M. Desikan

Speech Facilitation by Left Inferior Frontal Cortex Stimulation

Summary Electrophysiological studies in humans and animals suggest that noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting [1], polarity-dependent [2] changes in neocortical excitability. Application of tDCS can have significant and selective behavioral consequences that are associated with the cortical location of the stimulation electrodes and the task engaged during stimulation [3–8]. However, the mechanism by which tDCS affects human behavior is unclear. Recently, functional magnetic resonance imaging (fMRI) has been used to determine the spatial topography of tDCS effects [9–13], but no behavioral data were collected during stimulation. The present study is unique in this regard, in that both neural and behavioral responses were recorded using a novel combination of left frontal anodal tDCS during an overt picture-naming fMRI study. We found that tDCS had significant behavioral and regionally specific neural facilitation effects. Furthermore, faster naming responses correlated with decreased blood oxygen level-dependent (BOLD) signal in Brocas area. Our data support the importance of Brocas area within the normal naming network and as such indicate that Brocas area may be a suitable candidate site for tDCS in neurorehabilitation of anomic patients, whose brain damage spares this region.

Interaction between visual and motor cortex: a transcranial magnetic stimulation study

The major link between the visual and motor systems is via the dorsal stream pathways from visual to parietal and frontal areas of cortex. Although the pathway appears indirect, there is evidence that visual input can reach the motor cortex at relatively short latency. To shed some light on its neural bases, we studied the visuo-motor interaction using paired transcranial magnetic stimulation (paired-TMS). Motor evoked potentials (MEPs) were recorded from the right FDI in sixteen healthy volunteers. A conditioning stimulus (CS) was applied over the phosphene hotspot of visual cortex, followed by a test stimulus (TS) over left M1 at random interstimulus intervals (ISIs, 12-40 ms). The effects of paired stimulation were re-tested during visual and auditory reaction-time tasks (RT). Finally, we measured the effects of a CS on short-interval intracortical inhibition (SICI). At rest, a CS over the occiput significantly (p Language: enWe studied the interaction between the primary visual cortex and the primary motor cortex using paired transcranial magnetic stimulation (TMS) with an interstimulus interval (ISI) in the range 12–40 ms. The connection is inhibitory at rest and possibly mediated by inhibitory interneurones in the motor cortex. The effect with an ISI of 40 ms reverses into facilitation during a visuomotor (but not audiomotor) reaction task. By contrast, there is no change in inhibition with an ISI of 18 ms, suggesting that separate pathways can be probed at different ISIs. We conclude that a physiologically relevant occipito‐motor connection can be activated by means of TMS. It may contribute to visuomotor integration, as well as being involved in certain types of visual epilepsy.

Spontaneously Fluctuating Motor Cortex Excitability in Alternating Hemiplegia of Childhood: A Transcranial Magnetic Stimulation Study

Background Alternating hemiplegia of childhood is a very rare and serious neurodevelopmental syndrome; its genetic basis has recently been established. Its characteristic features include typically-unprovoked episodes of hemiplegia and other transient or more persistent neurological abnormalities. Methods We used transcranial magnetic stimulation to assess the effect of the condition on motor cortex neurophysiology both during and between attacks of hemiplegia. Nine people with alternating hemiplegia of childhood were recruited; eight were successfully tested using transcranial magnetic stimulation to study motor cortex excitability, using single and paired pulse paradigms. For comparison, data from ten people with epilepsy but not alternating hemiplegia, and ten healthy controls, were used. Results One person with alternating hemiplegia tested during the onset of a hemiplegic attack showed progressively diminishing motor cortex excitability until no response could be evoked; a second person tested during a prolonged bilateral hemiplegic attack showed unusually low excitability. Three people tested between attacks showed asymptomatic variation in cortical excitability, not seen in controls. Paired pulse paradigms, which probe intracortical inhibitory and excitatory circuits, gave results similar to controls. Conclusions We report symptomatic and asymptomatic fluctuations in motor cortex excitability in people with alternating hemiplegia of childhood, not seen in controls. We propose that such fluctuations underlie hemiplegic attacks, and speculate that the asymptomatic fluctuation we detected may be useful as a biomarker for disease activity.

Motor cortex synchronization influences the rhythm of motor performance in premanifest huntington's disease: M1 Synchronization and Motor Performance

Background: In Huntingtons disease there is evidence of structural damage in the motor system, but it is still unclear how to link this to the behavioral disorder of movement. One feature of choreic movement is variable timing and coordination between sequences of actions. We postulate this results from desynchronization of neural activity in cortical motor areas.

GYG1 causing progressive limb girdle myopathy with onset during teenage years (polyglucosan body myopathy 2)

An 84-year-old lady with slowly progressive limb and axial muscle weakness with onset in her teens was referred for genetic investigations. Targeted next generation sequencing (NGS) revealed a homozygous mutation GYG1 in exon5:c.487delG:p.D163fs, confirming the diagnosis of Polyglucosan Body Myopathy 2 (PGBM2). Retrospective review of muscle pathology revealed a florid vacuolar myopathy with histochemical and ultrastructural features consistent with a polyglucosan storage myopathy. No cardiac symptoms were reported. Our case is consistent with the core phenotype of GYG1-related PGBM2 apart from an early onset of weakness without cardiac symptoms. The presence of α-amylase resistant PAS-positive material in skeletal muscle biopsy of patients with slowly progressive limb girdle muscle weakness should prompt the search for GYG1 mutations. This case highlights the combined role of muscle pathology and NGS in the molecular resolution of patients with undiagnosed neuromuscular conditions.

Interaction between visual and motor cortex: a transcranial magnetic stimulation study: Visuomotor interaction

The major link between the visual and motor systems is via the dorsal stream pathways from visual to parietal and frontal areas of cortex. Although the pathway appears indirect, there is evidence that visual input can reach the motor cortex at relatively short latency. To shed some light on its neural bases, we studied the visuo-motor interaction using paired transcranial magnetic stimulation (paired-TMS). Motor evoked potentials (MEPs) were recorded from the right FDI in sixteen healthy volunteers. A conditioning stimulus (CS) was applied over the phosphene hotspot of visual cortex, followed by a test stimulus (TS) over left M1 at random interstimulus intervals (ISIs, 12-40 ms). The effects of paired stimulation were re-tested during visual and auditory reaction-time tasks (RT). Finally, we measured the effects of a CS on short-interval intracortical inhibition (SICI). At rest, a CS over the occiput significantly (p Language: enWe studied the interaction between the primary visual cortex and the primary motor cortex using paired transcranial magnetic stimulation (TMS) with an interstimulus interval (ISI) in the range 12–40 ms. The connection is inhibitory at rest and possibly mediated by inhibitory interneurones in the motor cortex. The effect with an ISI of 40 ms reverses into facilitation during a visuomotor (but not audiomotor) reaction task. By contrast, there is no change in inhibition with an ISI of 18 ms, suggesting that separate pathways can be probed at different ISIs. We conclude that a physiologically relevant occipito‐motor connection can be activated by means of TMS. It may contribute to visuomotor integration, as well as being involved in certain types of visual epilepsy.