Monday, October 3, 2016

Greenville Neuromodulation Center Professional Newsletter
Volume 2, No. 9
September 30, 2016
Caution Advised - Deep Brain Stimulation (DBS) is Not Normal
and Does Not Restore Normality
Erwin B. Montgomery Jr. MD
Professor –     As Abraham Maslow said, “when all you have is a hammer, the whole world looks like a nail.”

Student –       The statement presupposes that one knows that something other than a hammer exists even if it is not available.  It would not make sense if only “hammers” existed because there would be nothing to differentiate “hammer” from anything else.  Indeed, there would be no word “hammer.”  The saying must imply that there are known alternatives to hammers, yet still the whole world looks like a nail.  What is that?

Professor –      Willful ignorance.

Student –         I would call that being stupid.

Professor –      I was trying to be kind.

Student –         They need to “own it.”

               In addition to the remarkable clinical benefits attributable to Deep Brain Stimulation (DBS), it has become an increasingly used tool to investigate the operations of the brain.  Scientists examine the effects of DBS on a specific target, such as the subthalamic nucleus, for various physiological or psychological functions, to infer the role of the target in the function.  In the large majority of research publications, the effects of DBS are attributed to the structure being stimulated. Further, the effects are then thought to reflect the physiology or pathophysiology of the structure targeted by DBS.

               Such inferences are invalid.  This is not to say the inferences are true or false, only that the experiments (arguments) that contain the inference are invalid.  For example, consider an experiment examining the effects of DBS targeted at the subthalamic nucleus on lexical function.  Differences are noted in tests of lexical function when the stimulator is turned on compared to the situation when the stimulator is turned off.  The inference is made that the subthalamic nucleus is involved in lexical functions.  This is an example of the logical fallacy Post Hoc Ergo Propter Hoc (since b follows a, a must be the cause of b).  This fallacy is a special case of the Fallacy of Limited Alternatives because b could be due to any number of causes other than a, particularly if a is complex and multifaceted.

In the case above, DBS in the vicinity of the subthalamic nucleus generates action potentials in virtually any axon in the vicinity. These include axons terminating on neurons within the subthalamic nucleus, which affects the next or post-synaptic neuron but also antidromically activates the neurons outside of the subthalamic nucleus.  If these neurons have axon collaterals to other structures, then antidromic action potentials will proceed down the branch in an orthodromic manner to activate structures that have nothing to do with the subthalamic nucleus.  Indeed, axons passing in the vicinity without any connection to the subthalamic nucleus may be activated.

The situation becomes even more complex.  Within tens of milliseconds, activities generated in the vicinity of the DBS lead, such as in the subthalamic nucleus, can spread extensively.  This spread is reinforced by resonance with repeated DBS pulses.  Such extension with repeated pulses has been demonstrated by wider distribution of the electroencephalographic evoked potential to a brief train of DBS pulses in the vicinity of the subthalamic nucleus compared to single pulses (Baker KB, et al. 2002).

The DBS pulse is fairly indiscriminate in which axons within the volume of the electrical field are activated. Factors include proximity to the cathode, myelination, axonal diameter and axonal branching patterns.  The DBS pulse stimulates anything where it is put, and targeting seldom obeys physiological organization.  Further, the action potentials initiated in the axons are simultaneously affecting a great many axons.  The DBS pulse is more analogous to a lightning bolt striking a large group of people and then inferring that the mass convulsions are a normal phenomenal.  It is not as though a single person is struck and the effects on those remaining can be understood based on the physiological properties and contributions of that single strike.

None of the criticisms offered above is to say that DBS is not a valuable tool in research, quite the contrary.  Clearly the clinical effects of DBS demonstrate the interactions between the DBS pulses and the physiology.  Rather, the criticism is necessary to properly use DBS as a tool, particularly in drawing inferences from DBS experiments.  Given the complexity of the responses to DBS, including those without any direct relationship to the target of DBS, how can anybody reasonably ascribe the effects of DBS to the physiology of the target?  Specifically, how can anybody reasonable ascribe the effects of DBS in the vicinity of the subthalamic nucleus to physiology of the subthalamic nucleus?  Note, anyone can say just about anything they want to say.  However, if one wanted to be scientifically responsible, then one would withhold attribution or at the very least append the appropriate caveats.  Yet this is seldom done.

One might argue that scientific reports making inferences attributing some property or function to the DBS target really is only describing the “facts” of the experiments and that inferences are only secondary or peripheral.  They may argue that the reader is free to draw whatever inferences she may want.  However, such as claim is not only disingenuous and self-serving, it is a disservice to science.  It reduces science to “stamp collecting”.  If that position was seriously adopted, then science would be reduced to the Solipsism of the Present Moment where no knowledge exists beyond very narrow and exact circumstances of a particular experiment.  There would not be any generalizable knowledge.  Most importantly, the actual observation resulting from a particular experiment could not be used to justify or support any future experiment.  Science always would be just a set of dots (each dot corresponding to a specific and limited observation) and there would never be any lines connecting the dots.  These lines are critical because it is interpolation between the dots onto the line and extrapolation of the lines connecting the dots that point to possible future knowledge.

Inferences are very important and consequently, it is important that inferences are sound.  The epistemic importance of inferences is demonstrated above.  The practical importance of inferences is seen in scientific publications.  Most scientific publications are structured with introductions and discussions which serve the important purpose of connecting previous dots (in the introduction) to justify and set the context for the new dots (experimental observations).  Finally, the new and old dots are interconnected by lines of inference to provide new knowledge and understanding and very importantly point the way to future research.  Yet, it the great majority of scientific publications, the old dots are the past inferences and rarely if ever the actual observations of previous experiments.  Thus, the past inferences take on the epistemic status of facts as they are used in lieu of the original observations in the argument that comprises the research.  Inferences, regardless of their lack of soundness, become quasi-facts.

