Julian Paul Keenan

Study and modulation of human cortical excitability with transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) can be applied in different paradigms to obtain a measure of various aspects of cortical excitability. These different TMS paradigms provide information about different neurotransmitter systems, enhance our understanding about the pathophysiology of neuropsychiatric conditions, and in the future may be helpful as a guide for pharmacological interventions. In addition, repetitive TMS (rTMS) modulates cortical excitability beyond the duration of the rTMS trains themselves. Depending on rTMS parameters, a lasting inhibition or facilitation of cortical excitability can be induced. These effects can be demonstrated neurophysiologically or by combining rTMS with neuroimaging techniques. The effects do not remain limited to the cortical area directly targeted by rTMS, but affect a wider neural network transynaptically. Modulation of cortical excitability by rTMS may in the future be useful not only as a research tool but also as a therapeutic intervention in neurology, psychiatry, and neurorehabilitation.

Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation

OBJECTIVE Repetitive transcranial magnetic stimulation (rTMS) is able to modulate the corticospinal excitability and the effects appear to last beyond the duration of the rTMS itself. Different studies, employing different rTMS parameters, report different modulation of corticospinal excitability ranging from inhibition to facilitation. Intraindividual variability of these effects and their reproducibility are unclear. METHODS We examined the modulatory effects of rTMS to the motor cortex at various frequencies (1, 10, 20 Hz) and at different time-points in twenty healthy volunteers. RESULTS We observed significant inhibition of MEPs following 1 Hz rTMS and significant facilitation of MEPs following 20 Hz rTMS for both day1 and day 2. Interestingly, at 1 Hz and 20 Hz rTMS, the modulatory effect produced by rTMS was greater on day 2. However, there was no significant change in corticospinal excitability following 10 Hz rTMS neither on day 1 nor day 2. CONCLUSION Our findings raise questions as to how stimulation parameters should be determined when conducting studies applying rTMS on multiple days, and in particular, studies exploring rTMS as a treatment modality in neuropsychiatric disorders.

The self and social cognition : The role of cortical midline structures and mirror neurons

Recent evidence suggests that there are at least two large-scale neural networks that represent the self and others. Whereas frontoparietal mirror-neuron areas provide the basis for bridging the gap between the physical self and others through motor-simulation mechanisms, cortical midline structures engage in processing information about the self and others in more abstract, evaluative terms. This framework provides a basis for reconciling findings from two separate but related lines of research: self-related processing and social cognition. The neural systems of midline structures and mirror neurons show that self and other are two sides of the same coin, whether their physical interactions or their most internal mental processes are examined.

Lesions of the fusiform face area impair perception of facial configuration in prosopagnosia

Background: Prosopagnosia, the inability to recognize faces, is associated with medial occipitotemporal lesions, especially on the right. Functional imaging has revealed a focal region in the right fusiform gyrus activated specifically during face perception. Objective: The study attempted to determine whether lesions of this region were associated with defects in face perception in patients with prosopagnosia. Methods: Five patients with acquired prosopagnosia were tested. They were asked to discriminate faces in which the spatial configuration of features had been altered. This was contrasted with their discrimination of changes in feature color, an alteration that does not affect spatial relations. Results: All four patients whose lesions included the right fusiform face area were severely impaired in discriminating changes in the spatial position of features. The one patient with anterior bilateral lesions was normal in this perceptual ability. For three of the five patients, accuracy was normal for changes in eye color. When subjects knew that only changes in mouth position would be shown, performance improved markedly in two of the four patients who were impaired in the initial test. Conclusion: Perception of facial configuration is impaired in patients with prosopagnosia whose lesions involve the right fusiform gyrus. This deficit is especially manifest when attention must be distributed across numerous facial elements. It does not occur with more anterior bilateral temporal lesions. Loss of this ability may contribute to the recognition defect in some forms of prosopagnosia.

