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BRIEF COMMUNICATIONS: B. Boroojerdi, M. Phipps, L. Kopylev, C.M. Wharton, L.G. Cohen, and J. Grafman Enhancing analogic reasoning with rTMS over the left prefrontal cortex Neurology 2001; 56: 526-528 [Abstract] [Full text] [PDF]

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Reply to Boylan

Babak Boroojerdi, "Jordan Grafman, Leonardo G Cohen"   (5 May 2001)

Enhancing analogic reasoning with rTMS over the left prefrontal cortex

Laura S Boylan   (5 May 2001)

Reply to Boylan 5 May 2001
Babak Boroojerdi Cognitive Neuroscience Section, NIH, "Jordan Grafman, Leonardo G Cohen" Send Correspondence to journal: Re: Reply to Boylan grafmanj{at}ninds.nih.gov Babak Boroojerdi, et al.	We thank Dr. Boylan for her brief discussion on our study of the positive effects of repetitive transcranial magnetic stimulation (rTMS) over the left prefrontal cortex (PFA) on analogical reasoning. As reported in the study, magnetic stimulation over the left M1 induced a condition-independent significant reduction in response times (RT) in all but one condition (simultaneous trials in the literal condition. Even under this condition, there was a strong trend towards a TMS-induced reduction of RT( p=0.003). We do not believe the reported results are based on a difference in statistical power. RT under each condition was compared to the RT under sham stimulation in the same subgroup of subjects and not to RT under motor cortex stimulation. Thus, comparisons of literal and analogical conditions with the results of sham stimulation over the left PFC were performed using the same subjects (N=8) and the RT reduction was found despite the lower number of subjects in this group compared to motor cortex condition (N=14). A direct comparison between M1 and PFC stimulation results in this experiment was not possible. Dr. Boylan declares caution is required in interpreting our results. Besides the usual caution in interpreting results using transcranial magnetic stimulation, the scientific method always requires that an initial study reporting interesting and potentially surprising results be replicated. We have also been unable to find positive effects of rTMS on motor function in patients with Parkinson’s disease. In addition, the reader should be aware that the temporal limitations of rTMS effects are typically of short duration and rTMS has been mainly used to disrupt cortical activity (ref. 6) with reports about positive rTMS effects on cognitive functions being rare (ref. 7, 8). In the latter case, the studies (including our study) have been performed with normal subjects and the results cannot be automatically generalized to patient populations with cognitive deficits. Given the lack of therapeutic alternatives to improve cognition for various patient populations, however, we believe that the possible therapeutic application of rTMS remains a promising area of research which should be further explored with different cognitive methods, rTMS measures, and study designs. References 6. Cohen LG, Celnik P, Pascual-Leone A, et al. Functional relevance of cross-modal plasticity in blind humans. Nature 1997;389:180-3. 7. Topper R, Mottaghy FM, Brugmann M, Noth J, Huber W. Facilitation of picture naming by focal transcranial magnetic stimulation of Wernicke's area. Exp Brain Res 1998;121:371-8. 8. Mottaghy FM, Hungs M, Brugmann M, et al. Facilitation of picture naming after repetitive transcranial magnetic stimulation. Neurology 1999;53:1806-12.
Enhancing analogic reasoning with rTMS over the left prefrontal cortex 5 May 2001
Laura S Boylan, Assistant Professor Department of Neurology, NY University School of Medicine Send Correspondence to journal: Re: Enhancing analogic reasoning with rTMS over the left prefrontal cortex laura.boylan{at}med.nyu.edu Laura S Boylan	I read with interest the report by Boroojerdi et al and its accompanying editorial. (ref. 1,2). Boroojerdi et al conclude that repetitive transcranial magnetic stimulation (rTMS) to the left prefrontal cortex (PFC) specifically enhances analogic reasoning. However, their data show improved response time (RT) with stimulation of the left primary motor cortex (M1) as well as with the left PFC. In the case of M1 stimulation, improvement is attributed to a non-specific effect although significant effects were not demonstrated in all conditions. One of the cited references provides evidence that stimulation to M1 specifically improves reaction time on more complex tasks. (ref. 3). The statistical power of the M1 analysis (based on 14 subjects) is greater than that of the left PFC analysis (based on 8 subjects). The failure to demonstrate significant RT improvement in the literal condition with left PFC stimulation might simply have been an issue of power. Did the amount of improvement in the literal condition differ between M1 and left PFC stimulation? The blind provided by sham-controlled, within-subject comparisons with rTMS has been demonstrated to be ineffective in at least one study. (ref. 4) Another approach is to compare active stimulation to target and non-target sites. Direct comparisons between M1 and left and right PFC stimulation are not included in the report but would be of interest. The editorial by Triggs and Kirshner suggests that rTMS effects on brain function might be exploited in neurorehabilitation. I would add further cautionary notes to their remarks. The editorial refers to the few studies that demonstrate beneficial effects of rTMS on cognition and motor behavior without acknowledging that rTMS is best established as a means of disrupting brain function through the creation of "virtual lesions". (ref. 5) My colleagues and I recently sought a therapeutic effect of rTMS in Parkinson's disease but inadvertently induced worsening of motor performance. (ref. 4). While it has been suggested that brain effects of rTMS are dependent on the frequency of stimulation, the relationship of stimulus measures to physiologic effect is unpredictable. (ref. 4). Another issue of therapeutic relevance not addressed in the editorial is the transient nature of rTMS effects. To my knowledge there are no reports of controlled studies that demonstrate effects of rTMS on cognition or motor behavior more than an hour following stimulation. Caution is required in the interpretation of the study by Boroojerdi et al in particular and in the contemplation of therapeutic potential of rTMS in general. 1. Boroojerdi B, Phipps M, Kopylev L, Wharton CM, Cohen LG, Grafman J. Enhancing analogic reasoning with rTMS over the left prefrontal cortex. Neurology 2001;56:526-528. 2. Triggs WJ, Kirshner HS. Improving brain function with transcranial magnetic stimulation? Neurology 2001;56:429-430. 3. Sawaki L, Okita T, Fujiwara M, Mizuno K. Specific and non- specific effects of transcranial magnetic stimulation on simple and go/no- go reaction time. Exp Brain Res 1999;127:402–408. 4. Boylan LS, Pullman SL, Lisanby SH, Spicknall KE, Sackeim HA. Repetitive transcranial magnetic stimulation to SMA worsens complex movements in Parkinson’s disease. Clin Neurophysiol 2001;112(2):259-264. 5. Pascual-Leone A, Walsh V, Rothwell J. Transcranial magnetic stimulation in cognitive neuroscience--virtual lesion, chronometry, and functional connectivity. Curr Opin Neurobiol 2000 Apr;10(2):232-237