Most inferences derive from the hypotheses used in the scientific method.  A hypothesis not refuted during the application of the Scientific Method is then taken as true and becomes the inference derived from the observational data.  However, there is a flaw.  The Scientific Method where a hypothesis gives rise to a testable prediction that if found is thought to validate the hypothesis.  However, this use of the Scientific Method is the Fallacy of Confirming the Consequence which is of the form if a (hypothesis) implies b (prediction) is true and b is true, then a is true.  However, b could be true for many reasons other than a.  In the case of DBS in the vicinity of the subthalamic nucleus inducing a change in behavior or functions, the Scientific Method becomes if the subthalamic nucleus is involved in behavior A or function B, then DBS of the subthalamic nucleus should affect behavior A or function B, the experiments demonstrate this to be the case, thus the subthalamic nucleus is involved in behavior A or function B.  However, as discussed above, DBS affects far more than the neurons in the subthalamic nucleus and these other effects could be responsible for the change in behavior A or function B.  There is no way from the experiment alone to know which of the many possible responses to the DBS pulse is responsible for the change. Note, this does not mean that an effect of the DBS pulse directly on subthalamic nucleus neurons cannot mediate the change in behavior or function; only that one cannot conclude that is the case from the experiment alone.

Even if one were to grant that a change, such as a restoration of normal function, was consequent to DBS, this is not to say that the manner by which DBS restores the appearance of normal function is the same as the normal intact physiological mechanisms.  The inability to attribute the mechanisms by which DBS restores a normal function to the same mechanisms that operate normally is due to the Inverse Problem.  Typically, behaviors are mediated by the actions of the lower motor neurons in the brainstem and spinal cord.  These neurons receive multiple and diverse inputs.  Consequently, one cannot know from observing the consequence of lower motor neuron activations what is the source of the relevant actions onto the lower motor neurons.

To argue that normalization of behavior with DBS utilizes the same physiological mechanism normally involved in the behavior would be the logical Fallacy of Four Terms.  Therefore, one cannot attribute presumed DBS-related mechanisms as providing insight into normal physiological mechanisms.  The fallacy would be the following: Major premise -  Normal function implies normal physiology; Minor premise - DBS restores normal function; and Conclusion – DBS is normal physiology.  It would appear there are two terms, “normal physiology” and “DBS” that are linked through the third bridging term “normal function.” However, as described above, the “normal function” in the case of the normal condition may not be the same as “normal function” in the case of DBS.  Thus, there are two different bridging terms, hence the fallacy of Four Terms.  Again, it is important to appreciate that the fallacy does not mean that the DBS mechanisms cannot be the same as the normal mechanisms, but only that the experiment cannot provide confidence that they are the same.  Once again, it is not that the scientists cannot offer the theory that normal mechanisms underlying the normal function is similar to DBS mechanisms.  However, such inferences can only be tentative and thus, demand that the appropriate caveats be explicitly appended to any inferences, which is seldom done.

As can be appreciated, the inferences derived from demonstrating the predictions of hypotheses using the Scientific Method are indeterminate except when the experiments fail to demonstrate the prediction.  In the latter case, failure to demonstrate the prediction is clear evidence for the falsehood of the hypothesis.  Also, the Inverse Problem demonstrates that the same phenomena may have many causes and the phenomena alone cannot determine which cause is relevant.  One has to bring knowledge extraneous to and independent of the experiment to help adjudicate which of the multiple causes is most probable.  But it is important to note, the additional evidence cannot be directed solely at the inference that is being made.  The additional evidence must be directed at all the reasonable alternative inferences.  Failure to do so represents Confirmation Bias.  Yet, rarely in scientific reports are alternative inferences and the relevant external knowledge ever raised.

The tendency towards limited reviews within the introductions and discussions of scientific papers risking Confirmation Bias has a long history.  Charles Bazerman analyzed the rhetoric of scientific reports in the Philosophical Transactions of the Royal Society from 1665 – 1800 (Bazerman, C. 1997, pages 169-186).  In the essay, Bazerman described four stages with indistinct boundaries.  In the first period, 1665-1700, scientific papers were uncontested reports of events.  In the second stage, from 1700-1760, experimental results appeared and the discussions centered over the results.  It was not until the third period, 1760-1780, that papers “explored the meaning of unusual events through discovery accounts (Bazerman, C. 1997, page 184), which can be taken as discussions of the inferences drawn from the accounts. 

During the fourth period, approximately 1790-1800, experiments were reported as claims for which the experiments were to constitute proof, but most were the Fallacy of Confirming the Consequence as described above.  Further, experimenters were presenting claims that were solely the result of their individual efforts and not “recognizing the communal project of constructing a world of claims… Although the individual scientist has an interest in convincing readers of a particular set of claims, he does not yet explicitly acknowledge the exact placement of the claims in the larger framework of claims representing the shared knowledge of the discipline” (Bazerman, C., 1997, page 184).

The operative words are “communal project” and “shared knowledge of the discipline.”  Since the founding of the Royal Society of London in 1661, the community charged with the scientific project was highly selective (Shapin S., Schaffer S., 1985).  Public demonstrations of experiments meant to vouchsafe the results were limited to a select group, perhaps a very early instantiation of Confirmation Bias.  Critics, such as the famous natural philosopher, Thomas Hobbes, were vigorously excluded.  Certainly, the historical analysis of the progress of modern science by Thomas Kuhn (1962) demonstrates that this sort of exclusivity maintains Confirmation Bias even today.

               In the final analysis, the state of knowledge regarding DBS is such that inferring neurophysiological functions from DBS effects is not possible.  Rather, only possibilities can be offered and consequently, all reasonable possibilities should be considered.  Papers attempting to do so have the obligation to clearly state the tentative and problematic nature of such inferences, which is best accomplished by vigorously presenting alternatives based on a thorough understanding of all the relevant literature.  Editors of scientific journals should insist that this be done.


