Friedhelm C. Hummel

Transcranial direct current stimulation: State of the art 2008

Effects of weak electrical currents on brain and neuronal function were first described decades ago. Recently, DC polarization of the brain was reintroduced as a noninvasive technique to alter cortical activity in humans. Beyond this, transcranial direct current stimulation (tDCS) of different cortical areas has been shown, in various studies, to result in modifications of perceptual, cognitive, and behavioral functions. Moreover, preliminary data suggest that it can induce beneficial effects in brain disorders. Brain stimulation with weak direct currents is a promising tool in human neuroscience and neurobehavioral research. To facilitate and standardize future tDCS studies, we offer this overview of the state of the art for tDCS.

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS)

A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years.

Brain Oscillatory Substrates of Visual Short-Term Memory Capacity

The amount of information that can be stored in visual short-term memory is strictly limited to about four items. Therefore, memory capacity relies not only on the successful retention of relevant information but also on efficient suppression of distracting information, visual attention, and executive functions. However, completely separable neural signatures for these memory capacity-limiting factors remain to be identified. Because of its functional diversity, oscillatory brain activity may offer a utile solution. In the present study, we show that capacity-determining mechanisms, namely retention of relevant information and suppression of distracting information, are based on neural substrates independent of each other: the successful maintenance of relevant material in short-term memory is associated with cross-frequency phase synchronization between theta (rhythmical neural activity around 5 Hz) and gamma (> 50 Hz) oscillations at posterior parietal recording sites. On the other hand, electroencephalographic alpha activity (around 10 Hz) predicts memory capacity based on efficient suppression of irrelevant information in short-term memory. Moreover, repetitive transcranial magnetic stimulation at alpha frequency can modulate short-term memory capacity by influencing the ability to suppress distracting information. Taken together, the current study provides evidence for a double dissociation of brain oscillatory correlates of visual short-term memory capacity.

Transcallosal inhibition in chronic subcortical stroke

Movements of the paretic hand in patients with chronic subcortical stroke are associated with high interhemispheric inhibition (IHI) targeting the motor cortex in the lesioned hemisphere relative to healthy controls. The purpose of this investigation was to determine whether this abnormality also involves IHI operating during movements of the non-paretic hand. Here, we studied IHI in the process of generation of voluntary index finger movements by the paretic and non-paretic hands in a simple reaction time paradigm in a group of patients with chronic subcortical stroke. With movements of the non-paretic index finger, IHI targeting the contralateral primary motor cortex ((c)M1) decreased progressively to turn into facilitation at around movement onset, similar to healthy controls. In contrast, movements of the paretic index finger resulted in significantly deeper inhibition at all premovement timings relative to the non-paretic hand. In conclusion, these results document a deeper premovement IHI with paretic than non-paretic hand movements of patients with chronic subcortical stroke, a possible mechanism underlying deficits in motor control.

Improvement of Motor Function with Noninvasive Cortical Stimulation in a Patient with Chronic Stroke

This manuscript reports the effects of transcranial DC stimulation (tDCS), a technique that enhances cortical plasticity in healthy humans, on motor function in a patient with chronic subcortical ischemic stroke. tDCS but not sham applied in a double-blind protocol to motor regions of the affected hemisphere led to improvements in pinch force, Jebsen-Taylor Hand Function Test, and simple reaction times in the paretic hand that outlasted the stimulation period for at least 40 min. These changes were accompanied by increased corticomotor excitability identified by enhanced recruitment curves and reduced intracortical inhibition to transcranial magnetic stimulation. These results document a beneficial effect of noninvasive brain stimulation on motor function in a human patient with stroke and raise the hypothesis of its potential application in neurorehabilitation.

Dissociation of sustained attention from central executive functions: local activity and interregional connectivity in the theta range

Human brain oscillatory activity was analysed in the electroencephalographic theta frequency range (4–7 Hz) while subjects executed complex sequential finger movements with varying task difficulty and memory load. Local frontal‐midline theta activity was associated with the general level of cognitive demand, with the highest amplitudes in the most demanding condition. Using low‐resolution electromagnetic tomography analysis (LORETA), this theta activity was localized in the anterior cingulate gyrus including the cingulate motor area. These results suggest that local theta activity in the anterior cingulate gyrus represents correlates of an attentional system that allocate cognitive resources. In addition, interregional connectivity in the theta frequency range was modulated by memory‐related executive functions independently of task difficulty. Connectivity analyses revealed a more distributed long‐range network including frontal and parietal cortices during execution of novel compared with well‐trained finger movement sequences. Thus, these results are compatible with a model in which theta long‐range coupling indicates integration of sensory information into executive control components of complex motor behaviour.