Tactile spatial resolution in blind Braille readers

Objective: To determine if blind people have heightened tactile spatial acuity. Background: Recently, studies using magnetic source imaging and somatosensory evoked potentials have shown that the cortical representation of the reading fingers of blind Braille readers is expanded compared to that of fingers of sighted subjects. Furthermore, the visual cortex is activated during certain tactile tasks in blind subjects but not sighted subjects. The authors hypothesized that the expanded cortical representation of fingers used in Braille reading may reflect an enhanced fidelity in the neural transmission of spatial details of a stimulus. If so, the quantitative limit of spatial acuity would be superior in blind people. Methods: The authors employed a grating orientation discrimination task in which threshold performance is accounted for by the spatial resolution limits of the neural image evoked by a stimulus. The authors quantified the psychophysical limits of spatial acuity at the middle and index fingers of 15 blind Braille readers and 15 sighted control subjects. Results: The mean grating orientation threshold was significantly (p = 0.03) lower in the blind group (1.04 mm) compared to the sighted group (1.46 mm). The self-reported dominant reading finger in blind subjects had a mean grating orientation threshold of 0.80 mm, which was significantly better than other fingers tested. Thresholds at non-Braille reading fingers in blind subjects averaged 1.12 mm, which were also superior to sighted subjects’ performances. Conclusion: Superior tactile spatial acuity in blind Braille readers may represent an adaptive, behavioral correlate of cortical plasticity.Objective: To determine if blind people have heightened tactile spatial acuity. Background: Recently, studies using magnetic source imaging and somatosensory evoked potentials have shown that the cortical representation of the reading fingers of blind Braille readers is expanded compared to that of fingers of sighted subjects. Furthermore, the visual cortex is activated during certain tactile tasks in blind subjects but not sighted subjects. The authors hypothesized that the expanded cortical representation of fingers used in Braille reading may reflect an enhanced fidelity in the neural transmission of spatial details of a stimulus. If so, the quantitative limit of spatial acuity would be superior in blind people. Methods: The authors employed a grating orientation discrimination task in which threshold performance is accounted for by the spatial resolution limits of the neural image evoked by a stimulus. The authors quantified the psychophysical limits of spatial acuity at the middle and index fingers of 15 blind Braille readers and 15 sighted control subjects. Results: The mean grating orientation threshold was significantly ( p = 0.03) lower in the blind group (1.04 mm) compared to the sighted group (1.46 mm). The self-reported dominant reading finger in blind subjects had a mean grating orientation threshold of 0.80 mm, which was significantly better than other fingers tested. Thresholds at non-Braille reading fingers in blind subjects averaged 1.12 mm, which were also superior to sighted subjects’ performances. Conclusion: Superior tactile spatial acuity in blind Braille readers may represent an adaptive, behavioral correlate of cortical plasticity.

Self-recognition and the right hemisphere.

Although monkeys can perceive complex stimuli such as faces, only the higher apes are capable of recognizing their own face in a mirror. Here we show that in humans the right hemisphere of the brain seems to be preferentially involved in self-face recognition. Our findings indicate that neural substrates of the right hemisphere may selectively participate in processes linked to self-awareness.

Transcranial magnetic stimulation and neuroplasticity.

We review past results and present novel data to illustrate different ways in which TMS can be used to study neural plasticity. Procedural learning during the serial reaction time task (SRTT) is used as a model of neural plasticity to illustrate the applications of TMS. These different applications of TMS represent principles of use that we believe are applicable to studies of cognitive neuroscience in general and exemplify the great potential of TMS in the study of brain and behavior. We review the use of TMS for (1) cortical output mapping using focal, single-pulse TMS; (2) identification of the mechanisms underlying neuroplasticity using paired-pulse TMS techniques; (3) enhancement of the information of other neuroimaging techniques by transient disruption of cortical function using repetitive TMS; and finally (4) modulation of cortical function with repetitive TMS to influence behavior and guide plasticity.

Left hand advantage in a self-face recognition task

Subjects were exposed to pictures of self and others (e.g., friend, stranger, and famous people) to determine if there was an advantage in reaction time and accuracy in identifying the self. It was found that upright and inverted self-faces were identified more rapidly than non-self faces when subjects responded with their left hand, which in other tasks has corresponded with contralateral hemispheric dominance. These data suggest that self-recognition may be correlated with neural activity in the right hemisphere, and that the differences observed may not be unique to self-face recognition. These results are in agreement with previous research indicating that self-directed awareness is correlated with right prefrontal activity.

Where in the brain is the self

Localizing the self in the brain has been the goal of consciousness research for centuries. Recently, there has been an increase in attention to the localization of the self. Here we present data from patients suffering from a loss of self in an attempt to understand the neural correlates of consciousness. Focusing on delusional misidentification syndrome (DMS), we find that frontal regions, as well as the right hemisphere appear to play a significant role in DMS and DMS related disorders. These data are placed in the context of neuroimaging findings.

Alexia for Braille following bilateral occipital stroke in an early blind woman

Recent functional imaging and neurophysiologic studies indicate that the occipital cortex may play a role in Braille reading in congenitally and early blind subjects. We report on a woman blind from birth who sustained bilateral occipital damage following an ischemic stroke. Prior to the stroke, the patient was a proficient Braille reader. Following the stroke, she was no longer able to read Braille yet her somatosensory perception appeared otherwise to be unchanged. This case supports the emerging evidence for the recruitment of striate and prestriate cortex for Braille reading in early blind subjects.