Baker KB, Montgomery EB Jr, Rezai AR, Burgess R, Lüders HO. Subthalamic nucleus deep brain stimulus evoked potentials: physiological and therapeutic implications. Mov Disord. 2002 Sep;17(5):969-83. PubMed PMID: 12360546

Bazerman, C. “Reporting the Experiment: The Changing Account of Scientific Doings of the Philosophical Transactions of the Royal Society, 1665-1800”, in Landmark Essays on Rhetoric of Science: Case Studies, Vol. 11, R. A. Harris ed., Hermagoras Press, 1997, pages 169-186

Kuhn T. The Structure of Scientific Revolutions, University of Chicago Press, 1962

Shapin S, Schaffer S. Leviathan and the Air-Pump: Hobbes, Boyle, and the Experimental Life. Princeton University Press, Princeton, New Jersey, 1985, ISBN 0-691-08393-2

Monday, September 12, 2016

A Chain is Only as Strong as its Weakest Link – The Microelectrode

Erwin B. Montgomery Jr. MD

August 25, 2016

Volume 2; Issue 8

The targets for Deep Brain Stimulation (DBS) for movement disorders are not the subthalamic nucleus (STN), globus pallidus interna (GPi) or the ventral intermediate nucleus of the thalamus (Vim).  It is the sensori-motor region of the STN.  It is the motor homunculus appropriate to the patient’s symptomology in the GPi and Vim.  To date, the only way to confidentially know whether the target has been obtained is by microelectrode recordings of extracellular action potentials (spikes) generated in individual neurons with simultaneous sensori-motor activations of the periphery.

               Critical to successful microelectrode recordings is the prevention and recognition and elimination of noise and artifact.  Noise and artifact are ubiquitous but nonetheless, can be dealt with successfully.  Modern electronic electrophysiological recording systems are remarkably robust at preventing or reducing noise and artifact from the external electrical environment.  However, a sound knowledge of electricity, electronics and electroneurophysiology is still necessary for successful intraoperative neurophysiological monitoring because an “ideal” recording environment cannot be guaranteed for each and every case.

               Environment sources of noise and artifact generally are appreciated.  What may not be appreciated is that actual neuronal spikes are a predominant source of “noise” as systems become increasingly robust at preventing environmental noise.  This seems counterintuitive and hence a source of confusion.

The voice in the crowd

               The challenge for the intraoperative neurophysiologist is to hear the seemingly one-sided conversations of individual neurons in a crowd of many neurons.  The situation can be likened to attempting to listen to the conversation of a single fan in a stadium of fans where everyone is talking.  The neurophysiologist is in the arena with a microphone trying to listen to the single fan.  If the neurophysiologist is using the wrong microphone, it is unlikely that she will be able to disambiguate the speech of the single fan of interest from the speech of the crowd.

               More importantly, it is critical that the neurophysiologist in the arena  knows whether or not the voice she is listening to is that of the single fan of interest.  To do so, the speech volume must “stand out” from the volume of the other voices in the crowd.  If she would use a volume meter, the voices in the crowd would create amplitudes that vary by some small magnitude, while intermittently, the voice of the single fan of interest would be substantially larger than all the other voices.  Also, the frequency at which the single fan speaks must be much less than the voices of the crowd.  If the single fan of interest was talking incessantly, there would be no way to distinguish the voice of the single fan.

               Another way the neurophysiologist in the arena can have confidence that she is listening to the voice of the single fan of interest is if what the neurophysiologist is hearing “makes sense.”    If what is heard appears to be strands of different conversations being superimposed, then the neurophysiologist cannot be sure that she is listening to the single fan.

The voice of neurons

               The issues described above for recording the speech of a single fan in a stadium crowd hold true for analyzing and interpreting the train of neuronal spikes.  The amplitude of the spike of the neuron of interest must “stand out” from the amplitude of the spikes from all the other neurons (perhaps hundreds) that are in the vicinity of the microelectrode tip.  This is critical in determining whether the neuron of interest is related to sensori-motor activations of the periphery.  If the spikes of other neurons not related to sensori-motor activations are approximately the same size, then the pattern of spikes indicating relationship to the peripheral activations will not be seen over the unrelated spikes of other neurons.  The key then is to ensure that only a few neurons have relatively large spikes and all the other neurons have small spikes.

               No electronic amplifiers, filters or computer systems can ensure that only a few neurons have relatively large spikes and all the others have small spikes.  This critical condition can only be assured by the proper microelectrode.  Thus, the appropriate use of the proper microelectrode is critical to identifying the actual target for DBS.  It is important that the intraoperative neurologist have a sophisticated understanding of the physics of microelectrodes.

Physics of microelectrode recording

               As might be appreciated, one way to “zero in” on the voice of the single fan in the crowd is to use a microphone that is so small that it can only pick up one voice at a time and then move the microphone close to the person of interest.  In actuality, as one cannot know which voice is the one of interest, it is necessary to move the microphone from one person to another.

               Similarly, one would like a microelectrode with a recording tip so small as to pick up the spikes from one or a few neurons in the immediate vicinity of the microelectrode tip and far enough away from the dendrites and cell body (soma) of other neurons so spikes from those neurons are much smaller in amplitude.  However, the small tip presents challenges. 

The recording tip typically is made of a conductive metal such as an alloy of platinum-iridium.  As metal atoms loosely hold onto electrons, the electrical field generated by a neuronal spike “pushes” the loosely held electrons towards the electronic amplifier, filter and computer systems.  However, the metal conductor has an impedance to movement of the electrons, thereby reducing the signal that can be recorded.  The smaller electrode tip creates greater impedance and smaller the signal.  The higher impedance also increases the risk of artifact and noise.  Thus, one is confronted with wanting a recording tip that is very small, but at the same time, one that does not create too much impedance.

It is not the volume (size) of the microelectrode tip that is the major determinant of impedance, but rather the surface area.  Thus, an optimal microelectrode has the highest surface area to smallest volume possible.  The human brain is an example.  While the volume of the human brain is relatively small compared to some large animals, its wrinkled (walnut-like) surface greatly increases the surface area relative to the volume.  Likewise, the tip of the microelectrode can be wrinkled in manufacturing to increase the surface area relative to the volume.