Consensus: Can transcranial direct current stimulation and transcranial magnetic stimulation enhance motor learning and memory formation?

Noninvasive brain stimulation has developed as a promising tool for cognitive neuroscientists. Transcranial magnetic (TMS) and direct current (tDCS) stimulation allow researchers to purposefully enhance or decrease excitability in focal areas of the brain. The purpose of this article is to review information on the use of TMS and tDCS as research tools to facilitate motor memory formation, motor performance, and motor learning in healthy volunteers. Studies implemented so far have mostly focused on the ability of TMS and tDCS to elicit relatively short-lasting motor improvements and the mechanisms underlying these changes have been only partially investigated. Despite limitations, including the scarcity of data, work that has been already accomplished raises the exciting hypothesis that currently available noninvasive transcranial stimulation techniques could modulate motor learning and memory formation in healthy humans and potentially in patients with neurologic and psychiatric disorders.

Effects of brain polarization on reaction times and pinch force in chronic stroke

BackgroundPrevious studies showed that anodal transcranial DC stimulation (tDCS) applied to the primary motor cortex of the affected hemisphere (M1affected hemisphere) after subcortical stroke transiently improves performance of complex tasks that mimic activities of daily living (ADL). It is not known if relatively simpler motor tasks are similarly affected. Here we tested the effects of tDCS on pinch force (PF) and simple reaction time (RT) tasks in patients with chronic stroke in a double-blind cross-over Sham-controlled experimental design.ResultsAnodal tDCS shortened reaction times and improved pinch force in the paretic hand relative to Sham stimulation, an effect present in patients with higher impairment.ConclusiontDCS of M1affected hemisphere can modulate performance of motor tasks simpler than those previously studied, a finding that could potentially benefit patients with relatively higher impairment levels.

Intermanual Differences in Movement-related Interhemispheric Inhibition

Interhemispheric inhibition (IHI) between motor cortical areas is thought to play a critical role in motor control and could influence manual dexterity. The purpose of this study was to investigate IHI preceding movements of the dominant and nondominant hands of healthy volunteers. Movement-related IHI was studied by means of a double-pulse transcranial magnetic stimulation protocol in right-handed individuals in a simple reaction time paradigm. IHI targeting the motor cortex contralateral (IHIc) and ipsilateral (IHIi) to each moving finger was determined. IHIc was comparable after the go signal, a long time preceding movement onset, in both hands. Closer to movement onset, IHIc reversed into facilitation for the right dominant hand but remained inhibitory for left nondominant hand movements. IHIi displayed a nearly constant inhibition with a trough early in the premovement period in both hands. In conclusion, our results unveil a more important modulation of interhemispheric interactions during generation of dominant than nondominant hand movements. This modulation essentially consisted of a shift from a balanced IHI at rest to an IHI predominantly directed toward the ipsilateral primary motor cortex at movement onset. Such a mechanism might release muscles from inhibition in the contralateral primary motor cortex while preventing the occurrence of the mirror activity in ipsilateral primary motor cortex and could therefore contribute to intermanual differences in dexterity.

Dopaminergic Influences on Formation of a Motor Memory

The ability of the central nervous system to form motor memories, a process contributing to motor learning and skill acquisition, decreases with age. Dopaminergic activity, one of the mechanisms implicated in memory formation, experiences a similar decline with aging. It is possible that restoring dopaminergic function in elderly adults could lead to improved formation of motor memories with training. We studied the influence of a single oral dose of levodopa (100mg) administered preceding training on the ability to encode an elementary motor memory in the primary motor cortex of elderly and young healthy volunteers in a randomized, double‐blind, placebo‐controlled design. Attention to the task and motor training kinematics were comparable across age groups and sessions. In young subjects, encoding a motor memory under placebo was more prominent than in older subjects, and the encoding process was accelerated by intake of levodopa. In the elderly group, diminished motor memory encoding under placebo was enhanced by intake of levodopa to levels present in younger subjects. Therefore, upregulation of dopaminergic activity accelerated memory formation in young subjects and restored the ability to form a motor memory in elderly subjects; possible mechanisms underlying the beneficial effects of dopaminergic agents on motor learning in neurorehabilitation. Ann Neurol 2005;58:121–130