Ketogenic diet: electrophysiological effects on the normal human cortex.
OBJECTIVE
To explore the cortical electrophysiology of the ketogenic diet (KD) in the normal human. KD is effective against refractory epilepsy, but its precise mechanism is obscure. At the transmitter level, an enhancement of GABA inhibition has often been proposed.


METHODS
We studied eight healthy volunteers undergoing a "classic" KD for 2 weeks. We measured several biochemical variables at baseline (T0), after 1 week (T1) and 2 weeks (T2) of KD, then 3 months after the KD conclusion (T3). Ketosis was quantified as 24-h ketonuria. At the same time, we studied the motor cortical excitability by means of transcranial magnetic stimulation (TMS). We also quantitatively evaluated the EEG signal in search of frequency shifts over the rolandic areas.


RESULTS
Significant (p < 0.05) neurophysiological changes appeared at T2. These consisted of a strengthening of short-latency cortical inhibition (SICI), a TMS index which is thought to reflect GABA-A inhibition in the cortex. Then, there was an enhancement of the beta EEG band over the perirolandic region, similar to that following administration of GABA-A agonists. All changes disappeared at T3.


CONCLUSIONS
A standard, short-term KD affected the cortical physiology of the normal human. The main changes were an augmented SICI and an increased perirolandic beta EEG activity, which are compatible with a lower level of neural excitation within the cortex.
Cantello
Roberto
R
Department of Clinical and Experimental Medicine, Section of NeurologySection of Clinical Chemistry, "A. Avogadro" University, Novara, ItalyDepartment of Diet and Nutrition, "Maggiore della Carità" Hospital, Novara, ItalyDepartment of Child Neurology and Psychiatry, IRCCS Fondazione, Istituto Neurologico Casimiro Mondino, University of Pavia, Italy.
Varrasi
Claudia
C
Department of Clinical and Experimental Medicine, Section of NeurologySection of Clinical Chemistry, "A. Avogadro" University, Novara, ItalyDepartment of Diet and Nutrition, "Maggiore della Carità" Hospital, Novara, ItalyDepartment of Child Neurology and Psychiatry, IRCCS Fondazione, Istituto Neurologico Casimiro Mondino, University of Pavia, Italy.
Tarletti
Roberto
R
Department of Clinical and Experimental Medicine, Section of NeurologySection of Clinical Chemistry, "A. Avogadro" University, Novara, ItalyDepartment of Diet and Nutrition, "Maggiore della Carità" Hospital, Novara, ItalyDepartment of Child Neurology and Psychiatry, IRCCS Fondazione, Istituto Neurologico Casimiro Mondino, University of Pavia, Italy.
Cecchin
Michela
M
Department of Clinical and Experimental Medicine, Section of NeurologySection of Clinical Chemistry, "A. Avogadro" University, Novara, ItalyDepartment of Diet and Nutrition, "Maggiore della Carità" Hospital, Novara, ItalyDepartment of Child Neurology and Psychiatry, IRCCS Fondazione, Istituto Neurologico Casimiro Mondino, University of Pavia, Italy.
D'Andrea
Federico
F
Department of Clinical and Experimental Medicine, Section of NeurologySection of Clinical Chemistry, "A. Avogadro" University, Novara, ItalyDepartment of Diet and Nutrition, "Maggiore della Carità" Hospital, Novara, ItalyDepartment of Child Neurology and Psychiatry, IRCCS Fondazione, Istituto Neurologico Casimiro Mondino, University of Pavia, Italy.
Veggiotti
Pierangelo
P
Department of Clinical and Experimental Medicine, Section of NeurologySection of Clinical Chemistry, "A. Avogadro" University, Novara, ItalyDepartment of Diet and Nutrition, "Maggiore della Carità" Hospital, Novara, ItalyDepartment of Child Neurology and Psychiatry, IRCCS Fondazione, Istituto Neurologico Casimiro Mondino, University of Pavia, Italy.
Bellomo
Giorgio
G
Department of Clinical and Experimental Medicine, Section of NeurologySection of Clinical Chemistry, "A. Avogadro" University, Novara, ItalyDepartment of Diet and Nutrition, "Maggiore della Carità" Hospital, Novara, ItalyDepartment of Child Neurology and Psychiatry, IRCCS Fondazione, Istituto Neurologico Casimiro Mondino, University of Pavia, Italy.
Monaco
Francesco
F
Department of Clinical and Experimental Medicine, Section of NeurologySection of Clinical Chemistry, "A. Avogadro" University, Novara, ItalyDepartment of Diet and Nutrition, "Maggiore della Carità" Hospital, Novara, ItalyDepartment of Child Neurology and Psychiatry, IRCCS Fondazione, Istituto Neurologico Casimiro Mondino, University of Pavia, Italy.
D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D001835:Body Weight; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D004035:Diet Therapy / Q000706:statistics & numerical data*; D004041:Dietary Fats / Q000378:metabolism; D004569:Electroencephalography / Q000379:methods / Q000706:statistics & numerical data; D004594:Electrophysiology; D019305:Epilepsy, Rolandic / Q000178:diet therapy / Q000378:metabolism / Q000503:physiopathology; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D007839:Functional Laterality / Q000502:physiology / Q000528:radiation effects; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007657:Ketone Bodies / Q000096:biosynthesis / Q000652:urine; D007662:Ketosis / Q000378:metabolism* / Q000652:urine; D008297:Male; D008954:Models, Biological; D050781:Transcranial Magnetic Stimulation / Q000379:methods / Q000706:statistics & numerical data; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D004041:Dietary Fats; D007657:Ketone Bodies; D005680:gamma-Aminobutyric Acid