new activations were rarely observed for the right little finger. The TMS study revealed new motor representation sites for the left little finger in the PMA or supplementary motor area (SMA). Unexpectedly, TMS motor maps for the right little finger were reduced significantly. Among new fMRI activations for sensory stimuli of the left little finger, the cluster of highest activation was located in the SMA. Collectively, these data provide insight into orchestrated reorganization of the sensorimotor and temporal association cortices contributing to the skillful fingering and musical processing after the practice of playing stringed instruments.     

Crossed effects of muscle vibration on motor-evoked potentials.

OBJECTIVES: Muscle vibration (MV) to a forearm muscle augments motor-evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) and the underlying mechanism involves cortical structures. Although MV-induced cortical activation is bilateral, the effects of MV on MEPs in contralateral muscles have not been investigated. METHODS: Low-amplitude MV (80 Hz, amplitude 0.5 mm, duration 4 s), subthreshold for the tonic vibration reflex, was applied to the right extensor carpi radialis muscle (ECR). MEPs were elicited (0.5, 3 and 5 s after MV onset) in the left and right ECR and flexor carpi radialis muscle (FCR) by TMS (120% of threshold at rest) to the left and right hemisphere, respectively. RESULTS: During MV of right ECR the left ECR revealed a slight non-significant augmentation of MEPs. In contrast, the left FCR showed a gradual depression of MEPs with ongoing MV and at 3 s the reduction of MEPs was significant. The time course of MEP changes in left FCR correlated with the facilitation of the vibrated right ECR. Post-vibration MEPs at 1 s after the offset of MV were still significantly decreased. CONCLUSIONS: The study demonstrates crossed effects of MV on motor cortex excitability, suggesting transcallosal MEP modulation.     

Interhemispheric imbalance during visuospatial attention investigated by unilateral and bilateral TMS over human parietal cortices

We used single-pulse transcranial magnetic stimulation (TMS) to study visuospatial attention. TMS was applied over one hemisphere, or simultaneously over both the right and left posterior parietal cortex (PPC), at two different interstimulus intervals (ISI) during a visual detection task. Unilateral TMS over the right and left PPC, respectively, impaired detection of contralateral presented visual stimuli at an ISI of 150 ms. By contrast, simultaneous biparietal TMS induced no significant changes in correct stimulus detection. TMS at an ISI of 250 ms evoked no changes for magnetic stimulation over either the right or the left parietal cortex. These results suggest that both PPC play a crucial role at a relatively early stage in the widely distributed brain network of visuospatial attention. The abolition of behavioral deficits during simultaneous biparietal TMS underlines the common hypothesis that an interhemispheric imbalance might underlie the disorders of neglect and extinction seen following unilateral brain damage.     

Recovery of the corticospinal tract after injury by transtentorial herniation: a case report

Little is known about recovery of the corticospinal tract (CST) after injury by transtentorial herniation (TH). We present with a patient who showed recovery of the CST after injury by TH, using diffusion tensor tractography (DTT) and transcranial magnetic stimulation (TMS). A 69-year-old female underwent craniotomy and drainage of an intracerebral hemorrhage in the left corona radiata and basal ganglia. Brain CT showed left TH and brain MRI revealed a leukomalactic lesion at the left cerebral peduncle. The patient presented with complete paralysis of the right extremities at ICH onset, but slowly recovered some function to the point of being able to move the affected extremities against gravity at about 6 months after onset. Three-week DTT showed disruption of the left CST below the cerebral peduncle; however, this disruption was recovered on 1-year DTT. Three-week TMS showed no motor evoked potential for the affected hemisphere; in contrast, motor evoked potentials that were compatible with regenerated CST were obtained from the affected hand muscle at 6 months. Using DTT and TMS in a patient with ICH, we demonstrated recovery of the CST after injury by TH.     