Perhaps the best way to increase the surface area relative to the volume is to use very porous metals, in other words, metals that have the microscopic appearance of a sponge rather than a solid mass.  The surface area within the crevices of the sponge is far larger than the actual volume of the sponge.  Platinum-iridium alloys are very porous and thus, are most optimal for use in microelectrode records compared to the popular alternative, tungsten. 
It’s the size, not the impedance

               There is a common misconception that the impedance defines the optimal quality of the microelectrode.  This is incorrect.  Rather, it is the size of the microelectrode relative to the neuron that is critical.  The impedance is only secondarily related to the size of the microelectrode tip.  For example, a very small tip with a highly porous metal, such as platinum-iridium, may be significantly smaller than a microelectrode made with tungsten.  Thus, the platinum-iridium microelectrode, generally, will be more successful at isolating the spikes of the neurons of interest.

This author’s experience

               This author has conducted microelectrode recordings of neuronal extracellular action potentials for over 40 years using a variety of microelectrode types.  Invariably, platinum-iridium microelectrodes with tip exposures on the order of 20 microns and impedances between 0.5-0.6 megaohms have provided the best isolation of spikes from individual neurons and the most stable recordings.  The efficacy of neuronal recording is far better than with tungsten microelectrodes and certainly better than electrodes with impedances less than 0.4 megaohms.


               A careful analysis of the issues noted above invariably leads to the conclusion that platinum-iridium microelectrodes are superior.  Other applications may require somewhat different specifications.  To be sure, platinum-iridium microelectrodes may cost a bit more, but the additional costs likely pales in comparison to the added monitoring time and frustration from using suboptimal microelectrodes.

Monday, July 25, 2016

Risk Involved in Advancing Microelectrodes with Tips Withdrawn

Erwin B. Montgomery Jr. MD

Professional Newlsetter

Vol. 2, No. 7

July 25, 2016

We recently learned that some intraoperative neurophysiologists and neurosurgeons utilize the large indifferent or reference electrical contact for macrostimulation during targeting of the Deep Brain Stimulation (DBS) lead.  Such macrostimulation may be useful to infer the regional anatomy and physiology of the electrode location and to, perhaps, anticipate post-operative clinical response. Those interested in a fuller discussion of these benefits might consult Montgomery Jr. E.B., Intraoperative Neurophysiological Monitoring for Deep Brain Stimulation: Principles, Practice and Cases, Oxford University Press, 2015. 

There is a problem with some microelectrodes in that the sharp recording tip may extend many millimeters beyond the indifferent or reference electrode on the outer cannula of the microelectrode.  Thus, advancing the indifferent or reference electrode to the desired depth also means advancing the extended sharp tip, perhaps to a depth that could injure important structures.

Apparently, some intraoperative neurophysiologists and neurosurgeons will withdraw or retract the sharp tip into the outer cannula and then continue to advance the microelectrode until the indifferent or reference electrical contact is at the desired depth.  However, this results in the open end of the cannula moving through brain tissue.  The concern is that this will result in the “coring out” of tissue similar to what occurs during procedures such as stereotactic biopsies.  Advancing the electrode with the tip withdrawn could lead to an increased risk of intracranial hemorrhage.

We examined this possibility by passing a standard DBS microelectrode through fresh cow brain.  The sharp tip was extended and then the electrode was inserted.  Once the tip of the outer cannula was well into the brain, the sharp tip was retracted and the electrode moved through the brain until the electrode emerged.  The tip of the electrode was inspected for brain tissue fragments and none were found.  When the sharp tip was extended, tissue fragments were extruded, indicating these fragments were within the outer cannula.  These results were repeated on a second pass.

While these observations warrant further examination, neurosurgeons and intraoperative neurophysiologists must at least consider the potential operative risk associated with advancing the electrode with the tip withdrawn. Both this incremental risk and the benefits referenced above must be included in the risk-to-benefit analysis of the procedure.  It is important to note that this issue is not evidence of a design or manufacturing problem.  Rather, the risk is only attendant on the use of these types of microelectrodes in this particular manner.

At least in the United States, if an FDA-approved microelectrode in used in a manner that is not warranted by the FDA-approved manufacturer labeling or manual, it is considered an “off-label” use of an FDA-approved device. Advancing the electrode with the tip withdrawn could be considered an example of this.  Physician discretion in such “off-label” use is well respected by the FDA; however, the FDA expects the physician to use due diligence.1

Unfortunately, there is no data currently available to determine the magnitude of the incremental risk associated with advancing a DBS microelectrode with the tip withdrawn.  As discussed in the last professional newsletter (“Is It a Sin If One Does Not Get Caught?”, Vol. 2 No. 6, June 25, 2016) the risk is already so low as to make detection of even a doubling or more of the risk unlikely.  Nevertheless, this is not license and does not obviate the responsibility of physicians to be reasonable and responsible.

1 It is important to note that this author does not speak for the FDA and is not an attorney providing legal opinion.

Friday, July 1, 2016

Is It a Sin If One Does Not Get Caught?

Erwin B. Montgomery Jr. MD
Medical Director

Greenville Neuromodulation Center

Professional Newsletter

Vol. 2, No. 6

June 25, 2016

Person A – If you use this method you can double the risk of problems.

Person B – We rarely have problems.

Person A – How would you know? And you still are doubling the risk.

               Fortunately, the major risks associated with Deep Brain Stimulation lead implantation surgery are relatively rare.  For example, while post-operative scanning may reveal an intracerebral hemorrhage rate of nearly 10%, only approximately 2% result in a clinically significant hemorrhage.  The problem is that such rare events make surveillance and judgments difficult.  Statistical analysis and judgment depends on the Theory of Large Numbers.  The Central Tendency of a data set, such as the mean or median of the sample, stabilizes as the number of observations increases.  Prior to some critical number of observations, one cannot “trust” measures of Central Tendency.

               Consider the situation where the risk of significant hemorrhage with optimal methods is 1%.  This means that with each surgery, the risk is 1% or 0.01.  Assuming that the risk for each subsequent patient is independent, then the cumulative risk of witnessing a significant hemorrhage is n * 0.01, where n is the number of persons having surgery.  For example, the average risk for a significant hemorrhage occurring after 10 subjects is only 10%, or 0.1.  However, this number is misleading.  An individual patient cannot have a 10% significant hemorrhage.  Even if 49 patients were observed, the probability of having seen a significant hemorrhage in one patient still is less than 50%, or 0.5.  Even this assumes that the sample from which patients are drawn is representative of the population at risk.

