TMS Role in Epilepsy- Can it treat seizures rather than cause them?

It is no secret that one of the dangers of transcranial magnetic stimulation is the possibility of inducing a seizure in subjects. This often causes people to regard TMS in a negative light, as the current statistics available that describe the likelihood that TMS will cause a seizure are shoddy at best. Dr. Harris referenced one group of TMS researchers that claimed that the stimulation only induces a seizure in about 4% of subjects. Apart from this, there seems to be relatively little information regarding the potential dangers of seizures that TMS carries along with it. Subjects with history of epilepsy in their families are cautioned from participating in TMS trials, however.

What then, would you say if I claimed that TMS could be used as a treatment for epileptic patients? One study, published in "Epilepsy Current," written by William H. Theodore argues for this capability of TMS. Results from TMS performed on epileptic subjects shows that people prone to seizures suffer from increased cortical excitability, as well as a reduced motor threshold. This means that the neurons in their brain require less of a stimulation to induce electric changes in them.

Theodore claims that the risk of seizures in patients with epilepsy during TMS is low. I think that their is some inherent useful components of TMS that can be helpful to epileptic subjects, but am still a little wary about this sort of use. I would like to see some more statistics on the chance of inducing a harmful seizure.

Can Young Children Understand Others' Mental States?

Part of the process of mentalizing involves the understanding of others' mental states, as well as the acknowledgment that others may hold false beliefs. Mentalizing is an important topic in social neuroscience research since it is what we use to explain the behavior of others, and ultimately to empathize and relate to people other than ourselves. Much of the research regarding theory of mind questions has held the belief that young children are not capable of understanding mental states in others. In fact, one group of researchers concluded that preschoolers could not comprehend the idea that people may have false beliefs, after results of their study demonstrated the failure of this age group in completing verbal tasks that dealt with false beliefs in others.

A more recent wave of research however, is re-exploring these previously accepted notions regarding the mental capabilities of young children. One particular study, published in Science and undertaken by Kristine Onishi & Renee Baillargeon suggests that 15-month old infants can understand false beliefs. A non-verbal task was run on the infants in which they were required to predict future behaviors of a person based on their belief as to where a toy was hidden. Results of the study indicated that infants appealed to the differences between true and false beliefs in their prediction of future behavior.

This is an interesting result, in that it suggests that even babies can undertake the process of mentalizing that allows us to understand what drives other people's behavior. Additional research needs to be done in this area to give more conclusive information, however I think this is a pretty bold start.

rTMS Improves Motor Function in Stroke Patients

Depending on the severity of a stroke, it is possible that motor function of the upper limbs could be affected in the long term. Recovering from a stroke involves the process of rehabilitation in order to restore function to the damaged motor system of the upper limbs. Some are left with no function, while others manage to work themselves through rehabilitation to a near complete restoration. In a study that seeks to provide beneficial scientific knowledge on the functional reorganization of the motor cortex after a devastating shock to the brain such as a stroke, Nowak, Bosi, Podubecka & Carey found that rTMS could be used to help facilitate beneficial neural plasticity in the cortical motor system. Their study was published in the Journal of Restorative Neurology and Neuroscience, and presents results that claim cortical excitation provided by rTMS can induce changes within the broader cortical network that go great lengths to improving motor coordination after a stroke.

These results are pretty powerful support of rTMS as a treatment method for stroke patients. While I was at first a little skeptical of the methods behind TMS (based on what we learned in class), there is no denying its benefits when reading results like these. Nowak et al do not deny that their are several methodological and theoretical issues that need be addressed before this can be a fully effective treatment method, but I am interested to see what will come of this research (it was only published in 2010).

rTMS Improves Cell Viability in Rats

A recent study performed by Post, Muller, Engelmann & Keck published in the European Journal of Neuroscience suggests a counter theory to the ideas suggested in class regarding the possible long-term dangers of rTMS. While there remains the possibility that using TMS on the wrong person may cause them to have a seizure, Post et al actually contend that long term rTMS may have positive benefits for the vitality of brain cells. To test this hypothesis, the researchers performed long-term rTMS on a group of rat subjects for about 11 weeks. After the treatment ended, the rats were tested for cognitive impairments or structural changes in the brain regions stimulated. No impairments or significant structural changes were found however. In fact, Post et al found that the long term viability of the cells was increased, especially in HT22 cells (a particularly type of hippocampal neuron that was one focus of the stimulation during the 11 weeks of testing). The increased viability was due to a neuroprotective effect against oxidation of the cells caused by the release of secreted amyloid precursor protein (sAPP) into the supernatant of the HT22 cells as well as the cerebrospinal fluid of rats. sAPP was found to protect cells against oxidative stressors such as amyloid beta and glutamate.