Lateral preferences and cerebral speech dominance

Four types of lateral preference (hand, foot, eye, ear) were measured in 73 patients, who underwent sodium Amytal speech testing. In 63 cases, speech was on the left side whereas in 10, speech was on the right. All of the patients with right hemisphere lesions had speech represented in the left hemisphere. Only a third of the patients with left hemisphere damage prior to the end of the first year of life continued to have speech on the left side. By contrast, 82% of those with left hemisphere damage after this sensitive period had speech exclusively mediated by the left hemisphere. In short, the occurrence of right hemisphere speech dominance without an early lesion to the left hemisphere is rare. The majority of patients with right-sided motor and sense organ preferences had speech represented in the left hemisphere, independent of location or age of onset of the damage. By contrast, in individuals with a clinical history of early left hemisphere injury, left-sided motor and sense organ preferences were linked to right hemisphere speech dominance. In those cases without evidence of early cerebral damage, most of the non-right-sided individuals had speech in the left hemisphere. However, the proportion of unilateral, left hemisphere speech representation in the right-handed and right-footed was higher than that observed in the left-handed and left-footed, even when those with early onset of damage were excluded from analysis. It was suggested that in the normal population, handedness and footedness are relevant factors in predicting cerebral speech dominance. Knowledge of eye and ear preference may be of little predictive value. Further, in a neurological population the overall congruency across the four patterns of lateral preference may provide useful information regarding cerebral speech dominance. A small group (5) of patients with bilateral representation of speech was also examined. Contrary to the experience at the Montreal Neurological Institute, most of these patients preferred the right limb and sense organ. Differences in investigative approach may account for the conflicting observations.     

Singing can improve speech function in aphasics associated with intact right basal ganglia and preserve right temporal glucose metabolism: Implications for singing therapy indication

Clinically, we know that some aphasic patients can sing well despite their speech disturbances. Herein, we report 10 patients with non-fluent aphasia, of which half of the patients improved their speech function after singing training. We studied ten patients with non-fluent aphasia complaining of difficulty finding words. All had lesions in the left basal ganglia or temporal lobe. They selected the melodies they knew well, but which they could not sing. We made a new lyric with a familiar melody using words they could not name. The singing training using these new lyrics was performed for 30 minutes once a week for 10 weeks. Before and after the training, their speech functions were assessed by language tests. At baseline, 6 of them received positron emission tomography to evaluate glucose metabolism. Five patients exhibited improvements after intervention; all but one exhibited intact right basal ganglia and left temporal lobes, but all exhibited left basal ganglia lesions. Among them, three subjects exhibited preserved glucose metabolism in the right temporal lobe. We considered that patients who exhibit intact right basal ganglia and left temporal lobes, together with preserved right hemispheric glucose metabolism, might be an indication of the effectiveness of singing therapy.     

Right-shift for non-speech motor processing in adults who stutter

Introduction

In adults who do not stutter (AWNS), the control of hand movement timing is assumed to be lateralized to the left dorsolateral premotor cortex (PMd). In adults who stutter (AWS), the network of speech motor control is abnormally shifted to the right hemisphere. Motor impairments in AWS are not restricted to speech, but extend to non-speech orofacial and finger movements. We here investigated the lateralization of finger movement timing control in AWS.

Methods

We explored PMd function in 14 right-handed AWS and 15 age matched AWNS. In separate sessions, they received subthreshold repetitive transcranial magnetic stimulation (rTMS) for 20 min at 1 Hz over the left or right PMd, respectively. Pre- and post-stimulation participants were instructed to synchronize their index finger taps of either hand with an isochronous sequence of clicks presented binaurally via earphones. Synchronization accuracy was measured to quantify the effect of the PMd stimulation.

Results

In AWNS inhibition of left PMd affected synchronization accuracy of the left hand. Conversely, in AWS TMS over the right PMd increased the asynchrony of the left hand.

Conclusions

The present data indicate an altered functional connectivity in AWS in which the right PMd seems to be important for the control of timed non-speech movements. Moreover, the laterality-shift suggests a compensatory role of the right PMd to successfully perform paced finger tapping.     

Charting the excitability of premotor to motor connections while withholding or initiating a selected movement