               Next, consider the situation where a surgeon adopts a method that increases the risk of significant hemorrhage to 2%, or 0.02.  On average, it would take at least 25 subjects to have a 50% chance of detecting a single significant hemorrhage, and again more than 50 subjects to detect the excess hemorrhage over what would be expected under optimal conditions.

               The scenarios described above are  best-case, or idealized, situations.   Decision-making  becomes even more problematic when the actual occurrence is a stochastic process.  Thus, in one group of 50 patients, no hemorrhages are encountered.  In the next group of 50, 2 patients with significant hemorrhages are encountered.  Though the overall risk is unchanged,  the physician’s experience is very different.  If one wants to have confidence in the rate of significant hemorrhages, typically a much larger number of patients is required to conform to the Theory of Large Numbers that underlies statistical judgments.

The great danger is that the physician will make judgments based only on the group of 50 patients that he or she experiences.  If it is the first group, then the physician likely will underestimate the risk.  If it is the second group, there is the chance of overestimating the risk.  The scenario just described is also idealized by assuming complete knowledge of all the patients.  It is not clear if patients are followed in such a manner as to have complete knowledge.

The risk that it may not be possible to know
               As can be seen, judgments based on small numbers are very difficult.  One cannot have confidence in the various measures upon which physicians and healthcare professionals depend.  Yet the patient is in front of the physician and healthcare professional, and the latter are obliged to help.  The responsibilities and interactions between the patient, physician and healthcare professional can be understood in terms of the ethical principles of beneficence, autonomy, non-malfeasance (meant as not harming rather than suggesting incompetence), and justice. 

The obligation to beneficence is fundamental to medicine in the presumption that persons become physicians and healthcare professionals just to help.  The issue of non-malfeasance is more difficult.  In the general sense, malfeasance is unavoidable.  It harms the patient to make an incision in the scalp, yet we counterbalance that necessary harm with the benefit hoped to be obtained.  It is an age-old problem of trying to strike a balance between necessary harm and the greater hope of benefit.  One approach to the situation is the Principle of Double Effect, which explains how an action causing harm may be justified when it is inseparable from the good effect that is desired. One of the clearest explications of this was described by Thomas Aquinas (1225 - 1275) in his work Summa Theologica. According to this principle, a key determinant in balancing harm versus good is the intention of the physician and healthcare professional.  The intentions relate not only to the good, but also to the harm; thus the harm must be minimized.

               As we, physicians and healthcare professionals, must intend to minimize harm, how do we gauge our efforts?  What is the basis for our accountability?  Is it based on actuarial experience, that is, how many patients we may have harmed with the judgment based on more harm than is standard?  In this case, accountability is retrospective.  Given the difficulty of ascertaining harm, holding strictly to a retrospective accountability may risk allowing us a “get out of jail free” card.

               Alternatively, should not accountability be prospective?  Clearly, the large majority of physicians and healthcare professionals implicitly display prospective accountability by their judicious considerations prior to causing harm in order to obtain benefit.  But the question is how to construct the prospective accountability?  What is the basis for determining that certain methods should or should not be used?  As discussed above, subsequent demonstrations of harm are not likely helpful in a great many decisions physicians and healthcare professionals must make.

Obligation to use reason
               Much of the argument against “cookbook” medicine is based on the skepticism that any “recipe” could address the variability among patients.  Most every physician and healthcare professional recognizes the necessity of individualizing the care of a particular patient.  Thus, by necessity, physicians and healthcare professionals must exercise reason, even if reasoning is not valued by Evidence-Based Medicine.  Indeed, courts of law have been defining standards of medical care, not by what similarly- situated physicians would do, but rather based on what reasonable physicians would do.

               That same obligation to use reason is inherent in virtually every decision.  Fortunately, many of these issues have already been settled by consensus or consilience.  Nevertheless, the individual physician and healthcare professional are expected to use their own reasoning.  It is no less the case in the decisions about what methods to use for DBS lead implantation surgery.  The use of microelectrode recordings clearly increases the risk of hemorrhage, even if that increased risk does not show up in clinical trials.  To appreciate how this must be so, consider making the contrary statement that it does not matter how many times you puncture the brain in terms of risk.  To maintain this position, one would have to argue that the second microelectrode penetration somehow has less risk and the next one, if necessary, has even less risk.  This clearly does not make sense.  Thus, the obligation is to minimize the risks while maintaining the benefit.  This is also true of the type of microelectrodes used and how they are used.  In the absence of unobtainable data, one has to reason using principles and physics.

Monday, May 23, 2016

A Calling to be Better than Ourselves

Erwin B. Montgomery Jr. MD

Greenville Neuromodulation Center

Professional Newsletter

Vol 2 No. 5

May 23, 2016

Dear Dr. Montgomery:

I did not refer the patient [to you].  I don’t need your help.  Here is your evaluation and recommendations back.

Dr. X


The patient sought a second opinion, as is any patients’ right.  The patient asked that the evaluation and recommendations be sent to Dr. X, which any physician so asked would be obligated to do.  The paradox is that Dr. Montgomery agreed with the diagnosis set forth by Dr. X and only offered one additional consideration in the treatment.  Clearly, the description of the event may be out of context and there could be mitigating circumstances, but it is hard to envision circumstances that would justify the aforementioned response.  Apart from not being collegial, it is not in the patient’s best interest.  Most physicians and healthcare professionals would likely agree.  So the question for our profession is how are such incidences handled, not just for this specific case, but also how to prevent future occurrences?  Essentially, the question is one of accountability.

This author has yet to meet any physician and/or healthcare professional whose first intention was not to help patients.  Physicians and healthcare professionals are intelligent, hardworking, and likely would find better financial remuneration in fields other than medicine; furthermore, the practice environment is difficult. A very large percentage of physicians would not recommend others to enter the practice of medicine. However, we know that there are other motivations that can affect intentions. 