This is an interesting finding in that it suggests TMS may have some long term benefits for the health and overall survival rate for cells. It is important however not to discount the possibility of negative effects that TMS carries with it. This is only one positive benefit from a neurochemical perspective, so while it does suggest that there are benefits to using TMS, it does not discount the potential cons.

TPJ Involvement in Mentalizing

Since many years ago, it has been a tenant of neuroscience research that the way we mentalize others' cognitive states is largely through the processes of the frontal lobe. This area is implicated in much 'theory of mind' abilities; meaning the process of inferring another's belief, desire, or intention through a reasoned analysis of their actions. A recent study conducted by Samson, Apperly, Chiavarino & Humphreys (In Nature Neuroscience), however, has shown that the the left tempoparietal junction is not only involved in this type of mental processing but perhaps necessary for this ability. While previous research regarding theory of mind in healthy adults had shown (in addition to the normal degree of activation in the frontal lobes) mild levels of activation in the TPJ, no conclusive data had been collected that established a correlation between the activation and mental reasoning. By testing brain lesioned patients with damage in the TPJ and their abilities on a false-belief reasoning test, Samson et al have established that the TPJ is a necessary mediator for high-level cognitive reasoning such as that related to theory of mind ablities.

The study seems pretty convincing in its argument for the TPJ's role in mentalizing. Not only is there a shown correlation between damage in the TPJ and scores on the reasoning tests, but the researchers examine alternative explanations for the low scores of the lesioned patients and explain why they do not apply. I think it is interesting that such a large area of the brain (frontal lobe and TPJ) is used when inferring another's mental state, and it stands as another example that most brain functions are not restricted to one area only, but rather shared throughout the brain.

rTMS in the Cerebellum- Can it Improve your mood?

Dennis Schutter, Dorien Enter and Sylco Hoppenbrouwers, three Danish psychologists recently conducted a study (published in the Journal of Psychiatry Neuroscience) in which they tested the supposed mood-improving abilities of rTMS in the cerebellum and its effects on the processing of different facial expressions. Other recent studies have shown that as little as a single session of high frequency rTMS in the cerebellum can elicit positive emotional responses, as well as increase the reactivity of subjects to implicit positive stimuli. This increased sensitivity to the subconscious presentation of positive expressions usually occurred before a change in mood had been perceived or experienced by the subjects, indicating that the effects of rTMS in the cerebellum may be at lower levels of information processing rather than the conscious experience of mood. Schutter et al found consistent results with this idea, in that cerebellar rTMS was shown to increase implicit processing of happy facial expressions but not create any change in experienced mood. The researchers discussed possible reasons behind this latter finding, and introduced the possibility that their methods for mood detection were unfit to measure barely conscious changes in mood.

I find these results particularly interesting in light of our recent class discussion regarding the amygdala's role in vigilance detection in the presence of danger. In much the same way that the amygdala creates a subconscious reaction to danger before our conscious mind can even process what the source of danger is, the cerebellum seems to react to high-frequency rTMS by increasing subconscious processing of happy faces without communicating a change in mood to our conscious mind. While it is disputed whether a change in mood is actually present in these scenarios, the results are nonetheless interesting for their possible implications regarding the treatment of depression using rTMS.

Decreased Cortical Inhibtion in Patients Exhibiting Unipolar Depression

A 2006 study done by Malek Bajbouj et al published in Biological Psychiatry has revealed some interesting results regarding differences in cortical inhibition in patients exhibiting unipolar depression compared to healthy controls. Much prior research has been done on the subject of neurotransmitters such as GABA (gamma-aminobutyric acid) that play a role in the pathophysiology of depression. GABA is a known mechanism of cortical inhibition (the overall activity of the brain and the process by which chemical transmitters regulate brain function), and several previous studies have established that in depressed subjects GABA levels are unusually low. This can have several implications for the process of communication in the brain. Bajbouj et al use transcranial magnetic stimulation (TMS) to directly measure the effects that low GABA levels have on cortical inhibition, in this case specifically in the motor cortex. Areas of the motor cortex known for controlling hand movement were stimulated by TMS and the subsequent muscle action potential was recorded by EMG. Depressive patients were shown to have lower motor thresholds and shorter silent periods (periods of inactivity between potentials) than those of the healthy controls. This is an interesting finding in that it suggests a correlation between depression and motor control and function. I think that it is particularly interesting in the way that it manages to build on previous studies and knowledge regarding the function of GABA in cortical inhibition. While previous research provided a sort of background theory regarding the role of GABA, TMS allowed the researchers to directly measure the implications of decreased neurotransmitters on cortical inhibition. This shows the importance of using a multi-faceted approach in research. The study also exhibits the way that brain function is a distributive process, in that motor control was affected by as seemingly unrelated a thing as depression.