In 19 healthy volunteers, we used transcranial magnetic stimulation (TMS) to probe the excitability in pathways linking the left dorsal premotor cortex and right primary motor cortex and those linking the left and right motor cortex during the response delay and the reaction time period while subjects performed a delayed response [symbol 1 (S1) - symbol 2 (S2)] Go-NoGo reaction time task with visual cues. Conditioning TMS pulses were applied to the left premotor or left motor cortex 8 ms before a test pulse was given to the right motor cortex at 300 or 1800 ms after S1 or 150 ms after S2. S1 coded for right-hand or left-hand movement, and S2 for release or stopping the prepared movement. Conditioning of the left premotor cortex led to interhemispheric inhibition at 300 ms post-S1, interhemispheric facilitation at 150 ms post-S2, and shorter reaction times in the move-left condition. Conditioning of the left motor cortex led to inhibition at 1800 ms post-S1 and 150 ms post-S2, and slower reaction times for move-right conditions, and inhibition at 300 and 1800 ms post-S1 for move-left conditions. Relative motor evoked potential amplitudes following premotor conditioning at 150 ms post-S2 were significantly smaller in 'NoGo' than in 'Go' trials for move-left instructions. We conclude that the excitability in left premotor/motor right motor pathways is context-dependent and affects motor behaviour. Thus, the left premotor cortex is engaged not only in action selection but also in withholding and releasing a preselected movement generated by the right motor cortex.     

Speech production after stroke: the role of the right pars opercularis

Recovery of speech after infarction of the left pars opercularis (POp) may be due to recruitment of homotopic cortex in the right hemisphere. Using positron emission tomography, we investigated activity within left and right POp during everyday propositional speech. We studied seven aphasic patients with left anterior perisylvian infarction which included the POp. We compared their data with two control groups: 12 normal subjects and 7 anterior aphasic patients whose infarcts spared the left POp. During propositional speech, normal subjects activated the left POp, left posterior perisylvian cortex, and a distributed, predominantly left-lateralized, extrasylvian neural network. Importantly, activity in the right POp was reduced relative to a baseline nonspeech condition. In patients with infarction of the left POp, activity in the right POp was reversed: speech activated the right POp above baseline. Patient controls activated the left POp but did not show the normal relative reduction in activity in the right POp. In both patient groups, posterior perisylvian and extrasylvian activations remained unchanged from normal. This result demonstrates that infarction of the left POp is associated with a chronic change in function of the contralateral homotopic cortex during speech.     

Hemispheric lateralization of number comparison

In order to clarify the respective contribution of the right and left posterior parietal cortex (PPC) to number comparison, transcranial magnetic stimulation (TMS) was used to disrupt PPC processing in subjects instructed to determine whether a digit was smaller or larger than 5. Single pulse TMS was applied over the PPC, either unilaterally or bilaterally, 150, 200, or 250 ms after digit presentation. Sham TMS was used as a control condition to take into account the unspecific effects of TMS on reaction time (RT). The main finding of the present study is a significant increase in RTs when comparing digits close to 5 following a disruption either of the left PPC alone or of both PPC simultaneously. The comparison of digits far from 5 was unaltered by disrupting only one PPC but RTs were found increased after bilateral PPC stimulation. These disruptive effects were observed irrespective of the TMS delay. We concluded that coding precise numerical values requires the integrity of the left PPC, as suggested by the deficit in discriminating close digits consequent to its disruption. In contrast, approximate comparisons can be processed either by the left or right PPC, since simultaneous bilateral TMS was needed to alter the comparison of digits far from 5.     

Changes in hypothalamic–pituitary–thyroid axis following successful treatment with low-frequency right prefrontal transcranial magnetic stimulation in treatment-resistant depression

Hypothalamic-pituitary-thyroid (HPT) axis abnormalities have been reported in some patients with major depression. To knowledge, however, the effects of low-frequency right prefrontal transcranial magnetic stimulation (TMS) on the HPT axis have not yet been elucidated. The goal of this study was to evaluate alterations in the HPT axis associated with the therapeutic efficacy of TMS treatments. Twenty patients with treatment-resistant depression received five 60-s 1-Hz trains over the right dorsolateral prefrontal cortex. Twelve treatment sessions were administered within a 3-week period (total pulses, 3600). Responders were defined as a ≥ 50% decrease in the Hamilton Depression Rating Scale (HDRS) score. Serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) were measured, respectively, at pre- and post-treatment. There were no significant changes in fT3 and fT4 levels measured at either pre- or post-treatment in either responders or nonresponders; however, TSH levels of responders elevated significantly after TMS treatments. In addition, there was a significant negative correlation between TSH levels at pretreatment and decrease (%) in the HDRS score. These findings suggest that the HPT axis is associated with antidepressant effects of low-frequency right prefrontal TMS, and indicate that lower TSH levels at pre-treatment are correlated with better therapeutic efficacy.