Nevertheless, we cannot default to assuming that every medical professional holds themselves accountable and this is sufficient.  Experience with human experimentation demonstrates this will not work.  Many physicians and clinical scientists opposed mandating Institutional Review Boards to govern human research consequent to the Belmont report in 1978 (Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, Report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Department of Health, Education and Welfare [DHEW] [30 September 1978]). Washington, DC: United States Government Printing Office).   Many of these physicians and clinical scientists held that good ethical practice is just what good clinicians do.  The numerous scandals of unethical research, continuing to this day, demonstrates the incredulity of such claims.

This is NOT to say that these physicians and clinical scientists, and by extension medical professionals, intended unethical behavior.  Rather, it is reasonable that many physicians and healthcare professionals may not appreciate the ethical complexities that are exacerbated by the many conflicts of interest that are imposed on medical professionals.  Accountability is part of the ethical practice of medicine.  The purpose of this newsletter is to explore some of the issues surrounding accountability.  Further, if we consider patients’ rights on par with civil rights, we cannot take solace even if 99% of patients have their rights respected for by physicians who hold themselves accountable.

The remarkable extent of authority in contrast to the extent of accountability

            It is hard to point to any profession that allows their practitioners such authority with so little accountability.  Airline pilots are frequently observed for their flying skills, both in real situations and in simulations of circumstances that are hoped never to occur in reality.  They face mandatory retirement at age 65 in many countries.  Air traffic controllers are required to retire at 56 years.   Among the reasons is the risk of sudden medical problems at these ages, which may place the passengers at an unacceptable risk.  Yet, there is nothing comparable for physicians and healthcare professionals.  While US Supreme Court justices have lifetime appointments, their decisions are held in the public eye and at least in some fashion, the justices are held accountable.

With respect to accountability, courts of law are evolving in the standards by which physicians and healthcare professionals are held accountable.  Courts of law are departing from definitions of malpractice as departures from standards of care that are determined by the conduct of similarly situated medical professionals to what a reasonable medical professional would do.  This evolution is a direct consequence of the realization that the prior standards established by peer practice could be self-severing thus shielding medical professionals from accountability.  This author has seen peer review conferences where less than the best professional conduct was deemed standard in order to avoid other medical professionals from being held to the best standard of professional conduct in the future.

Malpractice and accountability

            In 2000, the Institute of Medicine reported that medical errors cause between 44,000 and 98,000 deaths every year in American hospitals (Kohn LT, Corrigan JM, Donaldson MS, eds. To err is human: building a safer health system. Washington, D.C.: National Academy Press, 2000).  While the percentages that were preventable is open for debate, it is a serious problem (Brennan TA. The Institute of Medicine report on medical errors--could it do harm? N Engl J Med. 2000 Apr 13;342(15):1123-5. PubMed PMID: 10760315).  In 2016, medical errors were estimated to be the third leading cause of death in the United States (Martin A Makary, Michael Daniel, Medical error—the third leading cause of death in the US, BMJ 2016; 353 doi: (Published 03 May 2016) Cite this as: BMJ 2016;353:i2139).  Yet, only 1 in 7 adverse effects result in a malpractice claim (Oyebode F. Clinical errors and medical negligence. Med Princ Pract. 2013;22(4):323-33. doi: 10.1159/000346296. Epub 2013 Jan 18. Review. PubMed PMID: 23343656) and thus, the deterrence of the threat of malpractice accusations as a means of accountability would appear inadequate.  Further, deterrence, in the risk of a medical malpractice claim, is only effective if those whose actions are the subject find the deterrence credible.  This author once asked a chair of a department whether the chair was concerned about the physician members of the department being sued because of poor practice.  The reply was “our patients don’t sue”.  Further, rightly or wrongly, most medical professionals view the application of malpractice claims as capricious and consequently, despite the discomfort at the possibility of being sued for malpractice, it is ineffective in establishing any meaningful accountability.

            The threats of disciplinary actions by state medical boards are most likely in the same situation as medical malpractice claims.  In the state of Texas, 28.7% of revocations of medical licenses were due to incompetency or negligence in the years of 1989-1998 (Cardarelli R, Licciardone JC. Factors associated with high-severity disciplinary action by a state medical board: a Texas study of medical license revocation. J Am Osteopath Assoc. 2006 Mar;106(3):153-6. PubMed PMID: 16585383).  This rate would seem incongruent with the frequency of medical errors as described above.  Also, medical malpractice claims, as well as a large number of state medical board actions, require an aggrieved party to make a claim and thus, will likely underestimate the extent of the problems, further undermining any use in the interest of accountability.


            Self-policing within the medical disciplines has been advocated as a means of accountability.  An archetype is the Morbidity and Mortality Conference whose intended purpose is to review cases that went wrong.  This certainly should provide an opportunity for accountability, but studies have shown that the issue of errors in reasoning is rarely addressed (Gore D.C., National survey of surgical morbidity and mortality conferences. The American Journal of Surgery Volume 191, Issue 5, Pages 708–714, May 2006 DOI:; Orlander JD, Fincke BG. Morbidity and mortality conference: a survey of academic internal medicine departments. J Gen Intern Med. 2003;18:656-658; Pierluissi E, Fischer MA, Campbell AR, et al. Discussion of medical errors in morbidity and mortality conferences. JAMA. 2003;290:2838-2842) despite that most governments provide legal protection against self-incrimination. 

This author knows of situations where a physician, concerned about the conduct of a surgeon, explicitly followed the instructions of the departmental chair only to find themselves removed from any position to observe the surgeon’s subsequent behaviors and further was subjected to retaliation by constructive dismissal.  In another situation of unprofessional conduct of a physician in a private practice, another physician attempted to enlist the help of the local medical society to find an informal and less threatening means to address the conduct after direct attempts to personally discuss the situation failed.  The medical society said they had no means and referred the concerned physician to the state medical board who stated they would only intervene if a formal complaint was lodged after speaking to the board’s attorney.  Such actions would only escalate the tension and cause the physician of concern to become defensive.  Making an opportunity to seek accountability into a “nuclear option” effectively takes such interventions off the table.

Too few to fail

One could argue that in a free capitalist market, the consumer, in this case the patient, could “vote with their feet” and find a physician or healthcare professional they find accountable.  One could argue to let the “free hand of the market” force accountability.  However, for any free market to be effective, there must be transparency and choice.   In this case, consumers (patients) cannot force transparency because of their lack of knowledge compared to the provider.  Further, there is really little choice.  Whatever choice patients may have had, has been lost by HMOs and PPO’s that severely limit the patient’s choice.

Whatever choice, by which to enforce accountability, is further eroded by the shortage of physicians generally.  It is estimated that the shortage of neurologists from what is needed will grow from 11% (from 2012) to 19% by 2025 (Dall TM, Storm MV, Chakrabarti R, Drogan O, Keran CM, Donofrio PD, Henderson VW, Kaminski HJ, Stevens JC, Vidic TR. Supply and demand analysis of the current and future US neurology workforce. Neurology. 2013 Jul 30;81(5):470-8. doi: 10.1212/WNL.0b013e318294b1cf. Epub 2013 Apr 17. PubMed PMID: 23596071; PubMed Central PMCID: PMC3776531).  The concern is that a healthcare provider system will not risk alienating a neurologist (or any other physician and healthcare professional) by insisting on higher standards of accountability.

Ethical principles and moral theory

            From a number of ethical and moral perspectives, physicians and healthcare professionals have a responsibility to hold themselves, and each other, accountable.  Such accountability is inherent in the ethical principle of autonomy, meaning respect for the patient.  Similarly, accountability is inherent in the ethical principle of justice, whether that principle of justice is informed by libertarian or Kantian (deontological) morality.  The Kantian notion of morality holds that each person (patient) is an end unto themselves and not a means by which others achieve their ends.  Libertarian moral theory holds the maximum freedom is the greatest good.  Libertarianism avoids anarchy by mutually agreed contracts, either implicit or explicit, where benefits and obligations are freely traded with a set of constraints that enforce good faith and fair dealing.  Clearly, this is a call for accountability.

            In many ways, patients (or their legal representatives) have a contract with their physician and healthcare professional. It may be explicit between them or a surrogate can intervene on behalf of the patient, such as the insurer, government or society.  For example, the government, such as state medical boards, require physicians to treat every patient to the standards of practice and it is not necessary for any patient to negotiate such treatment with the medical professional.  Further, there is a contract between the government and medical professionals representing an exchange of goods and obligations.  The government grants medical professionals a form of monopoly.  Only those licensed by the government can enjoy the goods that come from providing professional medical care.  In exchange, medical professionals are expected to act in the patient’s best interest.  The state holds the physician accountable.

            Physicians and many healthcare professionals have an additional obligation of beneficence to the patient.  It is highly unlikely that any physician or healthcare professional paid for their education and training on their own.  It is society that provides the opportunity for individuals to become physicians and healthcare professionals.  This implies an obligation to reciprocate by caring for patients as patients deserve.

A matter of personal choice

            All the ethical principles and moral theories, in themselves, cannot compel the best efforts of medical professionals.  As discussed, there is very little in the way of effective outside enforcement of accountability.  Consequently, the only real recourse is internal accountability.  In other words, it is up to each physician and healthcare professional to hold themselves accountable.  Thus, we come back around to the issue of personal motivation.  Hopefully the motivations will have a perspective that is outwardly directed to the benefit of patients.  There would be much to gain by such a perspective.  One can learn a great deal about themselves in the process.  It is striking that Mohandas (Mahatma) Gandhi entitled his autobiography describing his efforts on behalf of his fellow citizens, The Story of My Experiments with Truth (1948).

Thursday, May 5, 2016

Preoperative Neuropsychological Testing for Deep Brain Stimulation: The Right Action Perhaps for the Wrong Reason

Emily R. Friedrich, B.A.
Remote Specialist

Erwin B. Montgomery Jr. MD
Medical Director

Greenville Neuromodulation Center
Volume 2, Issue 4

                Many, if not most centers implanting Deep Brain Stimulation (DBS) leads conduct neuropsychological testing prior to surgery.  The reasonable question is why?  Perhaps it is because neuropsychological testing was used in Randomized Control Trials (RCTs) of DBS.  However, just importing inclusion/exclusion criteria from RCTs into general practice is problematic and often counterproductive (Montgomery Jr. E.B., Twenty Things to Know About Deep Brain Stimulation, Oxford University Press, 2015).  Perhaps such testing is “standard” in these types of surgeries; borrowing from the long tradition of pre-operative neuropsychological testing for epilepsy surgery.  It is reasonable to ask how is “standard” in this case different from just habit; however, one should not confuse habit for knowledge.

Lack of predictive value

                The question of whether or not to conduct pre-operative neuropsychological testing preparatory to DBS surgery is reasonable, given that no study has demonstrated that neuropsychological status is a reliable predictor of post-operative outcomes.  If the benefit to be gained is some prediction of outcome, then it hardly seems that pre-operative neuropsychological testing is justified due to cost and risk.  Note, the risk of neuropsychological testing cannot be dismissed.  What do the clinicians do in a case where there is evidence of mild cognitive impairment?  Do clinicians then raise the issue of possible progression to Alzheimer’s disease?  Does one decline to offer DBS surgery, although there is no evidence supporting the decision to do so?  What if these abnormal test results are false positives?  These are not insignificant concerns.

                Note the claim that neuropsychological test performance is not prognostic of post-operative outcome is not to say that pre- and post-operative neuropsychological functions are not a concern.  Rather, the lack of prognostic value may well be methodological, then an absence of data of the appropriate kind and quantity.  As Carl Sagan said “the absence of evidence is not evidence of absence”.  Then how is it possible, with all the clinical trials of DBS, that one does not know whether neuropsychological testing is predictive of post-operative outcome.

                One possible explanation is that the neuropsychological screening of patients in DBS clinical trials excluded patients with significant pre-existing neuropsychological abnormalities. Upon review of several recent DBS and neuropsychological peer-reviewed studies, the inclusion criteria included patients without neurocognitive and mood deficits (Aono, M., Iga, J., Ueno, S., Agawa, M., Tsuda, T., & Ohmori, T. (2014). Neuropsychological and psychiatric assessments following bilateral brain stimulation of the subthalamic nucleus in Japanese patients with Parkinson's disease. Journal of Clinical Neuroscience, 21, 1595 - 1598.; Borden, A., Wallon, D., Lefaucher, R., Derrey, S., Fetter, D., Verin, M., & Maltête, D. (2014). Does early verbal fluency decline after STN implantation predict long-term cognitive outcome after STN-DBS in Parkinson's disease. Journal of the Neurological Sciences, 346, 299-302.; and Houvenaghel, J. F., Le Jeune, F., Dondaine, T., Esquevin, A., Robert, G. H., Péron, J., … & Sauleau, P. (2015). Reduced verbal fluency following subthalamic deep brains stimulation: A frontal-related cognitive deficit?. PLOS One).  This results in a floor effect.  The consequence is that there is relatively little variance in the neuropsychological outcomes and consequently one cannot parse out the variance over the variance in the pre-operative testing.  Thus, if pre-operative neuropsychological status was predictive of outcome, one would not know it.  Certainly, there is the exception of verbal fluency that does appear to worsen in many patients following DBS lead implantation.  However, the effect is mild to moderate.  Whether or not pre-existing deficits in verbal fluency places the patient at a greater risk for worsening of verbal fluency is unknown.

Identification of concerns

                There certainly are neuropsychological concerns regarding DBS, but it is more likely that the benefit is detecting them early and constructing appropriate pre-operative treatment and/or post-operative surveillance.  For example, depression is not an absolute contraindication to DBS, unless the patient has or will be in definite need for Electroconvulsive Therapy.  However, identifying a patient with depression pre-operatively allows proactive intervention by assuring that mental health professionals are aware that the patient will undergo DBS and are prepared to intervene if necessary. Often times, mental health care professionals encourage patients to treat the depression prior to DBS depending on the severity of the depressive symptoms.

                Impulsivity also can be a major problem identified in patients with Parkinson’s disease.  Again, it is unclear whether impulsivity is a contraindication to DBS or if it is a post-operative outcome to recognize and then intervene following surgery.  It is important to note that even successful DBS can cause a severe disruption of the psycho-social circumstances around the patient (Schüpbach M, Gargiulo M, Welter ML, Mallet L, Béhar C, Houeto JL, Maltête D, Mesnage V, Agid Y. Neurosurgery in Parkinson disease: a distressed mind in a repaired body? Neurology. 2006 Jun 27;66(12):1811-6. PubMed PMID: 16801642).

                The realistic expectations of patients, family members and caregivers is critical to successful DBS outcomes.  Unrealistic positive expectations can lead to serious disappointments.  Unrealistic negative expectations can lead to a failure to get definitive help.  Verbal fluency and impulsivity may be symptomatic of significant medical, psychological and sociological problems that deserve investigation and treatment in their own right.

                One could argue that formal neuropsychological testing lacks sufficient positive and negative predictive values when detecting problems like depression, impulsivity and unrealistic expectations.  Alternatively, the predictive value of neuropsychological testing is no better than the seasoned experience and judgment of physicians and nurses.  However, in our experience (EBM), this is not likely or consistently the case.  Interviews by expert neuropsychologists of the patients, family members and caregivers in addition to the formal testing often uncovers problems of depression, impulsivity and unrealistic expectations missed by the treating physicians and nurses.

Understanding post-operative changes

                Slowly progressing declines in neuropsychological functions often go unnoticed even while advancing to a severe degree.  For that reason, family members, caregivers, and healthcare professionals who have been involved in the patient’s care over long periods of time may not notice the degree of impairments, depression, and impulsivity.  A fresh look by an expert neuropsychologist may recognize these problems missed by those chronically involved in the patient’s care.

                The slow progressive change can often go unnoticed until a spotlight is placed on the patient, and then the extent of the problem(s) is finally realized.  DBS surgery is quite a spotlight.  Unfortunately, there is a tendency to jump to the conclusion that DBS surgery caused the neuropsychological problems.  In actuality, they are often times present before DBS, but were unrecognized post-operatively.  In those patients with pre-operative testing as a baseline, a repeat neuropsychological evaluation can help determine whether there actually was a significant change.  That knowledge benefits all involved in the patient’s care.

Advising all when the patient has significant cognitive problems

                Advising patients with a cognitive impairment whether to undergo DBS surgery is problematic.  The lack of studies capable of determining the prognostic value of neuropsychological testing, as described above, is a significant handicap.  One cannot even say that DBS meaningfully worsens cognitive functioning and thus, one cannot extrapolate to say that those with pre-existing cognitive problems are at greater risk.

                The situation above places physicians and healthcare professionals at risk for ethical problems.  No physician or healthcare professional wants to be responsible for worsening a patient in their care.  This can lead to an Omission bias where there is the false notion that errors of commission are worse than errors of omission.  While this may be psychologically true for physicians and healthcare professionals, it makes little difference to patients, family members and caregivers who suffer with either the continued disability and pain of the disease being treated or the suffering as a consequence of DBS surgery.  Physicians and healthcare professionals defaulting to the Omission bias are guilty of patronizing the patient and violating the ethical principle of autonomy.

                One approach to resolving these issues, at least for some patients, is to determine what is the “rate limiting” factor for the patient’s quality of life.  If the cognitive problems are severe enough that the patient’s quality of life would not be substantially improved with DBS, even as the problems due to the disease for which the DBS is administered improves, the patient will have gained little and therefore the risk and suffering associated with DBS surgery is not justified.  However, determining if the cognitive problems are the rate limiting effect requires some ability to prognosticate the impact of the cognitive problems on the quality of life.  Neuropsychologists and Speech Language Pathologists experienced with patients with dementia can help in those determinations.

Greenville Neuromodulation Center’s Recommendation

                Pre-operative neuropsychological testing is valuable and warranted even if the reasons are not what may have been originally expected.  Neuropsychologists assessing DBS candidates conduct a battery of neuropsychological assessments, including measures of intelligence, fine motor functions, frontal executive tasks including attention, concentration, and problem solving, language and verbal fluency, verbal memory and learning, visual memory, dementia rating, and quality of life. Pre-operative neuropsychological testing is highly recommended for patients being considered for DBS.